Hyperlipoproteinemia combined

Simvastatin is indicated in patients with coronary heart disease and hypercholesteremia, for the reduction of elevated total and LDL cholesterol in patients with primary hypercholesterolemia (type Ila and Ilb hyperlipoproteinemia), combined hypercholesterolemia and hypertriglyceridemia. 

Dyslipidemia is defined as elevated total cholesterol, low-density lipoprotein (LDL) cholesterol, or triglycerides a low high-density lipoprotein (HDL) cholesterol or a combination of these abnormalities. Hyperlipoproteinemia describes an increased concentration of the lipoprotein macromolecules that transport lipids in the plasma. Abnormalities of plasma lipids can result in a predisposition to coronary, cerebrovascular, and peripheral vascular arterial disease. 

BARs are useful in treating primary hypercholesterolemia (familial hypercholesterolemia, familial combined hyperlipidemia, type Ila hyperlipoproteinemia). 

The bile acid sequestering resins lower elevated LDL cholesterol and therefore are useful in the treatment of type Ila hyperlipoproteinemia. However, because the resins can raise plasma VLDL in some patients, they are not recommended for treatment of combined hyperlipidemias (type Ilb) when both LDL cholesterol and VLDL triglycerides are high or in other conditions of elevated triglycerides. 

Drug Reduced CHD Risk Lipoprotein Affected Hyperlipoproteinemia Treated In Singly Combination Principal Adverse Effects... 

Familial combined hyperlipoproteinemia VLDL predominantly increased Niacin, fibrate, reductase inhibitor Two or three of the individual drugs... 

As described, some persons with familial combined hyperlipoproteinemia have only an elevation in LDL. Serum cholesterol is usually less than 350 mg/dL. Dietary and drug treatment, usually with a reductase inhibitor, is indicated. It may be necessary to add niacin or ezetimibe to normalize LDL. 

This synergistic combination is useful in the treatment of familial hypercholesterolemia but may not control levels of VLDL in some patients with familial combined hyperlipoproteinemia. Statins should be given at least 1 hour before or 4 hours... 

This combination effectively controls VLDL levels during resin therapy of familial combined hyperlipoproteinemia or other disorders involving both increased VLDL and LDL levels. When VLDL and LDL levels are both initially increased, doses of niacin as low as 1-3 g/d may be sufficient in combination with a resin. The niacin-resin combination is effective for treating heterozygous familial hypercholesterolemia. 

This regimen is more effective than either agent alone in treating hypercholesterolemia. Experience indicates that it is an efficacious and practical combination for treatment of familial combined hyperlipoproteinemia. 

Fenofibrate appears to be complementary with certain statins in the treatment of familial combined hyperlipoproteinemia and other conditions involving elevations of both LDL and VLDL. The combination of fenofibrate with rosuvastatin is particularly effective. Some other statins may interact unfavorably owing to effects on cytochrome P450 metabolism. 

Familial combined hyperlipoproteinemia VLDL increased Niacin, fibrate ... 

In kindreds with this disorder, individuals may have elevated levels of VLDL, LDL, or both, and the pattern may change with time. Familial combined hyperlipoproteinemia involves an approximate doubling in VLDL secretion. It seems to be transmitted as a semidominant trait. Triglycerides can be increased by the factors noted above. Elevations of cholesterol and triglycerides are generally moderate, and xanthomas are usually absent. Drug treatment is warranted because the risk of coronary atherosclerosis is increased and diet alone does not normalize lipid levels. A reductase inhibitor or ezetimibe in combination with niacin is usually required to treat these patients. 

Therapeutic uses Niacin lowers plasma levels of both cholesterol and triacylglycerol. Therefore, it is particularly useful in the treatment of Type lib and IV hyperlipoproteinemia, in which both VLDL and LDL are elevated. Niacin is also used to treat other severe hypercholesterolemias, often in combination with other antihyperlipidemic agents (see p. 215). In addition, it is the most potent antihyperlipidemic agent for raising plasma HDL levels. 

A decrease in serum cholesterol levels results in a decrease not only in the lipid content but also in the size of experimentally induced atherosclerotic lesions. Evidence of this association in man has been demonstrated by coronary angiography. " Human femoral atherosclerosis regressed in response to diet and/or drug therapy (clofibrate, NA, or clofibrate in combination with neomycin). "> The degree of retardation of atherosclerosis was directly correlated with the decrease in serum cholesterol levels. " Regression in patients with Type IV hyperlipoproteinemia was also associated with the decrease in serum triglyceride levels however, no such correlation was found in another study. ... 

Type TV hyperlipoproteinemia is common and occurs in adulthood primarily in patients who are obese, diabetic, and hyperuricemic and do not have xanthomas. It may be secondary to alcohol ingestion and can be aggravated by stress, progestins, oral contraceptives, thiazides, or 8-blockers. Two genetic patterns occur in type IV hyperlipoproteinemia familial hypertriglyceridemia, which does not carry a great risk for premature CAD, and familial combined hyperlipidemia, which is associated with increased risk of cardiovascular disease. 

Type lib Combined hyperlipoproteinemia (1 LDL receptors) (T apo B production) Increased LDL increased VLDL lovastatin, nicotinic add, gemfibrozil... 

Bile acid sequestrants are indicated for the treatment of hypercholesterolemia in patients who do not adequately respond to dietary modifications. They may be used either alone or in combination with HMGRIs or niacin. These combinations often can achieve a 50% reduction in plasma LDL levels. Cholestyramine, but neither colestipol nor colesevelam, also is approved for the relief of pruritus associated with partial biliary obstruction. Bile acid sequestrants should not be used to treat hypertriglyceridemias or mixed hyperlipoproteinemias in which hypertriglyceridemia is the primary concern. These compounds also are contraindicated in patients with cholelithiasis or complete biliary obstruction because of the impaired secretion of bile acids caused by these conditions. Finally, cholestyramine and colestipol are contraindicated in patients with primary biliary cirrhosis, because this can further raise serum cholesterol (7,15,21). 

Familial combined hyperlipoproteinemia has been considered to exhibit enhanced apoB production, resulting in expression... 

Primary type IV hyperlipoproteinemia is associated with enhanced VLDL production and/or impaired VLDL removal and caused mostly by familial hypertriglyceridemia or combined hyperlipoproteinemia. There has been a lot of discussion on a causative association between enhanced VLDL production and bile acid and cholesterol synthesis. U i6 23 Some evidence has also been presented that a primary change in bile acid and cholesterol synthesis would alter secondarily VLDL synthesis. 

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