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Lipoprotein(a) levels tied to atherosclerotic heart disease risk

JAMA Cardiology
European Atherosclerosis Society 2020
Reuters Health - 08/10/2020 - Higher levels of lipoprotein(a) and higher LPA genetic risk scores are associated with an increased risk of developing atherosclerotic cardiovascular disease (ASCVD), according to data from the U.K.

"As genetic testing becomes increasingly commonplace, we anticipate there will be increased recognition of lipoprotein(a), since its corresponding risk information is fully captured by genetic testing," said Dr. Pradeep Natarajan of Massachusetts General Hospital, in Boston.

"First-cardiovascular-disease-event risk prediction for lipoprotein(a), whether via genetics or direct measurement, appears most suitable for individuals at borderline or intermediate risk," told Reuters Health by email. "Both genetic information and direct measurement carry redundant risk-prediction information."

The findings were published in JAMA Cardiology to coincide with a presentation October 6 at the European Atherosclerosis Society 2020 virtual conference.

Lipoprotein(a), which consists of a low-density lipoprotein (LDL) particle covalently linked to apolipoprotein(a), is more atherogenic than LDL, because the apolipoprotein(a) component can exacerbate atherothrombosis. Lipoprotein(a) levels are determined largely by single-nucleotide variants at the LPA gene, information that is captured in the LPA genetic risk score (GRS).

Dr. Natarajan and colleagues evaluated whether lipoprotein(a) measurement and LPA GRS have clinical utility in assessing ASCVD risk. Lipoprotein(a) levels of 120 nmol/L (approximately 50 mg/dL) or higher and LPA GRS of at least 120 were considered elevated.

In the overall study population of more than 374,000 individuals, LPA GRS correlated significantly with measured lipoprotein(a) levels among white/European individuals, South Asians, East Asian individuals, and Black/African individuals.

Among the 300,839 individuals without prevalent ASCVD and not using cholesterol-lowering medication, elevated measured lipoprotein(a) levels were associated with significantly increased risk of incident ASCVD events for white/European, South Asian, East Asian, and mixed individuals, but not among Black/African individuals or individuals of unknown ethnicity.

In the subgroup of white/European individuals without prevalent ASCVD and not using cholesterol-lowering medication, elevated lipoprotein(a) or LPA GRS was associated with a significantly increased risk of incident peripheral arterial disease, coronary-artery disease, myocardial infarction, ischemic stroke and cardiovascular mortality.

"I was surprised to observe that a single genetic test for lipoprotein(a) can fully recapitulate the predictive properties of measuring lipoprotein(a) in the blood," Dr. Natarajan said. "This is not the case for other well-established cardiovascular-disease risk factors, such as blood cholesterol, blood pressure, and diabetes mellitus."

The associations between LPA GRS and these risks were substantially attenuated when models were additionally adjusted for measured lipoprotein(a) levels, and there was no significant difference in the risk of an incident, composite ASCVD event between individuals with and without an elevated LPA GRS after matching for lipoprotein(a) levels.

Adding measured lipoprotein(a) or LPA GRS to clinical risk scores (QRISK3 and Pooled Cohort Equations 10-year ASCVD risk) provided modest improvements to the predicted risk of incident ASCVD events.

"Our finding implies that genetic profiling may fully capture the necessary laboratory information to guide precision medicine approaches for cardiovascular disease prevention, namely candidacy for forthcoming lipoprotein(a)-reducing therapies to potentially reduce cardiovascular-disease risk," Dr. Natarajan said.

"Whether genetic information or direct measurement carry differential prediction with respect to response to preventive therapies, including lipoprotein(a)-lowering therapies, requires further study," he said.

Dr. Gerald Watts of the University of Western Australia, in Perth, who has researched various aspects of lipoprotein(a), including its value as a CVD risk factor, told Reuters Health by email, "Lipoprotein(a) mass and molar concentrations (can be useful) as risk-assessment biomarkers in the context of intermediate cardiovascular risk patients or when unclear to step up therapy in high-risk patients on statins."

"Genetic risk scores are not validated biomarkers and not routinely available," added Dr. Watts, who was not involved in the new study. "Clinicians better understand mass or molar estimations of lipoprotein(a). Lipoprotein(a) molar assays are underway and will be preferred tools."

By Will Boggs MD

SOURCE: https://bit.ly/30J8Qbz JAMA Cardiology, online October 6, 2020.

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