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    Don't trust an LDL over 70?

    New data requires revising NCEP III guidelines for middle-age and older adults


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    Wilbert S. Aronow, MD
    Numerous recent studies have shown that treating hypercholesterolemia in high-risk patients with statins decreases cardiovascular morbidity and mortality, particularly in the geriatric population.1 The National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP III) guidelines recommend that serum low-density lipoprotein (LDL) cholesterol be decreased to <100 mg/dL in persons with coronary heart disease (CHD), other clinical forms of atherosclerotic vascular disease, diabetes, metabolic syndrome, and with multiple risk factors that confer a 10-year risk for CHD >20%, regardless of age.2 But these recommendations are 3 years old; based on newer data this author recommends these guidelines be changed in older and younger adults at high risk for cardiovascular events.

    The Heart Protection Study3 was a randomized controlled trial of the effect of statin therapy for primary prevention of CHD in high-risk adults as well as secondary prevention in those with existing CHD. The study included 20,536 adults age 40 to 80 (28% age 70 to 80 at entry and age 75 to 85 at follow-up) with a serum total cholesterol } 135 mg/dL and prior MI (41%), other CHD (24%), or no CHD (35%). Of the 7,150 adults without CHD, 25% had cerebrovascular disease, 38% had peripheral arterial disease (PAD), 56% had diabetes, and 3% had only treated hypertension without atherosclerotic vascular disease or diabetes. (Percentages totaled 122% due to coexisting conditions.) Participants were randomized to simvastatin 40 mg/d or placebo. Mean follow-up was 5 years.

    Compared with placebo, simvastatin caused significant decreases in all-cause mortality by 13%, any vascular death by 17%, major coronary events by 27%, any stroke by 25%, coronary or noncoronary revascularization by 24%, and any major vascular event by 24%.3 In the 3,500 persons with an initial serum LDL cholesterol <100 mg/dL with and without CHD, lowering 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. 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. Based on this data, the Heart Protection Study Investigators recommended treating patients at high risk for vascular events with statins, regardless of the initial serum lipid levels, age, or sex.

    In a 3-year follow-up of 1,410 adults, mean age 81 at entry, with prior MI and serum LDL cholesterol }125 mg/dL, lowering serum LDL cholesterol by statins to <90 mg/dL was associated with a 20% incidence of new coronary events. Lowering serum LDL cholesterol to only 90 to 99 mg/dL, however, was associated with a 48% incidence of new coronary events.4 (Curves differed significantly after 11 months of follow-up.) Statins significantly reduced the incidence of new coronary events in persons age >90 (12% of persons at entry). Curves were significantly different after 1 year of follow up.4 The incidence of new stroke was 7% if serum LDL cholesterol was decreased to <90 mg/dL and 16% if serum LDL cholesterol was decreased to 90 to 99 mg/dL.5 Statins significantly reduced new stroke in persons age 90 but not age >90.5

    The Lipid Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes trial, a primary prevention trial of statins in high risk adults included 10,305 persons (6,570 persons age 61 to 79 at entry, age 64 to 82 at follow up) 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. Patients were randomized to atorvastatin 10 mg/d or placebo.6 At 3.3-year follow-up, serum LDL cholesterol was 90 mg/dL in persons treated with atorvastatin. Atorvastatin significantly reduced the incidence of fatal CHD and nonfatal MI by 34% in persons age 60 and by 36% in persons age >60.6 Atorvastatin significantly reduced fatal and nonfatal stroke by 27%.6 (These authors did not address when the curves became significant.)

    12

    12

    Wilbert S. Aronow, MD
    Numerous recent studies have shown that treating hypercholesterolemia in high-risk patients with statins decreases cardiovascular morbidity and mortality, particularly in the geriatric population.1 The National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP III) guidelines recommend that serum low-density lipoprotein (LDL) cholesterol be decreased to <100 mg/dL in persons with coronary heart disease (CHD), other clinical forms of atherosclerotic vascular disease, diabetes, metabolic syndrome, and with multiple risk factors that confer a 10-year risk for CHD >20%, regardless of age.2 But these recommendations are 3 years old; based on newer data this author recommends these guidelines be changed in older and younger adults at high risk for cardiovascular events.

    The Heart Protection Study3 was a randomized controlled trial of the effect of statin therapy for primary prevention of CHD in high-risk adults as well as secondary prevention in those with existing CHD. The study included 20,536 adults age 40 to 80 (28% age 70 to 80 at entry and age 75 to 85 at follow-up) with a serum total cholesterol } 135 mg/dL and prior MI (41%), other CHD (24%), or no CHD (35%). Of the 7,150 adults without CHD, 25% had cerebrovascular disease, 38% had peripheral arterial disease (PAD), 56% had diabetes, and 3% had only treated hypertension without atherosclerotic vascular disease or diabetes. (Percentages totaled 122% due to coexisting conditions.) Participants were randomized to simvastatin 40 mg/d or placebo. Mean follow-up was 5 years.

    Compared with placebo, simvastatin caused significant decreases in all-cause mortality by 13%, any vascular death by 17%, major coronary events by 27%, any stroke by 25%, coronary or noncoronary revascularization by 24%, and any major vascular event by 24%.3 In the 3,500 persons with an initial serum LDL cholesterol <100 mg/dL with and without CHD, lowering 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. 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. Based on this data, the Heart Protection Study Investigators recommended treating patients at high risk for vascular events with statins, regardless of the initial serum lipid levels, age, or sex.

    In a 3-year follow-up of 1,410 adults, mean age 81 at entry, with prior MI and serum LDL cholesterol }125 mg/dL, lowering serum LDL cholesterol by statins to <90 mg/dL was associated with a 20% incidence of new coronary events. Lowering serum LDL cholesterol to only 90 to 99 mg/dL, however, was associated with a 48% incidence of new coronary events.4 (Curves differed significantly after 11 months of follow-up.) Statins significantly reduced the incidence of new coronary events in persons age >90 (12% of persons at entry). Curves were significantly different after 1 year of follow up.4 The incidence of new stroke was 7% if serum LDL cholesterol was decreased to <90 mg/dL and 16% if serum LDL cholesterol was decreased to 90 to 99 mg/dL.5 Statins significantly reduced new stroke in persons age 90 but not age >90.5

    The Lipid Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes trial, a primary prevention trial of statins in high risk adults included 10,305 persons (6,570 persons age 61 to 79 at entry, age 64 to 82 at follow up) 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. Patients were randomized to atorvastatin 10 mg/d or placebo.6 At 3.3-year follow-up, serum LDL cholesterol was 90 mg/dL in persons treated with atorvastatin. Atorvastatin significantly reduced the incidence of fatal CHD and nonfatal MI by 34% in persons age 60 and by 36% in persons age >60.6 Atorvastatin significantly reduced fatal and nonfatal stroke by 27%.6 (These authors did not address when the curves became significant.)

    12

    Wilbert S. Aronow, MD
    Dr. Aronow is clinical professor of medicine, department of medicine, divisions of cardiology and geriatrics, New York Medical College, ...