Lipoprotein (a): understanding its effect as a cardiovascular risk factor

Based on research between the association of lipoprotein a (LPA) levels and an increased risk for cardiovascular disease, some researchers are recommending that physicians measure levels at least once in their patients’ lifetime.The recommendation came from Dr. Husam Abdel-Qadir, a clinical epidemiologist and clinical researcher with the University of Toronto and the Toronto General Hospital Research Institute.“What we’ve seen is that levels of LPA are higher in Black people,” said Dr. Abdel-Qadir, who presented research in a session at the Black Physicians Association of Ontario’s (BPAO) 16th annual Health Symposium in February. LPA is genetically inherited, he said, and a common risk factor for cardiovascular disease. At a molecular level, Dr. Abdel-Qadir said that LPA is made of an low-density lipoprotein (LDL)-like lipid core with cholesterol, triglycerides, phospholipids and apolipoprotein b, where it differs is the addition of apolipoprotein a, which is coded by the LPA gene and includes 10 subtupes of kringle IV, including kringle IV-2, and repeat numbers of it.Dr. Abdel-Qadir said those repeats are genetically encoded, and the length relates to cardiovascular risk.“This is not so new, we’ve known this, but it is coming more into our field of consciousness,” he said. According to his presentation, level of LPA is genetically determined in all ethnicities and the highest levels are seen in Black populations, while the lowest levels of it are seen in East Asian and people of European descent. “People with the highest 5% of LPA have triple the risk of heart attacks, triple the risk of aortic-valve stenosis and higher risk of myocardial infraction,” he said. According to the data that Dr. Abdel-Qadir cited from the Copenhagen City Heart Study and the Copenhagen General Population study, people with more than 90-milligrams-per-deciliter (mg/dL) or 190-nanomoles-per-liter (nmol/L) of LPA are in the top 5% of LPA concentrations. People with lower levels of LDA have higher risk of diabetes, said Dr. Abdel-Qadir: “But this is something we don’t currently understand.” ImplicationsLPA is completely not impacted by lifestyle, said Dr. Abdel-Qadir, who said that related interventions like smoking cessation, switching to a plant-based diet, weight loss and physical exercise produced no change in lowering LPA levels. While there are drugs in development, such as riboneulaic acid (RNA)-based therapeutics like Pelacarsen, which has shown an 80% reduction in LPA levels, many of those drugs are still in clinical development, he said. Results from phase three clinical testing of the drug are expected in 2025 to 2026.Proprotein convertase subtilisin/kexin 9 (PCSK9)-inhibitors have also been shown to lower LPA levels, but according to Dr. Abdel-Qadir, that is not a reason to start them in 2024 without other indications. RecommendationsDr. Abdel-Qadir recommends that physicians follow the Canadian Cardiovascular Society’s 2021 Guidelines for managing LPA and preventing cardiovascular disease in adults.The guidelines recommend that physicians: Measure LPA level once in a person’s lifetime as a part of the initial lipid screening.Provide early and intensive health behaviour modification counselling and management of other cardiovascular disease risk factors for all patients with an LPA of 50 mg/dL or higher (100 nmol/L).When treating Black patients, Dr. Abdel-Qadir urges physicians to remember that there are differences in Black genetics depending on ethnicity. Part of a research project that will be published later this year took a closer look at the biological differences within different ethnicities of the Black population. “You can’t measure genetics by race, but by ethnicity and geography,” he said.

Lipoprotein (a): understanding its effect as a cardiovascular risk factor

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