A combination of four substances the body produces in response to heart and kidney damage may help predict the risk of death from cardiovascular disease, at least in older men. A study published in the May 15 New England Journal of Medicine concludes that considering levels of these biomarkers along with more traditional risk factors greatly improves risk prediction.
Those traditional factors— high blood pressure, diabetes, smoking, high cholesterol levels, and unhealthy body mass index—are associated with risk of death from cardiovascular disease. The four biomarkers, Troponin I, NT-pro BNP (N-terminal pro-brain natriuretic peptide), cystatin C, and CRP (C-reactive protein) reflect damage to heart muscle cells, dysfunction of the heart’s left ventricle, kidney failure, and inflammation, respectively.
Biomarker Combination Gets Results
Researchers from Sweden’s Uppsala University measured levels of each of the four biomarkers in 1,153 men of median age 71 who participated in a long-term survey focused on cardiovascular risk factors. Researchers tracked these men for a median of 10 years. During that time, researchers recorded 315 deaths, 136 of which resulted from cardiovascular disease. Only 26 of these cardiovascular deaths occurred among the 486 men who did not have elevations in any of the biomarkers.The researchers’ analysis finds that the biomarkers enhanced prediction of risk, both in the entire study population and among those who did not have cardiovascular disease at the study’s start. Men with elevated levels of any two biomarkers had a three-fold increase risk of death. Elevated levels of all four conferred a dramatic, 16-fold increase in risk.
Noting that previous studies of multiple biomarkers’ ability to predict risk showed only very minor benefit, the researchers point to key differences between earlier research and their own. For instance, their research involved men who were more than 10 years older than the other studies’ subjects and focused on different biomarker combinations. The four biomarkers are associated with both cardiovascular and renal damage believed to be more common among their study population, the researchers write.
But they caution that the findings "should not be construed as implying a direct benefit of a reduction in the biomarkers." While many studies point to the benefits of modifying conventional cardiovascular risk factors, "there is currently little evidence that reducing the levels of the biomarkers will reduce the risk," the researchers add.
More Studies Needed
An accompanying editorial emphasizes the need for more research on the four biomarkers in other populations. One major reason is that the study population is so unique. Participants were all lean white men of the same age, write James A. de Lemos, MD, of the University of Texas Southwest Medical Center and Donald Lloyd-Jones, MD, of the Feinberg School of Medicine at Northwestern University. They suggest that “these findings need to be validated in younger cohorts of men and women who are free from cardiovascular disease and should be updated . . . as newer, and better, biomarkers emerge from discovery research programs.” More importantly, they note that the most difficult challenge will be to determine how clinical practice should change and what should be done differently on the basis of these biomarkers.Sources
- Zethelius B et al. Use of multiple biomarkers to improve the prediction of death from cardiovascular causes. N Engl J Med 2008 May 15; 358: 2107.
- De Lemos J and Lloyd-Jones D. Multiple Biomarker Panels for Cardiovascular Risk Assessment. N Engl J Med May 15; 358:2172.
- Fairchild D. Biomarkers Improve Prediction of Cardiovascular Death in Elderly Men. Physician’s First Watch 2008 May 15.
- Multiple Biomarkers as Predictors of Cardiovascular Death. Journal Watch General Medicine 2008 May 15.
Reviewed by Ramaz Mitaishvili, MD
Biomarker Combination Gets Results
Researchers from Sweden’s Uppsala University measured levels of each of the four biomarkers in 1,153 men of median age 71 who participated in a long-term survey focused on cardiovascular risk factors. Researchers tracked these men for a median of 10 years. During that time, researchers recorded 315 deaths, 136 of which resulted from cardiovascular disease. Only 26 of these cardiovascular deaths occurred among the 486 men who did not have elevations in any of the biomarkers.The researchers’ analysis finds that the biomarkers enhanced prediction of risk, both in the entire study population and among those who did not have cardiovascular disease at the study’s start. Men with elevated levels of any two biomarkers had a three-fold increase risk of death. Elevated levels of all four conferred a dramatic, 16-fold increase in risk.
Noting that previous studies of multiple biomarkers’ ability to predict risk showed only very minor benefit, the researchers point to key differences between earlier research and their own. For instance, their research involved men who were more than 10 years older than the other studies’ subjects and focused on different biomarker combinations. The four biomarkers are associated with both cardiovascular and renal damage believed to be more common among their study population, the researchers write.
But they caution that the findings "should not be construed as implying a direct benefit of a reduction in the biomarkers." While many studies point to the benefits of modifying conventional cardiovascular risk factors, "there is currently little evidence that reducing the levels of the biomarkers will reduce the risk," the researchers add.
More Studies Needed
An accompanying editorial emphasizes the need for more research on the four biomarkers in other populations. One major reason is that the study population is so unique. Participants were all lean white men of the same age, write James A. de Lemos, MD, of the University of Texas Southwest Medical Center and Donald Lloyd-Jones, MD, of the Feinberg School of Medicine at Northwestern University. They suggest that “these findings need to be validated in younger cohorts of men and women who are free from cardiovascular disease and should be updated . . . as newer, and better, biomarkers emerge from discovery research programs.” More importantly, they note that the most difficult challenge will be to determine how clinical practice should change and what should be done differently on the basis of these biomarkers.Sources
- Zethelius B et al. Use of multiple biomarkers to improve the prediction of death from cardiovascular causes. N Engl J Med 2008 May 15; 358: 2107.
- De Lemos J and Lloyd-Jones D. Multiple Biomarker Panels for Cardiovascular Risk Assessment. N Engl J Med May 15; 358:2172.
- Fairchild D. Biomarkers Improve Prediction of Cardiovascular Death in Elderly Men. Physician’s First Watch 2008 May 15.
- Multiple Biomarkers as Predictors of Cardiovascular Death. Journal Watch General Medicine 2008 May 15.
