Genetically Low Triglycerides and Mortality: Further Support for “the Earlier the Better”?

Extract

In this issue of Clinical Chemistry, Mette Thomsen and colleagues contribute another gem from the treasure trove that is the Copenhagen City Heart Study (1). This mendelian randomization study builds upon the investigators' prior work linking genetically increased circulating triglyceride concentrations (a marker of remnant lipoproteins) with higher risk of ischemic heart disease (2). The present study gives the other bookend, linking genetically lower nonfasting circulating triglyceride concentrations with lower all-cause mortality. This work at the intersection of lipidology and preventive cardiology will be of interest to those working at many different scientific and clinical levels to improve the prevention of cardiovascular disease.

Strengths of the study include the long duration of follow-up spanning 2 decades and the completeness of outcome ascertainment, with 100% of patients accounted for thanks to the Danish Central Person Register. In addition, the study takes advantage of a modern epidemiologic technique—the so-called “randomized trial of biomarkers”—mendelian randomization. In linking genetic information with biomarker concentrations and clinical outcomes, this technique is thought to limit much of the bias in traditional epidemiologic approaches and allow causal inference. An additional strength of this study is the nonfasting measurement of circulating triglyceride concentrations. Indeed, we as humans spend most of our lives in a nonfasting state and nonfasting triglyceride concentrations have a stronger association with incident cardiovascular events than fasting values (3). Triglycerides measured 2–4 h postprandially have an especially strong association with cardiovascular disease risk, illuminating the importance of postprandial lipid metabolism in cardiovascular disease.