A combined analysis of three blood biomarkers—lipoprotein(a) (Lp(a)), remnant cholesterol, and high-sensitivity C-reactive protein (hsCRP)—may significantly improve the early identification of individuals at high risk for heart attack, according to research to be presented at the American Heart Association’s Scientific Sessions 2025. The study, based on data from over 300,000 participants in the UK Biobank, found that those with elevated levels of all three biomarkers had nearly triple the risk of heart attack compared to those with normal levels, even after adjusting for traditional risk factors.
Each biomarker measures a distinct pathway to cardiovascular disease: Lp(a) is a genetically inherited form of cholesterol that promotes plaque buildup; remnant cholesterol consists of harmful fat particles often missed by standard tests; and hsCRP indicates systemic inflammation. Individually, each biomarker confers only a modest increase in risk—about 45% for one elevated marker—but the risk escalates with each additional marker. Participants with two elevated biomarkers had more than double the risk, while those with all three had nearly three times 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 findings suggest that a simple blood panel including these three tests could help clinicians identify hidden risks that standard cholesterol and blood pressure checks might miss.
Currently, Lp(a) and hsCRP tests are available at most laboratories upon request, and remnant cholesterol can be calculated from a standard lipid panel (total cholesterol minus LDL and HDL cholesterol). Dr. Kazibwe noted that this combination approach may be more accessible than it initially appears and could be particularly beneficial for individuals with a family history of heart disease, Type 2 diabetes, or other risk factors.
The study’s results underscore the potential for more personalized prevention strategies. The American Heart Association’s 2025 AHA/ACC High Blood Pressure Guideline already recommends using the PREVENT™ risk calculator to assess cardiovascular risk. Adding these biomarkers could refine risk estimates for patients in whom treatment decisions are uncertain. Dr. Pamela Morris, an American Heart Association volunteer expert, commented, “This study supports recommendations that consideration of risk enhancers including Lp(a), hsCRP and remnant cholesterol can play an important role in personalizing risk estimates.”
Despite the promise, the study has limitations. As an observational analysis, it cannot prove causation, and the UK Biobank cohort is predominantly white, so further research is needed in diverse populations. The findings are considered preliminary until published in a peer-reviewed journal. Nonetheless, the research adds to a growing body of evidence that combining multiple biomarkers can unlock a more complete picture of cardiovascular risk, potentially enabling earlier interventions to prevent heart attacks.
