What is the treatment for elevated cholesterol?

Treatment for Elevated Cholesterol

The first-line treatment for elevated cholesterol should be lifestyle modifications, including diet changes, weight reduction, and increased physical activity, followed by statin therapy if lifestyle changes are insufficient to reach target LDL-C levels. 1

Initial Assessment and Treatment Goals

Target Lipid Levels

• LDL-C < 100 mg/dL for most adults with diabetes or other CHD risk factors 1
• LDL-C < 70 mg/dL for very high-risk patients (e.g., those with established cardiovascular disease) 1
• HDL-C > 40 mg/dL in men and > 50 mg/dL in women 1
• Triglycerides < 150 mg/dL 1

Lifestyle Modifications (First-Line Treatment)

Dietary Changes

• Reduce saturated fat to < 7% of total calories 1
• Reduce dietary cholesterol to < 200 mg/day 1
• Reduce trans-fatty acids to < 1% of caloric intake 1
• Add plant stanols/sterols (2 g/day) to enhance LDL-C lowering 1
• Increase viscous (soluble) fiber (10-25 g/day) 1
• Consider omega-3 fatty acids (1 g/day) for general risk reduction; higher doses (2-4 g/day) for elevated triglycerides 1

Physical Activity

• At least 30 minutes of moderate-intensity physical activity on most (preferably all) days of the week 1
• For additional benefits, consider vigorous-intensity activity (≥ 60% of maximum capacity) for 20-40 minutes, 3-5 days/week 1
• Include resistance training with 8-10 different exercises, 1-2 sets per exercise, 10-15 repetitions at moderate intensity, 2 days/week 1

Weight Management

• For overweight/obese individuals, aim to reduce body weight by 10% in the first year 1
• Target a healthy BMI of 18.5-24.9 kg/m² 1
• Even modest weight loss can significantly reduce blood pressure (2 mmHg systolic and 1 mmHg diastolic per kg of weight loss) 1

Pharmacological Therapy (When Lifestyle Changes Are Insufficient)

When to Consider Medication

• After 3 months of lifestyle modifications if LDL-C remains above goal 1
• Immediately along with lifestyle changes for patients with clinical cardiovascular disease or very high LDL-C levels (> 200 mg/dL) 1

Medication Options by Priority

For LDL-C Lowering

1. First choice: HMG-CoA reductase inhibitors (statins) 1

   • High-potency statins (atorvastatin, rosuvastatin, pitavastatin) are preferred 1

2. Second choice:

   • Bile acid binding resins or fenofibrate 1
   • Ezetimibe (10 mg daily) - particularly useful in combination with statins 2

For Triglyceride Lowering

1. Improve glycemic control (priority for diabetic patients) 1
2. Fibric acid derivatives (gemfibrozil, fenofibrate) 1
3. High-dose statins (moderately effective in patients with high LDL-C and high triglycerides) 1

For HDL-C Raising

• Behavioral interventions (weight loss, smoking cessation, increased physical activity) 1
• Pharmacological options are limited:
  • Nicotinic acid (niacin) - use with caution in diabetic patients 1
  • Fibrates 1

Combination Therapy for Mixed Dyslipidemia

1. First choice: Improved glycemic control plus high-dose statin 1
2. Second choice: Improved glycemic control plus statin plus fibric acid derivative (with caution due to increased myositis risk) 1
3. Third choice: Improved glycemic control plus bile acid resin plus fibric acid derivative 1

Special Considerations

Cautions and Monitoring

• Monitor liver enzymes when starting statins, particularly in patients with history of liver disease, excess alcohol, or adverse drug interactions 1
• Watch for myopathy with statin therapy, especially when combined with fibrates or niacin 1
• The combination of high-dose statin plus fibrate increases risk for severe myopathy - keep statin doses relatively low with this combination 1
• For patients with triglycerides > 200 mg/dL, bile acid sequestrants are relatively contraindicated 1
• Patients with very high triglycerides should avoid alcohol consumption 1

Familial Hypercholesterolemia

• For patients with heterozygous familial hypercholesterolemia (HeFH), consider combination therapy with high-potency statin, ezetimibe, and PCSK9-targeted therapy as first-line treatment, especially in extremely high-risk patients 1

Treatment Algorithm

1. Start with comprehensive lifestyle modifications for all patients 1, 3
2. Assess LDL-C response after 6 weeks 1
3. If target LDL-C not achieved:
   • Reinforce dietary changes and add plant stanols/sterols and increased soluble fiber 1
   • Reassess after another 6 weeks 1
4. If still not at goal:
   • For most patients: Start with maximally tolerated high-potency statin 1
   • For extremely high-risk patients: Consider combination of high-potency statin, ezetimibe, and PCSK9-targeted therapy as first-line pharmacological treatment 1
5. If LDL-C goal still not achieved with statin therapy:
   • Add ezetimibe 2
   • Consider adding bempedoic acid if available 1
   • Consider PCSK9-targeted therapy for those not reaching goals with other medications 1