Combined Biomarker Analysis Reveals Triple Heart Attack Risk in High-Risk Individuals
A new study shows that analyzing three specific biomarkers together can identify individuals with nearly triple the risk of heart attack, potentially enabling earlier intervention and personalized prevention strategies.
Adults with elevated levels of three biomarkers for heart disease had nearly triple the risk of heart attack compared to those without elevated levels, according to preliminary research to be presented at the American Heart Association's Scientific Sessions 2025. The study found that lipoprotein a (Lp(a)), remnant cholesterol and high-sensitivity C-reactive protein (hsCRP) work together to reveal a much clearer picture of cardiovascular risk than any single biomarker alone.
Researchers analyzed health data from more than 300,000 participants in the UK Biobank, one of the world's largest health databases, following them for a median of 15 years. The analysis revealed a clear stepwise pattern: participants with one elevated biomarker had a 45% increased heart attack risk, those with two elevated biomarkers had double the risk, and individuals with all three biomarkers elevated faced nearly triple the risk. "These biomarkers work together like pieces of a puzzle. One piece cannot show the full picture, yet when combined, we can see a much clearer and more complete depiction of heart attack risks," said lead researcher Richard Kazibwe, M.D., M.S., assistant professor of internal medicine at Wake Forest University School of Medicine.
The three biomarkers measure different pathways to cardiovascular disease. Lipoprotein(a) is a genetically inherited cholesterol that can cause plaque buildup in arteries. Remnant cholesterol refers to harmful fat particles that standard cholesterol tests often miss but can still clog arteries. High-sensitivity C-reactive protein measures inflammation in the body, signaling when the body is under stress and potentially indicating artery damage risk. The American Heart Association's PREVENT™ risk calculator, available at https://professional.heart.org, already incorporates multiple factors for cardiovascular risk assessment, and these biomarkers could enhance its precision.
What makes this approach particularly valuable is that these tests are already accessible in most clinical settings. Lp(a) and hsCRP tests are available at most laboratories upon request, and health care professionals can calculate remnant cholesterol from standard cholesterol panels performed during routine checkups. "Even if traditional risk factors like cholesterol and blood pressure are under control, these simple blood tests can identify hidden inflammation, genetic risk and cholesterol abnormalities," Kazibwe noted. The results could help detect heart disease risk earlier and guide preventive measures before symptoms appear or cardiac events occur.
The study's implications extend to clinical decision-making, particularly for patients where treatment decisions remain uncertain. Pamela Morris, M.D., FAHA, an American Heart Association volunteer expert not involved in the study, emphasized that "consideration of risk enhancers including Lp(a), hsCRP and remnant cholesterol can play an important role in personalizing risk estimates." The American Heart Association provides additional cardiovascular health information at https://www.heart.org to help both patients and providers understand heart disease risks and prevention strategies.
While the research shows promising patterns, the authors acknowledge important limitations. As an observational study, the findings cannot prove that elevated biomarker levels directly caused heart attacks. Additional research is needed to determine if using these tests to guide treatment decisions actually improves patient outcomes. The study population was predominantly white, so further investigation is required to confirm whether the results apply broadly to diverse populations. The full study abstract can be viewed through the American Heart Association's Scientific Sessions 2025 Online Program Planner at https://professional.heart.org.