Elevated Triglycerides and Cardiovascular Disease Risk

Pathophysiological Mechanisms

Elevated triglycerides alter lipoprotein metabolism, increasing cardiovascular disease risk through several mechanisms, including the contribution of triglyceride-rich lipoproteins to atherogenesis 2
When triglycerides are elevated, there is an increase in remnant cholesterol particles, which are causally linked to atherosclerosis 3

A long-standing association exists between elevated triglyceride levels and cardiovascular disease, though the direct causality has been debated for decades 2
Approximately 31% of the adult US population has triglyceride levels ≥150 mg/dL, with varying prevalence among ethnic groups 4
Current triglyceride classification designates levels as: Normal: <150 mg/dL, Borderline high: 150-199 mg/dL, High: 200-499 mg/dL, Very high: ≥500 mg/dL 4
The American Heart Association suggests that optimal fasting triglyceride levels should be <100 mg/dL as a parameter of metabolic health 1

Elevated triglycerides frequently cluster with other cardiovascular risk factors, including obesity, particularly visceral adiposity 6
Insulin resistance and type 2 diabetes mellitus are associated with elevated triglycerides 2
Sedentary lifestyle and high carbohydrate intake, especially added sugars and fructose, are also associated with elevated triglycerides 6

Despite the use of statin therapy, ASCVD event rates remain high in patients with elevated triglycerides, suggesting they represent a marker of residual cardiovascular risk 3
Elevated triglycerides are considered a "risk-enhancing factor" in primary ASCVD prevention according to the 2018 AHA/ACC/multisociety cholesterol guideline 3
Very high triglyceride levels (≥500 mg/dL) increase risk for pancreatitis, while moderate elevations (200-499 mg/dL) are more associated with atherosclerotic risk 1

Treatment of elevated triglycerides should focus first on intensive therapeutic lifestyle changes, including weight reduction, reducing carbohydrate intake, and increasing consumption of marine-based omega-3 products 1
Pharmacological options for triglyceride reduction include fibrates, immediate-release niacin, omega-3 fatty acids, and statins 6
Recent evidence from the REDUCE-IT trial showed that high-dose icosapent ethyl added to statin therapy led to significant reduction in ASCVD events in patients with elevated triglycerides 3