Two Important Cardiovascular Disease Risk Factors Operate Independently

Determination of blood levels of the cholesterol-rich biomarker lipoprotein(a) [Lp(a)] and the coronary artery calcium (CAC) score are independently associated with risk of developing coronary artery disease and may be useful concurrently for guiding therapy approaches to prevent its occurrence .

Lp(a) consists of a low density lipoprotein-like particle and the specific apolipoprotein(a), which is bound covalently to the apolipoprotein B contained in the outer shell of the particle. Lp(a) plasma concentrations are highly heritable and mainly controlled by the LPA gene located on chromosome 6q26-27. High Lp(a) in blood correlates with coronary heart disease (CHD) and cardiovascular disease (CVD).

A coronary CT calcium scan is a computed tomography (CT) scan of the heart for the assessment of severity of coronary artery disease. Specifically, it looks for calcium deposits in the coronary arteries that can narrow arteries and increase the risk of heart attack. This severity is presented as the coronary artery calcium (CAC) score. The CAC score is an independent marker of risk for cardiac events, cardiac mortality, and all-cause mortality. In addition, it provides additional prognostic information to other cardiovascular risk markers.

While it has been recognized that elevated Lp(a) and CAC score are individually associated with increased atherosclerotic cardiovascular disease (ASCVD) risk, the two markers have not been studied in combination. To rectify this situation investigators at the University of Texas Southwestern Medical Center (Dallas, USA) measured plasma Lp(a) and CAC at enrollment among asymptomatic participants of the MESA (Multi-Ethnic Study of Atherosclerosis) (n = 4,512) and DHS (Dallas Heart Study) (n = 2,078) cohorts. The Dallas Heart Study, an ongoing comprehensive study of diverse and heart-healthy patients, while the MESA is 6,000-participant study investigating early-stage atherosclerosis.

Results enabled identification of three distinct risk-related trends. Individuals with both elevated levels of Lp(a) and a high CAC score had the highest 10-year risk of heart attack or stroke. Those with elevated Lp(a) but with a CAC score of zero had a low 10-year heart attack and stroke risk. Finally, those with low Lp(a) but with a high CAC score had 10-year heart attack or stroke risk higher than average but lower than with high LP(a) and high CAC combined.

"We are hopeful that by making the connection between Lp(a) and CAC as dual risk drivers, we can raise awareness in the medical community and improve earlier heart attack prevention for these patients," said senior author Dr. Parag Joshi, associate professor of internal medicine at the University of Texas Southwestern Medical Center. "Our data may also expedite the development of treatments designed specifically for this high-risk population. Establishing the connection between Lp(a) and CAC means we can move to the important next phase of research, which will be defining and personalizing early screening protocols to identify patients at high risk of heart attack. With further research, this could mean selectively scanning patients with high Lp(a) for their CAC score, and studying therapies specifically designed to reduce Lp(a) among patients with high CAC."

The study was published in the March 1, 2022, issue of the Journal of the American College of Cardiology.

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