Hypertriglyceridemia and Cardiovascular
Disease Overview

Hypertriglyceridemia refers to a condition in which patients have levels of triglycerides in their blood above 200 mg/dL, and severe hypertriglyceridemia refers to a condition involving levels of triglycerides equal to or above 500 mg/dL. Triglycerides are fats that are carried in the blood, together with cholesterol within lipoproteins. High levels of triglyceride-rich lipoproteins are associated with an increased risk of atherosclerotic cardiovascular disease. Hypertriglyceridemia is due to both genetic and environmental factors. Environmental factors include obesity, sedentary lifestyle and high-caloric diets. Hypertriglyceridemia is also associated with comorbid conditions such as diabetes, chronic renal failure and nephrotic syndrome.

The prevalence of hypertriglyceridemia is rapidly increasing in the United States and throughout the world, correlating with the increasing incidence of obesity. Of the over 100 million patients with dyslipidemia in the United States, it is estimated that over 40 million are diagnosed with hypertriglyceridemia and over four million are diagnosed with severe hypertriglyceridemia. A recent National Health and Nutrition Examination Survey of dyslipidemia in the United States indicated that, while LDL-C levels have actually declined since the last National Health and Nutrition Examination Survey analysis, the percentage of patients with severe hypertriglyceridemia has risen sharply along with the dramatic increases in obesity. The National Cholesterol Education Program, or NCEP, Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol recommends that the first priority for the management of severe hypertriglyceridemia be triglyceride reduction to decrease the risk of pancreatitis. In addition, severe hypertriglyceridemia is also associated with markedly increased risk for cardiovascular disease and recent studies have demonstrated that elevated triglyceride levels can be regarded as an independent risk factor for cardiovascular disease related events such as myocardial infarction, ischemic heart disease and ischemic stroke.

Cardiovascular disease has been linked to a range of lipid disorders (LDL-C, HDL-C, triglycerides and non-HDL-C) collectively referred to as dyslipidemia. Historically, low HDL-C (commonly referred to as “good” cholesterol) and high LDL-C (commonly referred to as one of the components of “bad” cholesterol) levels were generally considered the determining risk factors for cardiovascular disease, resulting in therapeutic strategies designed primarily to manage cholesterol levels. However, recent investigations conclude that non-HDL-C (total cholesterol minus HDL-C) is a superior predictor of risk for cardiovascular disease compared to LDL-C, and when LDL-C and non-HDL-C levels are discordant, the risk appears to follow non-HDL-C. Non-HDL-C is a measure of the cholesterol and triglycerides carried by all apolipoprotein B-containing lipoproteins, including very low-density lipoprotein, or VLDL, chylomicron, intermediate density lipoprotein, LDL (including small, dense LDL), and lipoprotein. In addition, as obesity continues to become an increasing concern in United States, there is less focus on LDL-C and an emerging clinical consensus to also treat elevated concentrations of triglycerides that contribute to the total non-HDL-C which makes up all the “bad cholesterol.” A recent meta-analysis by Sarwar et al. included 29 prospective studies and was the largest and most comprehensive epidemiological assessment of the association between triglyceride values and cardiovascular disease risk in Western populations (262,525 participants; 10,158 cases). A combined analysis of the 29 studies yielded an adjusted odds ratio of 1.72 (72% higher risk) for the patients with triglyceride levels greater than or equal to 200 mg/dL compared to those with normal triglyceride levels. The conclusion of the study is that there is a strong and highly significant association between triglyceride value and cardiovascular disease risk.