Lipoprotein (a), also known as Lp(a), has been long suspected to be an independent risk factor for cardiovascular disease (CVD). Some studies have estimated that 20% of the Caucasian U.S. population may have increased CVD risk due to elevated plasma Lp(a) levels. However, until recently, a lack of robust assays to measure Lp(a) levels has prevented scientific consensus on the nature of Lp(a)-associated risk.
New guidelines for patient-centered care
Promising results from recent epidemiological studies have led the National Lipid Association in 2019 to issue guidelines that recommend selective Lp(a) screening based on shared decision-making with the patient. Among the groups who would benefit most strongly from Lp(a) measurements are those with premature atherosclerotic CVD, those with a family history of atherosclerotic CVD, those with high LDL-C levels or suspected familial hypercholesterolemia, and those with other risk factors for atherosclerotic CVD.
Catherine McNeal, MD, PhD, a physician at Baylor Scott & White Medical Center in Temple, TX, and a researcher with the Baylor Scott & White Research Institute (BSWRI), is a member of the National Lipid Association expert panel that produced the new consensus scientific statement, which was published in the Journal of Clinical Lipidology. According to Dr. McNeal “We now have robust assays for Lp(a) and we have genomic data to back up those assays. We also have new drugs coming to the market that target Lp(a). It is time to consider the importance of Lp(a) in CVD management.”
Lp(a): a “triple threat” in cardiovascular disease
Lp(a) is a form of LDL cholesterol that can cause atherosclerotic buildup of cholesterol in the arteries. In addition, Lp(a) can increase the formation of arterial thrombotic emboli and cause calcific aortic valve disease. The thrombogenic effects of Lp(a) are thought to be caused by apolipoprotein(a) (apo[a]), which is bound to the apolipoprotein B in the outer shell of the LDL particle of Lp(a). Apo(a) has homology to fibrinogen and can inhibit fibrinolysis. Therefore, elevated levels of Lp(a) could have at one time conferred a survival benefit by enhancing wound healing, but at the cost of increasing the risk of CVD later in life.
Lp(a): a biomarker for patient-centered risk profiling
Lp(a) levels are ~90% heritable, stable across the lifespan, and resistant to cholesterol-lowering drugs. This means that a single non-fasting Lp(a) measurement is all that is needed to determine whether there is Lp(a)-associated risk. However, the link between Lp(a) levels and risk appears to vary among ethnic groups and can be influenced by the presence of other risk factors. More research is needed to understand the factors that regulate the link between Lp(a) levels and CVD risk in order to develop patient-centered approaches to cardiovascular care.
Large-scale clinical research
Dr. McNeal, in collaboration with BSWRI, is contributing to an active international clinical study that will evaluate Lp(a) levels in 45,000 participants with established CVD (NCT03887520). Billy Don Jones, MD, a cardiologist with Baylor Scott & White Medical Center – Temple is also contributing to this study. This clinical study seeks to better understand the link between Lp(a) levels and CVD in an ethnically and geographically diverse population. According to Dr. McNeal, “We hope to find the patients with elevated Lp(a) levels, understand how their diseases progress, and identify their other risk factors. This research is being done on an unprecedented scale.”
Linking research to patient care
Dr. McNeal is an internist and pediatrician specializing in cardiovascular disease risk factor management with a particular focus on lipids. She is also on the Science Group Policy Board for the National Lipid Association, is the president elect of the Southwest Lipid Association, and is on the Scientific Advisory Board for the Lipoprotein(a) Foundation. This expertise provides a centralized resource for advanced lipid management and treatment at Baylor Scott & White Medical Center – Temple.
Looking toward the future, Dr. McNeal notes that spreading the word about Lp(a) screening guidelines is the next big hurdle. “We need to help primary care physicians understand why to screen, who to screen, when to screen, and what to do if Lp(a) levels are elevated. These changes can help individual patients get the care they need.”
Baylor Scott & White Health offers a comprehensive program in cardiovascular disease prevention, diagnosis, and treatment, at sites throughout North and Central Texas. This includes advanced patient care and access to clinical trials through BSWRI.