Management of Elevated Cholesterol (222 mg/dL), Triglycerides (374 mg/dL), and VLDL (1.92 mmol/L ≈ 75 mg/dL)
Initiate moderate‑to‑high intensity statin therapy immediately alongside aggressive lifestyle modifications; do not delay pharmacotherapy while pursuing lifestyle changes alone if cardiovascular risk is elevated (10‑year ASCVD risk ≥7.5%, diabetes age 40‑75 years, or established cardiovascular disease).
Risk Stratification & Lipid Classification
Your triglyceride level of 374 mg/dL falls into moderate hypertriglyceridemia (200‑499 mg/dL), which increases cardiovascular risk via atherogenic VLDL remnant particles but remains below the 500 mg/dL threshold that mandates immediate fibrate therapy for pancreatitis prevention. 1, 2, 3
Total cholesterol of 222 mg/dL is borderline elevated; however, the primary therapeutic targets are LDL‑C (calculated from your lipid panel) and non‑HDL‑C (total cholesterol minus HDL‑C), not total cholesterol alone. 1
VLDL of 1.92 mmol/L (≈75 mg/dL) is elevated and reflects the triglyceride burden; VLDL‑C is typically estimated as triglycerides ÷ 5 in mg/dL units, yielding approximately 75 mg/dL in your case. 1
Calculate your LDL‑C using the Friedewald equation: LDL‑C = Total cholesterol − HDL‑C − (Triglycerides ÷ 5). If your HDL‑C is known, this will determine whether LDL‑C is elevated and guide statin intensity. 1
Calculate non‑HDL‑C (total cholesterol − HDL‑C) and aim for <130 mg/dL as a secondary target when triglycerides are elevated; non‑HDL‑C reflects the total atherogenic lipoprotein burden (LDL + VLDL + IDL). 1, 2, 3
Persistently elevated triglycerides ≥175 mg/dL constitute a cardiovascular risk‑enhancing factor that should influence statin initiation or dose escalation decisions. 1, 2, 3
Evaluation for Secondary Causes (First Step Before Initiating Therapy)
Check hemoglobin A1c and fasting glucose immediately; uncontrolled diabetes is a common driver of hypertriglyceridemia, and optimizing glycemic control can lower triglycerides by 20‑50% independent of lipid‑lowering drugs. 2, 3
Measure thyroid‑stimulating hormone (TSH) to exclude hypothyroidism, which must be treated before expecting a full lipid‑lowering response. 2, 3
Obtain a detailed alcohol history; even modest intake (≈1 oz daily) can raise triglycerides by 5‑10%, and the effect is amplified when combined with high saturated‑fat meals. 2, 3
Review current medications for agents that raise triglycerides (e.g., thiazide diuretics, beta‑blockers, oral estrogen, corticosteroids, antiretrovirals, atypical antipsychotics) and discontinue or substitute when possible. 2, 3
Assess renal (creatinine, eGFR) and hepatic (AST, ALT) function because chronic kidney or liver disease contributes to hypertriglyceridemia and influences drug selection and dosing. 2, 3
Lifestyle Interventions (Foundational Therapy for All Patients)
Weight Loss
- Target a 5‑10% reduction in body weight, which yields an approximate 20% decrease in triglycerides—the most effective single lifestyle measure; in some individuals, weight loss alone can achieve 50‑70% triglyceride reduction. 2, 3
Dietary Modifications
Limit added sugars to <6% of total daily calories (≈30 g on a 2,000‑kcal diet) to curb hepatic triglyceride synthesis. 2, 3
Keep total dietary fat at 30‑35% of calories for moderate hypertriglyceridemia (your triglyceride level of 374 mg/dL). 2, 3
Restrict saturated fat to <7% of total energy intake and replace with monounsaturated or polyunsaturated fats (e.g., olive oil, nuts, avocado, fatty fish). 1, 2, 3
Eliminate trans fatty acids completely because they raise triglycerides and atherogenic lipoproteins. 1, 2, 3
Increase soluble fiber intake to >10 g/day from sources such as oats, beans, lentils, and vegetables. 2, 3
Consume ≥2 servings of fatty fish per week (salmon, trout, sardines, mackerel) to provide dietary omega‑3 fatty acids. 2, 3
Physical Activity
- Engage in ≥150 minutes/week of moderate‑intensity aerobic exercise (or 75 minutes/week vigorous activity), which reduces triglycerides by approximately 11%. 2, 3
Alcohol Restriction
- Limit or avoid alcohol; even modest intake raises triglycerides by 5‑10%, and abstinence may be required as levels approach 500 mg/dL. 2, 3
Pharmacologic Therapy Decision Algorithm
Statin Therapy (First‑Line for Moderate Hypertriglyceridemia with Elevated Cardiovascular Risk)
Initiate moderate‑to‑high intensity statin therapy (e.g., atorvastatin 10‑20 mg daily or rosuvastatin 5‑10 mg daily) immediately if any of the following are present:
Do not delay statin initiation while pursuing lifestyle changes; both should start concurrently in high‑risk patients. 1, 2, 3
Statins provide a dose‑dependent 10‑30% reduction in triglycerides in addition to proven cardiovascular mortality benefit via LDL‑C lowering. 1, 2, 3, 4
Lipid targets while on statin therapy:
Patients with Lower Cardiovascular Risk
For individuals with 10‑year ASCVD risk <7.5% and no diabetes or established cardiovascular disease, prioritize intensive lifestyle modification for at least 3 months before considering pharmacotherapy. 2, 3
Re‑measure fasting lipid panel 6‑12 weeks after implementing lifestyle changes. 2, 3
Consider a moderate‑intensity statin after shared decision‑making if risk‑enhancing factors are present (family history of premature ASCVD, chronic kidney disease, metabolic syndrome, triglycerides ≥175 mg/dL). 1, 2, 3
Add‑On Therapy When Triglycerides Remain >200 mg/dL After 3 Months of Optimized Lifestyle and Statin Therapy
Icosapent Ethyl (Prescription EPA) – Preferred Add‑On
Add icosapent ethyl 2 g twice daily (total 4 g/day) if triglycerides remain ≥150 mg/dL after 3 months of optimized lifestyle and statin therapy AND the patient has:
The REDUCE‑IT trial demonstrated a 25% relative risk reduction in major adverse cardiovascular events (NNT = 21 over 4.9 years); this is Level A evidence from a large randomized controlled trial. 2, 3
Icosapet ethyl is the only triglyceride‑lowering agent FDA‑approved for cardiovascular risk reduction. 2, 3
Monitor for a modest increase in atrial fibrillation (3.1% vs 2.1% with placebo in REDUCE‑IT). 2, 3
Fenofibrate (Alternative Add‑On)
Add fenofibrate 54‑160 mg daily if triglycerides remain >200 mg/dL after 3 months of optimized lifestyle and statin therapy AND the patient does not meet icosapent ethyl criteria. 2, 3, 4
Fenofibrate produces a 30‑50% triglyceride reduction. 2, 3, 4
When combined with statins, use fenofibrate (not gemfibrozil) because fenofibrate does not inhibit statin glucuronidation and has a superior safety profile; consider lower statin doses (atorvastatin ≤20 mg or rosuvastatin ≤10 mg) in patients >65 years or with renal impairment. 2, 3
The ACCORD trial demonstrated no cardiovascular event reduction when fenofibrate was added to simvastatin in diabetics; fenofibrate's role is limited to triglyceride lowering, not cardiovascular risk reduction. 2, 3
Monitoring Strategy
Calculate non‑HDL‑C (total cholesterol − HDL‑C) and aim for <130 mg/dL as a secondary target when triglycerides are elevated. 1, 2, 3
Re‑assess fasting lipid panel:
If fenofibrate is added, obtain baseline and follow‑up creatine kinase levels and monitor for muscle symptoms. 2, 3
Monitor renal function at baseline, at 3 months, and then every 6 months when fenofibrate is used; adjust dose if eGFR 30‑59 mL/min/1.73 m² (max 54 mg daily) and avoid use if eGFR <30 mL/min/1.73 m². 2, 3
Treatment Goals
Primary goal: Reduce triglycerides to <200 mg/dL (ideally <150 mg/dL) to lower cardiovascular risk. 2, 3
Tertiary goal: Attain LDL‑C <100 mg/dL (or <70 mg/dL for very high‑risk patients). 1, 2, 3
Critical Pitfalls to Avoid
Do not postpone statin initiation while attempting lifestyle changes alone in high‑risk patients (ASCVD risk ≥7.5%, diabetes, established ASCVD); both should be started concurrently. 1, 2, 3
Do not overlook secondary causes (uncontrolled diabetes, hypothyroidism, excess alcohol, offending medications); correcting these can lower triglycerides by 20‑50% and may obviate the need for additional lipid agents. 2, 3
Do not start fenofibrate immediately at a triglyceride level of 374 mg/dL; statins are first‑line for moderate hypertriglyceridemia when cardiovascular risk is elevated. 1, 2, 3
Do not combine gemfibrozil with statins; fenofibrate has a markedly better safety profile with lower myopathy risk when combined with statins. 2, 3
Do not rely on over‑the‑counter fish‑oil supplements for cardiovascular benefit; only prescription icosapent ethyl has proven outcome data. 2, 3
Do not add fibrates or omega‑3 agents before completing at least 3 months of intensive lifestyle and statin therapy (unless triglycerides exceed 500 mg/dL). 2, 3
Fasting vs. Non‑Fasting Lipid Panels
For initial assessment and treatment decisions, either fasting or non‑fasting lipid panels are acceptable; total cholesterol and HDL‑C change minimally with food intake, and non‑fasting triglycerides are approximately 20% higher on average but still predict cardiovascular risk. 1, 5, 6, 7
If your initial lipid panel was non‑fasting and triglycerides are 374 mg/dL, a fasting panel should be obtained to confirm the triglyceride level and accurately calculate LDL‑C using the Friedewald equation (LDL‑C = Total cholesterol − HDL‑C − Triglycerides ÷ 5). 1, 5, 6
Non‑fasting triglycerides ≥400 mg/dL (≥4.5 mmol/L) require a repeat fasting lipid panel to assess fasting triglyceride levels and baseline LDL‑C. 1
For patients with triglycerides <400 mg/dL, non‑fasting lipid panels are reasonable for cardiovascular risk assessment and treatment monitoring, although fasting panels may be preferred for precise LDL‑C calculation and therapeutic monitoring in high‑risk patients. 1, 5, 6, 7, 8