Lipoprotein(a) as a Causal Risk Factor for Cardiovascular Disease

Abstract Purpose of Review Lipoprotein(a) [Lp(a)], an atherogenic low-density lipoprotein cholesterol (LDL-C)-like molecule, has emerged as an important risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). This review summarizes the evidence supporting Lp(a) as a causal risk factor for ASCVD and calcific aortic valve stenosis (CAVS). Recent Findings Lp(a) is largely (~ 90%) genetically determined and approximately 20% of the global population has elevated Lp(a). The unique structure of Lp(a) leads to proatherogenic, proinflammatory, and antifibrinolytic properties. Data from epidemiological, genome-wide association, Mendelian randomization, and meta-analyses have shown a clear association between Lp(a) and ASCVD, as well as CAVS. There are emerging data on the association between Lp(a) and ischemic stroke, peripheral arterial disease, and heart failure; however, the associations are not as strong. Summary Several lines of evidence support Lp(a) as a causal risk factor for ASCVD and CAVS. The 2024 National Lipid Association guidelines, 2022 European Atherosclerosis Society, and 2021 Canadian Cardiology Society guidelines recommend testing Lp(a) once in all adults to guide primary prevention efforts. Further studies on cardiovascular outcomes with Lp(a) targeted therapies will provide more insight on causal relationship between Lp(a) and cardiovascular disease.