Link Between LDL and Heart Disease Confirmed

New genetic research adds weight to existing evidence showing the effects that genetics, cholesterol and other lipids in the blood have on coronary heart disease (CHD). Earlier research has shown elevated levels of low-density lipoprotein cholesterol (LDLc, or “bad” cholesterol) are known to cause heart disease; less clear is the effect of other lipids such as high-density lipoprotein (HDLc, or “good” cholesterol) and triglycerides (TG).

Researchers from the Perelman School of Medicine at the University of Pennsylvania and the Children’s Hospital of Philadelphia used genetic variants to construct gene scores for each of the major lipid traits (LDLc, HDLc and TG) for every individual in more than 60,000 participants from 17 studies. Approximately 12,000 of these participants had experienced a heart disease event.

The research team used the gene scores to estimate the causal effect of the major lipid traits on the risk of heart disease. They were able to generate these causal estimates because the gene scores mimicked effects of randomized trials to alter these lipid traits. The study team utilized a recently developed epidemiology tool called Mendelian randomization (MR).

“First, as we expected, our data show that LDLc causes heart disease, and we already know this from clinical trials,” says study co-author Michael Holmes, MD, PhD, research assistant professor of surgery in the division of transplant at Penn Medicine.

“This LDLc effect helped to validate our methods. We then identified that, similar to LDLc, triglycerides are very likely to cause heart disease. We found that individuals with genetically higher triglycerides had a higher risk of heart disease. In contrast, our data suggests that HDLc is unlikely to play an important role in the development of heart disease.”

These findings are important because although HDLc may be a marker of heart disease risk, treatments aimed at targeting HDLc may not have an actual impact on reducing heart disease events.

“And this is what we have seen recently with large-scale randomized trials of CETP inhibitors, drugs that were designed to target HDLc,” explains Dr. Holmes.

“This suggests that further trials of therapies that alter HDLc may not reduce the risk of heart disease. But importantly, our findings are very suggestive that drugs that reduce triglycerides should have an important impact on reducing risk of heart disease events, and I think this is an area in which trials for heart disease treatment and/or prevention should be prioritized.”

--Adrianne O’Brien

Reference

Holmes M, Keating B, Asselbergs F, Palmer T, Drenos F, et al. Mendelian Randomization of Blood Lipids for Coronary Heart Disease. European Heart Journal. 2014.