Do high triglycerides contribute to cardiovascular risk?
Dr. Michael Fulks, Consulting Medical Director, discusses current research on triglyceride levels and their impact on cardiovascular mortality risk.
Way back in 2009, the researchers at CRL published on mortality associated with various lipid measures using their huge pool of blood-tested life insurance applicants. We found that once HDL and total cholesterol was accounted for, the triglyceride level was not predictive of mortality risk. As referenced in that article, some research at that time suggested triglycerides matter and other research disagreed. And since then, the question is still a matter of conflicting results and debate.
Complicating current research on the topic is the huge change in lipid management with widespread use of statins which control LDL levels, but not triglycerides, as well as increasing prevalence of diabetes and obesity.
One approach to answering the triglyceride question in today’s world is to use diet or drugs to reduce triglyceride levels in high-risk patients who either have cardiovascular disease or diabetes and follow mortality or cardiovascular events. In 2020 a major study was reported in JAMA of omego-3 fatty acid supplementation which was abandoned because it did not reduce events even though triglyceride levels were reduced by 20%. In 2022 another important study was reported in NEJM using pemafibrate to reduce triglyceride levels again in high-risk patients with high triglyceride levels. 96% were already on statins and all had controlled LDL and average to low HDL levels. The choice of drug and patients made it likely that any positive effect on mortality would be apparent. Unfortunately, while triglyceride levels were reduced by 31%, there was no impact on cardiovascular mortality and this trial was terminated for futility as well.
I think the answer is now in. When adjusted for other risk factors (other lipids, DM, etc.) triglycerides have little impact on all-cause or cardiovascular mortality risk and trying to reduce levels with drugs is futile. The focus of risk assessment and treatment should be on underlying conditions such as DM and obesity and using LDL, total cholesterol or apoB and HDL levels as risk measures.
About the Author
Michael Fulks, MD, Consulting Medical Director, is board-certified in internal and insurance medicine. After leaving practice, he served as a medical director, creating or editing several underwriting manuals and preferred programs. More recently, Mike has consulted for CRL participating in its mortality research on laboratory test results, BP and build, and in the development of risk-scoring tools for laboratory and non-laboratory data.