New findings from several studies conclude that high levels of triglycerides are independently associated with the increased risk for cardiovascular diseases (CVD).
An elevated serum level of LDL cholesterol (LDL-C) is a commonly known risk factor for CVD and specifically coronary artery disease (CAD). Reducing LDL-C levels decreases the risk of death due to CVD. However, the connection between high triglycerides and CVD risk has been inconsistent, to say the least. Hypertriglyceridemia (high triglycerides) is defined to be a fasting triglyceride serum level >1.7 mmol/l (>150 mg/dl). In the USA, data from NHANES showed that 47% of the population in 2010 had a fasting tri‐ glyceride level >1.7 mmol/l, driven largely by lifestyle factors.
Mild‐to‐moderate hypertriglyceridemia can result from an unhealthy diet or lifestyle and to a lower extent, gene mutations, low thyroid levels, pregnancy, weight regain after substantial weight loss and the use of certain medications (such as steroids and old types of oral estrogens). However, it most commonly due to diabetes type 2 or part of the metabolic syndrome which includes high blood pressure and a large waist size.
There was a large cohort study of above 90,000 Korean individuals who went in for a general health check-up between January 2007 and June 2011. The data of CVD events and/or death were collected to show correlation. The results revealed that high triglyceride levels are independently associated with an increased risk of major CVD events, heart attacks, and overall cardiovascular disease events. The association was very strong in patients who were not obese, had normal blood pressure and had no sign of diabetes. The individuals in this study were young and the follow-up period was short which could create problems when trying to compare this study with other future long-term studies. However, the association is not completely clear. Other studies have shown that when adjusting levels (i.e. HDL), the association between triglycerides and CVD can become non-significant.
The mechanism of triglyceride-induced CVD is understood to be: large triglyceride-rich fat cells and LDL particles causing atherosclerosis which clogs and hardens the arteries and eventually blocks blood flow. Smaller triglyceride‐rich remnants can penetrate the arterial intima, bind to and be retained by the connective tissue inside the body, leading to the increase of serum triglycerides.
For the treatment of high cholesterol, neither the 2011 ESC/EAS, 2012 European nor 2014 ACC/AHA guidelines mention triglycerides as being useful for management of the disease. However, they suggest that individuals with a triglyceride level >1.7 mmol/l (>150 mg/dl) should be considered at increased risk of CVD.
Weight loss is one of the most vital and effective approaches to lowering elevated triglyceride levels. This includes reducing the intake of alcohol, carbohydrates (especially sucrose and/or high-fructose corn syrup) and increase physical activity. Statins are the number one drug for high cholesterol but have a small impact on hypertriglyceridemia. Fibrates such as gemfibrozil and fenofibrate are the first-choice drugs for treatment of high triglyceride levels. There are new drugs in the pipeline, such as Volaneorsen, made to target apoC-III, which has the important role of regulating clearance of triglyceride-rich cells in the body.
Evidence for hypertriglyceridemia as an independent risk factor for CVD is increasing, but the link remains unresolved. We have many ways to lower triglyceride levels but there is not enough data to show that any of these methods will lead to favorable decreases in CVD events.
Written By: James A. Ogbeide Jr., PharmD