Lp(a) matches LDL as a cause of heart attacks but outweighs it for mortality risk, a head-to-head comparison in about 100,000 Danes (Curr Opin Lipidol 2020)

Purpose Of Review: To summarize the recent studies directly comparing LDL and lipoprotein(a) as causal factors for cardiovascular disease and mortality.

Recent Findings: In approximately 100,000 individuals from the Copenhagen General Population Study for risk of myocardial infarction, in observational analyses per 39 mg/dl (1 mmol/l) cholesterol increase, the hazard ratio was 1.3 (95% confidence interval: 1.2-1.3) for LDL cholesterol and 1.6 (1.4-1.9) for lipoprotein(a) cholesterol. In corresponding genetic analyses, the causal risk ratio was 2.1 (1.3-3.4) for LDL and 2.0 (1.6-2.6) for lipoprotein(a). Also, a 15 mg/dl (0.39 mmol/l) cholesterol increase was associated with a hazard ratio for cardiovascular mortality of 1.05 (1.04-1.07) for LDL cholesterol and 1.18 (1.12-1.25) for lipoprotein(a) cholesterol. Corresponding values for all-cause mortality were 1.01 (1.00-1.01) for LDL cholesterol and 1.07 (1.04-1.10) for lipoprotein(a) cholesterol. In genetic, causal analyses, the mortality increases for elevated lipoprotein(a) appeared to be through apolipoprotein(a) kringle IV-2 rather than through lipoprotein(a) levels per se.

Summary: On cholesterol scales, lipoprotein(a) and LDL appeared equal as causal factors for myocardial infarction; however, lipoprotein(a) was most important for mortality. Lipoprotein(a) effects may not only be due to cholesterol content but could also be due to the structure of lipoprotein(a) resembling plasminogen.