Lp(a) as a Cardiovascular Risk Factor

Genetic and epidemiological studies have unequivocally established that elevated levels of lipoprotein(a) [Lp(a)] represent an independent cardiovascular risk factor, particularly for myocardial infarction. Due to its structural similarity with a low-density lipoprotein particle and the homology of apolipoprotein(a) [apo(a)] with plasminogen, Lp(a) can exert multiple effects in atherosclerosis. Lp(a) levels are largely determined by variation in the LPA gene encoding apolipoprotein(a), are relatively stable throughout life, and may differ in individuals from diverse ancestries. For this reason, assessing Lp(a) level at least once in life may help to unmask individuals having elevated Lp(a) levels despite having other lipids in the normal range, and thus being classified as at increased cardiovascular risk. Lp(a) levels are usually higher in patients with coronary disease than in individuals of the general population; furthermore, patients with familial hypercholesterolemia (FH), characterized by genetically elevated low-density lipoprotein cholesterol (LDL-C) levels since birth and an elevated risk of premature cardiovascular disease, commonly present higher Lp(a) levels than non-FH individuals. Mendelian randomization analyses have shown that large absolute reductions in Lp(a) levels may be required to achieve a clinically relevant reduction in the CV risk. Available cholesterol-lowering drugs were shown to reduce Lp(a) levels modestly and do not provide a clinical benefit beyond that of LDL-C-lowering. Ongoing outcome trials with new drugs that specifically lower Lp(a) levels by >80% will reveal whether this reduction translates into a clinical benefit.