What is the management plan for a patient with hypercholesterolemia (elevated total cholesterol), hypertriglyceridemia (elevated triglyceride), and low high-density lipoprotein (HDL) cholesterol?

Management of Mixed Dyslipidemia

For a 39-year-old patient with elevated total cholesterol (6.3 mmol/L), elevated triglycerides (3.5 mmol/L), and borderline HDL cholesterol (1.16 mmol/L), intensive lifestyle modification should be initiated immediately, followed by consideration of statin therapy if lifestyle changes are insufficient to reach lipid targets. 1

Assessment of Cardiovascular Risk

First, evaluate the patient's overall cardiovascular risk profile:

• Calculate 10-year cardiovascular risk score
• Check for other components of metabolic syndrome (central obesity, hypertension, elevated fasting glucose)
• Evaluate for secondary causes of dyslipidemia:
  • Excessive alcohol intake
  • Uncontrolled diabetes
  • Hypothyroidism
  • Renal or liver disease
  • Medications that may affect lipid levels

Initial Management: Lifestyle Modifications

Implement intensive lifestyle modifications as first-line therapy 1:

• Weight reduction if indicated
• Mediterranean diet or DASH dietary pattern
• Reduction of saturated fat and trans fat intake
• Increase dietary n-3 fatty acids, viscous fiber, and plant stanols/sterols
• Regular physical activity (aim for at least 150 minutes per week)
• Limit alcohol consumption
• Smoking cessation if applicable

These lifestyle modifications can reduce LDL cholesterol by 15-25 mg/dL (0.39-0.65 mmol/L) and should be implemented even when medications are prescribed 1.

Pharmacotherapy

If after 3 months of intensive lifestyle modification, lipid targets are not achieved:

1. Statin therapy: First-line pharmacological treatment for elevated LDL-C

   • Start with moderate-intensity statin with goal of achieving 30-40% LDL-C reduction
   • For this patient with LDL-C of 3.7 mmol/L, aim for target of <3.4 mmol/L 1
   • Monitor lipid profile 4-12 weeks after initiation of therapy 2

2. If triglycerides remain elevated after statin therapy:

   • Consider adding fenofibrate, particularly effective for mixed dyslipidemia 3
   • Fenofibrate has been shown to lower triglycerides by 28.9-54.5% and increase HDL-C by 11-22.9% in clinical trials 3
   • Typical starting dose is 160 mg once daily with meals 3

Monitoring and Follow-up

• Check lipid profile 4-8 weeks after starting therapy or dose adjustment 1
• Once target levels are achieved, monitor every 6-12 months 1
• Monitor liver enzymes at baseline, 8-12 weeks after starting treatment, and as clinically indicated 1
• Evaluate for potential drug interactions, particularly if patient is on anticoagulants 3

Treatment Targets

For this patient, the following targets should be considered 1:

• LDL Cholesterol: < 3.4 mmol/L (< 130 mg/dL)
• Non-HDL Cholesterol: < 3.4 mmol/L + 0.8 mmol/L = < 4.2 mmol/L
• Triglycerides: < 1.7 mmol/L (< 150 mg/dL)
• HDL Cholesterol: > 1.0 mmol/L (> 40 mg/dL) for men

Important Considerations

• Mixed dyslipidemia (elevated LDL-C and triglycerides with low or normal HDL-C) is associated with increased cardiovascular risk, even when total cholesterol is at target 4, 5
• Patients with elevated triglycerides have a 35% higher risk of cardiovascular events compared to those with normal triglycerides, even when on statin therapy 5
• Combination therapy may be necessary to address all components of mixed dyslipidemia, as statins alone have modest effects on non-LDL-C components 4
• Fenofibrate is specifically indicated for mixed dyslipidemia and has shown efficacy in reducing LDL-C by 20.1-31.4% and triglycerides by 28.9-54.5% 3

By following this management approach, you can effectively address all components of this patient's dyslipidemia and reduce their overall cardiovascular risk.