Genetically Elevated Lipoprotein(a) and Increased Risk of Myocardial Infarction

This is one of the pivotal studies establishing that lipoprotein(a) causes heart attacks rather than merely accompanying them — using genetics to escape the confounding that plagues observation.

Drawing on Copenhagen population studies, the investigators used the KIV-2 genetic variant (which explains a large share of Lp(a) variation) as a natural randomizer. People genetically predisposed to high Lp(a) had increased myocardial infarction risk, and — the crucial test of causality — the genetic effect was concordant with the effect of measured Lp(a) levels. When the gene and the measured level point the same way, confounding cannot explain it.

This concordance is the hallmark of a causal relationship, and Kamstrup’s work was instrumental in shifting Lp(a) from “risk marker” to “causal factor” in the field’s consensus.

We rate the evidence strong. A well-conducted Mendelian randomization study from a leading group, it is a foundational citation for the causal case that underpins today’s Lp(a)-lowering drug trials.