Lipoprotein(a) Concentration and Risks of Cardiovascular Disease and Diabetes

This large Icelandic study, from deCODE genetics, resolved a debated question with direct implications for how to measure and treat lipoprotein(a): is it the amount of Lp(a) that matters, or the size of the apo(a) particle?

The answer was clear: molar concentration drives risk, not isoform size. Lp(a) concentration was dose-dependently associated with coronary disease, peripheral artery disease, aortic stenosis, heart failure, and even shorter lifespan — and once concentration was accounted for, particle size added nothing. The study also confirmed a curious inverse finding: very low Lp(a) causally raises type 2 diabetes risk slightly, though lowering high Lp(a) toward the population median is predicted to reduce heart disease without increasing diabetes.

This matters for drug development: it tells us that lowering the concentration of Lp(a) is the goal, and that the top 20 percent of individuals stand to benefit most.

We rate the evidence strong. A large study combining observation and genetics, it provided definitive, practically important answers about which aspect of Lp(a) to target.