RISK FACTORS : Obesity, Heredity, Physical inactivity
GENERAL MEASURES :
. Requires intervention: HDL less than 40 mg/dL (0.78 mmol/L), LDL greater than 160 mg/dL (4.14 mmol/L),
coronary heart disease (CHD) or CHD risk equivalent . Treatment depends on LDH, HDL, and triglyceride levels as modifi ed by the number of following risk factors:
. Smoking
. Male > 45
. Female > 55
. HDL < 40
. Hypertension
. MI or stroke in first degree relative (male < 55 and female < 65)
. CHD risk equivalent = diabetes mellitus; carotid, aortic or peripheral vascular disease; or a risk for major coronary events . 20% per 10 years per the Framingham point scale derived from the above risk factors
. Indications for initiating medications
. No coronary heart disease (CHD) and fewer than 2 risk factors: if after 3 months of diet, exercise, LDL - 190
. No CHD, but 2 or more risk factors: if after 3 months diet, exercise, LDL - 160
. CHD or CHD risk equivalents if after 6-12 week diet, exercise, LDL - 100
ACTIVITY : Walking or other sustained cardiovascular exercise for 2.5 hours per week or more. Important
for increasing HDL, lowering total cholesterol, and losing weight.
DIET :
. Reduce all dietary fats to approximately 30% of total calories. Olive oil should be preferentially used.
. Increase fiber, increase intake of fruits, vegetables, whole grains, and garlic
. Emphasize, vegetarian, meatless, eggless, cheese-less meals, with poultry, fish, and nonfat milk or yogurt
. Minimal daily alcohol use may increase HDL
. Dietary adherence to low fat and cholesterol generally may be expected to result in a 10% LDL reduction
. Intake of too many carbohydrates with a high glycemic index, eg, bread rice, pasta, potatoes, may make
weight loss and cholesterol reduction more difficult
DRUG(S) OF CHOICE :
HMG-CoA reductase inhibitors (statins) are the medications of choice for the treatment of LDLc elevations in patients with heterozygous FH because they have the greatest efficacy and are easily tolerated and because multiple randomized, placebo-controlled trials have shown that lowering LDLc levels with statins reduces coronary morbidity and mortality and, in some cases, total mortality. The strongest statins, rosuvastatin and atorvastatin, at their maximum approved doses, can be expected to reduce LDLc levels 50-60%.
The ATPIII update advises that the starting dose of a statin be sufficient to lower the LDLc 30-40% (see Table 3).
Even the maximum doses of the strongest statins are usually inadequate for patients with FH, and the addition of one or more nonstatin cholesterol-lowering medications is necessary.
Bile acid sequestrants (eg, cholestyramine, colestipol, colesevelam) can be added with no risk of drug interaction, with the exception of affecting the absorption of the statin (and many other medications) if taken at the same time. Bile acid sequestrants modestly decrease LDLc levels and slightly increase HDLc and triglyceride levels. Other medication should be taken 1 hour before or 4 hours after a bile acid sequestrant.
Nicotinic acid (niacin) not only lowers LDLc levels but also has significant HDL-raising and triglyceride-lowering effects. There is little data to support the belief that niacin even slightly increases the risk of myopathy if combined with a statin.
Fibric acid derivatives include gemfibrozil (Lopid) and fenofibrate (Tricor). Outside of the United States, bezafibrate is also available. The fibrates lower triglyceride levels and raise HDLc levels, but they do not reliably lower LDLc levels. They increase the risk of statin-induced myositis more so than niacin. Therefore, this class of drugs is not usually useful in patients with FH.
The cholesterol absorption inhibitor, ezetimibe, reduces LDLc levels approximately 18% and has a small HDLc-raising and triglyceride-lowering effects. Because the mechanism by which it inhibits cholesterol absorption is quite specific, ezetimibe does not cause the side effects or drug interactions associated with bile acid sequestrants. When combined with a statin, substantially greater LDLc decreases have been observed and this medication has a major role in LDL-lowering when a statin alone is not sufficient.
Two statin formulations are now available in combination with either extended-release niacin (Advicor) or ezetimibe (Vytorin). These are particularly appropriate medications for patients with FH, most of whom require 2 or more drugs to reach their LDLc goals. In addition, significantly greater than expected decreases in the LDLc level (~16%) are frequently observed when ezetimibe is added to statin therapy