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UC Irvine-led research team shows importance of under-recognized genetic factor lipoprotein(a) in predicting heart disease in a large multiethnic US population

Posted: 2024-04-15

Source: UCI School of Medicine
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Irvine, Calif., April 14, 2024 – In what is the largest, most ethnically diverse long-term study of a U.S. population, a University of California, Irvine research team found that an under-recognized genetic cholesterol-like particle called lipoprotein(a) [Lp(a)] can help predict future cardiovascular disease.

The study, published online today in the Journal of the American College of Cardiology, revealed that elevated levels of Lp(a) forecasted future atherosclerotic cardiovascular disease (ASCVD) events, especially heart attacks and revascularizations, as well as strokes and coronary heart disease deaths in a cohort of more than 27,000 adults from five major U.S. prospective studies of cardiovascular disease who were followed for an average of 21 years.

The investigators, led by Nathan D. Wong, PhD, a professor of medicine and epidemiology at UC Irvine and director of the Heart Disease Prevention Program in the Division of Cardiology at the UC Irvine School of Medicine, found that compared to persons with Lp(a) levels below the 50th percentile, those with levels at or above the 90th percentile (averaging 53 mg/dL) had a 46% higher risk of overall ASCVD events. More importantly, Lp(a) was an even stronger predictor of ASCVD events in those with diabetes. Among those with diabetes at baseline, this risk was 92% higher, while risks for future heart attacks, revascularizations, strokes and coronary heart disease deaths were 66%, 68%, 26% and 32% higher, respectively. 

“Lp(a) stands out as the most powerful genetic risk factor for cardiovascular disease, affecting one in five individuals, yet fewer than 1% of Americans know their levels,” said Wong. “Our study supports recent U.S. recommendations calling for Lp(a) to be measured at least once in every adult,” said Wong.     

Featuring a participant pool comprising 55% women and 36% African American participants, along with Asian and Hispanic representation, the study marks the largest and most ethnically diverse long-term U.S. study investigating the relation of Lp(a) with cardiovascular outcomes.   

“Our findings also indicate that elevated Lp(a) levels similarly predict outcomes in women and men and across race/ethnic groups,” said Wenjun Fan, MD, PhD, an assistant professor of epidemiology and medicine at UC Irvine and a key co-author of the study. “African American and South Asian populations have higher Lp(a) levels than other race/ethnic groups, emphasizing its further importance in these groups.”

While current U.S. recommendations advocate for intensified efforts to reduce overall cardiovascular disease risk, including with statin and other preventive therapies in those with Lp(a) levels of 50 mg/dL (or 125 nmol/L) or higher, Wong notes that several new RNA-targeted therapies that reduce Lp(a) by up to 80-100% are currently in development, with results from ongoing clinical trials examining their impact on cardiovascular outcomes due out in the next few years.

This research further documents the crucial role of Lp(a) in cardiovascular disease, emphasizing the importance of its measurement in all adults for identifying those who can benefit from risk-reduction efforts. “The failure to screen and identify those with Lp(a)-associated risks represents a missed opportunity to address this threat not only with our existing repertoire of treatments but with promising therapies currently in development that will be able to target Lp(a) in the future,” said Wong.

Lipoprotein(a) and Risk of Cardiovascular Disease in a Large US Pooled Cohort

About the UCI School of Medicine

Each year, the UCI School of Medicine educates more than 400 medical students and nearly 150 PhD and MS students. More than 700 residents and fellows are trained at the UCI Medical Center and affiliated institutions. Multiple MD, PhD and MS degrees are offered. Students are encouraged to pursue an expansive range of interests and options. For medical students, there are numerous concurrent dual degree programs, including an MD/MBA, MD/MPH, or an MD/MS degree through one of three mission-based programs: the Health Education to Advance Leaders in Integrative Medicine (HEAL-IM), the Program in Medical Education for Leadership Education to Advance Diversity-African, Black and Caribbean (PRIME LEAD-ABC), and the Program in Medical Education for the Latino Community (PRIME-LC). The UCI School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit