السبت، 16 أبريل 2011

Treatment of Atherosclerosis

The prevention and treatment of atherosclerosis require risk factor control, including the medical treatment of hypertension, hyperlipidemia, diabetes mellitus, and cigarette habituation.

Some studies have claimed reversal of atherosclerosis with pharmacologic agents such as statins and cilostazol, but these need to be further tested before it can be determined whether they offer any significant benefit in reducing clinical events.[7]

Advances in the understanding of the vascular biology of atherosclerosis have raised the possibility of using novel therapies to address more directly the various aspects of endothelial dysfunction and the role of endothelial dysfunction in atherogenesis. Potential cellular targets include vascular smooth muscle cells, monocyte/macrophage cell lines, platelets, and endothelial cells. Evidence exists that antiplatelet agents, antioxidant therapies, amino acid supplementation, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers may prove to prevent or slow the progression of the disease.

Treatment of hypertension
The dietary and pharmacologic treatment of hypertension is associated with a decreased incidence of stroke.

Management of hyperlipidemia and dyslipidemia 
The 3-hydroxy-3-methyl Co-A (HMG-CoA) reductase inhibitors inhibit the rate-limiting step of cholesterol synthesis in the liver. They are effective in lowering the serum total cholesterol, LDL cholesterol, and triglyceride levels and in raising the serum HDL cholesterol level. HMG-CoA reductase inhibitors also have a low incidence of adverse effects, the most common being hepatotoxicity and myopathy.

The success of the HMG-CoA reductase inhibitors in reducing circulating lipid levels and improving the clinical and anatomic course of atherosclerosis has focused attention on the management of hyperlipidemia.

In addition, an important role remains for other hypolipidemic agents that may be of particular benefit for patients with refractory LDL hypercholesterolemia, hypertriglyceridemia, low HDL cholesterol, and elevated lipoprotein(a).

Management of diabetes mellitus
For patients with diabetes mellitus, strict control of comorbid risk factors is especially important. Ample evidence exists that such control reduces the incidence of the clinical complications of microvascular and macrovascular disease.

The benefit of strict glycemic control in the prevention of macrovascular disease has been difficult to confirm, although this intuitively is beneficial and is known to retard the progression of microvascular disease.

Treatment of familial hypercholesterolemia
Treatment options for familial hypercholesterolemia include combination drug therapy, although drug therapy alone often is inadequate because of the relative or absolute deficiency of hepatic LDL receptors.

Lipid apheresis is an effective means of reducing circulating lipid levels. Liver transplantation has been performed on young patients with severe disease.

Drug Agents
HMG-CoA reductase inhibitors
These agents are competitive inhibitors of 3-hydroxy-3-methyl Co-A reductase, an enzyme that catalyzes the rate-limiting step in cholesterol biosynthesis, resulting in up-regulation of LDL receptors in response to the decrease in intracellular cholesterol. The HMG-CoA reductase inhibitors are indicated for the secondary prevention of cardiovascular events and for the treatment of hypercholesterolemia and mixed dyslipidemia.

A number of HMG-CoA reductase inhibitors are indicated for patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments. However, these agents may be less effective in patients with rare homozygous familial hypercholesterolemia, possibly because these patients are lacking functional LDL receptors, making it more likely to raise serum transaminases.

HMG-CoA reductase inhibitors include the following:
Pravastatin (Pravachol)
Simvastatin (Zocor)
Lovastatin (Mevacor, Altocor)
Fluvastatin (Lescol)
Atorvastatin (Lipitor)
Rosuvastatin (Crestor)
Pitavastatin (Livalo)

Vitamin E (Vita-Plus E, Softgels, Aquasol E) 
This antioxidant protects polyunsaturated fatty acids in membranes from attack by free radicals.

Bile acid sequestrants
The bile acid sequestrants block enterohepatic circulation of bile acids and increase the fecal loss of cholesterol. This results in a decrease in intrahepatic levels of cholesterol. The liver compensates by up-regulating hepatocyte LDL-receptor activity. The net effect is a 10-25% reduction in LDL cholesterol, but no consistent effect on triglycerides or HDL cholesterol exists.

Bile acid sequestrants include cholestyramine (Questran, LoCholest, Prevalite) and colestipol (Colestid).
    
 

  

 

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