During the 1990s, the cholesterol revolution occurred. Numerous studies documented the efficacy of low-density lipoprotein cholesterol (LDL-C) reduction in the reduction of coronary heart disease (CHD) events and, in some situations, the reduction of both CHD and total mortality rates.
Medical therapy involves lifestyle modification and pharmacologic therapy.
For patients with known atherosclerosis (clinical CHD, symptomatic carotid artery disease, peripheral arterial disease, or abdominal aortic aneurysm), the LDL-C goal is less than 100 mg/dL, although an LDL-C goal of less than 70 mg/dL is now considered a therapeutic option in patients considered to be at very high risk (acute coronary syndrome patients, diabetes mellitus, multiple risk factors with uncorrected risk factors such as continued smoking).
For patients with 2 or more risk factors, the LDL-C goal is less than 130 mg/dL, with recommendations for drug therapy that depend on the estimated 10-year risk of a CHD event based on the modified Framingham equation (see below).
For patients at low risk (0-1 risk factors), the LDL-C goal is less than 160 mg/dL.
The LDL-C goal for patients with CHD equivalent risk, including patients with diabetes mellitus, should also be less than 100 mg/dL. In patients considered to be very high risk, a goal of less than 70 mg/dL is an acceptable option
The evaluation generally begins with a risk-factor analysis. Patients are then categorized according to CHD or CHD risk equivalent (particularly diabetes), ie, those with multiple risk factors and those at low risk (<2 risk factors). Patients with CHD or CHD equivalent risk have a greater than 20% 10-year risk for CHD events. Low-risk patients generally have a 10-year CHD risk of less than 10%. Patients with multiple risk factors may or may not be at high risk.
The new National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines recommend calculating a Framingham risk score in patients with multiple risk factors to quantify risk and set LDL-C goals. The Framingham score calculator is available through the NCEP and the US National Heart, Lung, and Blood Institute (see Risk Assessment Tool for Estimating 10-year Risk of Developing Hard CHD).
Patients with CHD or CHD equivalent are prescribed drug therapy simultaneously with therapeutic lifestyle changes if their LDL-C concentration is greater than or equal to 130 mg/dL. Drug therapy is optional for patients whose LDL-C value is 100-129 mg/dL.
For patients with multiple risk factors, the LDL-C level at which drug treatment is recommended depends on the Framingham score. The LDL-C goal is less than 130 mg/dL. For patients with multiple risk factors and a 10-year risk of greater than 20%, the treatment is similar to that of patients with CHD. For patients with a 10-year risk of 10-20%, drug treatment is considered if their LDL-C level is greater than or equal to 130 mg/dL. For patients with multiple risk factors and a 10-year risk of less than 10%, drug therapy is considered if their LDL-C levels are greater than or equal to 160 mg/dL.
For patients at low risk, the LDL-C goal is less than 160 mg/dL, with therapeutic lifestyle changes for patients with higher values and drug therapy considered at LDL-C levels of greater than or equal to 190 mg/dL.
Therapeutic lifestyle treatment (ie, dietary changes and exercise) is recommended for patients whose LDL-C concentrations are greater than their goal LDL-C.
The new NCEP guidelines also recommend trying to identify patients with what has been called the metabolic syndrome. Such patients in particular should be targeted for therapeutic lifestyle changes. These patients meet at least 3 of the following criteria:
Abdominal obesity (waist >40 in for men, >35 in for women)
High triglyceride level (>150 mg/dL)
Low high-density lipoprotein cholesterol (HDL-C) value (<40 mg/dL for men, <50 mg/dL for women)
High blood pressure (>130/85 mm Hg)
Impaired fasting glucose (IFG) value (plasma glucose level >110 mg/dL, although the lower limit now generally used in the American Diabetes Association IFG cutpoint of 100 mg/dL or greater)
If the patient's serum triglyceride level remains greater than or equal to 200 mg/dL after the LDL-C goal is reached, a secondary nonβHDL-C goal is set. The nonβHDL-C goal is the LDL-C goal plus 30 mg/dL. This goal may be achieved with an increase in the statin dose, a more efficacious statin, or the addition of another agent (eg, fibrate, niacin, fish oil). Fenofibrate has less of a propensity for drug interactions; therefore, it is preferred in most situations. If fish oil is used, the correct dose is at least 2-3 g of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) daily. Because most 1-g fish oil capsules contain only approximately 300 mg of DHA and EPA, a patient must consume 10 1-g fish oil capsules daily to reach the goal. More highly concentrated fish oil capsules or liquids can be used, but the patient usually cannot find these in local pharmacies.
Screen all patients via a fasting lipid profile every 5 years beginning at age 20 years. Patients with CHD should undergo a lipid profile determination at least yearly. Patients with multiple risk factors should have their lipid profiles determined at least every other year.
In 3 months, recheck the lipid profiles of patients treated with therapeutic lifestyle intervention. In 6-12 weeks, recheck the lipid profiles of patients treated with drugs.
Liver function testing is indicated periodically for patients taking statins or fibrates, although the risk for hepatotoxicity is very low. Liver function abnormalities are more common at the highest doses of each of the approved statins. Checking liver test results 6-12 weeks after an increase in the dose is reasonable, particularly in patients on high-dose statins.
The dosage and approximate LDL-C lowering of various statins is as follows:
For atorvastatin at 10-80 mg/d, the LDL-C level is lowered by 39-60%.
For fluvastatin at 20-80 mg every bedtime or 40 mg twice daily, the LDL-C level is lowered by 22-36%.
For lovastatin at 20-40 mg every evening or 40 mg twice daily, the LDL-C level is lowered by 24-42%.
For pravastatin at 10-80 mg every bedtime, the LDL-C level is lowered by 22-34%.
For rosuvastatin at 5-40 mg/d, the LDL-C level is lowered by 45-63%.
For simvastatin at 20-80 mg every bedtime, the LDL-C level is lowered by 38-47%.
Diet
The NCEP has created dietary guidelines for all people older than 2 years. The reduction of saturated fat intake is vitally related to reduced LDL-C levels. In general, replacing fat with complex carbohydrates is helpful. Because carbohydrates are less calorically dense than fat, this substitution may also help prevent obesity. Adopting an appropriate diet may help patients reduce their LDL-C value by approximately 10-15%. However, in real-world studies, a 5% reduction is more likely. Reduction in trans fat intake also helps reduce LDL-C levels and may help raise HDL-C levels.
NCEP dietary guidelines are as follows:
Total fat - Less than 30% of energy intake (calories)
Saturated fat - Less than 7% of energy intake
Polyunsaturated fat - Less than or equal to 10% of energy intake
Monounsaturated fat - From 10-15% of energy intake
Cholesterol - Less than 200 mg/dL
Carbohydrates - From 50-60% of energy intake
Extreme fat and cholesterol restriction has been achieved with vegetarian diets, as demonstrated by the 1990 studies performed by Ornish and colleagues. This type of dietary restriction has resulted in a marked reduction in LDL-C levels and improvement in CHD symptoms. Whether these dietary restrictions are realistic for most Americans is debatable. Moreover, such a diet also reduces HDL-C levels and raises triglyceride levels.
Plant sterols and plant stanol esters can be included in the diet and may reduce LDL-C values by approximately 10-15%. Commercial preparations are available as margarine substitutes (eg, Benecol, Take Control).
Recently, after years of lay promotion, small, short-term (6 mo) studies have suggested that high-fat low-carbohydrate diets (eg, the Atkins diet) may facilitate weight loss without adversely affected serum lipid concentrations. However, the long-term effects of such diets remain to be determined.
Activity
Although exercise has little effect on LDL-C concentrations, aerobic exercise may improve insulin sensitivity, HDL-C concentrations, and triglyceride levels and, thus, may help reduce CHD risk. Patients who exercise and adhere to an appropriate diet appear to be more successful in long-term lifestyle modifications that improve their CHD risk profile.