Cholesterol and lipid disorders (dyslipidemia) involve abnormal levels of lipids â cholesterol, triglycerides, or both â in the blood. Dyslipidemia is a major modifiable risk factor for cardiovascular disease, the leading cause of death worldwide. Endocrinologists frequently manage lipid disorders, particularly when associated with diabetes, obesity, thyroid disease, or metabolic syndrome.
Understanding Cholesterol
Cholesterol is a fatty substance essential for cell membrane structure, hormone production, and vitamin D synthesis. It is transported in the blood by lipoproteins:
- LDL (Low-Density Lipoprotein) â "Bad" cholesterol. High levels deposit cholesterol in artery walls, contributing to atherosclerosis (plaque buildup) and cardiovascular events.
- HDL (High-Density Lipoprotein) â "Good" cholesterol. Transports cholesterol from arteries back to the liver for elimination. Higher levels are protective.
- Triglycerides â Another blood fat. Elevated levels increase cardiovascular risk, especially in the context of low HDL and high small-dense LDL particles.
- Non-HDL cholesterol â All atherogenic particles; a more comprehensive target than LDL alone.
Causes of Dyslipidemia
Lipid abnormalities can be primary (genetic) or secondary (due to other conditions):
- Secondary causes: Hypothyroidism (raises LDL and triglycerides), uncontrolled diabetes, obesity, chronic kidney disease, liver disease, medications (steroids, beta-blockers, some diuretics), and high saturated fat/refined carbohydrate diet
- Primary (genetic) causes: Familial hypercholesterolemia (FH) â an autosomal dominant condition causing severely elevated LDL from birth; affects 1 in 250 people and dramatically increases heart attack risk
ð Familial Hypercholesterolemia: FH is severely underdiagnosed. Look for: LDL consistently above 190 mg/dL, premature cardiovascular disease in close relatives (heart attack before 55 in men, before 65 in women), or tendon xanthomas. Genetic testing can confirm the diagnosis.
Cardiovascular Risk Assessment
Lipid treatment targets are individualized based on overall cardiovascular risk, not on absolute cholesterol numbers alone. The 10-year ASCVD (atherosclerotic cardiovascular disease) risk calculator (Pooled Cohort Equations) estimates risk based on age, sex, race, blood pressure, cholesterol, smoking status, and diabetes.
| Risk Category | 10-Year ASCVD Risk | Typical LDL Target |
|---|---|---|
| Low risk | <5% | <130 mg/dL |
| Borderline risk | 5â7.5% | <130 mg/dL |
| Intermediate risk | 7.5â20% | <100 mg/dL |
| High/very high risk | âĨ20% or established ASCVD | <70 mg/dL (often <55) |
| Diabetes | Automatic high risk | <70 mg/dL |
Treatment
- Lifestyle: Heart-healthy diet (Mediterranean), weight loss, exercise, smoking cessation â these can reduce LDL by 10â20%
- Statins: First-line medication for LDL lowering; reduce LDL 20â60%; also reduce inflammation and cardiovascular events independent of LDL effect
- Ezetimibe: Reduces intestinal cholesterol absorption; added to statins when additional LDL lowering is needed
- PCSK9 inhibitors (evolocumab/Repatha, alirocumab/Praluent): Injectable; reduce LDL by 50â60% on top of statins; used for very high risk patients and FH
- Fibrates, omega-3 fatty acids: Primarily used for elevated triglycerides
- Bempedoic acid: Oral LDL-lowering agent for statin-intolerant patients
Key Takeaways
- LDL ("bad") cholesterol is the primary target; HDL ("good") is protective
- Always rule out secondary causes of dyslipidemia (especially hypothyroidism and diabetes)
- Treatment targets are based on overall cardiovascular risk, not cholesterol numbers alone
- Statins are the cornerstone of medical lipid management
- Familial hypercholesterolemia is common and underdiagnosed â look for LDL >190