Combined Biomarker Analysis Reveals Triple Heart Attack Risk in High-Risk Individuals

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 preliminary research to be presented at the American Heart Association's Scientific Sessions 2025. The study analyzed lipoprotein a (Lp(a)), remnant cholesterol and high-sensitivity C-reactive protein (hsCRP) - three biomarkers that measure different pathways to cardiovascular disease including genetics, cholesterol metabolism and inflammation.

The analysis of health data from more than 300,000 participants in the UK Biobank revealed a clear stepwise pattern in heart attack risk. Participants with all three test results in the highest 20% of values had nearly triple the risk of heart attack, while those with two elevated results had more than double the risk, and participants with one elevated test result had about a 45% higher heart attack risk compared to those 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 represent different aspects of cardiovascular risk. 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 (hsCRP) measures inflammation in the body, with elevated levels potentially signaling risk of damage to arteries.

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 2025 AHA/ACC High Blood Pressure Guidelines recommend that health care professionals use the Predicting Risk of cardiovascular disease EVENTs (PREVENT™) equation to help assess cardiovascular disease risk and optimize primary prevention.

"Advances in the accuracy and precision of risk for atherosclerotic cardiovascular disease mean that clinicians can now more precisely identify individuals who are likely to benefit from preventive therapies," said Pamela Morris, M.D., FAHA, an American Heart Association volunteer expert and professor of cardiology at the Medical University of South Carolina. "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 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, and the findings come from a population where approximately 95% of participants identified as white, requiring further validation in diverse populations. The study abstract is available in the American Heart Association's Scientific Sessions 2025 Online Program Planner at https://professional.heart.org/en/meetings/scientific-sessions.