HDL levels

High-density lipoproteins (HDL) have much longer life spans in the body (5 to 6 days) than other lipoproteins. Newly formed HDL contains virtually no cholesterol ester. However, over time, cholesterol esters are accumulated through the action of lecithin cholesterol acyltransferase (LCAT), a 59-kD glycoprotein associated with HDLs. Another associated protein, cholesterol ester transfer protein, transfers some of these esters to VLDL and LDL. Alternatively, HDLs function to return cholesterol and cholesterol esters to the liver. This latter process apparently explains the correlation between high HDL levels and reduced risk of cardiovascular disease. (High LDL levels, on the other hand, are correlated with an increased risk of coronary artery and cardiovascular disease.)... 

HDL cholesterol protects against heart disease so the higher the numbers the better. An HDL level less than 40 mg dL is low and considered a major risk factor for heart disease Triglyceride levels Hiat are borderline (150-190 mg dL) or high (above 190 mg dL) may need treatment in some individuals. 

In many individuals, hyperlipidemia has no symptoms and the disorder is not discovered until laboratory tests reveal elevated cholesterol and triglyceride levels, elevated LDL levels, and decreased HDL levels. Often, these drags are initially prescribed on an outpatient basis, but initial administration may occur in the hospitalized patient. Seram cholesterol levels (ie, a lipid profile) and liver functions tests are obtained before the drugs are administered. 

Tacrolimus has shown the propensity to cause less severe hyperlipidemia when compared with cyclosporine. Thus conversion from cyclosporine-based immunosuppression to tacrolimus-based immunosuppression may be one way to counteract this disease in transplant recipients.66 Studies demonstrate that steroid withdrawal in renal transplant patients lowered total cholesterol by 17% and LDL-C by 16% unfortunately, an 18% decrease in high-density lipoprotein (HDL) levels also was noted in these patients.66... 

A 35-year-old male with markedly elevated plasma triglyceride and LDL levels, and low plasma HDL levels, is treated with gemfibrozil. What is the mechanism of action of gemfibrozil ... 

Measurement of plasma cholesterol (which is about 3% lower than serum determinations), triglyceride, and HDL levels after a 12-hour or longer fast is important, because triglycerides may be elevated in nonfasted individuals total cholesterol is only modestly affected by fasting. 

Regimens intended to increase HDL levels should include either gemfibrozil or niacin, bearing in mind that statins combined with either of these drugs may result in a greater incidence of hepatotoxicity or myositis. 

As indicated in Table 1, statins, which block cholesterol biosynthesis by inhibition of hepatic HMGCoA reductase, have been used extensively to reduce LDL-C levels. At most therapeutic doses, statins marginally increase HDL levels by 5-10% [3,16]. The HDL elevation observed with statins has been highly variable and not easily extrapolated from the effects on LDL. A recent study (STELLAR) demonstrated increased HDL elevation with the use of rosuvastatin compared to simvastatin, pravastatin or atorvastatin (10% vs. 2-6%) [16,24], Although the mechanism of HDL elevation by statins is not clearly understood, it is proposed that statins enhance hepatic apoA-I synthesis [25] and decrease apoB-containing lipoproteins [26]. A number of clinical trials have demonstrated that statins reduce the risk of major coronary events. However, it is not clear if the statin-induced rise in HDL levels is an independent contributor to the reduced risk of coronary events. The observed small increase in HDL and adverse side effect profile related to liver function abnormalities and muscle toxicity limits the use of statins as monotherapy for HDL elevation [27],... 

Fibrates, such as fenofibrate (1), gemfibrozil (2), bezafibrate (3), clofibrate (4) and ciprofibrate (5) moderately enhance HDL levels by 10-15% [17], Fibrates are... 

PPAR8 activation in animal models has been shown to elevate HDL levels. Using structure-guided studies, a high-affinity PPAR8 specific-ligand, GW-501516 (19) (EC50 = 8nM), was discovered, which recently advanced to Phase II... 

The elevation of HDL levels by fibrates may be due to two drug actions induced synthesis of apo-Al, the principal apoprotein of HDL, and increased assembly of new HDL particles in the circulation. Sirrface components of VLDL contribute to formation of HDL, as the VLDL particles are reduced in size through the action of LPL. The increased rate of catabolism of VLDL caused by the fibrates would provide more components for assembly of HDL particles. 

It is a potent HMG CoA reductase inhibitor. This enzyme catalyzes the conversion of HMG CoA to mevalonate in liver which is an important early and rate limiting step in the cholesterol synthesis. It causes marked reduction in LDL cholesterol and also raise HDL level and may lower the triglyceride level. After oral administration it is extensively metabolised in liver and metabolites are excreted in bile. 

HDL level and it is administered with HMG CoA reductase inhibitors e.g. simvastatin. 

It is cholesterol lowering agent with antioxidant property. It is only 1/10 absorbed when given orally. It reduces the serum cholesterol levels without reduction in serum triglycerides level and also reduces the HDL levels. It has no effect on VLDL and triglyceride levels. 

In the presence of hypertriglyceridemia, HDL cholesterol is low because of exchange of cholesteryl esters from HDL into triglyceride-rich lipoproteins. Treatment of the hypertriglyceridemia may increase or normalize the HDL level. 

Niacin (but not niacinamide) decreases VLDL and LDL levels, and Lp(a) in most patients. It often increases HDL levels significantly. 

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