What is the treatment for high non-HDL (non-high-density lipoprotein) cholesterol and high LDL (low-density lipoprotein) cholesterol diagnosis?

Treatment of High Non-HDL and High LDL Cholesterol

Begin with therapeutic lifestyle changes (TLC) immediately for all patients, and initiate statin therapy simultaneously if the patient has coronary heart disease (CHD) or CHD risk equivalent (10-year risk >20%), with LDL-C ≥100 mg/dL. 1

Risk Stratification Determines Treatment Intensity

Your first step is to calculate the patient's 10-year CHD risk using Framingham risk scoring, which requires total cholesterol, HDL cholesterol, blood pressure, smoking status, and age. 1 This risk calculation places patients into one of three treatment categories that dictate both LDL-C goals and when to initiate drug therapy. 1

High-Risk Category (CHD or CHD Risk Equivalent, 10-year risk >20%)

• LDL-C goal: <100 mg/dL 1
• Non-HDL-C goal: <130 mg/dL (30 mg/dL higher than LDL-C target) 1
• Start TLC at LDL-C ≥100 mg/dL 1
• Initiate statin therapy at LDL-C ≥130 mg/dL (drug therapy optional at LDL-C 100-129 mg/dL) 1
• CHD risk equivalents include: type 2 diabetes, other atherosclerotic disease, or calculated 10-year CHD risk ≥20% 1

Moderate-Risk Category (≥2 risk factors, 10-year risk <20%)

• LDL-C goal: <130 mg/dL 1
• Non-HDL-C goal: <160 mg/dL 1
• Start TLC at LDL-C ≥130 mg/dL 1
• Initiate drug therapy at LDL-C ≥130 mg/dL if 10-year risk is 10-20% 1
• Initiate drug therapy at LDL-C ≥160 mg/dL if 10-year risk is <10% 1

Lower-Risk Category (0-1 risk factor)

• LDL-C goal: <160 mg/dL 1
• Non-HDL-C goal: <190 mg/dL 1
• Start TLC at LDL-C ≥160 mg/dL 1
• Initiate drug therapy at LDL-C ≥190 mg/dL (optional at 160-189 mg/dL) 1

Therapeutic Lifestyle Changes (First-Line for All Patients)

Trial TLC for 12 weeks before adding drug therapy in moderate and low-risk patients, but initiate both simultaneously in high-risk patients. 1 This represents a change from older guidelines that recommended 6 months of lifestyle modification. 1

Dietary Modifications

• Reduce saturated fat to <7% of total calories 1
• Limit cholesterol intake to <200 mg/day in high-risk patients (300 mg/day in others) 1
• Eliminate trans fatty acids 1
• Replace saturated fats with monounsaturated fats (olive oil, canola oil) and polyunsaturated fats (corn oil, peanuts), which lower LDL-C without the adverse effect of raising triglycerides that occurs with high-carbohydrate diets 1
• Increase soluble fiber intake and consider plant stanols/sterols 2

Physical Activity and Weight Management

• Prescribe 30-60 minutes of moderate-intensity aerobic exercise most days of the week, which raises HDL-C by 5-14% while lowering triglycerides by 4-18% 2, 3
• Target BMI between 18.5-24.9 kg/m² and waist circumference <35 inches in women 1
• Combination of diet and exercise produces complementary effects: diet lowers total cholesterol and LDL-C by 7-18% and 7-15% respectively, while exercise increases HDL-C 3

Smoking Cessation

• Mandate complete smoking cessation, as this can increase HDL-C by up to 30% 2

Pharmacological Management

Statins: First-Line Drug Therapy

Statins are the drug of choice for elevated LDL-C and should be initiated preferentially in high-risk patients. 1, 4 They reduce LDL-C, total mortality, and coronary artery disease events. 5, 4

Statin Selection and Dosing

• Atorvastatin 10-80 mg daily reduces major cardiovascular events by 37% at 10 mg in diabetic patients and by an additional 22% when escalated to 80 mg versus 10 mg in patients with established CHD 5
• Higher-intensity statins (atorvastatin 20-80 mg, rosuvastatin 10-20 mg) achieve LDL-C targets in 64-84% of high-risk patients 6
• Statins increase HDL-C modestly by 5-15% 2

Monitoring Requirements

• Check liver function and creatine kinase levels when initiating therapy 7
• Reassess lipid panel 4-12 weeks after starting treatment 7
• Once goals achieved, monitor every 6-12 months 7

Non-HDL Cholesterol as Secondary Target

When triglycerides are ≥200 mg/dL, non-HDL-C becomes a secondary treatment target after achieving LDL-C goals. 1 Non-HDL-C represents all atherogenic cholesterol (LDL, VLDL, IDL, lipoprotein(a)) and is an independent predictor of cardiovascular events. 1

• Non-HDL-C is calculated as: Total cholesterol minus HDL-C 1
• Target non-HDL-C is 30 mg/dL higher than the corresponding LDL-C target for each risk category 1
• This measurement is particularly useful when triglycerides are elevated (200-500 mg/dL) 1

Additional Agents for Persistent Dyslipidemia

When to Add Non-Statin Therapy

After achieving LDL-C goals, if non-HDL-C remains elevated or HDL-C remains low (<40 mg/dL in men, <50 mg/dL in women), consider adding fibrates or niacin. 1, 2

Fibrates

• Increase HDL-C by 15-25% and are most effective for combined low HDL and high triglycerides 2
• Fenofibrate is first-line for triglycerides >200 mg/dL with low HDL-C 7
• Warning: Combining statins with fibrates increases myositis risk; use lower statin doses with this combination 7

Niacin

• Most potent HDL-raising agent available, increasing HDL-C by 15-35% 2
• Particularly useful for combined hyperlipidemia and low HDL-C 4
• Use with caution in diabetic patients and monitor glycemic control carefully 2

Ezetimibe

• Inhibits intestinal cholesterol absorption and reduces LDL-C, total cholesterol, apolipoprotein B, and non-HDL-C 8
• Can be added to statin therapy when LDL-C goals are not achieved with statin monotherapy 8
• No dosage adjustment needed in renal impairment; avoid in moderate-to-severe hepatic impairment 8

Bile Acid Resins

• Lower LDL-C and are often used to augment effects of statins and niacin 4

Common Pitfalls and Caveats

Do not rely solely on LDL-C when triglycerides are elevated, as substantial discordance exists between high non-HDL-C and high LDL-C—approximately 3.9 million US adults have high non-HDL-C with normal LDL-C, while 6.8 million have high LDL-C with normal non-HDL-C. 9 Persons with high non-HDL-C and normal LDL-C tend to be older, male, Hispanic, and have more CHD risk factors. 9

Avoid excessive weight loss in patients with lipoatrophy, as this can exacerbate the condition despite the benefits of increased physical activity. 1

For very high-risk patients (those with acute coronary syndrome or very high baseline LDL-C), some authorities recommend an even lower LDL-C target of <70 mg/dL, which can be achieved by switching to higher-dose statins like rosuvastatin 20 mg. 6

When triglycerides exceed 500 mg/dL, prioritize triglyceride reduction as the primary goal to minimize pancreatitis risk before focusing on LDL-C and non-HDL-C targets. 1, 7