Cardiovascular Complications of Diabetes

Transcription

1 VBWG Cardiovascular Complications of Diabetes Nicola Abate, M.D., F.N.L.A. Professor and Chief Division of Endocrinology and Metabolism The University of Texas Medical Branch Galveston, Texas

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3 Coronary Mortality in Patients With and Without Diabetes Mellitus 1 Men Women Survival Prior DM Prior MI Prior DM + MI Prior MI Prior DM Prior DM + MI Years Years Adjusted for age, study year, body mass index, systolic blood pressure, total cholesterol, and smoking. DM = diabetes mellitus; MI = myocardial infarction. 1. Hu G et al. J Am Coll Cardiol. 2005;45:

4 Patients With Diabetes Without Prior Myocardial Infarction (MI) Have As High a Risk of MI As Those Without Diabetes With Prior MI 4 Population Study Incidence of cardiovascular events during 7-year follow-up Incidence During Follow-Up, % No diabetes; prior MI No diabetes; no prior MI Diabetes; prior MI Diabetes; no prior MI P< No Diabetes Diabetes (n=69) (n=1,304) (n=169) (n=890) Events Per 100 Person-Year P<0.001 Haffner SM, et al. N Engl J Med. 1998;339(4):

5 Elevated Risk of CVD Prior to Clinical Diagnosis of Type 2 Diabetes Relative Risk Nondiabetic throughout the study Prior to diagnosis of diabetes After diagnosis of diabetes Diabetic at baseline Hu FB et al. Diabetes Care. 2002;25:

6 Obesity and Abdominal Adiposity Are Leading Drivers of Cardiometabolic Risk Body size Central BMI Adiposity Abdominal adiposity + Insulin resistance Glucose metabolism Uric acid metabolism Dyslipidemia Hemodynamic Inflammation/ Thrombosis PP-glucose IFG IGT T2DM Uric acid Urinary uric acid clearance TG PP lipemia HDL-C Small, dense LDL SNS activity Na retention Hypertension CRP PAI-1 Fibrinogen CORONARY HEART DISEASE Reaven G. Drugs. 1999;58(suppl):19-20.

7 Clinical Identification of the Metabolic Syndrome (NCEP)* Elevated waist circumference Men 40 in ( 102 cm) Women 35 in ( 88 cm) Triglycerides 150 mg/dl High-density lipoprotein (HDL) Men <40 mg/dl Women <50 mg/dl Blood pressure 130/ 85 mm Hg Fasting glucose 100 mg/dl *Diagnosis is established when 3 of these risk factors are present. Patients must either meet the indicated criteria for a risk factor OR be on drug treatment for that risk factor. National Institutes of Health. May NIH Publication No ; Grundy SM et al. Circulation. 2004;109: ; Grundy SM et al. Circulation. 2005;112:

8 The Evolving View of Adipose Tissue: An Endocrine Organ Old View: Inert Storage Depot Current View: Secretory/Endocrine Organ Fatty acids Glucose Fed Fasted Tg Tg Tg Muscle Multiple secretory products Fatty acids Glycerol Liver Vasculature Pancreas Lyon CJ, et al. Endocrinol. 2003;144:

9 Lipid Abnormalities in T2DM FFA/Insulin resistance Hypertriglyceridemia VLDL ApoCII/ApoCIII LPL IDL Non-HDL- Cholesterol HTLP HDL Low HDL-C Plaque LDL Small-dense LPL Apo-B

10 Does Statin Therapy Reduce CV Risk in the Metabolic Syndrome or Diabetes? VBWG Statin Placebo CHD Event Rate % WOSCOPS (n=1691) 23% P= % P=0.001 ASCOT-LLA (n=3926) Adverse CHD Events CARDS (N=2838) Mean LDL-C Reduction (%) Sattar N, et al. Circulation. 2003;108: ; Sever PS, et al. Lancet. 2003;361: ; Colhoun HM, et al. Lancet. 2004;364: ASCOT-LLA (n=3926) CARDS (N=2838) Mean LDL-C Reduction from Baseline

11 FIELD VBWG Fenofibrate Reduces CV Events in Patients with Diabetes Cumulative Risk (%) CHD Events (nonfatal MI plus CHD death) HR=0.89 (P=0.16) Placebo Fenofibrate Nonfatal MI and CHD Death *Nonfatal MI: HR=0.76 (P=0.010) CHD Death: HR=1.19 (P=0.22) * 15 Total CVD Events 15 Coronary Revascularization Cumulative Risk (%) HR=0.89 (P=0.035) Time Since Randomization (y) Keech A, et al. Lancet. 2005;366: HR=0.79 (P=0.003) Time Since Randomization (y)

12 Meta-analysis ( ) Treatment with Niacin or Fibrate Significantly Improves HDL-C, TG, and Outcomes * 15.7* Fibrates (53 trials, n=16,802) Niacin (30 trials, n=4749) Percent * -10.8* -9.7* * * HDL-C TG TC LDL-C MACE *P< vs controls; P= vs controls; P<0.001 vs controls Birjmohun RS, et al. J Am Coll Cardiol. 2005;45:

13 Effects of eicosapentaenoic acid on major coronary events in hypercholesterolemic patients: the JELIS Trial patients with hypercholesterolemia were randomized to either 1800 mg EPA with statin or statin only with a 5 year follow-up Primary endpoint was any major coronary event, and other non fatal events including unstable angina, angioplasty, stenting or CABG.

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19 VBWG

20 VBWG Multifactorial approaches in CVD prevention Lipid modification Lifestyle intervention Glucose lowering Optimal CV risk reduction BP lowering

21 VBWG Steno-2 supports aggressive multifactorial intervention in type 2 diabetes Objective: Target-driven, long-term, intensified intervention aimed at multiple risk factors compared with conventional therapy N = 160 patients with type 2 diabetes and microalbuminuria Intensive treatment targets BP <130/80 mm Hg A1C <6.5% Total-C <175 mg/dl Triglycerides <150 mg/dl Gæde P et al. N Engl J Med. 2003;348:

22 Steno-2: Effects of multifactorial intervention on macrovascular outcomes 60 VBWG Primary composite outcome (%) % RRR HR* 0.47 (95% CI ) P < 0.01 Conventional (n = 80) Longer duration of therapy may result in benefit Intensive (n = 80) 0 0 CV death, MI, stroke, revascularization, amputation *Unadjusted Total fat intake <30%, >30 min exercise 3 5x weekly, ACE inhibitor, aspirin, BP <130/80 mm Hg, total-c <175 mg/dl, TG <150mg/dL, A1C <6.5% Follow-up (months) Gæde P et al. N Engl J Med. 2003;348:

23 Lifestyle changes reduce need for drug therapy N = 3234 with IGT randomized to intensive lifestyle change, metformin 850 mg 2x/d, or placebo Lifestyle change goals Weight reduction of 7% initial body weight via low-fat, low-calorie diet Moderate-intensity physical activity 150 min/week At 3 years BP-lowering agents required Lipid-lowering agents required *P < vs other groups Lifestyle Metformin Placebo 23% 12% * * 32% 16% 31% 16% Diabetes Prevention Program Research Group. Diabetes Care. 2005;28:

24 Potential benefits of multifactorial approaches VBWG Adherence to multiple therapies is more likely if initiated simultaneously Early aggressive therapy targeting multiple risk factors could potentially have a major impact on CVD prevention Chapman RH et al. Arch Intern Med. 2005;165: Wald NJ and Law MR. BMJ. 2003;326:1419.

25 3-minute lifestyle interview: Nutrition VBWG How many servings do you eat per day: Fruits and vegetables? Whole grains? How many servings of fish do you eat per week? How often do you eat desserts? What are your favorite snack foods? Do you eat because you are hungry or because there is food around? Do you weigh the most now that you ve ever weighed? Are you interested in losing weight? Adapted from Eckel RH. AHA.

26 3-Minute lifestyle interview: Physical activity VBWG How many steps do you take each day? Do you have a regular exercise program? Do you typically take elevators or escalators or climb the stairs? Do you park as close as you can to your destination? What limits your level of physical activity? Have you been evaluated for this? Would you like to become more active? Adapted from Eckel RH. AHA.

27 ABCs of CVD prevention VBWG A B C D E Aspirin ACE inhibition A1C control BP control Cholesterol lowering Diet Don t smoke Exercise Adapted from Cohen JD. Lancet. 2001;357:972-3.

28 The Steno-2 Study Multiple CV Risk Factor Management in Diabetes: The Best, and Not Enough Primary Composite End-Point* (%) n=160; Follow-Up=7.8 years Aggressive treatment of Dyslipidemia Hypertension Hyperglycemia Microalbuminuria with Conventional Therapy Intensive Therapy Months of Follow-Up angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or combination Prothrombotic state (aspirin) Event Rate=24% *Death from CV causes, nonfatal myocardial infarction, coronary artery bypass graft, percutaneous coronary interventions, nonfatal stroke, amputation resulting from ischemia, or surgery for peripheral atherosclerotic artery disease. Behavior modification and pharmacologic therapy. Primary composite end-point: conventional therapy (44%) vs intensive therapy (24%). Gaede P, et al. N Engl J Med. 2003;348:

29 Conclusions Patients with diabetes have excessive risk for CVD: primary cause of morbidity and mortality in this patient population. Comprehensive risk management is effective in reducing cardiovascular events in patients with type 2 diabetes. Early intervention may reduce the substantial residual risk we observe even when comprehensive cardiovascular risk intervention is adopted.