What is VLDL (Very Low-Density Lipoprotein) and how is it decreased?

What VLDL Measures and How to Decrease It

VLDL (very low-density lipoprotein) measures the chief carrier of triglycerides in your blood and is atherogenic—meaning it directly contributes to cardiovascular disease—and should be decreased primarily through lifestyle modification followed by statin therapy if ASCVD risk is ≥7.5%. 1

What VLDL Actually Measures

VLDL represents the lipoprotein particle that transports triglycerides from the liver to peripheral tissues. 1

• VLDL is assembled in the liver from glycerol combined with fatty acids (either taken up from plasma or newly synthesized) plus cholesterol, with apolipoprotein B-100 forming the particle surface 1
• VLDL cholesterol (VLDL-C) is atherogenic and contributes to atherosclerotic cardiovascular disease (ASCVD) risk similarly to LDL cholesterol 1
• The combination of LDL-C and VLDL-C is called non-HDL cholesterol and is more atherogenic than either lipoprotein alone 1
• In moderate hypertriglyceridemia (triglycerides 175-499 mg/dL), excess triglycerides are carried primarily in VLDL particles 1
• VLDL levels correlate with triglyceride levels, as VLDL is 80-95% triglyceride by composition 1

How to Decrease VLDL: Algorithmic Approach

Step 1: Identify and Address Secondary Causes

Before initiating pharmacotherapy, screen for reversible causes of elevated VLDL/triglycerides. 2, 3

• Medications to review: oral estrogens, tamoxifen, beta blockers, thiazide diuretics, corticosteroids, atypical antipsychotics 2, 3
• Medical conditions to evaluate: poorly controlled diabetes (check HbA1c), hypothyroidism (check TSH), chronic kidney disease, chronic liver disease, nephrotic syndrome, obesity, metabolic syndrome 2, 3
• Lifestyle factors: excessive alcohol intake (must be eliminated completely), high refined carbohydrate diet 2, 3

Step 2: Implement Aggressive Lifestyle Modification

Lifestyle changes are the foundation of VLDL reduction and can achieve up to 48% triglyceride reduction. 2

Dietary Interventions (in order of effectiveness):

• Very-low-carbohydrate diets produce the greatest triglyceride reduction, with levels inversely associated with carbohydrate intake 2
• Higher-fat, lower-carbohydrate diets produce greater triglyceride reduction than lower-fat, higher-carbohydrate diets 2
• Replace 1% of energy from saturated fatty acids with polyunsaturated fatty acids (PUFAs) to lower triglycerides by 0.4 mg/dL 2
• For severe hypertriglyceridemia (≥500 mg/dL), implement a very low-fat diet restricting dietary fat to <10% of total calories 1, 2
• Eliminate refined carbohydrates and added sugars/fructose, which are directly converted to triglycerides 3
• Eliminate alcohol completely, as it significantly worsens hypertriglyceridemia 1, 2

Weight Loss and Exercise:

• Weight loss of 1 kg/week can decrease triglycerides by 30-40%, while 0.25-0.5 kg/week decreases triglycerides by 10-20% 2
• Intermittent fasting can reduce triglycerides 16-42%, with greatest decreases associated with greatest weight loss 2
• Aerobic exercise, resistance training, or combined modalities all improve cholesterol levels and lipid profile 1
• Regular physical activity increases lipoprotein lipase activity, which breaks down VLDL triglycerides 1

Step 3: Initiate Statin Therapy for ASCVD Risk Reduction

For patients with elevated VLDL and ASCVD risk ≥7.5%, initiate statin therapy as first-line pharmacologic treatment. 2

• Start with atorvastatin 10-20 mg daily, which provides 35.7-52.2% LDL reduction and significant triglyceride lowering 2
• Statins reduce VLDL similarly to fibrates but have proven ASCVD risk reduction, unlike fibrates 2
• Target at least 30-40% reduction in LDL-C in high-risk patients 2
• Recheck lipid panel 4-6 weeks after initiating therapy 2
• If LDL goal not achieved on atorvastatin 10-20 mg, increase to 40 mg daily 2
• If target still not met, add ezetimibe 10 mg daily for additional 15-20% LDL reduction 2

Step 4: Consider Additional Therapy Based on Triglyceride Severity

For Moderate Hypertriglyceridemia (175-499 mg/dL) with Residual Risk:

• In patients with ischemic stroke/TIA, fasting triglycerides 135-499 mg/dL, LDL-C 41-100 mg/dL on moderate/high-intensity statin, icosapent ethyl 2 g twice daily is reasonable to reduce recurrent stroke risk 1
• Icosapent ethyl reduced major adverse cardiovascular events by 25% in the REDUCE-IT trial 1

For Severe Hypertriglyceridemia (≥500 mg/dL):

• Continue statin therapy and add fenofibrate if triglycerides remain ≥500 mg/dL despite lifestyle changes, particularly to prevent acute pancreatitis 2
• Fenofibrate 160 mg daily decreased VLDL triglycerides by 44-51% and VLDL cholesterol by 45-49% in clinical trials 4
• Fenofibrate can be combined with statins, but avoid gemfibrozil due to increased myopathy risk 2
• For very severe hypertriglyceridemia (≥1,000 mg/dL), extreme dietary fat restriction and fibrate therapy are necessary to prevent pancreatitis 3

Step 5: Target Non-HDL Cholesterol as Secondary Goal

Non-HDL cholesterol represents the total pool of atherogenic lipoproteins including VLDL. 2

• For patients with triglycerides ≥200 mg/dL, target non-HDL cholesterol <130 mg/dL (30 mg/dL higher than LDL goal) 2
• Non-HDL cholesterol is highly correlated with apolipoprotein B and has strong predictive power for coronary events 2

Common Pitfalls to Avoid

• Do not use statins alone for severe hypertriglyceridemia (≥500 mg/dL), as they typically reduce triglycerides by only 10-30% 3
• Do not focus only on fat restriction without addressing refined carbohydrate intake, as carbohydrates are converted to triglycerides 3
• Do not fail to identify medications as potential causes, particularly oral estrogens, beta blockers, and thiazides 3
• Do not overlook glycemic control in diabetic patients, as improved glucose management directly lowers triglyceride levels 2, 3
• Do not combine gemfibrozil with statins due to significantly increased myopathy risk; fenofibrate is the safer fibrate option 2
• Monitor for statin-associated side effects including muscle pain and liver enzyme elevation 2