Most of us have heard of the “good cholesterol” and “bad cholesterol” coursing through our bloodstream. In the conventional wisdom of the past 30 years, having more of the “good” variety — high-density lipoprotein, or HDL — can lower your risk of heart disease, while more “bad” cholesterol — low-density lipoprotein, or LDL — increases your risk. Indeed, over the years, clinical trials and other studies have found that drugs that lower LDL also lower your probability of heart disease.
However, trials have not shown heart-health benefits to increasing HDL or to lowering triglycerides, a third type of blood lipid. But now a new study from The Children’s Hospital of Philadelphia and the University of Pennsylvania, published recently in European Heart Journal, sheds light on the role of genes and blood lipid levels in cardiovascular health. Newer tools for gene analysis show how variations in DNA are underlying actors affecting heart disease, a major worldwide cause of death and disability.
“Now we are able to pinpoint gene signals that actually cause some of these conditions,” said geneticist Brendan J. Keating, DPhil, of The Center for Applied Genomics. “Unraveling how genetic variants that influence lipid traits are related to heart disease risk is a step toward designing treatments.” Dr. Keating collaborated with University of Pennsylvania clinical epidemiologist Michael V. Holmes, MD, PhD.
The investigators used a recently developed tool called Mendelian randomization (MR), which analyzes genetic variations using a method that identifies genes responsible for particular diseases, independent of confounding factors such as differences in behavior or environmental influences that often limit the conclusions of epidemiology research.
The researchers analyzed DNA data from 17 studies including over 60,000 individuals, of whom more than 12,000 had experienced coronary heart disease, including heart attacks. They confirmed that higher levels of LDL, the “bad cholesterol,” were more likely to cause heart disease. But there were new results: high levels of triglyceride also caused higher risk of heart disease. At the same time, there was little evidence that higher levels of HDL, the “good cholesterol,” had a protective effect.
The novelty of their approach, say the authors, lies in their use of a gene score MR analysis using individual participant data. These results build on previous findings and help clarify in further detail the separate roles of triglycerides and HDL in risk for coronary heart disease.
“These findings are important in understanding which blood lipids cause heart disease, and will enable clinicians to better target those lipids with drugs to reduce the risk of heart disease,” noted Dr. Holmes.