What are the health implications of elevated triglycerides?

Health Implications of Elevated Triglycerides

Elevated triglycerides represent a significant health problem primarily through two mechanisms: increased cardiovascular disease risk (particularly at levels 150-499 mg/dL) and acute pancreatitis risk (particularly at levels ≥500 mg/dL), while also serving as a marker for underlying metabolic dysfunction including insulin resistance, type 2 diabetes, and metabolic syndrome. 1

Cardiovascular Disease Risk

Elevated triglycerides are causally linked to atherosclerotic cardiovascular disease through multiple pathophysiological mechanisms:

• Triglyceride-rich lipoproteins and their remnant particles directly contribute to atherogenesis and plaque formation 2, 3
• When triglycerides are elevated, small dense LDL particles form that are more susceptible to oxidation and more atherogenic than large buoyant LDL particles 3, 4
• The "lipid triad" of elevated triglycerides, low HDL-C, and small dense LDL represents a particularly atherogenic profile 3

The magnitude of cardiovascular risk increases substantially with triglyceride elevation:

• Nonfasting triglycerides >440 mg/dL versus <88 mg/dL were associated with 17-fold and 5-fold increased risk of myocardial infarction in women and men respectively over 27 years of follow-up 1
• For ischemic heart disease, the corresponding risks were 6-fold and 3-fold increases 1
• For ischemic stroke, risks increased 5-fold and 3-fold in women and men 1
• All-cause mortality increased 4-fold and 2-fold in women and men with severely elevated triglycerides 1

Elevated triglycerides represent residual cardiovascular risk even in patients adequately treated with statins, making them a "risk-enhancing factor" in primary prevention according to 2018 AHA/ACC guidelines. 2, 3

Pancreatitis Risk

Very high triglyceride levels (≥500 mg/dL) substantially increase the risk of acute pancreatitis:

• Severe hypertriglyceridemia (1,000-1,999 mg/dL) and very severe hypertriglyceridemia (≥2,000 mg/dL) are the primary triglyceride-related thresholds for pancreatitis risk 1
• Only 10% of acute pancreatitis cases are directly caused by hypertriglyceridemia, and only 20% of patients with extremely high levels develop pancreatitis 1
• Levels ≥1,000 mg/dL are arbitrarily defined as the threshold for increased pancreatitis risk, though documentation for a specific threshold is lacking 1
• Patients with triglycerides consistently below 1,000 mg/dL are unlikely to present pancreatitis risk 5

Other rare but serious complications of severe hypertriglyceridemia include retinal thrombosis and, in rare cases, blindness. 1

Metabolic Dysfunction and Associated Conditions

Elevated triglycerides cluster with and serve as a marker for multiple metabolic abnormalities:

• Approximately 31% of US adults have triglyceride levels ≥150 mg/dL 2, 3
• Triglycerides are strongly associated with visceral adiposity, insulin resistance, and type 2 diabetes mellitus 1, 2
• Elevated triglycerides are a core component of metabolic syndrome, which includes increased blood pressure, elevated plasma glucose, and a prothrombotic state 6
• Triglyceride levels serve as a biomarker for nonalcoholic hepatic steatosis (fatty liver) 1

The rise in mean triglyceride levels in the United States since 1976 has occurred in concert with the growing epidemic of obesity, insulin resistance, and type 2 diabetes. 6

Secondary Causes Requiring Evaluation

Patients with elevated triglycerides should be systematically evaluated for secondary causes that require specific treatment:

• Excessive alcohol intake, untreated diabetes, and endocrine conditions (particularly hypothyroidism) 1
• Renal or liver disease, pregnancy, and autoimmune disorders 1
• Medications including thiazides, beta blockers, estrogen, isotretinoin, corticosteroids, bile acid-binding resins, antiretroviral protease inhibitors, immunosuppressants, and antipsychotics 1, 3

Risk Stratification by Triglyceride Level

The Endocrine Society defines hypertriglyceridemia severity as follows:

• Mild: 150-199 mg/dL (1.7-2.3 mmol/L) 1
• Moderate: 200-999 mg/dL (2.3-11.3 mmol/L) 1
• Severe: 1,000-1,999 mg/dL (11.3-22.6 mmol/L) 1
• Very severe: ≥2,000 mg/dL (≥22.6 mmol/L) 1

The American Heart Association suggests optimal fasting triglyceride levels should be <100 mg/dL as a parameter of cardiometabolic health, as the lowest cardiovascular risk is consistently observed at these levels. 1, 2

Clinical Management Implications

Initial treatment for mild to moderate hypertriglyceridemia (150-499 mg/dL) should focus on intensive lifestyle modifications:

• Weight reduction of 5-10% can reduce triglycerides by approximately 20% 7
• Reducing carbohydrate intake (especially refined carbohydrates and added sugars) with limitation of added sugars to ≤10% of total energy intake 1, 6
• Limiting fructose intake to <50-100 g/day, as doses above this threshold show dose-dependent triglyceride increases 6
• Increasing dietary fiber and implementing a Mediterranean-style diet 1
• Consuming marine-derived omega-3 fatty acids (EPA and/or DHA) 1
• Eliminating industrial-produced trans fatty acids and restricting saturated fat 1

For patients with severe to very severe hypertriglyceridemia (≥500 mg/dL), the primary goal is reducing triglycerides to lower pancreatitis risk, which often requires pharmacological therapy:

• Fibrates offer 30-50% triglyceride reduction 1
• Immediate-release niacin provides 20-50% reduction 1
• Omega-3 fatty acids provide 20-50% reduction 1
• High-dose icosapent ethyl (purified EPA) added to statin therapy significantly reduced cardiovascular events in patients with elevated triglycerides (number needed to treat = 111 to prevent one cardiovascular death over 5 years) 2, 8

Common pitfall: Do not overlook that treatment with fibrates in patients with very high triglycerides may paradoxically increase LDL-cholesterol by 5-10%, requiring monitoring. 6, 5