What causes high cholesterol and how is it managed?

What Causes High Cholesterol and How Is It Managed?

High cholesterol comes from two main sources: genetic disorders that you're born with (like familial hypercholesterolemia) and lifestyle factors including poor diet, lack of exercise, obesity, and certain medical conditions like diabetes or thyroid problems. 1

What Causes High Cholesterol

Genetic Causes

• Familial hypercholesterolemia (FH) is the most important inherited cause, affecting 1 in 250 people worldwide and causing severely elevated cholesterol from birth 1
• FH results from mutations in genes that control how your liver removes cholesterol from your blood, most commonly in the LDLR, APOB, PCSK9, or LDLRAP1 genes 2, 3
• People with FH have a 50% risk of dying from heart disease by age 60 if untreated 4

Lifestyle and Secondary Causes

• Diet high in saturated fats (>7% of total calories) directly raises cholesterol 5
• Obesity and physical inactivity significantly contribute to elevated cholesterol 1
• Excessive alcohol consumption raises triglycerides and total cholesterol 1, 6
• Medical conditions including uncontrolled diabetes, hypothyroidism, kidney disease, and liver disease 1
• Certain medications such as thiazides, beta blockers, estrogen, corticosteroids, and antipsychotics 1

How High Cholesterol Is Managed

For Genetic High Cholesterol (Familial Hypercholesterolemia)

Start high-intensity statin therapy immediately upon diagnosis—this is non-negotiable. 5, 7

Step 1: Initial Treatment

• Begin atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily 7
• Goal is to reduce LDL cholesterol by at least 50% from baseline 5, 7
• Check liver function tests, creatine kinase, glucose, and creatinine before starting 7

Step 2: Add Second Medication if Needed (4-6 weeks later)

• If LDL cholesterol remains >100 mg/dL, add ezetimibe 10 mg daily, which provides an additional 15-25% reduction 7
• Recheck cholesterol levels 4-6 weeks after any medication change 7

Step 3: Add Third Medication if Still Not at Goal

• If LDL cholesterol stays ≥100 mg/dL despite maximum statin plus ezetimibe, add a PCSK9 inhibitor (injectable medication given every 2-4 weeks) for an additional 50% reduction 7

Critical Lifestyle Changes (Must Do Alongside Medications)

• Limit saturated fat to <7% of total daily calories 5
• Engage in at least 150 minutes per week of moderate exercise (like brisk walking) 6
• Maintain healthy body weight—even 5-10% weight loss can reduce cholesterol by 20% 6
• Completely avoid tobacco products 5

For Lifestyle-Related High Cholesterol

When to Start Medication

• If you have diabetes and are age 40-75: Start moderate-intensity statin therapy 1
• If your 10-year heart disease risk is ≥7.5%: Start statin therapy 1
• If LDL cholesterol is ≥190 mg/dL: Start high-intensity statin therapy immediately 1, 5

Lifestyle Modifications (Try First for 3 Months if Risk Is Lower)

• Reduce saturated fat to <7% of calories and limit added sugars to <6% of calories 6
• Aim for 5-10% weight loss if overweight 6
• Exercise at least 150 minutes weekly of moderate activity or 75 minutes of vigorous activity 6
• Add resistance training 2 days per week 6
• Eliminate or minimize alcohol consumption 6

For High Triglycerides Specifically

If triglycerides are ≥500 mg/dL, start fenofibrate immediately to prevent pancreatitis. 6

• Address all secondary causes first: optimize diabetes control, treat thyroid problems, stop alcohol completely 6
• If triglycerides remain 200-499 mg/dL after lifestyle changes, consider adding fenofibrate or prescription omega-3 fatty acids 6
• Target non-HDL cholesterol <130 mg/dL in this range 6

Monitoring Your Treatment

• Recheck cholesterol 4-6 weeks after starting or changing any medication 7
• Monitor liver enzymes periodically while on statins 7, 8
• Report muscle pain, weakness, or tenderness immediately—this can indicate a serious side effect requiring medication adjustment 8
• Once cholesterol is controlled, recheck annually or every 2 years 6

Family Screening Is Essential

If you're diagnosed with familial hypercholesterolemia, your blood relatives have a 50% chance of having it too and should be tested. 1, 5

• All first-degree relatives (parents, siblings, children) should have cholesterol screening 1
• Children with FH should start treatment by age 10 to prevent lifelong cholesterol damage 7
• Genetic testing helps identify which family members are affected 1

Common Pitfalls to Avoid

• Don't rely on diet and exercise alone if you have familial hypercholesterolemia—you've had elevated cholesterol since birth and need medication immediately 7
• Don't stop statins due to mild muscle aches—most muscle symptoms in statin users occur at the same rate as in people not taking statins 1, 8
• Don't use bile acid sequestrants if triglycerides are >200 mg/dL—they can worsen triglycerides 6, 7
• Don't delay treatment waiting for "one more try" with lifestyle changes if you have very high cholesterol (≥190 mg/dL) or established heart disease 1, 7