The NCEP III Guidelines Should Be Changed in Elderly and Younger Persons at High Risk for Cardiovascular Events
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The Heart Protection Study included 20,536 persons aged 40-80 years (5806 persons aged 70-80 years at study entry and 75-85 years at follow-up) with a serum total cholesterol of 135 mg/dL or higher and prior myocardial infarction (MI) (8510 persons), other CHD (4876 persons), or no CHD (7150 persons).4 Of the 7150 persons without CHD, 1820 had cerebrovascular disease, 2701 had peripheral arterial disease, and 3982 had diabetes. Although treated hypertension was present in 8457 persons, only 237 persons were included on the basis of hypertension alone. Persons were randomized to simvastatin 40 mg daily or to placebo. Mean follow-up was 5 years.
Compared with placebo, simvastatin caused significant decreases in all-cause mortality by 13%, in any vascular death by 17%, in major coronary events by 27%, in any stroke by 25%, in coronary or noncoronary revascularization by 24%, and in any major vascular event by 24%.4 In the 3500 persons with an initial serum LDL- cholesterol of lower than 100 mg/dL, reducing the serum LDL cholesterol from 97 mg/dL to 65 mg/dL by simvastatin caused a similar decrease in risk as did treatment of patients with higher serum LDL-cholesterol levels.4 Simvastatin significantly decreased all-cause mortality, vascular death, major coronary events, coronary or noncoronary revascularization, and any major vascular event regardless of initial levels of serum lipids, age, or gender.4 On the basis of these data, the Heart Protection Study Investigators recommended treating patients at high risk for vascular events with statins, regardless of the initial levels of serum lipids, age, or sex.4
At 3-year follow-up of 1410 persons, mean age 81 years, with prior MI and a serum LDL cholesterol of 125 mg/dL or higher, decreasing the serum LDL-cholesterol by statins to lower than 90 mg/dL was associated with a 20% incidence of new coronary events, whereas decreasing the serum LDL cholesterol to 90-99 mg/dL was associated with a 48% incidence of new coronary events.5 Statins significantly reduced the incidence of new coronary events in persons 60-70 years of age, in persons 70-80 years of age, in persons 80-90 years of age, and in persons 90-100 years of age.5 The incidence of new stroke was 7% if the serum LDL-cholesterol was decreased to lower than 90 mg/dL and 16% if the serum LDL cholesterol was decreased to 90-99 mg/dL.6 Statins significantly reduced new stroke in persons up to age 90 years but not in persons older than 90 years.6
In the Lipid Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes trial, 10,305 persons (6570 older than 60 years) with hypertension and at least 3 other cardiovascular risk factors with no history of CHD and a mean serum LDL cholesterol of 133 mg/dL were randomized to atorvastatin 10 mg daily or to placebo.11 At 3.3-year follow-up, the serum LDL cholesterol was 90 mg/dL in persons treated with atorvastatin. At 3.3-year follow-up, atorvastatin significantly decreased the incidence of fatal CHD and nonfatal MI by 34% in persons aged 60 years and younger and by 36% in persons older than 60 years.11 Atorvastatin significantly decreased fatal and nonfatal stroke by 27%.11
In the Reversal of Atherosclerosis With Aggressive Lipid Lowering (REVERSAL) study, intravascular ultrasound was used to measure progression of atherosclerosis in 502 patients, mean age 57 years (up to age 75), with CHD randomized to pravastatin 40 mg daily or atorvastatin 80 mg daily.15 The serum LDL cholesterol was decreased to 110 mg/dL in the pravastatin group and to 79 mg/dL in the atorvastatin group.
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