Triglycerides: the past, the present, and the future

The pastThe relationship between cholesterol (C) and arteriosclerotic cardiovascular disease (ASCVD) emerged early in the 20th century.In 1910, Windaus, a German chemist, found C in atherosclerotic plaques in human aortas.In 1913, Anitschkow, a young Russian experimental pathologist, fed large quantities of pure C to rabbits, causing vascular changes similar to those in developing arteriosclerotic plaques in patients. 1The importance of LDL-C in the development of ASCVD grew slowly but steadily as a consequence of basic research that was appropriately rewarded by nine separate Nobel Prizes, as well as multiple genetic, epidemiologic, and clinical studies.Drugs to reduce circulating C were developed and found to be effective in both primary and secondary preventions of ASCVD; they have prolonged the lives of millions of people around the world.Taken together, the C story has been one of the medical triumphs of the 20th century. 1 However, despite these notable advances, lowering LDL-C did not abolish ASCVD, and the search was on for other dyslipidaemias that could be responsible for residual atherogenesis.Triglycerides (TG), which provide important sources of energy, became obvious candidates.Indeed, in 1959, Albrink and Mann 2 reported that serum TG was frequently elevated in some persons who had experienced a myocardial infarction.This observation was repeatedly confirmed and extended to other manifestations of ASCVD.For example, in the PROVE IT (TIMI 22) trial, we observed that in statin-treated post-acute coronary syndrome patients, an elevated TG (>150 mg/dL/1.7 mmol/L) was associated with higher cardiovascular risk than those with lower (normal) levels. 3However, it was observed that TG levels were not independent of LDL-C and other ASCVD risk factors.