DISEASE INFLUENCING FACTORS : DIET, LIFE STYLE, ENVIRONMENT, SMOAKING, ALCOHOL, DRUG ABUSE, LACK OF EXERCISE, HYPERHOMOCYTEINEMIA, HYPERFIBROGENEMIA, HYPERTENSION, AGE, DIABETES MELLITUS, FAMILY H/O ATHEROSCLEROSIS, HYPERLIPEDEMIA
Medical Care: The prevention and treatment of atherosclerosis requires control of the known modifiable risk factors for this disease. This includes the medical treatment of hypertension, hyperlipidemia, diabetes mellitus, and cigarette habituation.
" Hypertension
o Hypertension is a risk factor for the development of atherosclerosis, atherosclerotic cardiovascular disease, and stroke. The mechanism by which hypertension causes these effects is not known, and some uncertainty exists as to what the primary and secondary factors are in a typically multifactorial syndrome. These factors may include hyperlipidemia, hypertension, diabetes mellitus, obesity, and physical inactivity.
o Dietary and pharmacological treatment of hypertension is associated with a decreased incidence of stroke and, to a lesser degree, atherosclerotic cardiovascular disease.
" Hyperlipidemia
o Convincing evidence that lowering serum cholesterol reduces the risk of subsequent coronary heart disease events and overall mortality exists.
o The HMG-CoA reductase inhibitors inhibit the rate-limiting step of cholesterol synthesis in the liver. HMG-CoA reductase inhibitors are effective in lowering the serum total cholesterol, LDL cholesterol, and triglyceride levels and in raising the serum HDL cholesterol level, and they have a low incidence of adverse effects, the most common being hepatotoxicity and myopathy.
o 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).
" Secondary prevention of coronary artery disease
o The Scandinavian Simvastatin Survival Study (4S) examined the effects of simvastatin on mortality in 4444 patients with established coronary heart disease and elevated total serum cholesterol. A statistically significant 29% reduction in the overall mortality rate (8.2% versus 11.5%) and a 42% reduction in the cardiac mortality rate (5% versus 8.5%) occurred after an average of 5.4 years of follow-up.
o The Cholesterol and Recurrent Events (CARE) study examined the effects of pravastatin on mortality rates and cardiac events in 1159 patients with established coronary heart disease and serum cholesterol concentrations that are within the reference range or are mildly elevated. A statistically significant 24% reduction in the incidence of fatal coronary heart disease or nonfatal myocardial infarction (9.9% versus 12.9%) occurred after an average of 5 years of follow-up. A lower total mortality rate (8.6% versus 9.4%) and coronary heart disease mortality rate (4.6% versus 5.7%) occurred in patients receiving pravastatin, although the results were not statistically significant.
o The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial examined the effects of 40 mg of pravastatin on the incidence of coronary events over a period of 6.1 years in 9014 patients with known coronary heart disease and a broad range of initial cholesterol levels. The following relative risk reductions occurred: 24% for death from coronary heart disease (P <0.001), 22% for the overall mortality rate (P <0.001), 29% for all cardiovascular outcomes (P <0.001), and 19% for stroke (P = 0.048). The effects were similar for all predefined subgroups.
" Primary prevention of coronary artery disease
o The West of Scotland Coronary Prevention Study (WOSCOPS) examined the effects of pravastatin on the incidence of nonfatal myocardial infarction and coronary mortality rates in 6595 men with moderate hypercholesterolemia and no prior history of coronary heart disease. A statistically significant 29% reduction in nonfatal myocardial infarction (4.6% versus 6.5%) and a 30% reduction in death from all cardiovascular causes (1.6% versus 2.3%) occurred after an average of 4.9 years of follow-up.
o The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) examined the effects of lovastatin on the incidence of a first major coronary event in 5608 men and 997 women with average total cholesterol and LDL cholesterol and below-average HDL cholesterol levels. A statistically significant 37% reduction in the incidence of the first major coronary event (4% versus 6.8%) occurred after an average of 5.2 years.
" Therapy with lipid-lowering agents should be a component of multiple risk factor intervention and only is indicated as an adjunct to diet therapy when the response to a diet restricted in saturated fat and cholesterol has been inadequate. The NCEP guidelines recommend aggressive lipid-lowering therapy for patients at high risk for coronary heart disease. More than 50 million individuals in the United States are candidates for some form of dietary and/or pharmacological intervention to modify their lipid profile. Pharmacoeconomic studies of implementation of the NCEP guidelines confirm the cost-effectiveness of primary and secondary prevention. Evidence exists that physicians are poorly compliant with these guidelines.
" For patients with diabetes mellitus, strict control of comorbid risk factors is especially important, and ample evidence exists that this reduces the incidence of the clinical complications of microvascular and macrovascular disease.
o Cholesterol lowering with the HMG-CoA reductase inhibitors has yielded important reductions in coronary heart disease events in patients with diabetes mellitus.
o 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.
" Cigarette habituation: The risks of cigarette smoking are reduced rapidly and significantly with smoking cessation. The relative risk is so significant that the incidence of coronary heart disease in people who have recently quit smoking is similar to that of people who have not smoked within 2 years.
Diet:
" The primary treatment of LDL hypercholesterolemia is dietary and includes restriction of caloric intake, saturated fats, and cholesterol. The NCEP and the American Heart Association (AHA) made specific recommendations for dietary therapy for coronary heart disease prevention. The recommended daily intake of nutrients is described by the step I and step II diets and is appropriately tailored to the level of coronary heart disease risk.
" Moderate alcohol intake is associated with a reduced incidence of coronary heart disease events. The mechanism(s) of this benefit is not well understood. Heavy alcohol intake probably is associated with an increased incidence of coronary heart disease events, as well as cardiomyopathy and arrhythmia and obviously should be discouraged.
Activity: Physical inactivity is a minor modifiable risk factor for coronary heart disease, and regular exercise has been shown to reduce the risk of coronary heart disease in a number of observational epidemiological studies. The mechanisms for this apparent benefit may include an increase in HDL cholesterol and a decrease in body weight, insulin resistance, and blood pressure. The optimal intensity and duration of exercise is not known; however, 20-30 minutes of aerobic exercise of mild-to-moderate intensity (including walking) 3 times per week probably is appropriate.
Prevention and treatment of atherosclerosis requires risk factor control, including the medical treatment of hypertension, diabetes mellitus, and cigarette habituation.
Advances in the understanding of the vascular biology of atherosclerosis raises the possibility of novel therapies that may 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 inhibitors, and angiotensin receptor blockers may prove to prevent or slow the progression of the disease.
Drug Category: 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.
DRUG TREATMENT :
1. PREVASTATIN
2. LOVASTATIN
3. FLUVASTATIN
FIBRIC ACID DERIVATIVES :
1. FENOFIBRATE
2. GEMFIBROZIL
BILE ACID SEQUESTRANTS :
1. CHOLESTYRAMINE
2. CHOLESTIPOL
ANTIOXIDANTS
1. VIT E
NICOTINIC ACID DERIVATIVES :
1. NIACIN
ANTITHROMBOTICS :
1. ASPIRIN