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Questions and Answers
What is the primary objective of dietary therapy in cholesterol management?
What is the primary objective of dietary therapy in cholesterol management?
Which group of patients is NOT specifically targeted for statin treatment according to the ACC/AHA Guidelines?
Which group of patients is NOT specifically targeted for statin treatment according to the ACC/AHA Guidelines?
What effect does fish oil supplementation have on total and LDL cholesterol levels?
What effect does fish oil supplementation have on total and LDL cholesterol levels?
Which statement about the combination therapy of statins and ezetimibe is accurate?
Which statement about the combination therapy of statins and ezetimibe is accurate?
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What is the significance of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in cholesterol biosynthesis?
What is the significance of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in cholesterol biosynthesis?
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What is the role of ezetimibe when combined with statins?
What is the role of ezetimibe when combined with statins?
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Which treatment is specifically indicated for patients with homozygous familial hypercholesterolemia?
Which treatment is specifically indicated for patients with homozygous familial hypercholesterolemia?
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What dietary recommendation is advised regarding total daily fat intake?
What dietary recommendation is advised regarding total daily fat intake?
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Which drug therapy is indicated when dietary changes alone are insufficient for managing hyperlipoproteinemia?
Which drug therapy is indicated when dietary changes alone are insufficient for managing hyperlipoproteinemia?
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Which pharmacologic therapy is used to reduce cholesterol that the liver assembles and secretes?
Which pharmacologic therapy is used to reduce cholesterol that the liver assembles and secretes?
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Study Notes
Dyslipidemia Definition
- Dyslipidemia is defined as high total cholesterol, low HDL cholesterol, high LDL cholesterol, or high triglycerides, or a combination.
- It plays a major role in atherosclerosis and plaque formation, leading to coronary heart disease (CHD) and other forms of atherosclerotic cardiovascular disease (ASCVD).
- CHD is a leading cause of death and disability in adults.
Pathophysiology
- Cholesterol is essential for cell walls and hormones.
- Cholesterol, triglycerides, and phospholipids travel in the blood as lipoproteins (Chylomicrons, VLDL, IDL, LDL, HDL).
- Total cholesterol measures all cholesterol in the major lipoproteins. LDL cholesterol can be estimated by the Friedewald equation (total cholesterol - (HDL + triglycerides/5) or (total cholesterol - (HDL + triglycerides/2.2)).
- This formula is inaccurate if triglycerides are over 400mg/dL (4.52mmol/L), if chylomicrons are present, or if the patient has familial dysbetalipoproteinemia, in which case direct measurement is necessary.
- Cholesterol biosynthesis is regulated by existing cholesterol levels; higher intake leads to less production in the liver.
- HMG-CoA reductase is the enzyme in cholesterol production (the target of statins).
Pathophysiology (continued)
- High total and LDL cholesterol, and low HDL cholesterol contribute to CHD development.
- CHD can lead to angina, myocardial infarction, stroke, peripheral arterial disease, and even death.
- Repeated injury to atherosclerotic plaque leads to a fibrous cap over the core of lipids, collagen, calcium, and inflammatory cells.
- Primary dyslipidemias result from genetic defects impacting cholesterol metabolism, like hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, or disorders of HDL metabolism. These elevate cholesterol risk.
- Secondary dyslipidemia can occur from medications like progestins, thiazides, glucocorticoids, etc.
Clinical Presentation
- Dyslipidemia is usually asymptomatic.
- Corneal arcus and xanthomas may appear in patients with genetic disorders and high LDL cholesterol (> 250 mg/dL).
- Symptomatic patients might experience chest pain, palpitations, sweating, anxiety, shortness of breath, abdominal pain, speech/movement difficulties, or loss of consciousness.
- Physical signs may include cutaneous xanthomas, high blood pressure, and increased BMI/waist size.
Diagnosis
- Adults over 20 should undergo lipid panels (fasting required) every 5 years.
- Non-fasting lipid panels are suitable for risk assessment.
- If triglycerides are high in a non-fasting sample, a fasting lipid panel may be needed for accurate LDL cholesterol assessment.
- Children between 2 and 20 with family history of early CHD or high cholesterol should be screened.
- Elevated non-HDL cholesterol or LDL cholesterol above target levels (for those above 40 to 75 years without diabetes) require assessing ASCVD risk.
- Triglyceride levels > 150mg/dL and HDL < 40mg/dL (men) or < 50mg/dL (women) are also evaluated.
Diagnosis (further considerations)
- History and physical exam are key for evaluating cardiovascular risk factors.
- Patients should be assessed for secondary causes (e.g., pancreatitis, kidney/liver disease, peripheral vascular disease), symptoms (e.g., xanthomas, abdominal pain), and family history of lipid disorders.
- Normal/desirable values for cholesterol, triglycerides, HDL, and LDL are provided in a table, and should be consulted when assessing parameters.
Non-Pharmacological Therapy
- Begin therapeutic lifestyle changes (TLCs) at the first visit: dietary changes, weight loss, increased physical activity, cessation of smoking, and managing hypertension.
- Dietary modifications include reducing total fat, saturated fat, and cholesterol intake, increasing soluble fiber (oat, bran, pectin). Dietary supplementation with fish oil can decrease triglycerides and VLDL-C but may not effect LDL/total cholesterol. Plant sterols may also lower LDL (6-15%).
Pharmacologic Therapy
- HMG-CoA reductase inhibitors (statins): inhibit cholesterol biosynthesis, increasing LDL receptor expression and reducing LDL levels.
- Combinations with drugs like ezetimibe (inhibits cholesterol absorption) further reduce cholesterol levels.
- Other medications like fibrates (gemfibrozil, fenofibrate, clofibrate) lower VLDL, often with less effect on LDL.
- Bile acid resins (cholestyramine, colestipol, colesevelam) sequesters bile acids, and increase LDL receptor production and reducing LDL.
- Nicotinic acid (niacin) can reduce VLDL and increase HDL.
- Fish oil supplementation can decrease triglycerides, LDL, and VLDL, increasing HDL.
- Mipomersen (an apolipoprotein B-100 synthesis inhibitor) is indicated for homozygous familial hypercholesterolemia.
- Lomitapide (an MTP inhibitor) lowers LDL, total cholesterol, apolipoprotein B, and non-HDL cholesterol, useful in homozygous familial hypercholesterolemia.
Treatment Recommendations
- Total daily fat intake should be 10-25% of calories.
- Primary hypercholesterolemia (familial hypercholesterolemia, familial combined dyslipidemia) uses statins, niacin or ezetimibe.
- Combined hyperlipidemia can be addressed by statins, niacin, and/or gemfibrozil
- In cases of low HDL cholesterol, primary focus remains LDL reduction, along with lifestyle measures like weight loss, increased activity, and smoking cessation.
- Fibrates and niacin may be used if response to lifestyle alone is insufficient.
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