Atherosclerosis - Treatment

Treatment of atherosclerosis involves actively eliminating risk factors to prevent new plaque formation and reduce existing plaque. Recent studies suggest that LDL levels should be < 70 mg/dL in patients with existing disease or high risk for cardiovascular disease. Lifestyle modifications include diet, smoking cessation, and regular physical activity. Drugs to treat dyslipidemia, hypertension, and diabetes are often needed. These lifestyle modifications and drugs directly or indirectly improve endothelial function, reduce inflammation, and improve clinical outcome. Antiplatelet drugs are effective in all patients.

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Diet

A significant reduction in saturated fat and simple carbohydrate intake is recommended, while the proportion of fruits, vegetables, and plant fiber is increased. Such dietary changes help normalize lipid levels and are essential for all patients. Caloric intake should be limited to maintain normal body weight.

A small reduction in dietary fat probably does not slow or stabilize the progression of atherosclerosis. Effective changes involve limiting fat intake to 20 g/day, including 6-10 g polyunsaturated fats containing -6 (linoleic acid) and -3 (eicosapentaenoic acid, docosahexaenoic acid, respectively) fatty acids in equal proportions, < 2 g saturated fats, the rest in the form of monounsaturated fats. Fatty acids that are highly atherogenic should be avoided.

Increasing carbohydrates to compensate for a reduction in saturated fat in the diet increases triglyceride levels and decreases HDL in plasma. Therefore, any calorie deficit should be made up with protein and unsaturated fats, not carbohydrates. Excessive sugar intake should be avoided, although it has no direct relationship with cardiovascular risk. Complex carbohydrates (e.g., vegetables, whole grains) are recommended instead of sugar.

Fruits and vegetables probably reduce the risk of coronary atherosclerosis, but whether this effect is due to flavonoid intake or to a reduction in saturated fat and an increase in fiber and vitamins is unclear. Flavonoids (found in red and purple grapes, red wine, black tea, and dark beer) have a protective effect; high levels in red wine may explain the relatively low incidence of coronary atherosclerosis in the French, who smoke more and consume more fat than Americans. However, no clinical studies indicate that eating flavonoid-rich foods or using supplements instead of foods prevents atherosclerosis.

Increasing the proportion of plant fiber reduces total cholesterol and may have a beneficial effect on insulin and glucose levels. A daily intake of at least 5-10 g of digestible fiber (eg, oat bran, beans, soy products) is recommended; this amount reduces LDL by about 5%. Indigestible fibers (eg, cellulose, lignin) probably do not affect cholesterol levels but may have additional health benefits (eg, reducing the risk of bowel cancer, possibly by stimulating intestinal motility or reducing the time of contact with dietary carcinogens). However, excessive fiber intake leads to impaired absorption of certain minerals and vitamins. In general, foods rich in flavonoids and vitamins are also rich in fiber.

Alcohol increases HDL and has weak antithrombotic, antioxidant, and anti-inflammatory properties. These effects appear to be similar for wine, beer, and hard liquor, and occur at moderate levels of consumption: 1 ounce 5-6 times per week has a protective effect against coronary atherosclerosis. However, at higher doses, alcohol can cause significant health problems. The relationship between alcohol consumption and all-cause mortality is known to be J-shaped, with mortality being lowest in men who drink < 14 drinks per week and in women who drink < 9 drinks per week.

There is little evidence that the presence of vitamins, flavonoids, and trace minerals in food reduces the risk of atherosclerosis. The only exception is fish oil supplements.

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Physical activity

Regular physical activity (eg, 30-45 min of walking, running, swimming, or cycling 3-5 times per week) is associated with lower rates of risk factors (hypertension, dyslipidemia, diabetes mellitus), lower rates of coronary artery disease (including MI), and lower rates of atherosclerotic death (with or without previous ischemia). It is unclear whether there is a clear causal relationship between physical activity and atherosclerosis or whether healthier individuals are more likely to engage in regular exercise. The optimal intensity, duration, frequency, and type of exercise have not been established, but most studies show an inverse linear relationship between outdoor physical activity and risk. Regular walking increases the distance that patients with peripheral arterial disease can walk without pain.

An exercise program that includes outdoor exercise has been shown to be beneficial in preventing atherosclerosis and reducing body weight. Before starting a new exercise program, older adults and patients with risk factors or a recent history of ischemia should undergo a physician evaluation (history, physical examination, and risk factor control assessment).

Antiplatelet drugs

Taking antiplatelet drugs orally is important because most complications occur due to plaque integrity or rupture with platelet activation and thrombosis.

Aspirin is the most widely used drug. It is prescribed for secondary prevention and is recommended for primary prevention of coronary atherosclerosis in high-risk patients (eg, patients with diabetes mellitus with or without atherosclerosis, patients with a 10-year risk of cardiac disease greater than 20%). The optimal dose and duration are unknown, but 70-160 mg once daily is usually prescribed for primary prevention because this dose is effective and the risk of bleeding is minimal. For secondary prevention and in patients with poorly controlled risk factors, a dose of 325 mg is effective. Approximately 10-20% of patients taking aspirin for secondary prevention have recurrent ischemic attacks. This may be due to resistance to aspirin; The effectiveness of thromboxane suppression (determined by urinary 11-dihydrothromboxane B2) is being studied for the possibility of widespread practical use. Some studies suggest that ibuprofen may counteract the antithrombotic effect of acetylsalicylic acid, so other NSAIDs are recommended for patients taking acetylsalicylic acid prophylactically.

Clopidogrel (usually 75 mg/day) replaces aspirin when ischemic events recur in patients taking it. Clopidogrel is used with aspirin to treat acute NSTEMI; this combination is also given for 9-12 months after PCI to reduce the risk of ischemia.

Ticlopidine is no longer widely used because it causes severe neutropenia in 1% of those taking the drug and has adverse gastrointestinal effects.

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Other drugs

ACE inhibitors, angiotensin II receptor blockers, statins, and thiazolidinediones (eg, rosiglitazone, pioglitazone) have anti-inflammatory properties that reduce the risk of atherosclerosis independent of their effects on BP, lipids, and glucose. ACE inhibitors prevent the effects of angiotensin on endothelial dysfunction and inflammation. Statins increase endothelial nitric oxide release, stabilize atherosclerotic plaques, reduce lipid accumulation in the arterial wall, and induce plaque shrinkage. Thiazolidinediones can control the expression of proinflammatory genes. Routine use of statins for primary prevention of ischemia is controversial. However, several controlled studies support their use in high-risk patients (eg, normotensive diabetics and patients with multiple risk factors, including hyperlipidemia and/or hypertension). Statins are sometimes recommended for patients with normal LDL and high CRP; there is little research to support this practice and study is ongoing.

Folic acid 0.8 mg twice daily is used to treat and prevent hyperhomocysteinemia, but it has not been established whether this reduces the risk of coronary atherosclerosis. Pyridoxine and cyanocobalamin also lower homocysteine levels, but there is little evidence to support their use; research is ongoing. Calcium supplements 500 mg twice daily may help normalize blood pressure in certain individuals. Macrolides and other antibiotics are also being studied to see if curing chronic C. pneumoniae carriage can help suppress inflammation and slow the development and manifestations of atherosclerosis.