1. Advances in Lipid Management

2. 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.

3. 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. 1998 Heart and Stroke Facts: Statistical Update.

4. 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.

5. Risk Stratification for Adults Without CHD Classification Based on LDL-C <130 mg/dL 130-159 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.

6. 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 1993. Risk Category

7. 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goal 83%55% High-Risk Adults Not Reaching LDL-C Goals in NHANES-III (National Health and Nutrition Examination Survey) Unpublished data from the Third National Health and Nutrition Examination Survey (NHANES-III), CDC 1994; data from 1988–1991.

8. 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.

9. 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 59 22 7 34 70 40 18 39 41 78 93 66 30 60 82 61 % FailureP-Value  0.001  Does not include patients who were nonevaluable. Person’s chi-square=682.91; d=2; P=0.001. 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.

10. 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.

11. 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.

12. 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 <130130-160>200161-200

13. 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  100 101-130>160131-160

14. Gotto AM Jr, et al. Circulation. 1990;81:1721-1733. 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)  204 205-234235-264265-294  295 150 200 250 300 0 50 40 30 20 10

15. 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, 1984. † 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;274:131-136. 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  167168-191192-217  218 Mean149.3179.8203.7245.3 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 † 125175225275325 Northern Europe Southern Europe, Mediterranean United States Serbia Southern Europe, Inland Japan