Lipoprotein(a): is it more, less or equal to LDL as a causal factor for cardiovascular disease and mortality?

Abstract

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