Types of Primary Hyperlipoproteinemias

Statins are a class of medications that lower cholesterol levels in the blood by inhibiting the enzyme HMG-CoA reductase, which is involved in cholesterol synthesis.

Most statins are metabolized by the enzyme CYP3A4, which means that medications that inhibit or induce this enzyme can affect statin blood levels.

Simvastatin is a commonly used statin that, at its highest recommended dose of 80 mg, can reduce LDL cholesterol by 45-50%.

Atorvastatin and Rosuvastatin are also potent statins, with higher doses (80 mg and 40 mg respectively) achieving significant LDL-CH reduction.

Rosuvastatin, a potent statin, stands out for its ability to raise HDL cholesterol by a larger margin compared to other statins (15-20% increase).

Nicotinic acid, a B vitamin, lowers triglyceride (TG) and very low-density lipoprotein (VLDL) levels in the blood.

Nicotinic acid effectively reduces triglycerides (TGs) by 20-50% and lowers cholesterol (CH) levels by 15-25%.

Nicotinic acid is a potent drug for raising high-density lipoprotein cholesterol (HDL-CH) levels, likely by slowing down HDL's breakdown.

Flushing is a common side effect of nicotinic acid, occurring due to the release of prostaglandins (PGs).

Common side effects of nicotinic acid include dyspepsia, vomiting, diarrhea, peptic ulcers, skin dryness, hyperpigmentation, and potential liver dysfunction.

Statin therapy is the preferred treatment for primary hyperlipidemia with elevated LDL and total cholesterol, with or without high triglycerides (Type IIa, IIb, V) and for secondary hypercholesterolemia (diabetes, nephrotic syndrome).

Statins have been proven to reduce mortality and morbidity associated with elevated LDL-C.

Statins have a well-established dose-response relationship, meaning increasing the dose results in a greater decrease in LDL-C. The initial dose should aim to reach the target LDL-C level, and subsequent adjustments should be made based on regular monitoring.

Bile acid sequestrants (resins) are medications that bind bile acids in the intestine, interrupting their enterohepatic circulation. This increases fecal excretion of bile salts and cholesterol, indirectly leading to enhanced hepatic metabolism of cholesterol into bile acids. This process also stimulates the expression of LDL receptors on liver cells, increasing the clearance of plasma IDL, LDL and indirectly VLDL.

Bile acid sequestrants (resins) are not preferred clinically due to their unpalatable taste, inconvenient administration, large doses required, potential for gastrointestinal side effects (flatulence), interference with absorption of other medications, and poor patient acceptance.

Fibrates, like bezafibrate and fenofibrate, are a class of drugs that primarily activate lipoprotein lipase, an enzyme that breaks down VLDL, leading to reduced triglyceride levels.

They interact with PPARα (peroxisome proliferator-activated receptor alpha), a receptor found in liver, fat, and muscles, influencing gene transcription and increasing lipoprotein lipase synthesis.

Fibrates lead to enhanced fatty acid oxidation. They also increase LDL receptor expression in the liver, particularly with second-generation fibrates, which helps remove LDL from the blood.

Studies have shown that statins like simvastatin and pravastatin can significantly reduce the risk of coronary artery disease mortality, overall mortality, and cerebrovascular events.

While primarily known for their effect on triglycerides, fibrates can also decrease hepatic triglyceride synthesis, further contributing to lipid management.