Hypercholesterolemia
characterized by increased serum levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL‑C), and apolipoprotein B (apo B). And these are associated with increased risk of cardiovascular disease (CVD) and mortality.
cholesterol is causal in development of atherosclerotic cardiovascular disease (ASCVD) & lowering cholesterol is associated with lower CV events.
CVD in secondary prevention, cholesterol lowering leads to a consistent reduction in total mortality and recurrent CV events.
Non-HDL cholesterol= total cholesterol – HDL cholesterol.
Non-HDL cholesterol is less sensitive to fasting status, and better predictor of CV risk compared to LDL cholesterol. Non-HDL-C is important measure of the total quantity of apolipoprotein B (apo B)–containing atherogenic lipid particles.
Lipoprotein(a), a subfraction of LDL, genetically determined, a causal factor in atherosclerosis.
Triglyceride > 1000 mg/dL result in formation of eruptive xanthomas, high LDL result in tendinous xanthomas, Lipemia retinalis (cream-colored blood vessels in fundus) in triglyceride >2000 mg/dL.
Triglycerides >1000 mg/dL is high risk for pancreatitis.
Causes:
primary genetic disorders (inborn genetic errors of lipid metabolism), or lifestyle, or both in combinations.
Secondary to type 2 diabetes, metabolic syndrome, obesity, chronic kidney disease, hypothyroidism, cholestatic liver disease, nephrotic syndrome, cushing syndrome, pregnancy, SLE, anorexia nervosa, multiple myeloma and selected medications (like anabolic steroids, furosemide, beta blockers, etc).
Lipid screening:
For cardiovascular risk assessment- men > 40 & women > 50 yrs old (or if postmenopausal) without known CV risk factors,
In patients with CV risk factors like established CVD, smoking, diabetes, severe CKD, family history of premature CVD, or familial hypercholesterolemia.
Suspect familial hypercholesterolemia: Family history or severe hypercholesterolemia without any secondary causes.
Management:
Lifestyle modifications- Diet- reduce intake of saturated fats (< 7% of kcals) and reduce calories percent from trans-fat and saturated fat to reduce LDL and non-HDL cholesterol.
Increased physical activity- 40 minutes of mod to vigorous intensity exercise 3 or 4 times a week
Treatment: statins (HMG Co-A reductase inhibitors), drugs of first choice for lowering LDL and non-HDL cholesterol.
Consider high-intensity statin for patients ≤ 75 yrs old with goal LDL cholesterol reduction ≥ 50%.
consider moderate to high intensity statin for patients > 75 years old after calculating risks and benefits of treatment.
Indications for high-intensity and moderate-intensity statins: recommendations of 2018 AHA/ACC/Multi-society guidelines.
Presence of clinical ASCVD- Use high-intensity statin or moderate-intensity statin if over age 75 years.
Primary elevation of LDL cholesterol ≥ 190 mg/dL- Use high-intensity statin.
Age 40–75 years, Presence of diabetes, LDL ≥ 70 mg/dL- Moderate-intensity statin Or high-intensity statin if 10-year CVD risk ≥ 7.5% or other risk enhancing criteria like “Diabetes duration > 10 years, microalbuminuria, CKD, and ankle brachial index < 0.9 favor aggressive treatment even for patients aged 20–39 years”.
Age 40–75 years, No clinical ASCVD or diabetes LDL 70–189 mg/dL, Estimated 10-year CVD risk ≥ 7.5% or coronary artery calcium score ≥ 100 or ≥ 75th percentile- moderate- to high-intensity statin.
High-intensity statins reduce LDL cholesterol ~ 50%, eg. atorvastatin 40–80 mg/day & rosuvastatin 20–40 mg/day.
Moderate-intensity statins reduce LDL cholesterol ~ 30–50%, eg. atorvastatin 10–20 mg/day and rosuvastatin 5–10 mg/day, pitavastatin 2–4 mg/day, simvastatin 20–40 mg/day, and pravastatin 40–80 mg/day.
All statins are given once daily in the morning or evening.
The fibrates are peroxisome proliferative-activated receptor-alpha (PPAR-alpha) agonist- significant reductions of triglycerides and increases HDL cholesterol. Fenofibrate, 48–145 mg daily. Consider if triglyceride more than 500-1000mg/dL to reduce pancreatitis.
Add ezetimibe after maximally-tolerated statin, with LDL-C ≥ 70 mg/dL in very high risk.
Add PCSK9 inhibitor in very high risk if LDL-C ≥ 70 mg/dL or non-HDL-C level ≥ 100 mg/dL after maximally tolerated statin & ezetimibe.
coronary artery calcium (CAC) score- if statin use remains uncertain
CAC score is 0, consider withholding statin, if no higher risk conditions.
CAC score is 1 to 99- statin therapy in ≥ 55 yrs old.
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