Nearly half of American adults have unhealthy cholesterol levels, yet many don’t know it or understand what their numbers mean. A lipid panel result showing “cholesterol: 220 mg/dL” might seem like a single number, but it conceals a complex picture involving multiple types of cholesterol particles, each with different effects on cardiovascular health. The difference between dangerous and protective cholesterol, between dietary and genetic drivers, between simple and comprehensive management — these distinctions often get lost in oversimplified advice to “lower your cholesterol.”

Dyslipidemia, the medical term for abnormal blood lipid levels, encompasses far more than just “high cholesterol.” It includes elevated LDL (“bad” cholesterol), low HDL (“good” cholesterol), high triglycerides, and various patterns of lipid abnormalities that dramatically increase heart disease and stroke risk. Each type requires different interpretation and management approaches, yet standard medical care often treats them all the same way: prescribe a statin and move on.

Understanding dyslipidemia comprehensively — what different cholesterol types actually do, why they become abnormal, how genetics and lifestyle each contribute, and how to address the full lipid profile rather than just total cholesterol — provides the foundation for truly effective cardiovascular risk reduction. The earlier abnormal lipid patterns are identified and addressed, the greater the opportunity to prevent the arterial damage that leads to heart attacks and strokes.

Quick Summary:

• Dyslipidemia means abnormal blood lipid levels: high LDL, low HDL, high triglycerides, or combinations
• “High cholesterol” is shorthand for various lipid abnormalities affecting cardiovascular risk
• LDL cholesterol promotes atherosclerosis; HDL protects against it; triglycerides indicate metabolic dysfunction
• Causes include genetics (familial hypercholesterolemia), poor diet, obesity, physical inactivity, insulin resistance, and other factors
• Dramatically increases heart attack and stroke risk; extent depends on LDL levels and other risk factors
• Diagnosed through fasting lipid panel measuring total cholesterol, LDL, HDL, and triglycerides
• Lifestyle changes (diet, exercise, weight loss) improve lipids significantly in most people
• Statins and other medications highly effective when lifestyle changes insufficient or risk is high
• Regular testing and monitoring essential; optimal targets vary by cardiovascular risk level

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What Is Dyslipidemia?

Dyslipidemia refers to any abnormality in blood lipid levels. While commonly called “high cholesterol,” dyslipidemia encompasses several distinct abnormalities that can occur individually or in combination.

Understanding Blood Lipids

Lipids are fats circulating in the bloodstream, including:

Cholesterol:
A waxy substance essential for cell membrane structure, hormone production (testosterone, estrogen, cortisol), vitamin D synthesis, and bile acid production. The body produces most cholesterol in the liver; diet contributes about 20-30%.

Triglycerides:
The storage form of fat. After eating, calories that aren’t immediately needed are converted to triglycerides and stored in fat cells. Between meals, hormones release triglycerides for energy.

Phospholipids:
Form cell membranes and help transport fats. Less clinically relevant for cardiovascular risk assessment.

Cholesterol Transport: Lipoproteins

Cholesterol and triglycerides can’t dissolve in blood. They’re packaged into particles called lipoproteins for transport. Different lipoproteins have very different effects on cardiovascular health.

LDL (Low-Density Lipoprotein):
Carries cholesterol from liver to tissues throughout the body. When LDL levels are high, cholesterol accumulates in artery walls, forming plaques that narrow arteries and cause atherosclerosis.

“Bad” cholesterol because elevated levels directly promote cardiovascular disease.

HDL (High-Density Lipoprotein):
Collects excess cholesterol from tissues and artery walls and transports it back to the liver for disposal or recycling (reverse cholesterol transport).

“Good” cholesterol because higher levels protect against cardiovascular disease.

VLDL (Very Low-Density Lipoprotein):
Produced by the liver, carries triglycerides to tissues. As VLDL releases triglycerides, it becomes progressively denser, eventually converting to LDL.

High triglycerides generally mean high VLDL levels.

Other Lipoproteins:

• Chylomicrons (transport dietary fat)
• IDL (intermediate-density lipoprotein)
• Lp(a) (lipoprotein(a)—genetic variant associated with increased cardiovascular risk)

Types of Dyslipidemia

Dyslipidemia includes several patterns:

Hypercholesterolemia:
Elevated total cholesterol, typically driven by high LDL.

Hypertriglyceridemia:
Elevated triglycerides.

Low HDL cholesterol:
HDL below optimal levels, reducing cardiovascular protection.

Mixed (Combined) Dyslipidemia:
Multiple abnormalities together—common in metabolic syndrome (high triglycerides + low HDL).

Familial Hypercholesterolemia:
Genetic condition causing severely elevated LDL from birth due to defective LDL receptors.

Each pattern has different causes, implications, and treatment approaches.

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How Dyslipidemia Develops

Abnormal lipid levels result from complex interactions between genetics, lifestyle, diet, and underlying medical conditions.

Genetic Factors

Familial Hypercholesterolemia (FH):
Inherited disorder affecting about 1 in 250 people. Mutations in genes encoding LDL receptors (or related proteins) prevent cells from removing LDL from blood effectively.

Characteristics:

• Very high LDL cholesterol (often >190 mg/dL, sometimes >300 mg/dL)
• Present from birth
• Causes premature cardiovascular disease (heart attacks in 30s-40s if untreated)
• Visible signs: tendon xanthomas (cholesterol deposits), corneal arcus (white ring around iris)

Inheritance: Autosomal dominant—if one parent has FH, each child has 50% chance of inheriting it.

Homozygous FH (two mutated genes, one from each parent) is rare (1 in 300,000-million) but extremely severe, with LDL >500 mg/dL and heart disease in childhood.

Polygenic Hypercholesterolemia:
More common than FH. Multiple genes each contribute small effects that add up to elevated cholesterol. Less severe than FH but still increases cardiovascular risk.

Other Genetic Lipid Disorders:
Familial combined hyperlipidemia (high LDL + high triglycerides), familial hypertriglyceridemia, familial low HDL, and others.

Genetic testing can identify FH and guide treatment, though routine genetic testing isn’t standard for most dyslipidemia.

Dietary Factors

Diet significantly influences lipid levels, though genetics determine how responsive you are to dietary changes.

Saturated Fat:
Found in red meat, full-fat dairy, butter, coconut oil, palm oil. Raises LDL cholesterol by increasing liver production and reducing LDL receptor expression.

Effect: For every 1% increase in saturated fat calories, LDL rises ~2 mg/dL on average (individual variation is substantial).

Trans Fats:
Artificially created through hydrogenation. Found in some margarine, baked goods, fried foods (though largely banned in many countries).

Effect: Raises LDL AND lowers HDL—worst possible combination. Even small amounts (2% of calories) significantly increase cardiovascular risk.

Dietary Cholesterol:
Found in animal products (egg yolks, shellfish, organ meats). Contrary to old beliefs, dietary cholesterol has modest effect on blood cholesterol for most people. The body compensates by reducing its own production.

Effect: For most people, dietary cholesterol raises LDL by 0-10 mg/dL. About 25% of people are “hyper-responders” with larger increases.

Refined Carbohydrates and Sugar:
High intake increases triglycerides and lowers HDL. The liver converts excess carbohydrates to fat (triglycerides) and packages them into VLDL particles.

Fiber:
Soluble fiber (oats, beans, apples, barley) binds bile acids, forcing the liver to use cholesterol to make more bile, thereby lowering blood cholesterol.

Effect: 5-10g daily soluble fiber lowers LDL by ~5%.

Healthy Fats:
Unsaturated fats (olive oil, avocados, nuts, fatty fish) improve lipid profile when replacing saturated fats—lower LDL, maintain or raise HDL, lower triglycerides.

Lifestyle Factors

Physical Inactivity:
Sedentary lifestyle worsens lipid profile:

• Lowers HDL cholesterol
• May increase triglycerides
• Contributes to weight gain and insulin resistance

Regular exercise improves lipids independent of weight loss.

Excess Body Weight and Obesity:
Particularly visceral (abdominal) fat:

• Increases triglyceride production
• Lowers HDL cholesterol
• May increase small, dense LDL particles (most atherogenic)
• Promotes insulin resistance, worsening metabolic dyslipidemia

Smoking:
Lowers HDL cholesterol, increases triglycerides, oxidizes LDL (making it more damaging), and damages blood vessel walls—multiplicative effect on cardiovascular risk.

Alcohol:
Moderate intake (1 drink/day for women, 2 for men) may modestly raise HDL.

Excessive intake raises triglycerides significantly, promotes weight gain, damages liver, and increases cardiovascular risk despite any HDL benefit.

Insulin Resistance and Metabolic Syndrome

Insulin resistance produces characteristic “metabolic dyslipidemia”:

• Elevated triglycerides (often >150 mg/dL)
• Low HDL cholesterol (often <40 mg/dL men, <50 mg/dL women)
• Increased small, dense LDL particles (more atherogenic than large, fluffy LDL)
• Often normal or only mildly elevated LDL cholesterol by standard measurement

This pattern is extremely common with obesity, prediabetes, type 2 diabetes, metabolic syndrome, and PCOS.

Mechanism:

• Insulin resistance impairs fat metabolism in liver
• Liver overproduces VLDL (triglyceride-rich particles)
• Metabolic changes reduce HDL production and increase breakdown
• Triglyceride-rich environment remodels LDL into smaller, denser particles

Medical Conditions

Diabetes:
Type 2 diabetes (and even prediabetes) typically causes metabolic dyslipidemia. Type 1 diabetes can too if poorly controlled.

Hypothyroidism:
Underactive thyroid slows metabolism, including cholesterol clearance. LDL and triglycerides rise; HDL may drop.

Kidney Disease:
Chronic kidney disease impairs lipid metabolism, typically raising triglycerides and lowering HDL.

Liver Disease:
Advanced liver disease impairs lipoprotein synthesis. Paradoxically, cholesterol may be low with severe liver failure.

Cushing’s Syndrome:
Excess cortisol raises LDL and triglycerides.

Polycystic Ovary Syndrome (PCOS):
Insulin resistance drives metabolic dyslipidemia in most women with PCOS.

Nephrotic Syndrome:
Kidney protein loss triggers compensatory liver overproduction of lipoproteins, dramatically raising cholesterol.

Medications

Certain drugs worsen lipid profile:

• Corticosteroids (prednisone): Raise LDL and triglycerides
• Some diuretics (thiazides): May modestly increase LDL and triglycerides at high doses
• Beta-blockers: Older non-selective types may lower HDL and raise triglycerides (newer cardio-selective agents have minimal effect)
• Immunosuppressants (cyclosporine, tacrolimus): Worsen lipids
• Protease inhibitors (HIV medications): Significantly worsen lipids
• Anabolic steroids: Lower HDL dramatically
• Some oral contraceptives: May affect lipids depending on formulation
• Retinoids (isotretinoin for acne): Can significantly raise triglycerides

If taking medications affecting lipids, weigh cardiovascular benefits vs. risks with your doctor. Often benefits outweigh lipid effects, or alternative medications exist.

Age and Sex

Age:
Cholesterol naturally rises with age until around 60-65, then may plateau or decline slightly. This reflects cumulative lifetime exposure to various factors.

Sex:

Premenopausal women:
Typically have lower LDL and higher HDL than men of similar age. Estrogen has favorable effects on lipid metabolism.

Postmenopausal women:
LDL rises and HDL may drop after menopause as estrogen declines. Women’s cardiovascular risk increases substantially post-menopause.

Men:
Develop dyslipidemia and cardiovascular disease earlier than premenopausal women but later risk converges.

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Signs and Symptoms

Most dyslipidemia produces no symptoms. You cannot feel high cholesterol. This is why screening through blood testing is essential.

Why Dyslipidemia Is Silent

Abnormal lipid levels themselves cause no direct symptoms. The danger lies in long-term consequences—atherosclerosis developing silently over decades until causing heart attack or stroke.

Visible Signs of Severe Dyslipidemia

Xanthomas:
Cholesterol deposits forming yellowish nodules under skin, particularly over tendons (elbows, knees, Achilles tendon, hands). Indicate very high cholesterol, often familial hypercholesterolemia.

Xanthelasmas:
Yellowish cholesterol deposits on eyelids. Can occur with high cholesterol but also in people with normal cholesterol.

Corneal Arcus:
White or grayish ring around the colored part of the eye (iris). In people under 45, suggests familial hypercholesterolemia. In older adults, may be normal aging.

Lipemia Retinalis:
Creamy appearance of retinal blood vessels visible on eye exam. Indicates extremely high triglycerides (typically >2,000 mg/dL).

These physical signs are rare and indicate severe dyslipidemia. Most people with elevated cholesterol have no visible signs.

Symptoms of Complications

Symptoms appear when dyslipidemia causes disease:

Atherosclerotic Cardiovascular Disease:

• Chest pain (angina) from coronary artery narrowing
• Heart attack (myocardial infarction)
• Stroke
• Leg pain with walking (claudication) from peripheral artery disease

Acute Pancreatitis:
When triglycerides exceed ~500 mg/dL (sometimes >1,000 mg/dL), risk of pancreatitis increases—severe abdominal pain, nausea, vomiting, requiring hospitalization.

By the time symptoms occur, significant damage has been done. This underscores the critical importance of screening and early treatment.

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Diagnosis and Testing

Dyslipidemia is diagnosed through blood testing.

Standard Lipid Panel (Fasting)

Typically requires 9-12 hour fast (water allowed) for accurate triglyceride and LDL measurement.

Tests included:

Total Cholesterol:
Sum of cholesterol in all lipoprotein particles (LDL + HDL + VLDL).

LDL Cholesterol:
Usually calculated from other measurements using Friedewald equation:
LDL = Total Cholesterol - HDL - (Triglycerides/5)

When triglycerides are very high (>400 mg/dL), direct LDL measurement is needed.

HDL Cholesterol:
Directly measured.

Triglycerides:
Directly measured.

VLDL Cholesterol:
Usually estimated as Triglycerides/5.

Interpreting Results

Total Cholesterol:

Level (mg/dL)	Classification
<200	Desirable
200-239	Borderline high
≥240	High

LDL Cholesterol:

Level (mg/dL)	Classification
<70	Optimal (for very high-risk patients)
<100	Optimal/Near Optimal
100-129	Near/Above Optimal
130-159	Borderline High
160-189	High
≥190	Very High

HDL Cholesterol:

Level (mg/dL)	Classification
<40 (men)	Low (increased risk)
<50 (women)	Low (increased risk)
40-59	Acceptable
≥60	High (protective)

Triglycerides:

Level (mg/dL)	Classification
<150	Normal
150-199	Borderline High
200-499	High
≥500	Very High (pancreatitis risk)

Important: Optimal targets vary based on overall cardiovascular risk. People with diabetes, prior heart attack, or very high risk may need LDL <70 mg/dL.

Advanced Lipid Testing

Not routinely ordered but provides additional information in certain situations:

Apolipoprotein B (ApoB):
Measures number of atherogenic particles (each LDL and VLDL particle contains one ApoB molecule). More accurate than LDL cholesterol for predicting cardiovascular risk, especially when triglycerides are elevated.

• Optimal: <90 mg/dL
• High risk: >120 mg/dL

Apolipoprotein A-I (ApoA-I):
Main protein in HDL. Reflects HDL particle number.

Lipoprotein(a) [Lp(a)]:
Genetic variant of LDL with additional protein attached. Independently increases cardiovascular risk. Elevated Lp(a) (>50 mg/dL) identifies people needing more aggressive LDL lowering.

Cannot be modified by lifestyle—largely genetic. Newer medications (PCSK9 inhibitors, emerging RNA therapies) can lower it.

LDL Particle Number (LDL-P) and Size:
Advanced testing distinguishes large, fluffy LDL particles from small, dense ones. Small, dense LDL are more atherogenic. LDL particle number (measured by NMR or ion mobility) may predict risk better than LDL cholesterol concentration alone.

Non-HDL Cholesterol:
Simple calculation: Total Cholesterol – HDL

Represents cholesterol in all atherogenic particles (LDL + VLDL + IDL). Useful when triglycerides are high. Doesn’t require fasting.

Target: <130 mg/dL (lower for high-risk patients)

Who Should Be Screened?

American Heart Association / American College of Cardiology guidelines:

All adults age 20-39:
Screen once between ages 20-39 (earlier and more frequently if family history or risk factors present)

All adults age 40-75:
Regular screening (every 4-6 years if normal; more frequently if abnormal)

Adults ≥76:
Continue screening if on treatment; shared decision-making about starting new treatment

Earlier/more frequent screening recommended for:

• Family history of premature cardiovascular disease or familial hypercholesterolemia
• Personal history of cardiovascular disease, diabetes, hypertension
• Smoking, obesity, metabolic syndrome
• Chronic kidney disease, inflammatory conditions

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Health Risks and Complications

Dyslipidemia dramatically increases risk for atherosclerotic cardiovascular disease—the leading cause of death globally.

Atherosclerosis

LDL particles penetrate artery walls, particularly at sites of endothelial damage or dysfunction. Once inside, LDL oxidizes, triggering inflammatory response. Immune cells attempt to clear oxidized LDL, becoming foam cells. This accumulation forms atherosclerotic plaques.

Plaque development:

1. Fatty streaks (earliest stage, can appear in youth)
2. Fibrous plaques (mature plaques with lipid core and fibrous cap)
3. Complicated plaques (calcified, ulcerated, thrombosed)

Plaque effects:

• Narrow arteries, reducing blood flow
• Rupture, triggering blood clot that blocks artery completely
• Weaken artery wall, causing aneurysm

The higher and longer LDL is elevated, the more atherosclerosis accumulates.

Coronary Heart Disease

Atherosclerosis in heart arteries.

Manifestations:

• Angina: Chest pain/pressure with exertion when narrowed arteries can’t supply enough blood
• Heart Attack (Myocardial Infarction): Plaque rupture triggers clot that completely blocks coronary artery, killing heart muscle
• Heart Failure: Chronic reduced blood flow or muscle damage from previous heart attack impairs heart pumping
• Sudden Cardiac Death: Dangerous heart rhythm from ischemia or scar tissue

Risk increases exponentially with LDL levels. Even mildly elevated LDL (130-159 mg/dL) increases risk substantially over decades.

Stroke

Atherosclerosis in brain arteries or arteries supplying brain (carotids).

Types:

• Ischemic stroke: Clot blocks brain artery (80-85% of strokes)
• Hemorrhagic stroke: Weakened artery ruptures, bleeding into brain

High cholesterol primarily increases ischemic stroke risk.

Peripheral Artery Disease

Atherosclerosis in leg arteries.

Symptoms:

• Leg pain with walking (claudication)
• Poor wound healing
• Cold extremities
• In severe cases: tissue death requiring amputation

Other Cardiovascular Complications

Carotid Artery Disease:
Narrowing of neck arteries supplying brain increases stroke risk

Aortic Aneurysm:
Atherosclerosis weakens aorta (main artery from heart), causing bulge that can rupture fatally

Renal Artery Stenosis:
Narrowing of kidney arteries causes hypertension and kidney damage

Mesenteric Ischemia:
Narrowing of intestinal arteries causes abdominal pain after eating

Acute Pancreatitis

Very high triglycerides (typically >500 mg/dL, especially >1,000 mg/dL) increase acute pancreatitis risk—severe inflammation of pancreas causing intense abdominal pain, nausea, vomiting. Can be life-threatening, requiring hospitalization.

Quantifying Risk

10-Year Cardiovascular Risk:
Calculators (like ACC/AHA Pooled Cohort Equations or Framingham Risk Score) estimate 10-year risk of heart attack or stroke based on:

• Age, sex, race
• Total cholesterol and HDL cholesterol
• Blood pressure
• Diabetes status
• Smoking status

Risk categories:

• Low risk: <5%
• Borderline risk: 5-7.5%
• Intermediate risk: 7.5-20%
• High risk: >20%

Treatment intensity depends on estimated risk. Higher risk = more aggressive LDL lowering targets.

Lifetime Risk:
Even people with low 10-year risk may have high lifetime risk if they’re young with elevated LDL. Cumulative exposure over decades causes atherosclerosis.

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Treatment and Management

Dyslipidemia management aims to reduce cardiovascular risk, primarily by lowering LDL cholesterol and addressing other lipid abnormalities.

Lifestyle Modifications

First-line treatment for most people, especially those with borderline or moderately elevated lipids and low-to-moderate cardiovascular risk.

Dietary Changes

Reduce Saturated Fat:

Target <7% of total calories (some guidelines say <10%). Means limiting:

• Red meat (beef, pork, lamb)
• Full-fat dairy (whole milk, cheese, butter, cream)
• Tropical oils (coconut, palm)
• Processed meats

Replace with unsaturated fats (olive oil, avocado, nuts, seeds, fatty fish).

Eliminate Trans Fats:
Read labels—avoid “partially hydrogenated oils.” Fortunately, trans fats largely banned or removed from food supply in many countries.

Increase Soluble Fiber:

Target 10-25g daily from:

• Oats, oat bran, barley
• Beans, lentils, peas
• Apples, oranges, pears
• Brussels sprouts, carrots

Mechanism: Soluble fiber binds bile acids, forcing liver to use cholesterol to make more bile.

Effect: 5-10g soluble fiber daily lowers LDL ~5%.

Add Plant Sterols/Stanols:
Found in fortified foods (margarine, orange juice, yogurt) or supplements. Structurally similar to cholesterol, block cholesterol absorption in intestines.

Dose: 2g daily lowers LDL ~10%.

Emphasize Healthy Fats:

Replace saturated fats with:

• Monounsaturated fats (olive oil, avocados, nuts)
• Polyunsaturated fats, especially omega-3s (fatty fish, walnuts, flaxseed)

Limit Refined Carbohydrates and Added Sugars:

Especially important for lowering triglycerides. Reduce:

• Sugary beverages
• Sweets, desserts
• White bread, white rice, refined pasta
• Processed snacks

Specific Dietary Patterns:

Mediterranean Diet:
Extensively studied, proven to reduce cardiovascular events by ~30%. Emphasizes vegetables, fruits, whole grains, legumes, olive oil, fish, moderate wine.

Portfolio Diet:
Combines multiple cholesterol-lowering foods: plant sterols, soluble fiber, soy protein, nuts. Can lower LDL 20-30%, rivaling low-dose statins.

DASH Diet:
Originally for hypertension but improves lipids too.

What About Dietary Cholesterol?
For most people, dietary cholesterol has modest effect on blood cholesterol. No need to strictly limit eggs or shellfish unless you’re a hyper-responder. Focus on saturated and trans fats instead.

Physical Activity

Aerobic Exercise:
Regular moderate-to-vigorous activity:

• Raises HDL cholesterol (2-3 mg/dL per regular exercise habit)
• Lowers triglycerides
• May modestly lower LDL
• Improves LDL particle size (shifts to larger, less atherogenic particles)
• Independent cardiovascular benefits beyond lipid effects

Target: 150-300 minutes moderate-intensity (or 75-150 minutes vigorous) weekly

Examples: Brisk walking, jogging, cycling, swimming, dancing

Resistance Training:
2-3 sessions weekly. Benefits lipids modestly but improves body composition, insulin sensitivity, overall metabolic health.

Reduce Sedentary Time:
Break up sitting with brief activity every 30-60 minutes.

Weight Loss

For people who are overweight or obese, weight loss of 5-10% improves lipid profile:

• Lowers triglycerides significantly
• Raises HDL
• May lower LDL
• Reduces small, dense LDL particles
• Improves insulin sensitivity

Smoking Cessation

Quitting improves HDL, reduces cardiovascular risk dramatically. One of the most impactful interventions.

Limit Alcohol

If drinking, keep to moderate amounts (1 drink/day women, 2/day men). Excessive alcohol raises triglycerides substantially.

Expected Results from Lifestyle:

Comprehensive lifestyle changes can:

• Lower LDL 10-30 mg/dL
• Raise HDL 5-15 mg/dL
• Lower triglycerides 20-50%

Individual variation is substantial. Genetics influence how responsive you are to dietary changes.

Medications

When lifestyle changes are insufficient or cardiovascular risk is high, medications are added.

Statins:

Mechanism: Inhibit HMG-CoA reductase, the enzyme controlling cholesterol synthesis in liver. Liver compensates by increasing LDL receptor expression, pulling more LDL from blood.

Effectiveness: Most effective LDL-lowering medications:

• Low-intensity statins: Lower LDL ~30%
• Moderate-intensity: Lower LDL ~30-50%
• High-intensity: Lower LDL ~50%+

Examples:

• Atorvastatin (Lipitor)
• Rosuvastatin (Crestor)
• Simvastatin (Zocor)
• Pravastatin (Pravachol)
• Lovastatin, fluvastatin, pitavastatin

Proven Benefits: Decades of evidence show statins reduce heart attacks, strokes, and cardiovascular death by 20-30% when used for primary or secondary prevention.

Side Effects:

• Muscle aches (5-10% of users)—usually mild, occasionally severe
• Elevated liver enzymes (rare, monitor initially)
• Increased diabetes risk (small increase in people already at risk)
• Cognitive effects (controversial, most studies show no impact)

Most people tolerate statins well. If one statin causes side effects, trying a different statin or lower dose often works.

Ezetimibe (Zetia):

Mechanism: Blocks cholesterol absorption in intestines.

Effectiveness: Lowers LDL ~20% as monotherapy, additional ~15-20% when added to statin.

Benefits: Adding ezetimibe to statin further reduces cardiovascular events beyond statin alone.

Side Effects: Minimal, very well tolerated.

PCSK9 Inhibitors:

Mechanism: Monoclonal antibodies that inhibit PCSK9 protein, which degrades LDL receptors. More LDL receptors = more LDL pulled from blood.

Examples: Evolocumab (Repatha), Alirocumab (Praluent)

Effectiveness: Dramatically lower LDL 50-60% beyond statin+ezetimibe.

Benefits: Reduce cardiovascular events in high-risk patients.

Administration: Subcutaneous injection every 2-4 weeks.

Side Effects: Injection site reactions; generally well tolerated.

Cost: Very expensive ($5,000-14,000/year), though insurance may cover for appropriate indications (familial hypercholesterolemia, prior cardiovascular events, statin intolerance).

Bempedoic Acid (Nexletol):

Mechanism: Inhibits cholesterol synthesis upstream of statins.

Effectiveness: Lowers LDL ~20%.

Advantage: Doesn’t cause muscle side effects like statins (works only in liver, not muscle).

Use: Alternative for statin-intolerant patients.

Fibrates:

Mechanism: Activate PPAR-alpha, improving triglyceride and HDL metabolism.

Examples: Fenofibrate, gemfibrozil

Effectiveness:

• Lower triglycerides 30-50%
• Raise HDL 10-20%
• Modest LDL lowering (or may increase LDL if triglycerides very high)

Use: Primarily for high triglycerides, especially >500 mg/dL (pancreatitis risk).

Side Effects: Generally well tolerated; may interact with statins (increased muscle side effect risk with gemfibrozil).

Omega-3 Fatty Acids (Prescription):

Mechanism: Reduce hepatic triglyceride production.

Medications:

• Icosapent ethyl (Vascepa) – EPA only, 4g daily
• Omega-3-acid ethyl esters (Lovaza) – EPA + DHA, 4g daily

Triglyceride reduction: 20-30% (higher doses for severe hypertriglyceridemia)

Use:

• Vascepa: Proven cardiovascular benefit in REDUCE-IT trial (25% event reduction) when added to statin
• Severe hypertriglyceridemia (>500 mg/dL) to prevent pancreatitis

Note: Over-the-counter fish oil supplements are less concentrated; prescription formulations contain 3-4x more omega-3 per pill.

Niacin (Nicotinic Acid):

Mechanism: Reduces triglyceride and LDL production, increases HDL.

Effects:

• Triglycerides: ↓20-30%
• HDL: ↑15-30% (most effective medication for raising HDL)
• LDL: ↓10-20%

Doses: 1-3g daily (start low, increase gradually)

Use: Has fallen out of favor; limited use now.

Evidence: No cardiovascular benefit when added to statin in major trials (AIM-HIGH, HPS2-THRIVE).

Side effects:

• Flushing (very common, can be severe)
• Liver toxicity
• Worsens glucose control (problematic in diabetes)
• Gastrointestinal upset

Understanding your complete lipid profile is essential for cardiovascular health. Comprehensive blood testing including total cholesterol, LDL, HDL, triglycerides, and advanced markers like ApoB and Lp(a) provides the foundation for effective prevention and treatment.