Perspective:

The following are 10 points to remember about triglycerides and cardiovascular disease (CVD):

1. This American Heart Association (AHA) Scientific Statement reviews the pivotal role of triglycerides in lipid metabolism and reaffirms that triglyceride is not directly atherogenic, but represents an important biomarker of CVD risk because of its association with atherogenic remnant particles and apo CIII.

2. Knowledge of the metabolic pathways of triglyceride-rich particles and the consequences of hypertriglyceridemia is crucial in understanding the characteristic lipid alterations in diabetes, lipodystrophic disorders including those seen with HIV, and chronic renal disease.

3. Measurements of non–high-density lipoprotein cholesterol (HDL-C), apo B, or both may be especially useful in those with prominent triglyceride and HDL abnormalities in which low-density lipoprotein cholesterol (LDL-C) measurements may underestimate true atherosclerotic vascular risk.

4. Considerable biological and, to a lesser extent, analytic variability exists in the measurement of triglycerides, with a median variation of 23.5% compared with 4.9% for total cholesterol, 6.9% for HDL-C, and 6.5% for calculated LDL-C. Although biological variability accounts for most of the intra-individual variation in triglycerides, other considerations that affect triglyceride measurements include postural effects, phlebotomy-related issues, and fasting versus nonfasting state. Optimally, triglyceride levels should be measured after sitting for 5 minutes and with the tourniquet applied no more than 1 minute.

5. The AHA recommendations include the following new designations:

• Optimal fasting triglyceride levels <100 mg/dl, as a parameter of metabolic health.
• Use nonfasting triglyceride levels to screen for those with high fasting triglyceride levels. A nonfasting level of <200 mg/dl is commensurate with a normal (<150 mg/dl) or optimal fasting triglyceride level and requires no further testing.
• Fasting samples are used to designate borderline high (150-199 mg/dl), high (200-499 mg/dl), and very high (>500 mg/dl) triglyceride levels.

6. The treatment of elevated triglyceride levels focuses on intensive therapeutic lifestyle change. For example, a 5-10% reduction in body weight anticipates a triglyceride-lowering response of 20%. Further offsets in CHO calories by reducing added sugars and fructose while increasing unsaturated fat intake may contribute an additional 10-20% reduction in triglyceride levels. Elimination of trans fats, restriction of saturated fatty acids, and increasing consumption of marine-based omega-3 products, coupled with aerobic activity, will further optimize triglyceride-lowering efforts. Taken together, reductions of 50% or more in triglyceride levels may be attained through intensive therapeutic lifestyle change.

7. In subjects with very high triglyceride levels or a history of triglyceride-induced pancreatitis, additional dietary considerations include complete abstinence from alcohol, the possible use of medium chain triglycerides, and pharmacological therapies.

8. Medications should be ruled out as a potential cause of elevated triglycerides: Examples include postmenopausal estrogens and oral contraceptives with estrogens, steroids, beta-blockers, bile acid resins, thiazides, and immunosuppressive drugs.

9. In those with a history of triglyceride-induced pancreatitis, it is especially important to keep triglyceride levels well controlled, and this will require both lifestyle and pharmacological approaches. What remains to be established is whether these modalities favorably influence CVD outcomes beyond proven therapies (e.g., statins). Effective agents to lower triglycerides in decreasing order of potency include fibrates, immediate-release niacin, high-dose marine oil, extended-release niacin, statins, and ezetamibe.

10. There is not conclusive evidence that adding a triglyceride-lowering agent to high-dose statins will further reduce CV events. However, in the ACCORD trial, adding fenofibrate to statins was effective in those in the highest triglyceride and lowest HDL-C tertiles.