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) in combination, revealing a clear stepwise pattern of increasing heart attack risk.
Researchers examined health data from 306,183 adults in the UK Biobank who were free from cardiovascular disease at enrollment. Over a median follow-up period of 15 years, scientists tracked heart attack rates and calculated how many participants had each of the three blood test results in the highest 20% of values. The analysis found that participants with all three test results in the highest ranges had nearly triple the risk of heart attack, 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.
"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 in the blood 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 the arteries.
This combined approach to risk assessment represents a significant advancement in preventive cardiology because it can identify high-risk individuals even when traditional risk factors appear controlled. The findings suggest that evaluating these three biomarkers together may help health care professionals detect heart disease risk earlier and provide more tailored care for people with the highest risk. Guidance that encourages healthy lifestyle changes or initiating treatment, such as medication to lower cholesterol and blood pressure, could help reduce risk and prevent heart attacks.
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 additional information about cardiovascular risk assessment through resources available at https://www.heart.org.
Pamela Morris, M.D., FAHA, an American Heart Association volunteer expert who was not involved in the study, emphasized the clinical importance of these findings. "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," said Morris, who is a professor of cardiology and director of the Seinsheimer Cardiovascular Health Program at the Medical University of South Carolina.
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. The complete study abstract can be found in the American Heart Association's Scientific Sessions 2025 Online Program Planner.
