1 / 30

Discussion

Discussion. Why is glucose control (intensive Rx) not more Closely related to CAD risk?.

delores
Download Presentation

Discussion

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Discussion Why is glucose control (intensive Rx) not more Closely related to CAD risk? • Glycemia may not be all bad! – While it may promote atherosclerosis generally, plaques so formed may be more stable (less vulnerable). – Result a weaker than anticipated association with clinical events and a lower benefit for glycemic improvement than anticipated.

  2. Possible Basis for Hypothesis That Glycemia May Lead to More Stable Plaques • Glycemia strongly related to LEAD (stable stenosis) and weakly related to CAD events (plaque rupture) • Diabetes complications are often sclerotic, e.g. connective tissue, kidney, fibrous proliferative retinopathy

  3. Possible Basis for Hypothesis That Glycemia May Lead to More Stable Plaques • Concentric v eccentric morphology • “Negative remodelling” • Enhanced cross linking AGE formation • Enhanced SMC proliferation • Decreased lipid content

  4. Atherogenesis in Diabetes:The “Black Box” • Abnormalities of apoprotein and lipoprotein particle distribution (“diabetic dyslipidemia”) • Procoagulant state • Insulin resistance and hyperinsulinemia • Glycation and advanced glycation of proteins in plasma and arterial wall • “Glycoxidation” and oxidation • Hormone, growth factor, and cytokine enhanced smooth muscle cell proliferation and foam cell formation Blerman EL. Arterioscler Thromb. 1992; 12(6): 647-656.

  5. Figure 2 Incidence density of coronary artery disease and overt nephropathy by estimated Glucose Disposal Rate at baseline n/1000 person years eGDR tertiles

  6. SCREENING FOR DIABETES Screening Patient has CHD Diabetes status? Patient has diabetes ? CAD status Annual • ECG • Clinical history • Ankle-brachial index measurement • Review the need for cardiac testing Yes Known diabetic? • Check risk factors • Check who is controlling the diabetes No diabetes determined in past 3 years? No Check fasting plasma glucose level (HbA1c) or order oral glucose tolerance test Yes Advise a recheck every 1-3 years

  7. PREVENTION CHECKLIST FOR ALL DIABETIC PATIENTSWHO HAVE CORONARY HEART DISEASE Who is looking after the diabetes? If no one is, assume responsibility personally or make referral Is blood pressure less than 130/80mg? If not, instigate or modify treatment or contact the primary care provider Is LDL cholesterol less than 100mg/dl? If not, instigate or modify treatment or contact the primary care provider Is HbA1c over 8.0%? If yes, instigate or modify treatment or contact the primary care provider or diabetologist Is patient a current smoker? If yes, instigate or modify cessation strategy or contact the primary care provider

  8. Benefits of Beta BlockersPost-MI in Diabetes

  9. SCREENING OF DIABETIC PATIENTS FOR CORONARY ARTERY DISEASE Benefits Implementation of prevention programs Early initiation of anti-ischemic medications Identification of patients for whom revascularization is appropriate Method Clinical history Annual resting ECG Annual ABI EBT (?)

  10. INDICATIONS FOR CARDIAC TESTING IN DIABETIC PATIENTSJOINT ACC/ADA RECOMMENDATIONS Typical or atypical cardiac symptoms Resting ECG suggestive of ischemia or infarction Peripheral or carotid occlusive arterial disease Sedentary lifestyle, age  35 years and plans to begin a vigorous exercise program Two or more of the following risk factors in addition to diabetes: Total cholesterol  240 mg/dl, LDL cholesterol  160 mg/dl, or HDL cholesterol <35mg/dl Blood pressure over 140/90mmHg Smoking Family history of premature coronary artery disease Positive microalbuminuria or macroalbuminuria test

  11. METHODS OF CARDIAC TESTING IN DIABETIC PATIENTSJOINT ADA/ACC RECOMMENDATIONS High probability of ischemia (e.g. Q wave on ECG) Lower probability of ischemia (e.g. two risk factors only) Stress perfusion imaging or stress echocardiography Regular stress test (EBT not currently recommended)

  12. Lipid Lowering 1o Prevention Diabetes Study Intervention Outcome HelsinkiGemfibrozil 68%  CHD death/MI (p=0.19) SendCapBezafibrateCarotid ultrasound-NS MI/ischemia-68% (p<0.01) AFCaps/Lovastatin21% CHD death/MI TexCapsor unstable angina

  13. Lipid Lowering 2o Prevention Diabetes Study Intervention Outcome 4SSimvastatin43%  mortality, p=0.09 55% MI/CHD death, p=0.002 CARE Pravastatin13%  CHD death/MI, p=NS 25%  “Expanded”, p=0.05 LIPID Pravastatin19%  CHD death, p=NS VAHIT Gemfibrozil24%  CHD death/MI, p=NS BIP Bezafibrate9.4%  CHD death/MI, p=NS DAIS Fenofibrate40%  Lumen diameter, p=0.03 42%  stenosis, p=0.02

  14. LIPID-MODULATING AGENTS AND DIABETES

  15. BP Lowering Diabetes Study Intervention Outcome (% reduction) HDFP “stepped care”Mortality Fasting > 140mg/dl  3.2 1 hr PG > 205mg/dl  17.9 h/o diabetes  4.9 SHEP chlorthalidone stroke  22* Atenolol/Reserpine CHD death/MI  54* CVD  34* ABCDNisoldipineMI  700* v Enalapril FACET Fosinopril CVD events  51* v Amlodipine

  16. BP Lowering Diabetes (cont.) Study Intervention Outcome (% reduction) UKPDS Captropil, Atenolol Diabetes events  24%** 150/85 v 180/105 Diabetes death  32%* Mortality  18% HOTFelodipine <90, <85, <80 90 v 80 mortality  43% CVD  51%* SystEurNitrendipine plus Total mortality  55%* enalpril/hydrochlorthazide CBVD  73% v placebo CAD  63% CAPP Captopril v Diuretic/Bblocker Fatal CVD  40%* Nonfatal MI/CVA All Stroke  24% All MI  76%**

  17. BLOOD PRESSURE TREATMENT IN DIABETES The goal is 130/85mmHg (or 130/80mmHg).

  18. MANAGEMENT OF TYPE 2 DIABETES FROM A CARDIOLOGIC VIEWPOINT HbA1c  8.0 percent (upper limit of normal is 6.0%) despite diet and exercise TZD Non-obese patients Sulfonylurea Obese patients Metformin BARI 2D addressing the issue, as to how best to treat the diabetes to benefit the heart. Insulin sensitization or provision? Combination sulfonylurea ± metformin± TZD ? Insulin therapy ± TZD

  19. SUMMARYREDUCTION OF CVD RISK IN DIABETES Constant surveillance of all CHD patients for diabetes and the repeated screening of all diabetic patients for CHD. Vigorous risk factor management (blood pressure goal of 130/80mmHg, LDL cholesterol levels of less than 100 mg/dl) is indicated for the majority of diabetic subjects, as is adequate glycemic control (HbA1c < 7.0-8.0%). Beta-blockers, ACE inhibitors and aspirin should also be used as vigorously as they are in the general population. Of fundamental importance, however, is the assumption of responsibility for these aspects of care.

  20. 4S: Diabetic Patients P(n-96) S(n=105) RR p-value # K-M # K-M Total24 0.69 15 0.84 0.56 0.08 Mortality CHD 17 0.75 12 0.87 0.64 0.23 Mortality CHD Death or 43 0.52 24 0.75 0.46 0.002 MI Diabetes, May 1995; 125

  21. CONCLUSIONS • The link between diabetes and atherosclerosis is multifactorial and varies by diabetes type. Nonetheless, insulin resistance (and ? hyperinsulinemia) is a frequent finding. • Future prevention of CVD in diabetic subjects may depend more on control of lipids and blood pressure than on glycemic control.

  22. Proportion of Subjects Without Diabetes During the Trial Click for larger picture

  23. WHITEHALL STUDY;NIDDM AND CVD RISK • 17,051 NGT; 999 > 95 pc; 56 – New NIDDM, and 121 Previously dx NIDDM Men Only • 15 yr Mortality, Relative Risk CHD All CHD BS > 95th pc 1.2 (1.0-1.5) 1.2 (1.0-1.5) New dx 2.6 (1.6-4.2) 2.2 (1.4-3.5) Known  2 yrs 2.3 (0.9-6.1) 2.5 (1.1-5.6) Known 3-6 yrs 2.2 (1.1-4.7) 2.4 (1.3-4.4) Known  7 yrs 2.5 (1.2-5.4) 1.9 (0.9-3.9) Diabetologia, 1998; 31: 737-740.

  24. Aggregate endpoints by treatments and relative risk EndpointIntensive Conventional RR for Intensive Treatment (N=2729) (N=1138) Any diabetes endpoint 963 438 0.88 (0.79-0.99) Diabetes-related death 285 129 0.90 (0.73-1.11) All-cause mortality 489 213 0.94 (0.8-1.10) MI 387 186 0.84 (0.71-1.00) Stroke 148 55 1.11 (0.81-1.51) Amputation/ PVD death 29 18 0.65 (0.36-1.18) Microvascular 225 121 0.75 (0.60-0.93) Lancet; Vol 352: Sept. 12, 1998; 837-53

  25. Click for larger picture

  26. In-hospital MI case fatality rate by sex, year, and diabetes statusMinnesota Heart Survey • Men Women • DiabeticNondiabetic DiabeticNondiabetic • Year Rate/100 Rate/100 Rate/100 Rate/100 • 1970 21.4 (42) 21.6 (521) 38.8 (38) 25.7 (195) • 17.6 (81) 13.7 (552) 36.6 (51) 16.6 (179) • 18.0 (105) 10.1 (555) 16.2 (67) 16.6 (194) • Sprafka JM, et al. Diabetes Care 1991; 14(7): 537-43.

  27. The Survival Curve for CAD by IR Status Percent free of event Follow-up (years)

  28. Diagnosis of Diabetes Mellitus and Impaired Glucose Tolerance by Oral Glucose Tolerance Test ADA and WHO criteria Diabetes mellitus IGT Fasting  140 mg/dL < 140 mg/dL* or or OGTT  200 mg/dL 140-199 mg/dL (2-h glucose) *Venous plasma American Diabetes Assoc. Medical Management of Non-insulin-Dependent (Type II) Diabetes; 1994; 1-99.

  29. Angiographic Changes in Placebo and Fenofibrate Groups DAIS. Lancet 2001; 357: 905-910. Click for larger picture

More Related