Three Biomarkers Combined Nearly Triple Heart Attack Risk, Study Finds

Adults with elevated levels of three specific biomarkers for heart disease had nearly triple the risk of heart attack compared to those without elevated levels, according to research to be presented at the American Heart Association's Scientific Sessions 2025. The study found that lipoprotein(a), remnant cholesterol, and high-sensitivity C-reactive protein (hsCRP) work together to provide a more complete picture of cardiovascular risk than any single biomarker alone.

The analysis of health data from more than 300,000 participants in the UK Biobank revealed a clear stepwise pattern in heart attack risk over a median follow-up period of 15 years. Participants with elevated levels of all three biomarkers had nearly three times the risk of heart attack, while those with two elevated biomarkers had more than double the risk, and those with one elevated biomarker had about a 45% higher risk compared to participants with normal levels.

"Each of the blood tests on its own indicate only a modest increase in heart attack risk, however, when we found elevated levels for all three, the risk of heart attack was nearly three times higher," said Richard Kazibwe, M.D., M.S., lead researcher and an assistant professor of internal medicine at Wake Forest University School of Medicine. "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."

The three biomarkers measure different pathways to cardiovascular disease. Lipoprotein(a) is a type of cholesterol that is largely inherited and can cause plaque buildup in arteries. Remnant cholesterol refers to harmful fat particles that standard cholesterol tests can miss but can also clog arteries. High-sensitivity C-reactive protein measures inflammation in the body, with elevated levels potentially signaling risk of arterial damage.

Although these blood tests are not yet part of routine screening guidelines, Kazibwe notes this combination approach may be more accessible than it initially appears. Lp(a) and hsCRP tests are available at most labs upon request, and health care professionals can calculate remnant cholesterol from standard cholesterol panels already performed during many routine checkups. The American Heart Association provides resources for understanding cardiovascular risks.

"Evaluating the combined results of all three blood tests may help health care professionals act more quickly and provide tailored care for people with the highest risk," Kazibwe said. "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."

The research has important limitations as an observational study that cannot prove elevated levels of these biomarkers directly caused the heart attacks. Additional research is needed to determine if using these tests to guide treatment decisions leads to improved patient outcomes. The findings also come from the UK Biobank, with approximately 95% of participants identifying as white, so further research would be needed to confirm whether the results apply broadly to diverse populations.

Pamela Morris, M.D., FAHA, an American Heart Association volunteer expert who was not involved in the study, noted that "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. The findings indicate that these biomarkers can aid in clinical decision making, particularly for those patients in whom treatment decisions are uncertain."