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2003 Thomson Professional Postgraduate Services LIPID: Reduction in Nonfatal MI and CHD Death Risk Stratified by Diabetic Status -19 -25 30 25 20 15 10 5 0 With diabetesWithout diabetes (n=782)(n=8,232) LIPID Study Group. N Engl J Med. 1998;339:1349-1357. % TM 1999 Professional Postgraduate Services 2003 Thomson Professional Postgraduate Services TM 1999 Professional Postgraduate Services 0 1 2 3 CHD mortality (per 1,000) Fontbonne AM et al. Diabetes Care. 1991;14:461-469. 2930-5051-7273-114115 Quintiles (pmol) of fasting plasma insulin P4 hr/wk 0.0011225 Fiber intake 15 g/1,000 kcal 0.0011126 Saturated-fat intake 5% % of subjects P value*ControlsInterventionGoals 2002 Thomson Professional Postgraduate Services 2003 Thomson Professional Postgraduate Services Finnish Diabetes Prevention Study: Reduction in Risk for Diabetes* Tuomilehto J et al. N Engl J Med. 2001;344:1343-1350. 11% 23% 0 5 10 15 20 25 InterventionControl (n=265) (n=257) * *P P50% of patients with newly diagnosed type 2 diabetes have CHD Risk for atherosclerotic events is 2- to 4-fold greater in diabetics than in nondiabetics Atherosclerosis accounts for 65% of all diabetic mortality 40% due to ischemic heart disease 15% due to other heart disease 10% due to cerebrovascular disease 2003 Thomson Professional Postgraduate Services TM 1999 Professional Postgraduate Services Framingham Heart Study 30-Year Follow-Up: CVD Events in Patients With Diabetes (Ages 35-64) 10 9 20 11 9638 19 3* 30 0 2 4 6 8 10 Age-adjusted annual rate/1,000 MenWomen Total CVDCHDCardiac failure Intermittent claudication Stroke Risk ratio Pmedian (n=1,384) 2228 LDL-C median, Hcy median, Hcy median (n=1,380) 2550 0.0 0.5 1.0 1.5 Lovastatin (L) better Placebo (P) better No. Needed to Treat 104 130 115 26 2002 Thomson Professional Postgraduate Services 2003 Thomson Professional Postgraduate Services AFCAPS/TexCAPS: RR of Acute Coronary EventsTC:HDL-C Ratio and CRP Level* *Median TC:HDL-C ratio=5.96; median CRP=0.16 mg/dL. Calculated on 5 patient-years at risk to prevent one event. RR=relative risk; CRP=C-reactive protein; CI=confidence interval. Adapted from Ridker PM et al. N Engl J Med. 2001;344:1959-1965. RR with 95% CI No. Patients with Events LP TC:HDL-Cmedian (n=1,346) 1735 TC:HDL-Cmedian, CRPmedian, CRPmedian (n=1,528) 3442 0.00.51.01.52.02.5 Lovastatin (L) better Placebo (P) better No. Needed to Treat 983 43 35 62 TM 2001, Professional Postgraduate Services 2003 Thomson Professional Postgraduate Services NonHDL-CNo. of Deaths (mg/dL)(Subjects) 160 110120130140150160 LDL-C (mg/dL) on-treatment n = 1,460 L-TAP: Majority of Patients With CHD Do Not Reach NCEP LDL-C Targets Pearson TA et al. Arch Intern Med. 2000;160:459-467. Other L-TAP data courtesy of TA Pearson. TM 2001, Professional Postgraduate Services 2003 Thomson Professional Postgraduate Services % of patients L-TAP: Majority of High-Risk Patients Without CHD Do Not Reach NCEP LDL-C Targets Pearson TA et al. Arch Intern Med. 2000;160:459-467. Other L-TAP data courtesy of TA Pearson. n = 2,285 200 LDL-C (mg/dL) on-treatment TM 2001, Professional Postgraduate Services 2003 Thomson Professional Postgraduate Services L-TAP: Patient Success in Achieving Target LDL-C Levels Pearson TA et al. Arch Intern Med. 2000;160:459-467. Nondrug therapy282 361 108 751 861 1,924 1,352 4,137 Drug therapy No. % patient success Low risk (P=0.001) High risk (P20%) 100 mg/dL in patients with CHD-related illness. TM 2001, Professional Postgraduate Services 2003 Thomson Professional Postgraduate Services Effects of Drug Therapy and Diet on Lipids * 84% reached NCEP LDL target (0.9 Het 2=0.01 2002 Thomson Professional Postgraduate Services 2003 Thomson Professional Postgraduate Services Updated Model of Lipoprotein Metabolism and Reverse Cholesterol Transport Brewer HB Jr. Arterioscler Thromb Vasc Biol. 2004;24:387-391. GI Tract Liver Remnant Chylomicron VLDL IDL LDL Oxidation Arterial Wall Macrophage Nascent PreB HDL Lipid poor ApoA-1 a-HDL X CETP Inhibitors TG CE CETP Bile Acids FC + PL HL LPL LPL ApoA-IABCA1 HL PLTP LCAT 2004 PPS 2003 Thomson Professional Postgraduate Services TM 1999 Professional Postgraduate Services Events/ 1,000 in 8 yr Assmann G et al. Am J Cardiol. 1992;70:733-737. TG (mg/dL) 44 93 132 81 0 50 100 150 220220220 TG 123 mg/dL TG 123 mg/dL Fasting TG and Risk for CHD Death: Paris Prospective Study 2003 Thomson Professional Postgraduate Services TM 1999 Professional Postgraduate Services 0 5 10 15 20 25 30 35 Gemfibrozil Placebo Incidence of cardiac events/ 1,000 person yr Adapted from Manninen V et al. Circulation. 1992;85:37-46. TG (mg/dL) 200200200200 LDL-C:HDL-C 5.0LDL-C:HDL-C 5.0 Fasting TG and Risk for CHD: Helsinki Heart Study 2003 Thomson Professional Postgraduate Services TM 1999 Professional Postgraduate Services 0.0 0.5 1.0 1.5 2.0 2.5 3.0 50100150200250300350400 Men Women RR TG (mg/dL) Castelli WP. Can J Cardiol. 1988;4:5A-10A. Impact of TG Levels on Relative Risk of CHD: Framingham Heart Study 2003 Thomson Professional Postgraduate Services TM 1999 Professional Postgraduate ServicesStampfer MJ et al. JAMA. 1996;276:882-888. Risk factor Case subjectControlP value Age, yr58.658.7Matching factor Body mass index, kg/m225.525.00.05 Alcohol consumption, drinks/day0.450.530.03 TC, mg/dL (mmol/L)229 (5.92)211 (5.46)40 mg/dL 2003 Thomson Professional Postgraduate Services 2003 Thomson Professional Postgraduate Services ADA: Treatment Decisions by LDL-C Levels* in Adults With Type 2 Diabetes InitiationLDL-CInitiationLDL-C Statuslevelgoallevelgoal With CHD, PVD, or CVD100100100100 Without CHD, PVD, and CVD100100130100 *Values represent mg/dL. Some authorities recommend initiation of drug therapy between 100 and 129 mg/dL. CHD=coronary heart disease; PVD=peripheral vascular disease; CVD=cardiovascular disease Medical nutrition Medical nutrition txtxDrug txDrug tx ADA. Diabetes Care. 2003;26(suppl 1):S83-S86. 2003 Thomson Professional Postgraduate Services 2003 Thomson Professional Postgraduate Services ADA: Order of Priorities for Treatment of Diabetic Dyslipidemia in Adults LDL-C lowering first choice: HMG-CoA reductase inhibitors (statins) second choice: bile acid binding resin or fenofibrate HDL-C raising behavioral interventions (weight loss, physical activity, smoking cessation) difficult to achieve except with niacin, which should be used with caution, or fibric acid derivative TG lowering* first priority: glycemic control fibric acid derivative (gemfibrozil, fenofibrate) statins (moderately effective at high dose in patients with TG and LDL-C) *Behavioral modification is also a first-line intervention. ADA. Diabetes Care. 2003;26(suppl 1):S83-S86. 2003 Thomson Professional Postgraduate Services 2003 Thomson Professional Postgraduate Services ADA: Order of Priorities for Treatment of Diabetic Dyslipidemia in Adults (contd) Combined hyperlipidemia first choice: improved glycemic control plus high-dose statin second choice: improved glycemic control plus statin* plus fibric acid derivative* (gemfibrozil or fenofibrate) third choice: improved glycemic control plus resin plus fibric acid derivative or improved glycemic control plus statin* plus niacin* (glycemic control must be monitored carefully) ADA. Diabetes Care. 2003;26(suppl 1):S83-S86. *Combination of statins with niacin and especially with gemfibrozil or fenofibrate may carry an increased risk for muscle toxicity. 2003 Thomson Professional Postgraduate Services 2003 Thomson Professional Postgraduate Services ADA: CHD Risk Stratification Based on Lipoprotein Levels* in Adults With Type 2 Diabetes RiskLDL-CHDL-CTG High13040400 Borderline100-12940-59150-399 Low10060150 *Values represent mg/dL. For women, HDL-C should be increased by 10 mg/dL. ADA. Diabetes Care. 2003;26(suppl 1):S83-S86. 2003 Thomson Professional Postgraduate Services First population-based study to evaluate nonHDL-C as predictor of CVD risk in patients with diabetes NonHDL-C: TC minus HDL-C (ie, all apolipoprotein B-containing atherogenic lipoproteins) VLDL, IDL, LDL, lipoprotein(a) May be useful marker of combined risk for all lipoprotein changes observed in diabetes ATP III recommends that nonHDL-C be used as secondary treatment target in people with TG 200 mg/dL, especially with diabetes or the metabolic syndrome Strong Heart Study: NonHDL-C as CVD Risk Predictor in Patients With Diabetes 2003 Thomson Professional Postgraduate Services Lu W et al. Diabetes Care. 2003;26:16-23. 2003 Thomson Professional Postgrad