Bruce Jancin

STOCKHOLM – Everolimus-eluting stents were associated with significantly lower risks of myocardial infarction, target vessel revascularization, and stent thrombosis than were sirolimus-eluting stents, during 3 years of follow-up in the LESSON-1 study.

A particularly striking finding in LESSON-1 (Long-Term Comparison of Everolimus-Eluting and Sirolimus-Eluting Stents for Coronary Revascularization) was the 70% lower rate of Q-wave MI in the everolimus-eluting stent (EES) group, Dr. Stephan Windecker noted, in presenting the study results at the annual congress of the European Society of Cardiology.

Some observers called the LESSON-1 findings interesting but nondefinitive, since the study was nonrandomized, single-center, observational, and reliant upon propensity score matching.

Dr. Windecker concurred. He noted there are four ongoing randomized trials comparing outcomes in everolimus- versus sirolimus-eluting stent (SES) recipients.

The LESSON-1 study involved 1,601 consecutive patients undergoing percutaneous coronary intervention with the Xience EES and 1,532 consecutive patients who received a Cypher SES. After propensity score matching, the final study population consisted of 1,342 matched subjects in each of the two treatment arms, explained Dr. Windecker of Bern (Switzerland) University Hospital.

The primary study end point was the 3-year rate of death, MI, or target vessel revascularization. It occurred in 14.9% of the everolimus group and 18.0% of the sirolimus cohort. The resultant 17% relative risk reduction fell just shy of statistical significance, owing to closely similar overall mortality rates in the two groups, he reported.

However, the EES group fared significantly better than SES recipients in terms of key prespecified secondary end points. For example, MI occurred in 3.3% of the everolimus recipients compared with 5.0% of the sirolimus group, for a significant 38% risk reduction. The MI rates diverged early and the gap increased steadily during follow-up.

Target vessel revascularization occurred in 7.0% of EES and 9.6% of SES recipients, for a significant 25% risk reduction.

Similarly, the everolimus group had a significantly lower rate of definite stent thrombosis during 3 years of follow-up: 0.5% vs. 1.6%. The rate of definite or probable stent thrombosis was 2.5% in the everolimus group and 4.0% with sirolimus. These differences were driven largely by the EES group’s zero incidence of very late stent thrombosis occurring after 1 year, compared with a 0.7% rate of definite very late stent thrombosis in the SES arm.

The lower incidence of MI in the EES group was partially explained by their significantly lower rate of stent thrombosis. Indeed, MIs occurring in association with definite stent thrombosis were 75% less frequent in the EES group, the cardiologist continued.

If this absence of stent thrombosis occurring beyond 1 year in EES recipients in LESSON-1 holds up in the ongoing large randomized trials, it will have important implications for the appropriate duration of dual antiplatelet therapy in patients with EES, Dr. Windecker said.

The divergent outcomes in patients with EES and SES may be due to the fact that “the two drugs are similar but nevertheless different,” he noted. “Everolimus is a semisynthetic analogue of sirolimus with a lower pharmacologic potency, and it is applied at lower doses than the sirolimus-eluting stent. So we have this counterintuitive finding that a drug that is somewhat less potent applied at a lower concentration nevertheless achieves higher efficacy.”

But there are other differences between EES and SES. The EES, which are of a newer generation than SES, utilize a substantially thinner polymer coating and have markedly less strut thickness.

“Which one of these components drives the difference is unknown at this point in time, but it may very well turn out to be a combination of all three,” according to Dr. Windecker.

He noted that EES have already been convincingly shown to provide clinical outcomes that are superior to paclitaxel-eluting stents in four randomized trials. He provided an updated meta-analysis with 3 years of follow-up in 6,789 patients in the COMPARE and SPIRIT II, III, and IV randomized trials, which showed that the rate of cardiac death or MI was 37% lower in the EES group. In addition, target lesion revascularization was 49% less likely with EES.

Discussant Dr. Petr Widimsky said the biggest of LESSON-1’s several limitations is the use of historical controls. While most EES recipients in the study received stents in 2007-2009, most SES recipients got their stents in 2004-2005.

“The knowledge about stent thrombosis and the skills in preventing it by appropriate implantation techniques improved during this period,” noted Dr. Widimsky of Charles University, Prague.

Disclosures: Dr. Windecker said that in the past he has been a consultant to numerous medical device companies that market stents.

STOCKHOLM – Everolimus-eluting stents were associated with significantly lower risks of myocardial infarction, target vessel revascularization, and stent thrombosis than were sirolimus-eluting stents, during 3 years of follow-up in the LESSON-1 study.

A particularly striking finding in LESSON-1 (Long-Term Comparison of Everolimus-Eluting and Sirolimus-Eluting Stents for Coronary Revascularization) was the 70% lower rate of Q-wave MI in the everolimus-eluting stent (EES) group, Dr. Stephan Windecker noted, in presenting the study results at the annual congress of the European Society of Cardiology.

Some observers called the LESSON-1 findings interesting but nondefinitive, since the study was nonrandomized, single-center, observational, and reliant upon propensity score matching.

Dr. Windecker concurred. He noted there are four ongoing randomized trials comparing outcomes in everolimus- versus sirolimus-eluting stent (SES) recipients.

The LESSON-1 study involved 1,601 consecutive patients undergoing percutaneous coronary intervention with the Xience EES and 1,532 consecutive patients who received a Cypher SES. After propensity score matching, the final study population consisted of 1,342 matched subjects in each of the two treatment arms, explained Dr. Windecker of Bern (Switzerland) University Hospital.

The primary study end point was the 3-year rate of death, MI, or target vessel revascularization. It occurred in 14.9% of the everolimus group and 18.0% of the sirolimus cohort. The resultant 17% relative risk reduction fell just shy of statistical significance, owing to closely similar overall mortality rates in the two groups, he reported.

However, the EES group fared significantly better than SES recipients in terms of key prespecified secondary end points. For example, MI occurred in 3.3% of the everolimus recipients compared with 5.0% of the sirolimus group, for a significant 38% risk reduction. The MI rates diverged early and the gap increased steadily during follow-up.

Target vessel revascularization occurred in 7.0% of EES and 9.6% of SES recipients, for a significant 25% risk reduction.

Similarly, the everolimus group had a significantly lower rate of definite stent thrombosis during 3 years of follow-up: 0.5% vs. 1.6%. The rate of definite or probable stent thrombosis was 2.5% in the everolimus group and 4.0% with sirolimus. These differences were driven largely by the EES group’s zero incidence of very late stent thrombosis occurring after 1 year, compared with a 0.7% rate of definite very late stent thrombosis in the SES arm.

The lower incidence of MI in the EES group was partially explained by their significantly lower rate of stent thrombosis. Indeed, MIs occurring in association with definite stent thrombosis were 75% less frequent in the EES group, the cardiologist continued.

If this absence of stent thrombosis occurring beyond 1 year in EES recipients in LESSON-1 holds up in the ongoing large randomized trials, it will have important implications for the appropriate duration of dual antiplatelet therapy in patients with EES, Dr. Windecker said.

The divergent outcomes in patients with EES and SES may be due to the fact that “the two drugs are similar but nevertheless different,” he noted. “Everolimus is a semisynthetic analogue of sirolimus with a lower pharmacologic potency, and it is applied at lower doses than the sirolimus-eluting stent. So we have this counterintuitive finding that a drug that is somewhat less potent applied at a lower concentration nevertheless achieves higher efficacy.”

But there are other differences between EES and SES. The EES, which are of a newer generation than SES, utilize a substantially thinner polymer coating and have markedly less strut thickness.

“Which one of these components drives the difference is unknown at this point in time, but it may very well turn out to be a combination of all three,” according to Dr. Windecker.

He noted that EES have already been convincingly shown to provide clinical outcomes that are superior to paclitaxel-eluting stents in four randomized trials. He provided an updated meta-analysis with 3 years of follow-up in 6,789 patients in the COMPARE and SPIRIT II, III, and IV randomized trials, which showed that the rate of cardiac death or MI was 37% lower in the EES group. In addition, target lesion revascularization was 49% less likely with EES.

Discussant Dr. Petr Widimsky said the biggest of LESSON-1’s several limitations is the use of historical controls. While most EES recipients in the study received stents in 2007-2009, most SES recipients got their stents in 2004-2005.

“The knowledge about stent thrombosis and the skills in preventing it by appropriate implantation techniques improved during this period,” noted Dr. Widimsky of Charles University, Prague.

Disclosures: Dr. Windecker said that in the past he has been a consultant to numerous medical device companies that market stents.

STOCKHOLM – Everolimus-eluting stents were associated with significantly lower risks of myocardial infarction, target vessel revascularization, and stent thrombosis than were sirolimus-eluting stents, during 3 years of follow-up in the LESSON-1 study.

A particularly striking finding in LESSON-1 (Long-Term Comparison of Everolimus-Eluting and Sirolimus-Eluting Stents for Coronary Revascularization) was the 70% lower rate of Q-wave MI in the everolimus-eluting stent (EES) group, Dr. Stephan Windecker noted, in presenting the study results at the annual congress of the European Society of Cardiology.

Some observers called the LESSON-1 findings interesting but nondefinitive, since the study was nonrandomized, single-center, observational, and reliant upon propensity score matching.

Dr. Windecker concurred. He noted there are four ongoing randomized trials comparing outcomes in everolimus- versus sirolimus-eluting stent (SES) recipients.

The LESSON-1 study involved 1,601 consecutive patients undergoing percutaneous coronary intervention with the Xience EES and 1,532 consecutive patients who received a Cypher SES. After propensity score matching, the final study population consisted of 1,342 matched subjects in each of the two treatment arms, explained Dr. Windecker of Bern (Switzerland) University Hospital.

The primary study end point was the 3-year rate of death, MI, or target vessel revascularization. It occurred in 14.9% of the everolimus group and 18.0% of the sirolimus cohort. The resultant 17% relative risk reduction fell just shy of statistical significance, owing to closely similar overall mortality rates in the two groups, he reported.

However, the EES group fared significantly better than SES recipients in terms of key prespecified secondary end points. For example, MI occurred in 3.3% of the everolimus recipients compared with 5.0% of the sirolimus group, for a significant 38% risk reduction. The MI rates diverged early and the gap increased steadily during follow-up.

Target vessel revascularization occurred in 7.0% of EES and 9.6% of SES recipients, for a significant 25% risk reduction.

Similarly, the everolimus group had a significantly lower rate of definite stent thrombosis during 3 years of follow-up: 0.5% vs. 1.6%. The rate of definite or probable stent thrombosis was 2.5% in the everolimus group and 4.0% with sirolimus. These differences were driven largely by the EES group’s zero incidence of very late stent thrombosis occurring after 1 year, compared with a 0.7% rate of definite very late stent thrombosis in the SES arm.

The lower incidence of MI in the EES group was partially explained by their significantly lower rate of stent thrombosis. Indeed, MIs occurring in association with definite stent thrombosis were 75% less frequent in the EES group, the cardiologist continued.

If this absence of stent thrombosis occurring beyond 1 year in EES recipients in LESSON-1 holds up in the ongoing large randomized trials, it will have important implications for the appropriate duration of dual antiplatelet therapy in patients with EES, Dr. Windecker said.

The divergent outcomes in patients with EES and SES may be due to the fact that “the two drugs are similar but nevertheless different,” he noted. “Everolimus is a semisynthetic analogue of sirolimus with a lower pharmacologic potency, and it is applied at lower doses than the sirolimus-eluting stent. So we have this counterintuitive finding that a drug that is somewhat less potent applied at a lower concentration nevertheless achieves higher efficacy.”

But there are other differences between EES and SES. The EES, which are of a newer generation than SES, utilize a substantially thinner polymer coating and have markedly less strut thickness.

“Which one of these components drives the difference is unknown at this point in time, but it may very well turn out to be a combination of all three,” according to Dr. Windecker.

He noted that EES have already been convincingly shown to provide clinical outcomes that are superior to paclitaxel-eluting stents in four randomized trials. He provided an updated meta-analysis with 3 years of follow-up in 6,789 patients in the COMPARE and SPIRIT II, III, and IV randomized trials, which showed that the rate of cardiac death or MI was 37% lower in the EES group. In addition, target lesion revascularization was 49% less likely with EES.

Discussant Dr. Petr Widimsky said the biggest of LESSON-1’s several limitations is the use of historical controls. While most EES recipients in the study received stents in 2007-2009, most SES recipients got their stents in 2004-2005.

“The knowledge about stent thrombosis and the skills in preventing it by appropriate implantation techniques improved during this period,” noted Dr. Widimsky of Charles University, Prague.

Disclosures: Dr. Windecker said that in the past he has been a consultant to numerous medical device companies that market stents.

STOCKHOLM – Everolimus-eluting stents were associated with significantly lower risks of myocardial infarction, target vessel revascularization, and stent thrombosis than were sirolimus-eluting stents, during 3 years of follow-up in the LESSON-1 study.

A particularly striking finding in LESSON-1 (Long-Term Comparison of Everolimus-Eluting and Sirolimus-Eluting Stents for Coronary Revascularization) was the 70% lower rate of Q-wave MI in the everolimus-eluting stent (EES) group, Dr. Stephan Windecker noted, in presenting the study results at the annual congress of the European Society of Cardiology.

Some observers called the LESSON-1 findings interesting but nondefinitive, since the study was nonrandomized, single-center, observational, and reliant upon propensity score matching.

Dr. Windecker concurred. He noted there are four ongoing randomized trials comparing outcomes in everolimus- versus sirolimus-eluting stent (SES) recipients.

The LESSON-1 study involved 1,601 consecutive patients undergoing percutaneous coronary intervention with the Xience EES and 1,532 consecutive patients who received a Cypher SES. After propensity score matching, the final study population consisted of 1,342 matched subjects in each of the two treatment arms, explained Dr. Windecker of Bern (Switzerland) University Hospital.

The primary study end point was the 3-year rate of death, MI, or target vessel revascularization. It occurred in 14.9% of the everolimus group and 18.0% of the sirolimus cohort. The resultant 17% relative risk reduction fell just shy of statistical significance, owing to closely similar overall mortality rates in the two groups, he reported.

However, the EES group fared significantly better than SES recipients in terms of key prespecified secondary end points. For example, MI occurred in 3.3% of the everolimus recipients compared with 5.0% of the sirolimus group, for a significant 38% risk reduction. The MI rates diverged early and the gap increased steadily during follow-up.

Target vessel revascularization occurred in 7.0% of EES and 9.6% of SES recipients, for a significant 25% risk reduction.

Similarly, the everolimus group had a significantly lower rate of definite stent thrombosis during 3 years of follow-up: 0.5% vs. 1.6%. The rate of definite or probable stent thrombosis was 2.5% in the everolimus group and 4.0% with sirolimus. These differences were driven largely by the EES group’s zero incidence of very late stent thrombosis occurring after 1 year, compared with a 0.7% rate of definite very late stent thrombosis in the SES arm.

The lower incidence of MI in the EES group was partially explained by their significantly lower rate of stent thrombosis. Indeed, MIs occurring in association with definite stent thrombosis were 75% less frequent in the EES group, the cardiologist continued.

If this absence of stent thrombosis occurring beyond 1 year in EES recipients in LESSON-1 holds up in the ongoing large randomized trials, it will have important implications for the appropriate duration of dual antiplatelet therapy in patients with EES, Dr. Windecker said.

The divergent outcomes in patients with EES and SES may be due to the fact that “the two drugs are similar but nevertheless different,” he noted. “Everolimus is a semisynthetic analogue of sirolimus with a lower pharmacologic potency, and it is applied at lower doses than the sirolimus-eluting stent. So we have this counterintuitive finding that a drug that is somewhat less potent applied at a lower concentration nevertheless achieves higher efficacy.”

But there are other differences between EES and SES. The EES, which are of a newer generation than SES, utilize a substantially thinner polymer coating and have markedly less strut thickness.

“Which one of these components drives the difference is unknown at this point in time, but it may very well turn out to be a combination of all three,” according to Dr. Windecker.

He noted that EES have already been convincingly shown to provide clinical outcomes that are superior to paclitaxel-eluting stents in four randomized trials. He provided an updated meta-analysis with 3 years of follow-up in 6,789 patients in the COMPARE and SPIRIT II, III, and IV randomized trials, which showed that the rate of cardiac death or MI was 37% lower in the EES group. In addition, target lesion revascularization was 49% less likely with EES.

Discussant Dr. Petr Widimsky said the biggest of LESSON-1’s several limitations is the use of historical controls. While most EES recipients in the study received stents in 2007-2009, most SES recipients got their stents in 2004-2005.

“The knowledge about stent thrombosis and the skills in preventing it by appropriate implantation techniques improved during this period,” noted Dr. Widimsky of Charles University, Prague.

Disclosures: Dr. Windecker said that in the past he has been a consultant to numerous medical device companies that market stents.

STOCKHOLM – Everolimus-eluting stents were associated with significantly lower risks of myocardial infarction, target vessel revascularization, and stent thrombosis than were sirolimus-eluting stents, during 3 years of follow-up in the LESSON-1 study.

A particularly striking finding in LESSON-1 (Long-Term Comparison of Everolimus-Eluting and Sirolimus-Eluting Stents for Coronary Revascularization) was the 70% lower rate of Q-wave MI in the everolimus-eluting stent (EES) group, Dr. Stephan Windecker noted, in presenting the study results at the annual congress of the European Society of Cardiology.

Some observers called the LESSON-1 findings interesting but nondefinitive, since the study was nonrandomized, single-center, observational, and reliant upon propensity score matching.

Dr. Windecker concurred. He noted there are four ongoing randomized trials comparing outcomes in everolimus- versus sirolimus-eluting stent (SES) recipients.

The LESSON-1 study involved 1,601 consecutive patients undergoing percutaneous coronary intervention with the Xience EES and 1,532 consecutive patients who received a Cypher SES. After propensity score matching, the final study population consisted of 1,342 matched subjects in each of the two treatment arms, explained Dr. Windecker of Bern (Switzerland) University Hospital.

The primary study end point was the 3-year rate of death, MI, or target vessel revascularization. It occurred in 14.9% of the everolimus group and 18.0% of the sirolimus cohort. The resultant 17% relative risk reduction fell just shy of statistical significance, owing to closely similar overall mortality rates in the two groups, he reported.

However, the EES group fared significantly better than SES recipients in terms of key prespecified secondary end points. For example, MI occurred in 3.3% of the everolimus recipients compared with 5.0% of the sirolimus group, for a significant 38% risk reduction. The MI rates diverged early and the gap increased steadily during follow-up.

Target vessel revascularization occurred in 7.0% of EES and 9.6% of SES recipients, for a significant 25% risk reduction.

Similarly, the everolimus group had a significantly lower rate of definite stent thrombosis during 3 years of follow-up: 0.5% vs. 1.6%. The rate of definite or probable stent thrombosis was 2.5% in the everolimus group and 4.0% with sirolimus. These differences were driven largely by the EES group’s zero incidence of very late stent thrombosis occurring after 1 year, compared with a 0.7% rate of definite very late stent thrombosis in the SES arm.

The lower incidence of MI in the EES group was partially explained by their significantly lower rate of stent thrombosis. Indeed, MIs occurring in association with definite stent thrombosis were 75% less frequent in the EES group, the cardiologist continued.

If this absence of stent thrombosis occurring beyond 1 year in EES recipients in LESSON-1 holds up in the ongoing large randomized trials, it will have important implications for the appropriate duration of dual antiplatelet therapy in patients with EES, Dr. Windecker said.

The divergent outcomes in patients with EES and SES may be due to the fact that “the two drugs are similar but nevertheless different,” he noted. “Everolimus is a semisynthetic analogue of sirolimus with a lower pharmacologic potency, and it is applied at lower doses than the sirolimus-eluting stent. So we have this counterintuitive finding that a drug that is somewhat less potent applied at a lower concentration nevertheless achieves higher efficacy.”

But there are other differences between EES and SES. The EES, which are of a newer generation than SES, utilize a substantially thinner polymer coating and have markedly less strut thickness.

“Which one of these components drives the difference is unknown at this point in time, but it may very well turn out to be a combination of all three,” according to Dr. Windecker.

He noted that EES have already been convincingly shown to provide clinical outcomes that are superior to paclitaxel-eluting stents in four randomized trials. He provided an updated meta-analysis with 3 years of follow-up in 6,789 patients in the COMPARE and SPIRIT II, III, and IV randomized trials, which showed that the rate of cardiac death or MI was 37% lower in the EES group. In addition, target lesion revascularization was 49% less likely with EES.

Discussant Dr. Petr Widimsky said the biggest of LESSON-1’s several limitations is the use of historical controls. While most EES recipients in the study received stents in 2007-2009, most SES recipients got their stents in 2004-2005.

“The knowledge about stent thrombosis and the skills in preventing it by appropriate implantation techniques improved during this period,” noted Dr. Widimsky of Charles University, Prague.

Disclosures: Dr. Windecker said that in the past he has been a consultant to numerous medical device companies that market stents.

STOCKHOLM – Everolimus-eluting stents were associated with significantly lower risks of myocardial infarction, target vessel revascularization, and stent thrombosis than were sirolimus-eluting stents, during 3 years of follow-up in the LESSON-1 study.

A particularly striking finding in LESSON-1 (Long-Term Comparison of Everolimus-Eluting and Sirolimus-Eluting Stents for Coronary Revascularization) was the 70% lower rate of Q-wave MI in the everolimus-eluting stent (EES) group, Dr. Stephan Windecker noted, in presenting the study results at the annual congress of the European Society of Cardiology.

Some observers called the LESSON-1 findings interesting but nondefinitive, since the study was nonrandomized, single-center, observational, and reliant upon propensity score matching.

Dr. Windecker concurred. He noted there are four ongoing randomized trials comparing outcomes in everolimus- versus sirolimus-eluting stent (SES) recipients.

The LESSON-1 study involved 1,601 consecutive patients undergoing percutaneous coronary intervention with the Xience EES and 1,532 consecutive patients who received a Cypher SES. After propensity score matching, the final study population consisted of 1,342 matched subjects in each of the two treatment arms, explained Dr. Windecker of Bern (Switzerland) University Hospital.

The primary study end point was the 3-year rate of death, MI, or target vessel revascularization. It occurred in 14.9% of the everolimus group and 18.0% of the sirolimus cohort. The resultant 17% relative risk reduction fell just shy of statistical significance, owing to closely similar overall mortality rates in the two groups, he reported.

However, the EES group fared significantly better than SES recipients in terms of key prespecified secondary end points. For example, MI occurred in 3.3% of the everolimus recipients compared with 5.0% of the sirolimus group, for a significant 38% risk reduction. The MI rates diverged early and the gap increased steadily during follow-up.

Target vessel revascularization occurred in 7.0% of EES and 9.6% of SES recipients, for a significant 25% risk reduction.

Similarly, the everolimus group had a significantly lower rate of definite stent thrombosis during 3 years of follow-up: 0.5% vs. 1.6%. The rate of definite or probable stent thrombosis was 2.5% in the everolimus group and 4.0% with sirolimus. These differences were driven largely by the EES group’s zero incidence of very late stent thrombosis occurring after 1 year, compared with a 0.7% rate of definite very late stent thrombosis in the SES arm.

The lower incidence of MI in the EES group was partially explained by their significantly lower rate of stent thrombosis. Indeed, MIs occurring in association with definite stent thrombosis were 75% less frequent in the EES group, the cardiologist continued.

If this absence of stent thrombosis occurring beyond 1 year in EES recipients in LESSON-1 holds up in the ongoing large randomized trials, it will have important implications for the appropriate duration of dual antiplatelet therapy in patients with EES, Dr. Windecker said.

The divergent outcomes in patients with EES and SES may be due to the fact that “the two drugs are similar but nevertheless different,” he noted. “Everolimus is a semisynthetic analogue of sirolimus with a lower pharmacologic potency, and it is applied at lower doses than the sirolimus-eluting stent. So we have this counterintuitive finding that a drug that is somewhat less potent applied at a lower concentration nevertheless achieves higher efficacy.”

But there are other differences between EES and SES. The EES, which are of a newer generation than SES, utilize a substantially thinner polymer coating and have markedly less strut thickness.

“Which one of these components drives the difference is unknown at this point in time, but it may very well turn out to be a combination of all three,” according to Dr. Windecker.

He noted that EES have already been convincingly shown to provide clinical outcomes that are superior to paclitaxel-eluting stents in four randomized trials. He provided an updated meta-analysis with 3 years of follow-up in 6,789 patients in the COMPARE and SPIRIT II, III, and IV randomized trials, which showed that the rate of cardiac death or MI was 37% lower in the EES group. In addition, target lesion revascularization was 49% less likely with EES.

Discussant Dr. Petr Widimsky said the biggest of LESSON-1’s several limitations is the use of historical controls. While most EES recipients in the study received stents in 2007-2009, most SES recipients got their stents in 2004-2005.

“The knowledge about stent thrombosis and the skills in preventing it by appropriate implantation techniques improved during this period,” noted Dr. Widimsky of Charles University, Prague.

Disclosures: Dr. Windecker said that in the past he has been a consultant to numerous medical device companies that market stents.

STOCKHOLM – Genetic profiling can identify the roughly one-fourth of patients with stable coronary artery disease who will not obtain clinical benefit from ACE inhibitor therapy, as well as a far larger group of superresponders.

“Our findings open the route to individualize therapy by pharmacogenetic profiling. Such individualized therapy could revolutionize drug therapy by enabling physicians to prescribe drugs only to those patients most likely to benefit from the therapy. This would not only increase efficacy, but also decrease unnecessary treatment of patients and avoid unwanted side effects, thereby decreasing overall costs,” Dr. Jasper J. Brugts said at the annual congress of the European Society of Cardiology.

Although developing the pharmacogenetic profile entailed a huge multinational research effort, the resultant gene test – which focuses on three single nucleotide polymorphisms on two genes – is simple and straightforward. However, pharmacogenetic profiling to target ACE inhibitor therapy is not yet ready for use in clinical practice. Further confirmatory studies need to be done first, added Dr. Brugts of Erasmus University, Rotterdam, the Netherlands.

He and his coworkers developed their pharmacogenetic score for predicting clinical outcomes in perindopril-treated patients who have stable CAD by analyzing data from the landmark placebo-controlled, randomized EUROPA (European Trial on Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease) trial. In that study, perindopril provided a 20% reduction in the relative risk of cardiac death or MI, compared with placebo, during 4.2 years of follow-up (Lancet 2003;362:782-8).

The investigators were able to isolate DNA from 9,454 of the 12,218 EUROPA participants. They analyzed 12 candidate genes and 52 haplotype-tagging single nucleotide polymorphisms (SNPs) lying within the pharmacogenetic pathway of ACE inhibitors.

In a multivariate analysis, three SNPs emerged as having a significant negative association with treatment benefit. Two are located on the angiotensin-II type 1 receptor gene; the third is on the bradykinin type 1 receptor gene. The greater the number of unfavorable alleles in these SNPs that a patient possessed, the lesser the treatment benefit of perindopril.

In the overall EUROPA study, for example, the absolute risk of cardiac death or MI during follow-up was 9.9% with placebo, compared with 8.0% with perindopril, meaning that the ACE inhibitor provided a 20% relative risk reduction. But in patients with none of the unfavorable alleles, the event rate was 12.2% with placebo, compared with 6.3% with perindopril – a 55% relative risk reduction.

These data illustrate an easily overlooked key point about clinical trial data, according to Dr. Brugts: “The treatment effect that is observed for the total group in a clinical trial does not necessarily count for the patient sitting in front of you at your desk. The risk reduction varies from patient to patient.”

Altogether, 74% of EUROPA patients who were included in the pharmacogenetic study were identified as perindopril responders via blinded genetic profiling. They averaged a 33% relative risk reduction vs. placebo, compared with the 20% figure for the overall study.

In contrast, 26% of study participants had a “nonresponder” genetic profile based upon the three SNPs. They averaged a 26% higher event rate than did placebo-treated patients with the same pharmacogenetic score, although this increased risk did not reach statistical significance.

The pharmacogenetic profile has held up in a preliminary confirmatory analysis of 1,051 patients with cerebrovascular disease who were randomized to perindopril or placebo in the previously reported PROGRESS trial (Lancet 2001;358:1033-41), Dr. Brugts continued.

In an interview, he said his research group is reaching out to leaders of major studies of other ACE inhibitors to see if the pharmacogenetic profile that was developed using perindopril would apply to the entire drug class. He suspects this will prove to be the case.

“At this moment, there is no clinical evidence that there is different clinical efficacy for different ACE inhibitors. They do have different biologic profiles, but there’s no evidence of any clinical difference in risk reduction. So you have to think that these data for perindopril would also be valid for enalapril and all the other ACE inhibitors,” Dr. Brugts said.

Disclosures: The pharmacogenetic research is funded by the Netherlands Heart Foundation. Dr. Brugts declared having no conflicts of interest.

STOCKHOLM – Genetic profiling can identify the roughly one-fourth of patients with stable coronary artery disease who will not obtain clinical benefit from ACE inhibitor therapy, as well as a far larger group of superresponders.

“Our findings open the route to individualize therapy by pharmacogenetic profiling. Such individualized therapy could revolutionize drug therapy by enabling physicians to prescribe drugs only to those patients most likely to benefit from the therapy. This would not only increase efficacy, but also decrease unnecessary treatment of patients and avoid unwanted side effects, thereby decreasing overall costs,” Dr. Jasper J. Brugts said at the annual congress of the European Society of Cardiology.

Although developing the pharmacogenetic profile entailed a huge multinational research effort, the resultant gene test – which focuses on three single nucleotide polymorphisms on two genes – is simple and straightforward. However, pharmacogenetic profiling to target ACE inhibitor therapy is not yet ready for use in clinical practice. Further confirmatory studies need to be done first, added Dr. Brugts of Erasmus University, Rotterdam, the Netherlands.

He and his coworkers developed their pharmacogenetic score for predicting clinical outcomes in perindopril-treated patients who have stable CAD by analyzing data from the landmark placebo-controlled, randomized EUROPA (European Trial on Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease) trial. In that study, perindopril provided a 20% reduction in the relative risk of cardiac death or MI, compared with placebo, during 4.2 years of follow-up (Lancet 2003;362:782-8).

The investigators were able to isolate DNA from 9,454 of the 12,218 EUROPA participants. They analyzed 12 candidate genes and 52 haplotype-tagging single nucleotide polymorphisms (SNPs) lying within the pharmacogenetic pathway of ACE inhibitors.

In a multivariate analysis, three SNPs emerged as having a significant negative association with treatment benefit. Two are located on the angiotensin-II type 1 receptor gene; the third is on the bradykinin type 1 receptor gene. The greater the number of unfavorable alleles in these SNPs that a patient possessed, the lesser the treatment benefit of perindopril.

In the overall EUROPA study, for example, the absolute risk of cardiac death or MI during follow-up was 9.9% with placebo, compared with 8.0% with perindopril, meaning that the ACE inhibitor provided a 20% relative risk reduction. But in patients with none of the unfavorable alleles, the event rate was 12.2% with placebo, compared with 6.3% with perindopril – a 55% relative risk reduction.

These data illustrate an easily overlooked key point about clinical trial data, according to Dr. Brugts: “The treatment effect that is observed for the total group in a clinical trial does not necessarily count for the patient sitting in front of you at your desk. The risk reduction varies from patient to patient.”

Altogether, 74% of EUROPA patients who were included in the pharmacogenetic study were identified as perindopril responders via blinded genetic profiling. They averaged a 33% relative risk reduction vs. placebo, compared with the 20% figure for the overall study.

In contrast, 26% of study participants had a “nonresponder” genetic profile based upon the three SNPs. They averaged a 26% higher event rate than did placebo-treated patients with the same pharmacogenetic score, although this increased risk did not reach statistical significance.

The pharmacogenetic profile has held up in a preliminary confirmatory analysis of 1,051 patients with cerebrovascular disease who were randomized to perindopril or placebo in the previously reported PROGRESS trial (Lancet 2001;358:1033-41), Dr. Brugts continued.

In an interview, he said his research group is reaching out to leaders of major studies of other ACE inhibitors to see if the pharmacogenetic profile that was developed using perindopril would apply to the entire drug class. He suspects this will prove to be the case.

“At this moment, there is no clinical evidence that there is different clinical efficacy for different ACE inhibitors. They do have different biologic profiles, but there’s no evidence of any clinical difference in risk reduction. So you have to think that these data for perindopril would also be valid for enalapril and all the other ACE inhibitors,” Dr. Brugts said.

Disclosures: The pharmacogenetic research is funded by the Netherlands Heart Foundation. Dr. Brugts declared having no conflicts of interest.

STOCKHOLM – Genetic profiling can identify the roughly one-fourth of patients with stable coronary artery disease who will not obtain clinical benefit from ACE inhibitor therapy, as well as a far larger group of superresponders.

“Our findings open the route to individualize therapy by pharmacogenetic profiling. Such individualized therapy could revolutionize drug therapy by enabling physicians to prescribe drugs only to those patients most likely to benefit from the therapy. This would not only increase efficacy, but also decrease unnecessary treatment of patients and avoid unwanted side effects, thereby decreasing overall costs,” Dr. Jasper J. Brugts said at the annual congress of the European Society of Cardiology.

Although developing the pharmacogenetic profile entailed a huge multinational research effort, the resultant gene test – which focuses on three single nucleotide polymorphisms on two genes – is simple and straightforward. However, pharmacogenetic profiling to target ACE inhibitor therapy is not yet ready for use in clinical practice. Further confirmatory studies need to be done first, added Dr. Brugts of Erasmus University, Rotterdam, the Netherlands.

He and his coworkers developed their pharmacogenetic score for predicting clinical outcomes in perindopril-treated patients who have stable CAD by analyzing data from the landmark placebo-controlled, randomized EUROPA (European Trial on Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease) trial. In that study, perindopril provided a 20% reduction in the relative risk of cardiac death or MI, compared with placebo, during 4.2 years of follow-up (Lancet 2003;362:782-8).

The investigators were able to isolate DNA from 9,454 of the 12,218 EUROPA participants. They analyzed 12 candidate genes and 52 haplotype-tagging single nucleotide polymorphisms (SNPs) lying within the pharmacogenetic pathway of ACE inhibitors.

In a multivariate analysis, three SNPs emerged as having a significant negative association with treatment benefit. Two are located on the angiotensin-II type 1 receptor gene; the third is on the bradykinin type 1 receptor gene. The greater the number of unfavorable alleles in these SNPs that a patient possessed, the lesser the treatment benefit of perindopril.

In the overall EUROPA study, for example, the absolute risk of cardiac death or MI during follow-up was 9.9% with placebo, compared with 8.0% with perindopril, meaning that the ACE inhibitor provided a 20% relative risk reduction. But in patients with none of the unfavorable alleles, the event rate was 12.2% with placebo, compared with 6.3% with perindopril – a 55% relative risk reduction.

These data illustrate an easily overlooked key point about clinical trial data, according to Dr. Brugts: “The treatment effect that is observed for the total group in a clinical trial does not necessarily count for the patient sitting in front of you at your desk. The risk reduction varies from patient to patient.”

Altogether, 74% of EUROPA patients who were included in the pharmacogenetic study were identified as perindopril responders via blinded genetic profiling. They averaged a 33% relative risk reduction vs. placebo, compared with the 20% figure for the overall study.

In contrast, 26% of study participants had a “nonresponder” genetic profile based upon the three SNPs. They averaged a 26% higher event rate than did placebo-treated patients with the same pharmacogenetic score, although this increased risk did not reach statistical significance.

The pharmacogenetic profile has held up in a preliminary confirmatory analysis of 1,051 patients with cerebrovascular disease who were randomized to perindopril or placebo in the previously reported PROGRESS trial (Lancet 2001;358:1033-41), Dr. Brugts continued.

In an interview, he said his research group is reaching out to leaders of major studies of other ACE inhibitors to see if the pharmacogenetic profile that was developed using perindopril would apply to the entire drug class. He suspects this will prove to be the case.

“At this moment, there is no clinical evidence that there is different clinical efficacy for different ACE inhibitors. They do have different biologic profiles, but there’s no evidence of any clinical difference in risk reduction. So you have to think that these data for perindopril would also be valid for enalapril and all the other ACE inhibitors,” Dr. Brugts said.

Disclosures: The pharmacogenetic research is funded by the Netherlands Heart Foundation. Dr. Brugts declared having no conflicts of interest.

STOCKHOLM – Genetic profiling can identify the roughly one-fourth of patients with stable coronary artery disease who will not obtain clinical benefit from ACE inhibitor therapy, as well as a far larger group of superresponders.

“Our findings open the route to individualize therapy by pharmacogenetic profiling. Such individualized therapy could revolutionize drug therapy by enabling physicians to prescribe drugs only to those patients most likely to benefit from the therapy. This would not only increase efficacy, but also decrease unnecessary treatment of patients and avoid unwanted side effects, thereby decreasing overall costs,” Dr. Jasper J. Brugts said at the annual congress of the European Society of Cardiology.

Although developing the pharmacogenetic profile entailed a huge multinational research effort, the resultant gene test – which focuses on three single nucleotide polymorphisms on two genes – is simple and straightforward. However, pharmacogenetic profiling to target ACE inhibitor therapy is not yet ready for use in clinical practice. Further confirmatory studies need to be done first, added Dr. Brugts of Erasmus University, Rotterdam, the Netherlands.

He and his coworkers developed their pharmacogenetic score for predicting clinical outcomes in perindopril-treated patients who have stable CAD by analyzing data from the landmark placebo-controlled, randomized EUROPA (European Trial on Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease) trial. In that study, perindopril provided a 20% reduction in the relative risk of cardiac death or MI, compared with placebo, during 4.2 years of follow-up (Lancet 2003;362:782-8).

The investigators were able to isolate DNA from 9,454 of the 12,218 EUROPA participants. They analyzed 12 candidate genes and 52 haplotype-tagging single nucleotide polymorphisms (SNPs) lying within the pharmacogenetic pathway of ACE inhibitors.

In a multivariate analysis, three SNPs emerged as having a significant negative association with treatment benefit. Two are located on the angiotensin-II type 1 receptor gene; the third is on the bradykinin type 1 receptor gene. The greater the number of unfavorable alleles in these SNPs that a patient possessed, the lesser the treatment benefit of perindopril.

In the overall EUROPA study, for example, the absolute risk of cardiac death or MI during follow-up was 9.9% with placebo, compared with 8.0% with perindopril, meaning that the ACE inhibitor provided a 20% relative risk reduction. But in patients with none of the unfavorable alleles, the event rate was 12.2% with placebo, compared with 6.3% with perindopril – a 55% relative risk reduction.

These data illustrate an easily overlooked key point about clinical trial data, according to Dr. Brugts: “The treatment effect that is observed for the total group in a clinical trial does not necessarily count for the patient sitting in front of you at your desk. The risk reduction varies from patient to patient.”

Altogether, 74% of EUROPA patients who were included in the pharmacogenetic study were identified as perindopril responders via blinded genetic profiling. They averaged a 33% relative risk reduction vs. placebo, compared with the 20% figure for the overall study.

In contrast, 26% of study participants had a “nonresponder” genetic profile based upon the three SNPs. They averaged a 26% higher event rate than did placebo-treated patients with the same pharmacogenetic score, although this increased risk did not reach statistical significance.

The pharmacogenetic profile has held up in a preliminary confirmatory analysis of 1,051 patients with cerebrovascular disease who were randomized to perindopril or placebo in the previously reported PROGRESS trial (Lancet 2001;358:1033-41), Dr. Brugts continued.

In an interview, he said his research group is reaching out to leaders of major studies of other ACE inhibitors to see if the pharmacogenetic profile that was developed using perindopril would apply to the entire drug class. He suspects this will prove to be the case.

“At this moment, there is no clinical evidence that there is different clinical efficacy for different ACE inhibitors. They do have different biologic profiles, but there’s no evidence of any clinical difference in risk reduction. So you have to think that these data for perindopril would also be valid for enalapril and all the other ACE inhibitors,” Dr. Brugts said.

Disclosures: The pharmacogenetic research is funded by the Netherlands Heart Foundation. Dr. Brugts declared having no conflicts of interest.

STOCKHOLM – Genetic profiling can identify the roughly one-fourth of patients with stable coronary artery disease who will not obtain clinical benefit from ACE inhibitor therapy, as well as a far larger group of superresponders.

“Our findings open the route to individualize therapy by pharmacogenetic profiling. Such individualized therapy could revolutionize drug therapy by enabling physicians to prescribe drugs only to those patients most likely to benefit from the therapy. This would not only increase efficacy, but also decrease unnecessary treatment of patients and avoid unwanted side effects, thereby decreasing overall costs,” Dr. Jasper J. Brugts said at the annual congress of the European Society of Cardiology.

Although developing the pharmacogenetic profile entailed a huge multinational research effort, the resultant gene test – which focuses on three single nucleotide polymorphisms on two genes – is simple and straightforward. However, pharmacogenetic profiling to target ACE inhibitor therapy is not yet ready for use in clinical practice. Further confirmatory studies need to be done first, added Dr. Brugts of Erasmus University, Rotterdam, the Netherlands.

He and his coworkers developed their pharmacogenetic score for predicting clinical outcomes in perindopril-treated patients who have stable CAD by analyzing data from the landmark placebo-controlled, randomized EUROPA (European Trial on Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease) trial. In that study, perindopril provided a 20% reduction in the relative risk of cardiac death or MI, compared with placebo, during 4.2 years of follow-up (Lancet 2003;362:782-8).

The investigators were able to isolate DNA from 9,454 of the 12,218 EUROPA participants. They analyzed 12 candidate genes and 52 haplotype-tagging single nucleotide polymorphisms (SNPs) lying within the pharmacogenetic pathway of ACE inhibitors.

In a multivariate analysis, three SNPs emerged as having a significant negative association with treatment benefit. Two are located on the angiotensin-II type 1 receptor gene; the third is on the bradykinin type 1 receptor gene. The greater the number of unfavorable alleles in these SNPs that a patient possessed, the lesser the treatment benefit of perindopril.

In the overall EUROPA study, for example, the absolute risk of cardiac death or MI during follow-up was 9.9% with placebo, compared with 8.0% with perindopril, meaning that the ACE inhibitor provided a 20% relative risk reduction. But in patients with none of the unfavorable alleles, the event rate was 12.2% with placebo, compared with 6.3% with perindopril – a 55% relative risk reduction.

These data illustrate an easily overlooked key point about clinical trial data, according to Dr. Brugts: “The treatment effect that is observed for the total group in a clinical trial does not necessarily count for the patient sitting in front of you at your desk. The risk reduction varies from patient to patient.”

Altogether, 74% of EUROPA patients who were included in the pharmacogenetic study were identified as perindopril responders via blinded genetic profiling. They averaged a 33% relative risk reduction vs. placebo, compared with the 20% figure for the overall study.

In contrast, 26% of study participants had a “nonresponder” genetic profile based upon the three SNPs. They averaged a 26% higher event rate than did placebo-treated patients with the same pharmacogenetic score, although this increased risk did not reach statistical significance.

The pharmacogenetic profile has held up in a preliminary confirmatory analysis of 1,051 patients with cerebrovascular disease who were randomized to perindopril or placebo in the previously reported PROGRESS trial (Lancet 2001;358:1033-41), Dr. Brugts continued.

In an interview, he said his research group is reaching out to leaders of major studies of other ACE inhibitors to see if the pharmacogenetic profile that was developed using perindopril would apply to the entire drug class. He suspects this will prove to be the case.

“At this moment, there is no clinical evidence that there is different clinical efficacy for different ACE inhibitors. They do have different biologic profiles, but there’s no evidence of any clinical difference in risk reduction. So you have to think that these data for perindopril would also be valid for enalapril and all the other ACE inhibitors,” Dr. Brugts said.

Disclosures: The pharmacogenetic research is funded by the Netherlands Heart Foundation. Dr. Brugts declared having no conflicts of interest.

STOCKHOLM – Genetic profiling can identify the roughly one-fourth of patients with stable coronary artery disease who will not obtain clinical benefit from ACE inhibitor therapy, as well as a far larger group of superresponders.

“Our findings open the route to individualize therapy by pharmacogenetic profiling. Such individualized therapy could revolutionize drug therapy by enabling physicians to prescribe drugs only to those patients most likely to benefit from the therapy. This would not only increase efficacy, but also decrease unnecessary treatment of patients and avoid unwanted side effects, thereby decreasing overall costs,” Dr. Jasper J. Brugts said at the annual congress of the European Society of Cardiology.

Although developing the pharmacogenetic profile entailed a huge multinational research effort, the resultant gene test – which focuses on three single nucleotide polymorphisms on two genes – is simple and straightforward. However, pharmacogenetic profiling to target ACE inhibitor therapy is not yet ready for use in clinical practice. Further confirmatory studies need to be done first, added Dr. Brugts of Erasmus University, Rotterdam, the Netherlands.

He and his coworkers developed their pharmacogenetic score for predicting clinical outcomes in perindopril-treated patients who have stable CAD by analyzing data from the landmark placebo-controlled, randomized EUROPA (European Trial on Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease) trial. In that study, perindopril provided a 20% reduction in the relative risk of cardiac death or MI, compared with placebo, during 4.2 years of follow-up (Lancet 2003;362:782-8).

The investigators were able to isolate DNA from 9,454 of the 12,218 EUROPA participants. They analyzed 12 candidate genes and 52 haplotype-tagging single nucleotide polymorphisms (SNPs) lying within the pharmacogenetic pathway of ACE inhibitors.

In a multivariate analysis, three SNPs emerged as having a significant negative association with treatment benefit. Two are located on the angiotensin-II type 1 receptor gene; the third is on the bradykinin type 1 receptor gene. The greater the number of unfavorable alleles in these SNPs that a patient possessed, the lesser the treatment benefit of perindopril.

In the overall EUROPA study, for example, the absolute risk of cardiac death or MI during follow-up was 9.9% with placebo, compared with 8.0% with perindopril, meaning that the ACE inhibitor provided a 20% relative risk reduction. But in patients with none of the unfavorable alleles, the event rate was 12.2% with placebo, compared with 6.3% with perindopril – a 55% relative risk reduction.

These data illustrate an easily overlooked key point about clinical trial data, according to Dr. Brugts: “The treatment effect that is observed for the total group in a clinical trial does not necessarily count for the patient sitting in front of you at your desk. The risk reduction varies from patient to patient.”

Altogether, 74% of EUROPA patients who were included in the pharmacogenetic study were identified as perindopril responders via blinded genetic profiling. They averaged a 33% relative risk reduction vs. placebo, compared with the 20% figure for the overall study.

In contrast, 26% of study participants had a “nonresponder” genetic profile based upon the three SNPs. They averaged a 26% higher event rate than did placebo-treated patients with the same pharmacogenetic score, although this increased risk did not reach statistical significance.

The pharmacogenetic profile has held up in a preliminary confirmatory analysis of 1,051 patients with cerebrovascular disease who were randomized to perindopril or placebo in the previously reported PROGRESS trial (Lancet 2001;358:1033-41), Dr. Brugts continued.

In an interview, he said his research group is reaching out to leaders of major studies of other ACE inhibitors to see if the pharmacogenetic profile that was developed using perindopril would apply to the entire drug class. He suspects this will prove to be the case.

“At this moment, there is no clinical evidence that there is different clinical efficacy for different ACE inhibitors. They do have different biologic profiles, but there’s no evidence of any clinical difference in risk reduction. So you have to think that these data for perindopril would also be valid for enalapril and all the other ACE inhibitors,” Dr. Brugts said.

Disclosures: The pharmacogenetic research is funded by the Netherlands Heart Foundation. Dr. Brugts declared having no conflicts of interest.

STOCKHOLM – Older middle-of-the-pack men and women marathoners do not appear to experience any lasting adverse effects on myocardial function as a result of completing the 26.2-mile distance, according to results of studies of participants in the Berlin Marathon and the Marathon of the Medoc in France presented at the Annual Congress of the European Society of Cardiology.

© ebraxas/Fotolia.com

“The concerns people have about marathon running causing sustained damage to the heart appear to be unfounded. We did not find any harmful effects of marathon running in this very large cohort of amateur runners. Myocardial performance after a marathon seems to be preserved in well-trained persons up to a high age,” Dr. Fabian Knebel said in summarizing the findings of his study of older runners in the Berlin Marathon.

He reported on 167 non-elite, older runners who toed the starting line in Berlin. They averaged 50 years in age, 53 km/week in training, and 14 prior marathons. The finishing time in Berlin averaged 4 hours 23 minutes. All study participants were free of any sort of baseline cardiac disease; 53% percent were women.

The subjects underwent extensive testing including treadmill ECGs, echocardiography with tissue Doppler, and measurement of cardiac biomarkers. The testing was done when subjects were at rest at least 10 days before the Berlin race, immediately after completing the marathon, and 2 weeks later.

The laboratory work showed that all the runners were markedly dehydrated right after the race. However, echocardiograms showed no relevant systolic left or diastolic right heart dysfunction after the marathon. A transient adaptation of diastolic myocardial function was noted, probably in response to the dehydration and prolonged tachycardia.

Fifty-eight percent of the runners had one or more elevated cardiac biomarkers immediately post marathon. Specifically, 21% had an n-terminal prohormone brain natriuretic peptide (NT-proBNP) level above their age-adjusted cut-point, 24% had a troponin T level greater than 0.01 ng/mL, and 13% had elevations in both. These elevated biomarkers were not correlated with training level, contrary to some reports by other investigators who found that inadequately trained runners were more likely to spike elevated biomarkers. Nor did the elevated biomarkers in the Berlin runners correlate with any echocardiographic variables. At follow-up studies 2 weeks post marathon, biomarkers were back to normal in all cases.

Dr. Knebel of Charite Hospital in Berlin noted there is debate among sports medicine researchers as to whether these sorts of elevations in cardiac biomarkers reflect true myocardial damage or simply physiologic adaptation to stress. He believes it’s the latter, given that he and his colleagues could find no echocardiographic evidence of myocardial damage.

“The troponin normalizes so quickly after the race that I don’t think ischemia can be involved. The glomerular filtration rate is considerably decreased after a marathon, and some of the biomarkers are excreted renally, so I think impaired renal function during the race has an impact on the biomarkers. Also, tachycardia and the inflammatory process can lead to liberation of the biomarkers,” the cardiologist said.

In a separate presentation, Dr. Françoise Carré reported on 67 healthy non-elite older women who entered the 2008 Marathon of the Medoc in the Bordeaux region of France. Their median age was 47 years and they trained for an average of 4 hours per week. Their average finishing time was 4 hours 22 minutes. This was the first marathon for 8 women, while 12 women had run more than 10 previously. The investigators obtained ECGs and performed lab tests, including measurement of cardiac biomarkers the day before the race, immediately after finishing, and again 4 hours later.

The women did not become dehydrated during the marathon, as evidenced by their modest mean 500-g weight loss. Nor did they display significant T-wave alterations or any other ECG changes after the event.

“We can say that the marathon race is clinically and electrically well tolerated by middle-aged female runners,” declared Dr. Carré of Rennes (France) University Hospital.

Seven percent of the women runners had a significantly elevated NT-proBNP level in excess of 300 mcg/L immediately after the run. Four percent had an elevated troponin Ic. There was a trend for elevated biomarkers to be found more often in undertrained women. Heart fatty acid binding protein, an indicator of heart muscle breakdown, was elevated in all subjects immediately post-race and at followup 4 hours later. C-reactive protein levels were elevated immediately after the race in all runners, indicating an inflammatory process arose during the long run.

Dr. Sanjay Sharma, medical director of the London Marathon, said these two studies are of particular importance because older non-elite marathoners constitute a large and understudied group – and that’s especially true for female runners. Worldwide, there are probably more than 1 million people per year running marathons, and the number is increasing by about 10% annually, he said.

Most marathoners lose around 3 kg of body weight during a race, so the women in the Medoc study, with their mean weight loss of only 500 g, were clearly well hydrated.

“We know that this is something that females do; they drink far more than males when they run,” according to Dr. Sharma of St. George’s Hospital in London.

He was particularly intrigued by the single-digit incidence of elevated cardiac biomarkers in the Medoc women. Rates are typically far higher in male runners. He proposed that this disparity raises a question: Could the gender gap in risk of sudden death during sports participation be related to testosterone?

“Maybe testosterone is bad for you,” the cardiologist mused. “Testosterone allows you to develop a big, lean body mass, allows you to push yourself much harder than the heart would like, maybe even causes endothelial dysfunction, may cause more cardiac hypertrophy, and it could in the long run be the reason why males are nine times more likely to die during exercise than females.”

In the London Marathon, for example, there have been 10 participant deaths in the last 30 years. All occurred in men.

Disclosures: Dr. Knebel, Dr. Carré, and Dr. Sharma reported no financial conflicts of interest.

STOCKHOLM – Older middle-of-the-pack men and women marathoners do not appear to experience any lasting adverse effects on myocardial function as a result of completing the 26.2-mile distance, according to results of studies of participants in the Berlin Marathon and the Marathon of the Medoc in France presented at the Annual Congress of the European Society of Cardiology.

© ebraxas/Fotolia.com

“The concerns people have about marathon running causing sustained damage to the heart appear to be unfounded. We did not find any harmful effects of marathon running in this very large cohort of amateur runners. Myocardial performance after a marathon seems to be preserved in well-trained persons up to a high age,” Dr. Fabian Knebel said in summarizing the findings of his study of older runners in the Berlin Marathon.

He reported on 167 non-elite, older runners who toed the starting line in Berlin. They averaged 50 years in age, 53 km/week in training, and 14 prior marathons. The finishing time in Berlin averaged 4 hours 23 minutes. All study participants were free of any sort of baseline cardiac disease; 53% percent were women.

The subjects underwent extensive testing including treadmill ECGs, echocardiography with tissue Doppler, and measurement of cardiac biomarkers. The testing was done when subjects were at rest at least 10 days before the Berlin race, immediately after completing the marathon, and 2 weeks later.

The laboratory work showed that all the runners were markedly dehydrated right after the race. However, echocardiograms showed no relevant systolic left or diastolic right heart dysfunction after the marathon. A transient adaptation of diastolic myocardial function was noted, probably in response to the dehydration and prolonged tachycardia.

Fifty-eight percent of the runners had one or more elevated cardiac biomarkers immediately post marathon. Specifically, 21% had an n-terminal prohormone brain natriuretic peptide (NT-proBNP) level above their age-adjusted cut-point, 24% had a troponin T level greater than 0.01 ng/mL, and 13% had elevations in both. These elevated biomarkers were not correlated with training level, contrary to some reports by other investigators who found that inadequately trained runners were more likely to spike elevated biomarkers. Nor did the elevated biomarkers in the Berlin runners correlate with any echocardiographic variables. At follow-up studies 2 weeks post marathon, biomarkers were back to normal in all cases.

Dr. Knebel of Charite Hospital in Berlin noted there is debate among sports medicine researchers as to whether these sorts of elevations in cardiac biomarkers reflect true myocardial damage or simply physiologic adaptation to stress. He believes it’s the latter, given that he and his colleagues could find no echocardiographic evidence of myocardial damage.

“The troponin normalizes so quickly after the race that I don’t think ischemia can be involved. The glomerular filtration rate is considerably decreased after a marathon, and some of the biomarkers are excreted renally, so I think impaired renal function during the race has an impact on the biomarkers. Also, tachycardia and the inflammatory process can lead to liberation of the biomarkers,” the cardiologist said.

In a separate presentation, Dr. Françoise Carré reported on 67 healthy non-elite older women who entered the 2008 Marathon of the Medoc in the Bordeaux region of France. Their median age was 47 years and they trained for an average of 4 hours per week. Their average finishing time was 4 hours 22 minutes. This was the first marathon for 8 women, while 12 women had run more than 10 previously. The investigators obtained ECGs and performed lab tests, including measurement of cardiac biomarkers the day before the race, immediately after finishing, and again 4 hours later.

The women did not become dehydrated during the marathon, as evidenced by their modest mean 500-g weight loss. Nor did they display significant T-wave alterations or any other ECG changes after the event.

“We can say that the marathon race is clinically and electrically well tolerated by middle-aged female runners,” declared Dr. Carré of Rennes (France) University Hospital.

Seven percent of the women runners had a significantly elevated NT-proBNP level in excess of 300 mcg/L immediately after the run. Four percent had an elevated troponin Ic. There was a trend for elevated biomarkers to be found more often in undertrained women. Heart fatty acid binding protein, an indicator of heart muscle breakdown, was elevated in all subjects immediately post-race and at followup 4 hours later. C-reactive protein levels were elevated immediately after the race in all runners, indicating an inflammatory process arose during the long run.

Dr. Sanjay Sharma, medical director of the London Marathon, said these two studies are of particular importance because older non-elite marathoners constitute a large and understudied group – and that’s especially true for female runners. Worldwide, there are probably more than 1 million people per year running marathons, and the number is increasing by about 10% annually, he said.

Most marathoners lose around 3 kg of body weight during a race, so the women in the Medoc study, with their mean weight loss of only 500 g, were clearly well hydrated.

“We know that this is something that females do; they drink far more than males when they run,” according to Dr. Sharma of St. George’s Hospital in London.

He was particularly intrigued by the single-digit incidence of elevated cardiac biomarkers in the Medoc women. Rates are typically far higher in male runners. He proposed that this disparity raises a question: Could the gender gap in risk of sudden death during sports participation be related to testosterone?

“Maybe testosterone is bad for you,” the cardiologist mused. “Testosterone allows you to develop a big, lean body mass, allows you to push yourself much harder than the heart would like, maybe even causes endothelial dysfunction, may cause more cardiac hypertrophy, and it could in the long run be the reason why males are nine times more likely to die during exercise than females.”

In the London Marathon, for example, there have been 10 participant deaths in the last 30 years. All occurred in men.

Disclosures: Dr. Knebel, Dr. Carré, and Dr. Sharma reported no financial conflicts of interest.

STOCKHOLM – Older middle-of-the-pack men and women marathoners do not appear to experience any lasting adverse effects on myocardial function as a result of completing the 26.2-mile distance, according to results of studies of participants in the Berlin Marathon and the Marathon of the Medoc in France presented at the Annual Congress of the European Society of Cardiology.

© ebraxas/Fotolia.com

“The concerns people have about marathon running causing sustained damage to the heart appear to be unfounded. We did not find any harmful effects of marathon running in this very large cohort of amateur runners. Myocardial performance after a marathon seems to be preserved in well-trained persons up to a high age,” Dr. Fabian Knebel said in summarizing the findings of his study of older runners in the Berlin Marathon.

He reported on 167 non-elite, older runners who toed the starting line in Berlin. They averaged 50 years in age, 53 km/week in training, and 14 prior marathons. The finishing time in Berlin averaged 4 hours 23 minutes. All study participants were free of any sort of baseline cardiac disease; 53% percent were women.

The subjects underwent extensive testing including treadmill ECGs, echocardiography with tissue Doppler, and measurement of cardiac biomarkers. The testing was done when subjects were at rest at least 10 days before the Berlin race, immediately after completing the marathon, and 2 weeks later.

The laboratory work showed that all the runners were markedly dehydrated right after the race. However, echocardiograms showed no relevant systolic left or diastolic right heart dysfunction after the marathon. A transient adaptation of diastolic myocardial function was noted, probably in response to the dehydration and prolonged tachycardia.

Fifty-eight percent of the runners had one or more elevated cardiac biomarkers immediately post marathon. Specifically, 21% had an n-terminal prohormone brain natriuretic peptide (NT-proBNP) level above their age-adjusted cut-point, 24% had a troponin T level greater than 0.01 ng/mL, and 13% had elevations in both. These elevated biomarkers were not correlated with training level, contrary to some reports by other investigators who found that inadequately trained runners were more likely to spike elevated biomarkers. Nor did the elevated biomarkers in the Berlin runners correlate with any echocardiographic variables. At follow-up studies 2 weeks post marathon, biomarkers were back to normal in all cases.

Dr. Knebel of Charite Hospital in Berlin noted there is debate among sports medicine researchers as to whether these sorts of elevations in cardiac biomarkers reflect true myocardial damage or simply physiologic adaptation to stress. He believes it’s the latter, given that he and his colleagues could find no echocardiographic evidence of myocardial damage.

“The troponin normalizes so quickly after the race that I don’t think ischemia can be involved. The glomerular filtration rate is considerably decreased after a marathon, and some of the biomarkers are excreted renally, so I think impaired renal function during the race has an impact on the biomarkers. Also, tachycardia and the inflammatory process can lead to liberation of the biomarkers,” the cardiologist said.

In a separate presentation, Dr. Françoise Carré reported on 67 healthy non-elite older women who entered the 2008 Marathon of the Medoc in the Bordeaux region of France. Their median age was 47 years and they trained for an average of 4 hours per week. Their average finishing time was 4 hours 22 minutes. This was the first marathon for 8 women, while 12 women had run more than 10 previously. The investigators obtained ECGs and performed lab tests, including measurement of cardiac biomarkers the day before the race, immediately after finishing, and again 4 hours later.

The women did not become dehydrated during the marathon, as evidenced by their modest mean 500-g weight loss. Nor did they display significant T-wave alterations or any other ECG changes after the event.

“We can say that the marathon race is clinically and electrically well tolerated by middle-aged female runners,” declared Dr. Carré of Rennes (France) University Hospital.

Seven percent of the women runners had a significantly elevated NT-proBNP level in excess of 300 mcg/L immediately after the run. Four percent had an elevated troponin Ic. There was a trend for elevated biomarkers to be found more often in undertrained women. Heart fatty acid binding protein, an indicator of heart muscle breakdown, was elevated in all subjects immediately post-race and at followup 4 hours later. C-reactive protein levels were elevated immediately after the race in all runners, indicating an inflammatory process arose during the long run.

Dr. Sanjay Sharma, medical director of the London Marathon, said these two studies are of particular importance because older non-elite marathoners constitute a large and understudied group – and that’s especially true for female runners. Worldwide, there are probably more than 1 million people per year running marathons, and the number is increasing by about 10% annually, he said.

Most marathoners lose around 3 kg of body weight during a race, so the women in the Medoc study, with their mean weight loss of only 500 g, were clearly well hydrated.

“We know that this is something that females do; they drink far more than males when they run,” according to Dr. Sharma of St. George’s Hospital in London.

He was particularly intrigued by the single-digit incidence of elevated cardiac biomarkers in the Medoc women. Rates are typically far higher in male runners. He proposed that this disparity raises a question: Could the gender gap in risk of sudden death during sports participation be related to testosterone?

“Maybe testosterone is bad for you,” the cardiologist mused. “Testosterone allows you to develop a big, lean body mass, allows you to push yourself much harder than the heart would like, maybe even causes endothelial dysfunction, may cause more cardiac hypertrophy, and it could in the long run be the reason why males are nine times more likely to die during exercise than females.”

In the London Marathon, for example, there have been 10 participant deaths in the last 30 years. All occurred in men.

Disclosures: Dr. Knebel, Dr. Carré, and Dr. Sharma reported no financial conflicts of interest.

STOCKHOLM – Older middle-of-the-pack men and women marathoners do not appear to experience any lasting adverse effects on myocardial function as a result of completing the 26.2-mile distance, according to results of studies of participants in the Berlin Marathon and the Marathon of the Medoc in France presented at the Annual Congress of the European Society of Cardiology.

© ebraxas/Fotolia.com

“The concerns people have about marathon running causing sustained damage to the heart appear to be unfounded. We did not find any harmful effects of marathon running in this very large cohort of amateur runners. Myocardial performance after a marathon seems to be preserved in well-trained persons up to a high age,” Dr. Fabian Knebel said in summarizing the findings of his study of older runners in the Berlin Marathon.

He reported on 167 non-elite, older runners who toed the starting line in Berlin. They averaged 50 years in age, 53 km/week in training, and 14 prior marathons. The finishing time in Berlin averaged 4 hours 23 minutes. All study participants were free of any sort of baseline cardiac disease; 53% percent were women.

The subjects underwent extensive testing including treadmill ECGs, echocardiography with tissue Doppler, and measurement of cardiac biomarkers. The testing was done when subjects were at rest at least 10 days before the Berlin race, immediately after completing the marathon, and 2 weeks later.

The laboratory work showed that all the runners were markedly dehydrated right after the race. However, echocardiograms showed no relevant systolic left or diastolic right heart dysfunction after the marathon. A transient adaptation of diastolic myocardial function was noted, probably in response to the dehydration and prolonged tachycardia.

Fifty-eight percent of the runners had one or more elevated cardiac biomarkers immediately post marathon. Specifically, 21% had an n-terminal prohormone brain natriuretic peptide (NT-proBNP) level above their age-adjusted cut-point, 24% had a troponin T level greater than 0.01 ng/mL, and 13% had elevations in both. These elevated biomarkers were not correlated with training level, contrary to some reports by other investigators who found that inadequately trained runners were more likely to spike elevated biomarkers. Nor did the elevated biomarkers in the Berlin runners correlate with any echocardiographic variables. At follow-up studies 2 weeks post marathon, biomarkers were back to normal in all cases.

Dr. Knebel of Charite Hospital in Berlin noted there is debate among sports medicine researchers as to whether these sorts of elevations in cardiac biomarkers reflect true myocardial damage or simply physiologic adaptation to stress. He believes it’s the latter, given that he and his colleagues could find no echocardiographic evidence of myocardial damage.

“The troponin normalizes so quickly after the race that I don’t think ischemia can be involved. The glomerular filtration rate is considerably decreased after a marathon, and some of the biomarkers are excreted renally, so I think impaired renal function during the race has an impact on the biomarkers. Also, tachycardia and the inflammatory process can lead to liberation of the biomarkers,” the cardiologist said.

In a separate presentation, Dr. Françoise Carré reported on 67 healthy non-elite older women who entered the 2008 Marathon of the Medoc in the Bordeaux region of France. Their median age was 47 years and they trained for an average of 4 hours per week. Their average finishing time was 4 hours 22 minutes. This was the first marathon for 8 women, while 12 women had run more than 10 previously. The investigators obtained ECGs and performed lab tests, including measurement of cardiac biomarkers the day before the race, immediately after finishing, and again 4 hours later.

The women did not become dehydrated during the marathon, as evidenced by their modest mean 500-g weight loss. Nor did they display significant T-wave alterations or any other ECG changes after the event.

“We can say that the marathon race is clinically and electrically well tolerated by middle-aged female runners,” declared Dr. Carré of Rennes (France) University Hospital.

Seven percent of the women runners had a significantly elevated NT-proBNP level in excess of 300 mcg/L immediately after the run. Four percent had an elevated troponin Ic. There was a trend for elevated biomarkers to be found more often in undertrained women. Heart fatty acid binding protein, an indicator of heart muscle breakdown, was elevated in all subjects immediately post-race and at followup 4 hours later. C-reactive protein levels were elevated immediately after the race in all runners, indicating an inflammatory process arose during the long run.

Dr. Sanjay Sharma, medical director of the London Marathon, said these two studies are of particular importance because older non-elite marathoners constitute a large and understudied group – and that’s especially true for female runners. Worldwide, there are probably more than 1 million people per year running marathons, and the number is increasing by about 10% annually, he said.

Most marathoners lose around 3 kg of body weight during a race, so the women in the Medoc study, with their mean weight loss of only 500 g, were clearly well hydrated.

“We know that this is something that females do; they drink far more than males when they run,” according to Dr. Sharma of St. George’s Hospital in London.

He was particularly intrigued by the single-digit incidence of elevated cardiac biomarkers in the Medoc women. Rates are typically far higher in male runners. He proposed that this disparity raises a question: Could the gender gap in risk of sudden death during sports participation be related to testosterone?

“Maybe testosterone is bad for you,” the cardiologist mused. “Testosterone allows you to develop a big, lean body mass, allows you to push yourself much harder than the heart would like, maybe even causes endothelial dysfunction, may cause more cardiac hypertrophy, and it could in the long run be the reason why males are nine times more likely to die during exercise than females.”

In the London Marathon, for example, there have been 10 participant deaths in the last 30 years. All occurred in men.

Disclosures: Dr. Knebel, Dr. Carré, and Dr. Sharma reported no financial conflicts of interest.

STOCKHOLM – Older middle-of-the-pack men and women marathoners do not appear to experience any lasting adverse effects on myocardial function as a result of completing the 26.2-mile distance, according to results of studies of participants in the Berlin Marathon and the Marathon of the Medoc in France presented at the Annual Congress of the European Society of Cardiology.

© ebraxas/Fotolia.com

“The concerns people have about marathon running causing sustained damage to the heart appear to be unfounded. We did not find any harmful effects of marathon running in this very large cohort of amateur runners. Myocardial performance after a marathon seems to be preserved in well-trained persons up to a high age,” Dr. Fabian Knebel said in summarizing the findings of his study of older runners in the Berlin Marathon.

He reported on 167 non-elite, older runners who toed the starting line in Berlin. They averaged 50 years in age, 53 km/week in training, and 14 prior marathons. The finishing time in Berlin averaged 4 hours 23 minutes. All study participants were free of any sort of baseline cardiac disease; 53% percent were women.

The subjects underwent extensive testing including treadmill ECGs, echocardiography with tissue Doppler, and measurement of cardiac biomarkers. The testing was done when subjects were at rest at least 10 days before the Berlin race, immediately after completing the marathon, and 2 weeks later.

The laboratory work showed that all the runners were markedly dehydrated right after the race. However, echocardiograms showed no relevant systolic left or diastolic right heart dysfunction after the marathon. A transient adaptation of diastolic myocardial function was noted, probably in response to the dehydration and prolonged tachycardia.

Fifty-eight percent of the runners had one or more elevated cardiac biomarkers immediately post marathon. Specifically, 21% had an n-terminal prohormone brain natriuretic peptide (NT-proBNP) level above their age-adjusted cut-point, 24% had a troponin T level greater than 0.01 ng/mL, and 13% had elevations in both. These elevated biomarkers were not correlated with training level, contrary to some reports by other investigators who found that inadequately trained runners were more likely to spike elevated biomarkers. Nor did the elevated biomarkers in the Berlin runners correlate with any echocardiographic variables. At follow-up studies 2 weeks post marathon, biomarkers were back to normal in all cases.

Dr. Knebel of Charite Hospital in Berlin noted there is debate among sports medicine researchers as to whether these sorts of elevations in cardiac biomarkers reflect true myocardial damage or simply physiologic adaptation to stress. He believes it’s the latter, given that he and his colleagues could find no echocardiographic evidence of myocardial damage.

“The troponin normalizes so quickly after the race that I don’t think ischemia can be involved. The glomerular filtration rate is considerably decreased after a marathon, and some of the biomarkers are excreted renally, so I think impaired renal function during the race has an impact on the biomarkers. Also, tachycardia and the inflammatory process can lead to liberation of the biomarkers,” the cardiologist said.

In a separate presentation, Dr. Françoise Carré reported on 67 healthy non-elite older women who entered the 2008 Marathon of the Medoc in the Bordeaux region of France. Their median age was 47 years and they trained for an average of 4 hours per week. Their average finishing time was 4 hours 22 minutes. This was the first marathon for 8 women, while 12 women had run more than 10 previously. The investigators obtained ECGs and performed lab tests, including measurement of cardiac biomarkers the day before the race, immediately after finishing, and again 4 hours later.

The women did not become dehydrated during the marathon, as evidenced by their modest mean 500-g weight loss. Nor did they display significant T-wave alterations or any other ECG changes after the event.

“We can say that the marathon race is clinically and electrically well tolerated by middle-aged female runners,” declared Dr. Carré of Rennes (France) University Hospital.

Seven percent of the women runners had a significantly elevated NT-proBNP level in excess of 300 mcg/L immediately after the run. Four percent had an elevated troponin Ic. There was a trend for elevated biomarkers to be found more often in undertrained women. Heart fatty acid binding protein, an indicator of heart muscle breakdown, was elevated in all subjects immediately post-race and at followup 4 hours later. C-reactive protein levels were elevated immediately after the race in all runners, indicating an inflammatory process arose during the long run.

Dr. Sanjay Sharma, medical director of the London Marathon, said these two studies are of particular importance because older non-elite marathoners constitute a large and understudied group – and that’s especially true for female runners. Worldwide, there are probably more than 1 million people per year running marathons, and the number is increasing by about 10% annually, he said.

Most marathoners lose around 3 kg of body weight during a race, so the women in the Medoc study, with their mean weight loss of only 500 g, were clearly well hydrated.

“We know that this is something that females do; they drink far more than males when they run,” according to Dr. Sharma of St. George’s Hospital in London.

He was particularly intrigued by the single-digit incidence of elevated cardiac biomarkers in the Medoc women. Rates are typically far higher in male runners. He proposed that this disparity raises a question: Could the gender gap in risk of sudden death during sports participation be related to testosterone?

“Maybe testosterone is bad for you,” the cardiologist mused. “Testosterone allows you to develop a big, lean body mass, allows you to push yourself much harder than the heart would like, maybe even causes endothelial dysfunction, may cause more cardiac hypertrophy, and it could in the long run be the reason why males are nine times more likely to die during exercise than females.”

In the London Marathon, for example, there have been 10 participant deaths in the last 30 years. All occurred in men.

Disclosures: Dr. Knebel, Dr. Carré, and Dr. Sharma reported no financial conflicts of interest.

STOCKHOLM – Older middle-of-the-pack men and women marathoners do not appear to experience any lasting adverse effects on myocardial function as a result of completing the 26.2-mile distance, according to results of studies of participants in the Berlin Marathon and the Marathon of the Medoc in France presented at the Annual Congress of the European Society of Cardiology.

© ebraxas/Fotolia.com

“The concerns people have about marathon running causing sustained damage to the heart appear to be unfounded. We did not find any harmful effects of marathon running in this very large cohort of amateur runners. Myocardial performance after a marathon seems to be preserved in well-trained persons up to a high age,” Dr. Fabian Knebel said in summarizing the findings of his study of older runners in the Berlin Marathon.

He reported on 167 non-elite, older runners who toed the starting line in Berlin. They averaged 50 years in age, 53 km/week in training, and 14 prior marathons. The finishing time in Berlin averaged 4 hours 23 minutes. All study participants were free of any sort of baseline cardiac disease; 53% percent were women.

The subjects underwent extensive testing including treadmill ECGs, echocardiography with tissue Doppler, and measurement of cardiac biomarkers. The testing was done when subjects were at rest at least 10 days before the Berlin race, immediately after completing the marathon, and 2 weeks later.

The laboratory work showed that all the runners were markedly dehydrated right after the race. However, echocardiograms showed no relevant systolic left or diastolic right heart dysfunction after the marathon. A transient adaptation of diastolic myocardial function was noted, probably in response to the dehydration and prolonged tachycardia.

Fifty-eight percent of the runners had one or more elevated cardiac biomarkers immediately post marathon. Specifically, 21% had an n-terminal prohormone brain natriuretic peptide (NT-proBNP) level above their age-adjusted cut-point, 24% had a troponin T level greater than 0.01 ng/mL, and 13% had elevations in both. These elevated biomarkers were not correlated with training level, contrary to some reports by other investigators who found that inadequately trained runners were more likely to spike elevated biomarkers. Nor did the elevated biomarkers in the Berlin runners correlate with any echocardiographic variables. At follow-up studies 2 weeks post marathon, biomarkers were back to normal in all cases.

Dr. Knebel of Charite Hospital in Berlin noted there is debate among sports medicine researchers as to whether these sorts of elevations in cardiac biomarkers reflect true myocardial damage or simply physiologic adaptation to stress. He believes it’s the latter, given that he and his colleagues could find no echocardiographic evidence of myocardial damage.

“The troponin normalizes so quickly after the race that I don’t think ischemia can be involved. The glomerular filtration rate is considerably decreased after a marathon, and some of the biomarkers are excreted renally, so I think impaired renal function during the race has an impact on the biomarkers. Also, tachycardia and the inflammatory process can lead to liberation of the biomarkers,” the cardiologist said.

In a separate presentation, Dr. Françoise Carré reported on 67 healthy non-elite older women who entered the 2008 Marathon of the Medoc in the Bordeaux region of France. Their median age was 47 years and they trained for an average of 4 hours per week. Their average finishing time was 4 hours 22 minutes. This was the first marathon for 8 women, while 12 women had run more than 10 previously. The investigators obtained ECGs and performed lab tests, including measurement of cardiac biomarkers the day before the race, immediately after finishing, and again 4 hours later.

The women did not become dehydrated during the marathon, as evidenced by their modest mean 500-g weight loss. Nor did they display significant T-wave alterations or any other ECG changes after the event.

“We can say that the marathon race is clinically and electrically well tolerated by middle-aged female runners,” declared Dr. Carré of Rennes (France) University Hospital.

Seven percent of the women runners had a significantly elevated NT-proBNP level in excess of 300 mcg/L immediately after the run. Four percent had an elevated troponin Ic. There was a trend for elevated biomarkers to be found more often in undertrained women. Heart fatty acid binding protein, an indicator of heart muscle breakdown, was elevated in all subjects immediately post-race and at followup 4 hours later. C-reactive protein levels were elevated immediately after the race in all runners, indicating an inflammatory process arose during the long run.

Dr. Sanjay Sharma, medical director of the London Marathon, said these two studies are of particular importance because older non-elite marathoners constitute a large and understudied group – and that’s especially true for female runners. Worldwide, there are probably more than 1 million people per year running marathons, and the number is increasing by about 10% annually, he said.

Most marathoners lose around 3 kg of body weight during a race, so the women in the Medoc study, with their mean weight loss of only 500 g, were clearly well hydrated.

“We know that this is something that females do; they drink far more than males when they run,” according to Dr. Sharma of St. George’s Hospital in London.

He was particularly intrigued by the single-digit incidence of elevated cardiac biomarkers in the Medoc women. Rates are typically far higher in male runners. He proposed that this disparity raises a question: Could the gender gap in risk of sudden death during sports participation be related to testosterone?

“Maybe testosterone is bad for you,” the cardiologist mused. “Testosterone allows you to develop a big, lean body mass, allows you to push yourself much harder than the heart would like, maybe even causes endothelial dysfunction, may cause more cardiac hypertrophy, and it could in the long run be the reason why males are nine times more likely to die during exercise than females.”

In the London Marathon, for example, there have been 10 participant deaths in the last 30 years. All occurred in men.

Disclosures: Dr. Knebel, Dr. Carré, and Dr. Sharma reported no financial conflicts of interest.

STOCKHOLM – The absence of signs and symptoms of congestion at discharge in patients hospitalized for acute decompensated heart failure does not predict a favorable prognosis, contrary to the conventional wisdom.

A new secondary analysis of the international EVEREST trial provides an important lesson in the everyday management of acute heart failure: “The fact that a patient improves in-hospital with diuretics and other medications is not sufficient. It’s not ‘mission accomplished,’ ” Dr. Mihai Gheorghiade said at the annual congress of the European Society of Cardiology.

“There is a dissociation between signs and symptoms of congestion at discharge and outcomes. In spite of having a very low congestion score, the event rate in EVEREST during 10 months of follow-up was astronomical,” said Dr. Gheorghiade, professor of medicine and surgery and associate chief of cardiology at Northwestern University, Chicago.

EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan) was a double-blind study that randomized 4,133 patients with worsening heart failure and a left ventricular ejection fraction of 40% or less to the oral vasopressin V2 receptor blocker tolvaptan or placebo within 48 hours of hospitalization.

Standard background therapy in both study arms included diuretics, ACE inhibitor or angiotensin II receptor blocker therapy, a beta blocker, and an aldosterone antagonist. In the previously reported primary results, tolvaptan proved to have no benefit over placebo during a mean follow-up of 9.9 months (JAMA 2007;297:1319-31).

Dr. Gheorghiade presented a secondary analysis focusing on the 2,061 patients in the placebo arm. At randomization, following initial treatment with diuretics, these patients had a mean congestion score of 4 points based upon their degree of jugular vein distention, rales, and peripheral edema.

At discharge, patients had lost a mean 2.8 kg of body weight, and 72% had a congestion score of 0 or 1. Although that appears to be a high rate of short-term treatment success, this large subgroup of patients with minimal or no signs or symptoms of congestion at discharge had a 15% all-cause mortality and a 29% rate of rehospitalization for heart failure during the next 9.9 months.

The adverse event rate was even greater in those with a higher congestion score at discharge. In the overall placebo group, all-cause mortality was 26%, with a 40% rate of rehospitalization for heart failure during follow-up. That is a particularly sobering statistic given that heart failure is the No. 1 reason for hospital admission in the Medicare population.

“We’re dealing with a disorder that has an event rate as high as 50%. There is no other medical condition for which patients are hospitalized and are improving with therapy that has a comparable event rate,” the cardiologist observed.

The new EVEREST analysis contains an important message for clinical trialists: Using signs and symptoms of congestion as a key target for treatment during hospitalization as well as the standard end point in acute heart failure studies, as has been common until now, is a recipe for a negative trial result.

“It’s very difficult to beat placebo, because placebo plus standard therapy has a tremendous effect on congestion,” Dr. Gheorghiade said. “Looking for new therapies that improve signs and symptoms of congestion in the whole population is a waste of time unless you’re dealing with special populations who don’t respond to standard therapies, such as patients with low blood pressure.”

Better surrogate markers than congestion are needed to guide therapy. One possibility is B-type natriuretic peptide (BNP). The mean BNP at admission in the placebo arm of EVEREST was 1,375 pg/mL. At discharge it was still markedly elevated at 948 pg/mL.

“The lesson here is that by treating the signs and symptoms of congestion, you can make patients feel much better, but even though they are now able to walk up a flight of stairs, inside, in terms of renal function and BNP, they are still very sick,” he said.

Until better treatments for acute heart failure are found, the best thing physicians can do for affected patients is try to identify specific targets amenable to current therapies, such as renal dysfunction or myocardial ischemia, Dr. Gheorghiade concluded.

Disclosures: The EVEREST trial was sponsored by Otsuka. Dr. Gheorghiade has received research grants and/or served as a consultant to Otsuka and numerous other pharmaceutical companies.

STOCKHOLM – The absence of signs and symptoms of congestion at discharge in patients hospitalized for acute decompensated heart failure does not predict a favorable prognosis, contrary to the conventional wisdom.

A new secondary analysis of the international EVEREST trial provides an important lesson in the everyday management of acute heart failure: “The fact that a patient improves in-hospital with diuretics and other medications is not sufficient. It’s not ‘mission accomplished,’ ” Dr. Mihai Gheorghiade said at the annual congress of the European Society of Cardiology.

“There is a dissociation between signs and symptoms of congestion at discharge and outcomes. In spite of having a very low congestion score, the event rate in EVEREST during 10 months of follow-up was astronomical,” said Dr. Gheorghiade, professor of medicine and surgery and associate chief of cardiology at Northwestern University, Chicago.

EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan) was a double-blind study that randomized 4,133 patients with worsening heart failure and a left ventricular ejection fraction of 40% or less to the oral vasopressin V2 receptor blocker tolvaptan or placebo within 48 hours of hospitalization.

Standard background therapy in both study arms included diuretics, ACE inhibitor or angiotensin II receptor blocker therapy, a beta blocker, and an aldosterone antagonist. In the previously reported primary results, tolvaptan proved to have no benefit over placebo during a mean follow-up of 9.9 months (JAMA 2007;297:1319-31).

Dr. Gheorghiade presented a secondary analysis focusing on the 2,061 patients in the placebo arm. At randomization, following initial treatment with diuretics, these patients had a mean congestion score of 4 points based upon their degree of jugular vein distention, rales, and peripheral edema.

At discharge, patients had lost a mean 2.8 kg of body weight, and 72% had a congestion score of 0 or 1. Although that appears to be a high rate of short-term treatment success, this large subgroup of patients with minimal or no signs or symptoms of congestion at discharge had a 15% all-cause mortality and a 29% rate of rehospitalization for heart failure during the next 9.9 months.

The adverse event rate was even greater in those with a higher congestion score at discharge. In the overall placebo group, all-cause mortality was 26%, with a 40% rate of rehospitalization for heart failure during follow-up. That is a particularly sobering statistic given that heart failure is the No. 1 reason for hospital admission in the Medicare population.

“We’re dealing with a disorder that has an event rate as high as 50%. There is no other medical condition for which patients are hospitalized and are improving with therapy that has a comparable event rate,” the cardiologist observed.

The new EVEREST analysis contains an important message for clinical trialists: Using signs and symptoms of congestion as a key target for treatment during hospitalization as well as the standard end point in acute heart failure studies, as has been common until now, is a recipe for a negative trial result.

“It’s very difficult to beat placebo, because placebo plus standard therapy has a tremendous effect on congestion,” Dr. Gheorghiade said. “Looking for new therapies that improve signs and symptoms of congestion in the whole population is a waste of time unless you’re dealing with special populations who don’t respond to standard therapies, such as patients with low blood pressure.”

Better surrogate markers than congestion are needed to guide therapy. One possibility is B-type natriuretic peptide (BNP). The mean BNP at admission in the placebo arm of EVEREST was 1,375 pg/mL. At discharge it was still markedly elevated at 948 pg/mL.

“The lesson here is that by treating the signs and symptoms of congestion, you can make patients feel much better, but even though they are now able to walk up a flight of stairs, inside, in terms of renal function and BNP, they are still very sick,” he said.

Until better treatments for acute heart failure are found, the best thing physicians can do for affected patients is try to identify specific targets amenable to current therapies, such as renal dysfunction or myocardial ischemia, Dr. Gheorghiade concluded.

Disclosures: The EVEREST trial was sponsored by Otsuka. Dr. Gheorghiade has received research grants and/or served as a consultant to Otsuka and numerous other pharmaceutical companies.

STOCKHOLM – The absence of signs and symptoms of congestion at discharge in patients hospitalized for acute decompensated heart failure does not predict a favorable prognosis, contrary to the conventional wisdom.

A new secondary analysis of the international EVEREST trial provides an important lesson in the everyday management of acute heart failure: “The fact that a patient improves in-hospital with diuretics and other medications is not sufficient. It’s not ‘mission accomplished,’ ” Dr. Mihai Gheorghiade said at the annual congress of the European Society of Cardiology.

“There is a dissociation between signs and symptoms of congestion at discharge and outcomes. In spite of having a very low congestion score, the event rate in EVEREST during 10 months of follow-up was astronomical,” said Dr. Gheorghiade, professor of medicine and surgery and associate chief of cardiology at Northwestern University, Chicago.

EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan) was a double-blind study that randomized 4,133 patients with worsening heart failure and a left ventricular ejection fraction of 40% or less to the oral vasopressin V2 receptor blocker tolvaptan or placebo within 48 hours of hospitalization.

Standard background therapy in both study arms included diuretics, ACE inhibitor or angiotensin II receptor blocker therapy, a beta blocker, and an aldosterone antagonist. In the previously reported primary results, tolvaptan proved to have no benefit over placebo during a mean follow-up of 9.9 months (JAMA 2007;297:1319-31).

Dr. Gheorghiade presented a secondary analysis focusing on the 2,061 patients in the placebo arm. At randomization, following initial treatment with diuretics, these patients had a mean congestion score of 4 points based upon their degree of jugular vein distention, rales, and peripheral edema.

At discharge, patients had lost a mean 2.8 kg of body weight, and 72% had a congestion score of 0 or 1. Although that appears to be a high rate of short-term treatment success, this large subgroup of patients with minimal or no signs or symptoms of congestion at discharge had a 15% all-cause mortality and a 29% rate of rehospitalization for heart failure during the next 9.9 months.

The adverse event rate was even greater in those with a higher congestion score at discharge. In the overall placebo group, all-cause mortality was 26%, with a 40% rate of rehospitalization for heart failure during follow-up. That is a particularly sobering statistic given that heart failure is the No. 1 reason for hospital admission in the Medicare population.

“We’re dealing with a disorder that has an event rate as high as 50%. There is no other medical condition for which patients are hospitalized and are improving with therapy that has a comparable event rate,” the cardiologist observed.

The new EVEREST analysis contains an important message for clinical trialists: Using signs and symptoms of congestion as a key target for treatment during hospitalization as well as the standard end point in acute heart failure studies, as has been common until now, is a recipe for a negative trial result.

“It’s very difficult to beat placebo, because placebo plus standard therapy has a tremendous effect on congestion,” Dr. Gheorghiade said. “Looking for new therapies that improve signs and symptoms of congestion in the whole population is a waste of time unless you’re dealing with special populations who don’t respond to standard therapies, such as patients with low blood pressure.”

Better surrogate markers than congestion are needed to guide therapy. One possibility is B-type natriuretic peptide (BNP). The mean BNP at admission in the placebo arm of EVEREST was 1,375 pg/mL. At discharge it was still markedly elevated at 948 pg/mL.

“The lesson here is that by treating the signs and symptoms of congestion, you can make patients feel much better, but even though they are now able to walk up a flight of stairs, inside, in terms of renal function and BNP, they are still very sick,” he said.

Until better treatments for acute heart failure are found, the best thing physicians can do for affected patients is try to identify specific targets amenable to current therapies, such as renal dysfunction or myocardial ischemia, Dr. Gheorghiade concluded.

Disclosures: The EVEREST trial was sponsored by Otsuka. Dr. Gheorghiade has received research grants and/or served as a consultant to Otsuka and numerous other pharmaceutical companies.

STOCKHOLM – Higher blood levels of the bone hormone osteoprotegerin are associated with an increased long-term risk of death in patients with chronic heart failure, according to Dr. Ragnhild R. Roysland.

The relationship between osteoprotegerin (OPG) and mortality in heart failure is independent of the conventional cardiovascular risk factors, based on a secondary analysis of results of the Italian GISSI-Heart Failure trial.

Osteoprotegerin, a cytokine that’s a member of the tumor necrosis factor superfamily, is drawing increasing attention among cardiovascular researchers as a likely key player in what’s known as “the calcification paradox.” In animal studies, low levels of OPG are associated with decreased skeletal calcification, osteoporosis, and increased calcification of the major arteries. But in recent human studies, increased OPG levels have been linked to a greater atherosclerotic burden; an increased risk of death following acute MI; and now, in GISSI-HF, to increased mortality in the setting of chronic heart failure, Dr. Ragnhild R. Roysland said at the annual congress of the European Society of Cardiology.

The GISSI-HF study was a randomized clinical trial in which 6,975 Italian patients with all kinds of chronic heart failure were assigned to rosuvastatin, fish oil, or placebo and followed up for a median of 3.9 years. The primary results have been published (Lancet 2008;372:1223-30;1231-9). Dr. Roysland presented a new substudy involving 1,229 GISSI-HF participants for whom baseline OPG levels were available.

The aim was to see if baseline OPG was predictive of all-cause mortality. This indeed proved to be the case. During follow-up 332 patients died. The mortality rate was 20% in those in the bottom tertile for baseline OPG with a value less than 1,210 ng/L, and more than twice as great at 45% among patients in the highest tertile, with an OPG of at least 1,923 ng/L. Patients with an intermediate-tertile baseline OPG of 1,210-1,922 ng/L split the difference in terms of mortality, said Dr. Roysland of Akershus University Hospital, Lørenskog, Norway.

Treatment assignment in GISSI-HF did not affect OPG levels. However, if a medication could be identified that reduces OPG levels and attenuates the risk associated with high OPG, then OPG could become an important marker to use in managing chronic heart failure in clinical practice. There is early evidence that treatments for osteoporosis reduce OPG levels in a non­–heart failure population, but studies have not yet been done in patients with chronic heart failure, she continued.

Dr. Marco Metra commented that as a member of the European Society of Cardiology congress scientific program committee, he’d reviewed all the heart failure studies scheduled for presentation at the meeting. Two other studies in addition to Dr. Roysland’s consistently showed that heart failure patients with high levels of OPG have a poor prognosis.

“We know that patients with heart failure have low levels of vitamin D and increased rates of osteoporosis and bone fractures. So the bone is in some way a target of heart failure,” observed Dr. Metra of the University of Brescia (Italy).

Disclosures: Dr. Roysland said she had no financial conflicts.

STOCKHOLM – Higher blood levels of the bone hormone osteoprotegerin are associated with an increased long-term risk of death in patients with chronic heart failure, according to Dr. Ragnhild R. Roysland.

The relationship between osteoprotegerin (OPG) and mortality in heart failure is independent of the conventional cardiovascular risk factors, based on a secondary analysis of results of the Italian GISSI-Heart Failure trial.

Osteoprotegerin, a cytokine that’s a member of the tumor necrosis factor superfamily, is drawing increasing attention among cardiovascular researchers as a likely key player in what’s known as “the calcification paradox.” In animal studies, low levels of OPG are associated with decreased skeletal calcification, osteoporosis, and increased calcification of the major arteries. But in recent human studies, increased OPG levels have been linked to a greater atherosclerotic burden; an increased risk of death following acute MI; and now, in GISSI-HF, to increased mortality in the setting of chronic heart failure, Dr. Ragnhild R. Roysland said at the annual congress of the European Society of Cardiology.

The GISSI-HF study was a randomized clinical trial in which 6,975 Italian patients with all kinds of chronic heart failure were assigned to rosuvastatin, fish oil, or placebo and followed up for a median of 3.9 years. The primary results have been published (Lancet 2008;372:1223-30;1231-9). Dr. Roysland presented a new substudy involving 1,229 GISSI-HF participants for whom baseline OPG levels were available.

The aim was to see if baseline OPG was predictive of all-cause mortality. This indeed proved to be the case. During follow-up 332 patients died. The mortality rate was 20% in those in the bottom tertile for baseline OPG with a value less than 1,210 ng/L, and more than twice as great at 45% among patients in the highest tertile, with an OPG of at least 1,923 ng/L. Patients with an intermediate-tertile baseline OPG of 1,210-1,922 ng/L split the difference in terms of mortality, said Dr. Roysland of Akershus University Hospital, Lørenskog, Norway.

Treatment assignment in GISSI-HF did not affect OPG levels. However, if a medication could be identified that reduces OPG levels and attenuates the risk associated with high OPG, then OPG could become an important marker to use in managing chronic heart failure in clinical practice. There is early evidence that treatments for osteoporosis reduce OPG levels in a non­–heart failure population, but studies have not yet been done in patients with chronic heart failure, she continued.

Dr. Marco Metra commented that as a member of the European Society of Cardiology congress scientific program committee, he’d reviewed all the heart failure studies scheduled for presentation at the meeting. Two other studies in addition to Dr. Roysland’s consistently showed that heart failure patients with high levels of OPG have a poor prognosis.

“We know that patients with heart failure have low levels of vitamin D and increased rates of osteoporosis and bone fractures. So the bone is in some way a target of heart failure,” observed Dr. Metra of the University of Brescia (Italy).

Disclosures: Dr. Roysland said she had no financial conflicts.

STOCKHOLM – Higher blood levels of the bone hormone osteoprotegerin are associated with an increased long-term risk of death in patients with chronic heart failure, according to Dr. Ragnhild R. Roysland.

The relationship between osteoprotegerin (OPG) and mortality in heart failure is independent of the conventional cardiovascular risk factors, based on a secondary analysis of results of the Italian GISSI-Heart Failure trial.

Osteoprotegerin, a cytokine that’s a member of the tumor necrosis factor superfamily, is drawing increasing attention among cardiovascular researchers as a likely key player in what’s known as “the calcification paradox.” In animal studies, low levels of OPG are associated with decreased skeletal calcification, osteoporosis, and increased calcification of the major arteries. But in recent human studies, increased OPG levels have been linked to a greater atherosclerotic burden; an increased risk of death following acute MI; and now, in GISSI-HF, to increased mortality in the setting of chronic heart failure, Dr. Ragnhild R. Roysland said at the annual congress of the European Society of Cardiology.

The GISSI-HF study was a randomized clinical trial in which 6,975 Italian patients with all kinds of chronic heart failure were assigned to rosuvastatin, fish oil, or placebo and followed up for a median of 3.9 years. The primary results have been published (Lancet 2008;372:1223-30;1231-9). Dr. Roysland presented a new substudy involving 1,229 GISSI-HF participants for whom baseline OPG levels were available.

The aim was to see if baseline OPG was predictive of all-cause mortality. This indeed proved to be the case. During follow-up 332 patients died. The mortality rate was 20% in those in the bottom tertile for baseline OPG with a value less than 1,210 ng/L, and more than twice as great at 45% among patients in the highest tertile, with an OPG of at least 1,923 ng/L. Patients with an intermediate-tertile baseline OPG of 1,210-1,922 ng/L split the difference in terms of mortality, said Dr. Roysland of Akershus University Hospital, Lørenskog, Norway.

Treatment assignment in GISSI-HF did not affect OPG levels. However, if a medication could be identified that reduces OPG levels and attenuates the risk associated with high OPG, then OPG could become an important marker to use in managing chronic heart failure in clinical practice. There is early evidence that treatments for osteoporosis reduce OPG levels in a non­–heart failure population, but studies have not yet been done in patients with chronic heart failure, she continued.

Dr. Marco Metra commented that as a member of the European Society of Cardiology congress scientific program committee, he’d reviewed all the heart failure studies scheduled for presentation at the meeting. Two other studies in addition to Dr. Roysland’s consistently showed that heart failure patients with high levels of OPG have a poor prognosis.

“We know that patients with heart failure have low levels of vitamin D and increased rates of osteoporosis and bone fractures. So the bone is in some way a target of heart failure,” observed Dr. Metra of the University of Brescia (Italy).

Disclosures: Dr. Roysland said she had no financial conflicts.

STOCKHOLM – Higher blood levels of the bone hormone osteoprotegerin are associated with an increased long-term risk of death in patients with chronic heart failure, according to Dr. Ragnhild R. Roysland.

The relationship between osteoprotegerin (OPG) and mortality in heart failure is independent of the conventional cardiovascular risk factors, based on a secondary analysis of results of the Italian GISSI-Heart Failure trial.

Osteoprotegerin, a cytokine that’s a member of the tumor necrosis factor superfamily, is drawing increasing attention among cardiovascular researchers as a likely key player in what’s known as “the calcification paradox.” In animal studies, low levels of OPG are associated with decreased skeletal calcification, osteoporosis, and increased calcification of the major arteries. But in recent human studies, increased OPG levels have been linked to a greater atherosclerotic burden; an increased risk of death following acute MI; and now, in GISSI-HF, to increased mortality in the setting of chronic heart failure, Dr. Ragnhild R. Roysland said at the annual congress of the European Society of Cardiology.

The GISSI-HF study was a randomized clinical trial in which 6,975 Italian patients with all kinds of chronic heart failure were assigned to rosuvastatin, fish oil, or placebo and followed up for a median of 3.9 years. The primary results have been published (Lancet 2008;372:1223-30;1231-9). Dr. Roysland presented a new substudy involving 1,229 GISSI-HF participants for whom baseline OPG levels were available.

The aim was to see if baseline OPG was predictive of all-cause mortality. This indeed proved to be the case. During follow-up 332 patients died. The mortality rate was 20% in those in the bottom tertile for baseline OPG with a value less than 1,210 ng/L, and more than twice as great at 45% among patients in the highest tertile, with an OPG of at least 1,923 ng/L. Patients with an intermediate-tertile baseline OPG of 1,210-1,922 ng/L split the difference in terms of mortality, said Dr. Roysland of Akershus University Hospital, Lørenskog, Norway.

Treatment assignment in GISSI-HF did not affect OPG levels. However, if a medication could be identified that reduces OPG levels and attenuates the risk associated with high OPG, then OPG could become an important marker to use in managing chronic heart failure in clinical practice. There is early evidence that treatments for osteoporosis reduce OPG levels in a non­–heart failure population, but studies have not yet been done in patients with chronic heart failure, she continued.

Dr. Marco Metra commented that as a member of the European Society of Cardiology congress scientific program committee, he’d reviewed all the heart failure studies scheduled for presentation at the meeting. Two other studies in addition to Dr. Roysland’s consistently showed that heart failure patients with high levels of OPG have a poor prognosis.

“We know that patients with heart failure have low levels of vitamin D and increased rates of osteoporosis and bone fractures. So the bone is in some way a target of heart failure,” observed Dr. Metra of the University of Brescia (Italy).

Disclosures: Dr. Roysland said she had no financial conflicts.

STOCKHOLM – Higher blood levels of the bone hormone osteoprotegerin are associated with an increased long-term risk of death in patients with chronic heart failure, according to Dr. Ragnhild R. Roysland.

The relationship between osteoprotegerin (OPG) and mortality in heart failure is independent of the conventional cardiovascular risk factors, based on a secondary analysis of results of the Italian GISSI-Heart Failure trial.

Osteoprotegerin, a cytokine that’s a member of the tumor necrosis factor superfamily, is drawing increasing attention among cardiovascular researchers as a likely key player in what’s known as “the calcification paradox.” In animal studies, low levels of OPG are associated with decreased skeletal calcification, osteoporosis, and increased calcification of the major arteries. But in recent human studies, increased OPG levels have been linked to a greater atherosclerotic burden; an increased risk of death following acute MI; and now, in GISSI-HF, to increased mortality in the setting of chronic heart failure, Dr. Ragnhild R. Roysland said at the annual congress of the European Society of Cardiology.

The GISSI-HF study was a randomized clinical trial in which 6,975 Italian patients with all kinds of chronic heart failure were assigned to rosuvastatin, fish oil, or placebo and followed up for a median of 3.9 years. The primary results have been published (Lancet 2008;372:1223-30;1231-9). Dr. Roysland presented a new substudy involving 1,229 GISSI-HF participants for whom baseline OPG levels were available.

The aim was to see if baseline OPG was predictive of all-cause mortality. This indeed proved to be the case. During follow-up 332 patients died. The mortality rate was 20% in those in the bottom tertile for baseline OPG with a value less than 1,210 ng/L, and more than twice as great at 45% among patients in the highest tertile, with an OPG of at least 1,923 ng/L. Patients with an intermediate-tertile baseline OPG of 1,210-1,922 ng/L split the difference in terms of mortality, said Dr. Roysland of Akershus University Hospital, Lørenskog, Norway.

Treatment assignment in GISSI-HF did not affect OPG levels. However, if a medication could be identified that reduces OPG levels and attenuates the risk associated with high OPG, then OPG could become an important marker to use in managing chronic heart failure in clinical practice. There is early evidence that treatments for osteoporosis reduce OPG levels in a non­–heart failure population, but studies have not yet been done in patients with chronic heart failure, she continued.

Dr. Marco Metra commented that as a member of the European Society of Cardiology congress scientific program committee, he’d reviewed all the heart failure studies scheduled for presentation at the meeting. Two other studies in addition to Dr. Roysland’s consistently showed that heart failure patients with high levels of OPG have a poor prognosis.

“We know that patients with heart failure have low levels of vitamin D and increased rates of osteoporosis and bone fractures. So the bone is in some way a target of heart failure,” observed Dr. Metra of the University of Brescia (Italy).

Disclosures: Dr. Roysland said she had no financial conflicts.

STOCKHOLM – Higher blood levels of the bone hormone osteoprotegerin are associated with an increased long-term risk of death in patients with chronic heart failure, according to Dr. Ragnhild R. Roysland.

The relationship between osteoprotegerin (OPG) and mortality in heart failure is independent of the conventional cardiovascular risk factors, based on a secondary analysis of results of the Italian GISSI-Heart Failure trial.

Osteoprotegerin, a cytokine that’s a member of the tumor necrosis factor superfamily, is drawing increasing attention among cardiovascular researchers as a likely key player in what’s known as “the calcification paradox.” In animal studies, low levels of OPG are associated with decreased skeletal calcification, osteoporosis, and increased calcification of the major arteries. But in recent human studies, increased OPG levels have been linked to a greater atherosclerotic burden; an increased risk of death following acute MI; and now, in GISSI-HF, to increased mortality in the setting of chronic heart failure, Dr. Ragnhild R. Roysland said at the annual congress of the European Society of Cardiology.

The GISSI-HF study was a randomized clinical trial in which 6,975 Italian patients with all kinds of chronic heart failure were assigned to rosuvastatin, fish oil, or placebo and followed up for a median of 3.9 years. The primary results have been published (Lancet 2008;372:1223-30;1231-9). Dr. Roysland presented a new substudy involving 1,229 GISSI-HF participants for whom baseline OPG levels were available.

The aim was to see if baseline OPG was predictive of all-cause mortality. This indeed proved to be the case. During follow-up 332 patients died. The mortality rate was 20% in those in the bottom tertile for baseline OPG with a value less than 1,210 ng/L, and more than twice as great at 45% among patients in the highest tertile, with an OPG of at least 1,923 ng/L. Patients with an intermediate-tertile baseline OPG of 1,210-1,922 ng/L split the difference in terms of mortality, said Dr. Roysland of Akershus University Hospital, Lørenskog, Norway.

Treatment assignment in GISSI-HF did not affect OPG levels. However, if a medication could be identified that reduces OPG levels and attenuates the risk associated with high OPG, then OPG could become an important marker to use in managing chronic heart failure in clinical practice. There is early evidence that treatments for osteoporosis reduce OPG levels in a non­–heart failure population, but studies have not yet been done in patients with chronic heart failure, she continued.

Dr. Marco Metra commented that as a member of the European Society of Cardiology congress scientific program committee, he’d reviewed all the heart failure studies scheduled for presentation at the meeting. Two other studies in addition to Dr. Roysland’s consistently showed that heart failure patients with high levels of OPG have a poor prognosis.

“We know that patients with heart failure have low levels of vitamin D and increased rates of osteoporosis and bone fractures. So the bone is in some way a target of heart failure,” observed Dr. Metra of the University of Brescia (Italy).

Disclosures: Dr. Roysland said she had no financial conflicts.

STOCKHOLM – Suboptimal glycemic control is an independent risk factor for a linear increase in the rate of new-onset heart failure in patients with type 2 diabetes, a large Scottish prospective case-control study indicates.

Moreover, in type 2 diabetes patients who already have established heart failure, poor glycemic control is independently associated with increased mortality, Dr. Chim Choy Lang reported at the annual congress of the European Society of Cardiology.

These were the key findings in a new analysis from the Tayside Study, which Dr. Lang directs. The ongoing project provides an unusual opportunity to prospectively follow an entire Scottish community, population 400,000.

“We can track patients with diabetes mellitus, looking at mean [hemoglobin A1c] over time, and see who develops heart failure. Our bioinformatics platform allows us to track all sorts of biologic variables, prescribing information, and outcomes data,” he explained in an interview.

The analysis was performed because controversy has arisen surrounding the relationship between glycemic control in type 2 diabetes and heart failure. Some recent evidence suggests tight metabolic control is actually associated with worse survival in the setting of heart failure.

“It should be noted that most of these studies were based on a single measure of HbA1c. I think there’s always cause for concern about that kind of analysis,” observed Dr. Lang, a cardiologist at the University of Dundee.

He reported on more than 9,000 Tayside residents with type 2 diabetes, 841 of whom developed heart failure during 1991-2008. Each diabetic heart failure patient was matched by age, gender, and date of diagnosis of diabetes to five controls.

In a multivariate logistic regression analysis, mean HbA1c during the study period was associated in linear fashion with the risk of later developing heart failure. Each 1% increase in HbA1c was independently linked to a 19% increase in incident heart failure after the researchers controlled for patients’ mean arterial pressure and use of thiazolidinediones.

Further, in type 2 diabetic patients with diagnosed heart failure, each 1% increase in mean HbA1c was independently associated with an adjusted 16% increase in all-cause mortality, according to Dr. Lang.

“I think our findings are an argument for tight glycemic control in diabetic patients with heart failure. The question is how to achieve that. I’m a big believer in metformin for that purpose,” the cardiologist said.

Asked if the increased risk of mortality documented in diabetic patients with poor glycemic control and heart failure is a marker for poor adherence to standard heart failure medications or is due to the adverse effects of high blood glucose, Dr. Lang said that’s a key unsettled question.

“We have the ability to look at treatment adherence in this cohort and are doing so at the moment,” he added.

Disclosures: He declared having no financial conflicts in connection with the study, which was conducted free of industry involvement.

STOCKHOLM – Suboptimal glycemic control is an independent risk factor for a linear increase in the rate of new-onset heart failure in patients with type 2 diabetes, a large Scottish prospective case-control study indicates.

Moreover, in type 2 diabetes patients who already have established heart failure, poor glycemic control is independently associated with increased mortality, Dr. Chim Choy Lang reported at the annual congress of the European Society of Cardiology.

These were the key findings in a new analysis from the Tayside Study, which Dr. Lang directs. The ongoing project provides an unusual opportunity to prospectively follow an entire Scottish community, population 400,000.

“We can track patients with diabetes mellitus, looking at mean [hemoglobin A1c] over time, and see who develops heart failure. Our bioinformatics platform allows us to track all sorts of biologic variables, prescribing information, and outcomes data,” he explained in an interview.

The analysis was performed because controversy has arisen surrounding the relationship between glycemic control in type 2 diabetes and heart failure. Some recent evidence suggests tight metabolic control is actually associated with worse survival in the setting of heart failure.

“It should be noted that most of these studies were based on a single measure of HbA1c. I think there’s always cause for concern about that kind of analysis,” observed Dr. Lang, a cardiologist at the University of Dundee.

He reported on more than 9,000 Tayside residents with type 2 diabetes, 841 of whom developed heart failure during 1991-2008. Each diabetic heart failure patient was matched by age, gender, and date of diagnosis of diabetes to five controls.

In a multivariate logistic regression analysis, mean HbA1c during the study period was associated in linear fashion with the risk of later developing heart failure. Each 1% increase in HbA1c was independently linked to a 19% increase in incident heart failure after the researchers controlled for patients’ mean arterial pressure and use of thiazolidinediones.

Further, in type 2 diabetic patients with diagnosed heart failure, each 1% increase in mean HbA1c was independently associated with an adjusted 16% increase in all-cause mortality, according to Dr. Lang.

“I think our findings are an argument for tight glycemic control in diabetic patients with heart failure. The question is how to achieve that. I’m a big believer in metformin for that purpose,” the cardiologist said.

Asked if the increased risk of mortality documented in diabetic patients with poor glycemic control and heart failure is a marker for poor adherence to standard heart failure medications or is due to the adverse effects of high blood glucose, Dr. Lang said that’s a key unsettled question.

“We have the ability to look at treatment adherence in this cohort and are doing so at the moment,” he added.

Disclosures: He declared having no financial conflicts in connection with the study, which was conducted free of industry involvement.

STOCKHOLM – Suboptimal glycemic control is an independent risk factor for a linear increase in the rate of new-onset heart failure in patients with type 2 diabetes, a large Scottish prospective case-control study indicates.

Moreover, in type 2 diabetes patients who already have established heart failure, poor glycemic control is independently associated with increased mortality, Dr. Chim Choy Lang reported at the annual congress of the European Society of Cardiology.

These were the key findings in a new analysis from the Tayside Study, which Dr. Lang directs. The ongoing project provides an unusual opportunity to prospectively follow an entire Scottish community, population 400,000.

“We can track patients with diabetes mellitus, looking at mean [hemoglobin A1c] over time, and see who develops heart failure. Our bioinformatics platform allows us to track all sorts of biologic variables, prescribing information, and outcomes data,” he explained in an interview.

The analysis was performed because controversy has arisen surrounding the relationship between glycemic control in type 2 diabetes and heart failure. Some recent evidence suggests tight metabolic control is actually associated with worse survival in the setting of heart failure.

“It should be noted that most of these studies were based on a single measure of HbA1c. I think there’s always cause for concern about that kind of analysis,” observed Dr. Lang, a cardiologist at the University of Dundee.

He reported on more than 9,000 Tayside residents with type 2 diabetes, 841 of whom developed heart failure during 1991-2008. Each diabetic heart failure patient was matched by age, gender, and date of diagnosis of diabetes to five controls.

In a multivariate logistic regression analysis, mean HbA1c during the study period was associated in linear fashion with the risk of later developing heart failure. Each 1% increase in HbA1c was independently linked to a 19% increase in incident heart failure after the researchers controlled for patients’ mean arterial pressure and use of thiazolidinediones.

Further, in type 2 diabetic patients with diagnosed heart failure, each 1% increase in mean HbA1c was independently associated with an adjusted 16% increase in all-cause mortality, according to Dr. Lang.

“I think our findings are an argument for tight glycemic control in diabetic patients with heart failure. The question is how to achieve that. I’m a big believer in metformin for that purpose,” the cardiologist said.

Asked if the increased risk of mortality documented in diabetic patients with poor glycemic control and heart failure is a marker for poor adherence to standard heart failure medications or is due to the adverse effects of high blood glucose, Dr. Lang said that’s a key unsettled question.

“We have the ability to look at treatment adherence in this cohort and are doing so at the moment,” he added.

Disclosures: He declared having no financial conflicts in connection with the study, which was conducted free of industry involvement.