Lipoprotein(a), or Lp(a), is a modified form of LDL cholesterol with an apolipoprotein(a) protein attached. It is produced in the liver, and the amount produced is almost entirely genetically determined, varying over a thousand-fold between individuals. Elevated Lp(a), broadly defined as above 50 mg/dL or 125 nmol/L, is present in approximately 20 percent of the population and is an independent, causal risk factor for atherosclerotic cardiovascular disease, myocardial infarction, stroke, and calcific aortic stenosis.
Why Lp(a) Is Unusually Important
The strength of the Lp(a) evidence is unusual because it includes Mendelian randomisation studies, which use genetic variants to test causality rather than mere association. These studies consistently demonstrate that the genes that raise Lp(a) raise cardiovascular risk, confirming that the relationship is causal rather than confounded. The 2010 meta-analysis by Nordestgaard et al. in the Journal of the American College of Cardiology, pooling data from 36 prospective studies, found that each standard deviation increment in Lp(a) was associated with a 13 to 22 percent increase in coronary heart disease risk, independent of all other conventional risk factors.
The Testing and Clinical Management Problem
Lp(a) should ideally be measured once in every adult, as the level is genetically determined and relatively stable throughout adult life. European guidelines recommend measuring Lp(a) at least once as part of a global cardiovascular risk assessment. Despite this, Lp(a) testing is not routinely offered in UK primary care, and many adults with significantly elevated levels are managed only for their conventional risk factors, which are insufficient. Statins, the most commonly prescribed lipid-lowering drugs, do not lower Lp(a) and in some cases may slightly raise it. New RNA-targeting therapies specifically designed to lower Lp(a) are in advanced clinical development.
Sources
- Nordestgaard, B.G., et al. (2010). Lipoprotein(a) as a cardiovascular risk factor: current status. European Heart Journal, 31(23), 2844-2853.
- Clarke, R., et al. (2009). Genetic variants associated with Lp(a) lipoprotein level and coronary disease. New England Journal of Medicine, 361(26), 2518-2528.
- Tsimikas, S. (2017). A test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. Journal of the American College of Cardiology, 69(6), 692-711.