Advances in Lipid Management
The National Cholesterol Education Program (NCEP) Launched by National Heart, Lung, and Blood Institute (NHLBI), a part of the NIH, in November, 1985 Impetus: Definitive evidence linking coronary heart disease (CHD) to elevated total cholesterol levels Goal: Educating, monitoring, and developing guidelines for lowering blood cholesterol levels NCEP web site.
50% Coronary Heart Disease 1%Congenital Heart Defects 1%Rheumatic Fever/ Rheumatic Heart Disease 4%Congestive Heart Failure 2% Atherosclerosis 4% High Blood Pressure 22% Other Coronary Heart Disease: Despite Advances, Still the #1 Killer Percentage Breakdown of Deaths From Cardiovascular Diseases United States: 1995 Mortality, Final Data 16% Stroke American Heart Association Heart and Stroke Facts: Statistical Update.
Major Risk Factors for CHD The NCEP Adult Treatment Panel Identifies Positive Risk Factors (RF) for CHD Risk Factors Family history of early CHD — parent or sibling <55 years of age if male, <65 years of age if female Age — male 45 years — female 55 years, or premature menopause without estrogen replacement therapy (ERT) Hypertensive (BP 140/90 mm/Hg or taking antihypertensive medication) Current smoker Diabetes mellitus Low HDL-cholesterol (<35 mg/dL) Negative Risk Factor If HDL-C is 60 mg/dL, subtract one risk factor Second Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, NHLBI; September 1993.
Risk Stratification for Adults Without CHD Classification Based on LDL-C <130 mg/dL mg/dL 160 mg/dL LDL-C Level Desirable Borderline-high risk High risk Classification Second Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, NHLBI; September 1993.
NCEP Primary CHD Risk Categories and Goals for Lowering LDL-C LDL-C Goal No CHD <2 RF<160 mg/dL No CHD 2 RF <130 mg/dL CHD 100 mg/dL The NCEP recommends lowering LDL-C even further than these goals, if possible. Second Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, NHLBI; September Risk Category
83% of CHD patients did not reach NCEP goal 55% of patients with 2 risk factors and no CHD did not reach NCEP goal 83%55% High-Risk Adults Not Reaching LDL-C Goals in NHANES-III (National Health and Nutrition Examination Survey) Unpublished data from the Third National Health and Nutrition Examination Survey (NHANES-III), CDC 1994; data from 1988–1991.
Lipid Treatment Assessment Project (L-TAP) Hypothesis — majority of dyslipidemic patients do not achieve NCEP target LDL-C levels Primary Objective — to determine percentage of primary care patients on diet and/or drug therapy who are achieving NCEP LDL-C goals Pearson TA, Laurora IM. Scientific Sessions of the American Heart Association; 1997; Abstract 361.
L-TAP: % of Patients at LDL-C Goal Diet therapy 2RF(n=282) 2RF(n=361) CHD(n=108) Total(n=751) Drug therapy 2RF(n= 861) 2RF(n=1924) CHD(n=1352) Total(n=4137) Risk group— Lipid-lowering therapy % Success % FailureP-Value Does not include patients who were nonevaluable. Person’s chi-square=682.91; d=2; P= LDL-C goal Data on file. Parke-Davis; Morris Plains, NJ. Pearson TA, Laurora IM. Scientific Sessions of the American Heart Association; 1997; Abstract 361.
L-TAP: Identifying the Patient at Risk Patient Profile With 2 Risk Factors 92%Male 45 years Female 55 years 70%Hypertensive ( 140/90 mm Hg) 41%Family history of early CHD 22%Low HDL-C level 21%Diabetes mellitus 19%Current smokers 47% 30% CHD Patients 23% No CHD <2 RF No CHD 2 RF Data on file. Parke-Davis; Morris Plains, NJ.
L-TAP: Many High-Risk Adults Are Not Reaching LDL-C Goals 63% of patients with 2 risk factors and no CHD did not reach NCEP goal 63%82% 82% of CHD patients did not reach NCEP goal Data on file. Parke-Davis; Morris Plains, NJ.
L-TAP: Distance From LDL-C Goal in Patients With 2 Risk Factors Data on file. Parke-Davis; Morris Plains, NJ. n=849 63% LDL-C (mg/dL) No. of patients Not at goal At goal n=816 n=494 n=126 < >
L-TAP: Distance From LDL-C Goal in Patients With CHD Data on file. Parke-Davis; Morris Plains, NJ. n=256 82% LDL-C (mg/dL) No. of patients Not at goal At goal n=545 n=416 n=243 >
Gotto AM Jr, et al. Circulation. 1990;81: Castelli WP. Am J Med. 1984;76:4-12. Relationship Between Cholesterol and CHD Risk: Epidemiologic Trials 10-year CHD death rate (Deaths/1000) Serum cholesterol (mg/dL) 1% reduction in total cholesterol resulted in a 2% decrease in CHD risk CHD indications per 1000 Each 1% increase in total cholesterol level is associated with a 2% increase in CHD risk Serum cholesterol (mg/100 mL) Framingham Study (n=5209) Multiple Risk Factor Intervention Trial (MRFIT) (n=361,662)
Relationship Between Cholesterol and CHD Risk: Epidemiologic Trials (cont’d) Cumulative incidence of AMI in each quartile of basal serum cholesterol, expressed per 100,000 screened subjects in 3 years. Serum cholesterol was measured between April 1, 1983 and March 31, † 25-year CHD mortality rates per baseline cholesterol quartile adjusted for age, cigarette smoking, and systolic blood pressure. Wakugami K, Iscki R, Kimura Y, et al. Japanese Circulation Journal. 1998;62:7-14. Verschuren WMM, Jacobs DR, Bloemberg BPM, et al. JAMA. 1995;274: Cumulative incidence of AMI per 100,000 screened subjects in 2 years Cumulative incidence of acute myocardial infarction (AMI) increased with the level of serum cholesterol Serum cholesterol (mg/dL) Range 218 Mean Okinawa, Japan CHD mortality rates (%) Using linear approximation, a 20-mg/dL increase in total cholesterol corresponded to a 17% increase in mortality risk Serum cholesterol (mg/dL) Seven Countries Study † Northern Europe Southern Europe, Mediterranean United States Serbia Southern Europe, Inland Japan