Treatment of Elevated LDL and Total Cholesterol
Begin with therapeutic lifestyle changes (TLC) for 3–6 months, then initiate statin therapy if LDL-C remains ≥130 mg/dL in patients without established cardiovascular disease, or ≥100 mg/dL in high-risk patients including those with diabetes. 1
Step 1: Establish Target LDL-C Goals Based on Risk Stratification
Your LDL-C target depends on cardiovascular risk:
High-risk patients (diabetes, established CVD, or 10-year CHD risk ≥20%): LDL-C goal <100 mg/dL 1
- For very high-risk patients: consider optional goal of <70 mg/dL 1
Moderately high-risk (≥2 risk factors, 10-year CHD risk 10–20%): LDL-C goal <130 mg/dL, with optional goal of <100 mg/dL 1
Lower-risk patients (0–1 risk factors): LDL-C goal <160 mg/dL if 0 risk factors, <130 mg/dL if 1 risk factor 1
Step 2: Initiate Therapeutic Lifestyle Changes (TLC) Immediately
All patients should begin comprehensive dietary and exercise modifications regardless of whether drug therapy will be needed. 1, 2
Dietary Modifications
Saturated fat: Reduce to ≤5–6% of total calories (lowers LDL-C by ~11–13 mg/dL); if not achievable, aim for <7% 2, 1
Trans fats: Eliminate completely from diet 2
Soluble fiber: Increase to 10–25 g/day (provides additional 5–10% LDL-C reduction) 1, 2
Plant stanols/sterols: Add 2 g/day (lowers LDL-C by ~10%) 1, 2
Overall dietary pattern: Emphasize vegetables, fruits, whole grains, low-fat dairy, fish, legumes, poultry, and lean meats 1, 2
Expected outcome: Maximal dietary therapy typically reduces LDL-C by 15–25 mg/dL (0.40–0.65 mmol/L) 1, 2
Physical Activity
- Aerobic exercise: 3–4 sessions per week, 40 minutes per session, at moderate-to-vigorous intensity 2
- Alternative: 30 minutes of moderate-intensity activity on most days 1
- Resistance training: 8–10 exercises, 1–2 sets, 10–15 repetitions at moderate intensity, 2 days/week 1
Weight Management
- Modest weight loss in overweight/obese patients lowers triglycerides and modestly reduces LDL-C 2
- Each kilogram of weight loss reduces systolic BP by ~2 mmHg and diastolic BP by ~1 mmHg 1
Step 3: Re-evaluate After 6 Weeks to 3 Months
Monitor lipid response to lifestyle changes at 6-week intervals initially, with consideration of pharmacotherapy between 3–6 months if goals are not met. 1, 2
Step 4: Initiate Statin Therapy When Indicated
Indications for Starting Statins
Start statin therapy if:
High-risk patients (diabetes, established CVD): LDL-C ≥100 mg/dL after TLC 1
- In diabetes patients over age 40 with total cholesterol ≥135 mg/dL, consider statin to achieve 30% LDL reduction regardless of baseline LDL 1
Moderately high-risk (≥2 risk factors, 10-year risk 10–20%): LDL-C ≥130 mg/dL after TLC 1
Lower-risk patients: LDL-C ≥190 mg/dL with 1 risk factor, or ≥160 mg/dL with 2+ risk factors and 10-year risk <10% 1
Statin Dosing Strategy
Intensity: Use doses sufficient to achieve at least 30–40% LDL-C reduction 1
Preferred agent: HMG-CoA reductase inhibitor (statin) is first-line pharmacotherapy 1
Monitoring: Assess LDL-C 4–12 weeks after initiation or dose change, then annually 1
Step 5: Alternative or Combination Therapy
If Statin Alone Is Insufficient or Not Tolerated
- Bile acid-binding resin (e.g., cholestyramine) 1
- Cholesterol absorption inhibitor (e.g., ezetimibe) 1
- Niacin 1
- Fenofibrate 1, 3
Combination Therapy Options
When LDL-C goal is not achieved with statin monotherapy:
Caution: Combining statins with gemfibrozil carries increased risk of myositis; fenofibrate is safer if fibrate combination is needed 1
If High Triglycerides or Low HDL-C Coexist
- Consider adding fibrate or niacin to statin therapy in high-risk patients with triglycerides ≥200 mg/dL or HDL-C <40 mg/dL 1
Step 6: Address Secondary Causes Before Escalating Therapy
Rule out reversible causes of dyslipidemia:
- Hypothyroidism: Check TSH 1
- Diabetes: Optimize glycemic control (improves triglycerides significantly) 1
- Renal insufficiency: Check urinalysis and creatinine 1
- Liver disease: Check liver function tests 1
- Medications: Estrogen therapy, thiazide diuretics, beta-blockers can worsen lipids 3
- Alcohol excess: Limit to ≤2 drinks/day (men) or ≤1 drink/day (women) 1
Common Pitfalls and How to Avoid Them
Do not delay statin therapy indefinitely in high-risk patients hoping lifestyle changes alone will suffice; most patients with significantly elevated LDL-C will require pharmacotherapy to reach goal 1
Do not increase total dietary fat when substituting monounsaturated fats for saturated fats, as this promotes weight gain 2
Do not rely solely on dietary cholesterol restriction; saturated and trans fat reductions have far greater impact on LDL-C 2
Do not combine statins with gemfibrozil due to myositis risk; use fenofibrate if fibrate combination is needed 1
Do not forget to monitor for statin side effects: Check for muscle symptoms and consider CK if myopathy suspected; assess liver enzymes if clinically indicated 1
Do not stop therapy prematurely: Withdraw fenofibrate only after 2 months at maximum dose (160 mg/day) if no adequate response 3
Special Populations
Patients with Diabetes
- Treat as high-risk with LDL-C goal <100 mg/dL 1
- Start statin at LDL-C ≥130 mg/dL after lifestyle intervention 1
- Improved glycemic control is critical for triglyceride management 1