Cardiology > Hyperlipidemia    

Background 

Hyperlipidemia refers to elevated levels of lipids in the blood, primarily cholesterol and triglycerides. It includes various lipid abnormalities such as elevated low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, and reduced high-density lipoprotein cholesterol (HDL-C). Hyperlipidemia significantly contributes to atherosclerosis and cardiovascular disease. 

II) Classification/Types

By Lipid Abnormality: 

• • Isolated hypercholesterolemia 

• • Isolated hypertriglyceridemia 

• • Mixed hyperlipidemia (combined elevation of cholesterol and triglycerides) 

• • Low HDL-C 

By Etiology: 

• • Primary (familial): Genetic disorders such as familial hypercholesterolemia 

• • Secondary: Due to underlying conditions (e.g., diabetes, hypothyroidism, nephrotic syndrome, alcohol use) 

III) Pathophysiology  

Lipoproteins transport cholesterol and triglycerides through the bloodstream. Elevated LDL-C penetrates the endothelium and accumulates in the subintimal space, triggering inflammatory responses and plaque formation. Triglyceride-rich lipoproteins can also contribute to endothelial dysfunction. Decreased HDL-C impairs reverse cholesterol transport, exacerbating atherogenesis. 

IV) Epidemiology

• • Affects ~50% of adults in the U.S. over age 20 

• • Higher prevalence with advancing age, obesity, and sedentary lifestyle 

• • Major modifiable risk factor for cardiovascular disease (CVD) 

• • Often asymptomatic and detected through routine screening 

Etiology 

I) Causes

• • Genetic mutations (e.g., LDL receptor mutations in familial hypercholesterolemia) 

• • Metabolic syndrome 

• • Hypothyroidism 

• • Diabetes mellitus 

• • Chronic kidney disease 

• • Alcohol overuse 

• • Medications (e.g., corticosteroids, thiazides, antipsychotics) 

II) Risk Factors

• • Obesity and sedentary lifestyle 

• • High saturated fat and trans fat intake 

• • Family history of premature cardiovascular disease 

• • Smoking 

• • Excessive alcohol intake 

• • Older age 

Clinical Presentation 

I) History (Symptoms)

• • Often asymptomatic 

• • Severe hypertriglyceridemia: abdominal pain, pancreatitis 

• • Xanthomas (in familial cases) 

• • Early onset coronary artery disease in familial forms 

II) Physical Exam (Signs)

• • Xanthelasma (yellow plaques on eyelids) 

• • Tendinous xanthomas (Achilles tendon, elbows) 

• • Corneal arcus (especially <45 years old) 

• • Hepatosplenomegaly (severe hypertriglyceridemia) 

Differential Diagnosis (DDx) 

• • Familial hypercholesterolemia 

• • Nephrotic syndrome 

• • Hypothyroidism 

• • Primary biliary cholangitis 

• • Diabetes mellitus 

• • Alcohol-induced hyperlipidemia 

Diagnostic Tests 

Initial Work-Up 

• • Fasting lipid profile (Total cholesterol, LDL-C, HDL-C, triglycerides) 

• • Repeat testing for confirmation 

• • Calculate 10-year ASCVD risk (using ACC/AHA calculator) 

• • TSH, HbA1c, liver enzymes, creatinine to assess secondary causes 

• • Genetic testing in suspected familial cases 

Treatment 

I) Initial Approach

• • Lifestyle modification for all patients: 

• • Diet: Low saturated fat, increased fiber, plant sterols 

• • Exercise: 150 min/week moderate intensity 

• • Weight loss, smoking cessation, moderate alcohol use 

II) Medications

III) Advanced Therapies 

• • Lipoprotein apheresis for familial hypercholesterolemia 

• • Liver transplant (rare, for homozygous familial hypercholesterolemia) 

Patient Education, Screening, Vaccines 

Education 

• • Importance of lifelong management 

• • Adherence to medications and lifestyle changes 

• • Cardiovascular risk and stroke prevention 

Screening 

• • Adults ≥20 years: lipid profile every 4–6 years 

• • High-risk individuals: screen more frequently 

• • Children with family history: screening at age 9–11 and 17–21 

Vaccinations 

• • Annual influenza vaccine 

• • COVID-19 vaccine 

• • Pneumococcal vaccine in high-risk patients 

Consults/Referrals 

• • Endocrinology: genetic dyslipidemias or severe metabolic syndrome 

• • Cardiology: established CVD or very high risk 

• • Nutritionist: dietary intervention 

Follow-Up 

Short-Term 

• • Lipid panel 4–12 weeks after medication initiation 

• • Monitor for statin side effects (myalgia, liver enzymes) 

Long-Term 

• • Annual lipid profile monitoring 

• • Monitor adherence, risk factor control 

• • Reassess ASCVD risk every 4–6 years 

Prognosis 

• • Excellent with early detection and management 

• • Untreated cases can lead to premature coronary artery disease, stroke, and pancreatitis 

• • Familial forms carry high risk of early morbidity and mortality