Ten Year Risk for CVD Event by Systolic HTN and CVD Risk Factors (Where s Age?)

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1 Prevention and Treatment of CVD in Older Patients with Diabetes and Pre Diabetes: Hypertension and Dyslipidemia ASP Workshop on Diabetes Mellitus and Cardiovascular Disease in Older Adults Pentagon City Ritz Carlton April 4 5, 2013 Robert H. Eckel, MD Professor of Medicine Professor of Physiology and Biophysics Charles A. Boettcher II Chair in Atherosclerosis University of Colorado Anschutz Medical Campus Aurora, CO Ten Year Risk for CVD Event by Systolic HTN and CVD Risk Factors (Where s Age?) Anderson KM et al, Circulation 83:356,

2 Effect of Treatment of Hypertension and Relative Risk of CVA in Older Adults (Mean 83 Yrs): Indana Group Meta Analysis Where s diabetes, only 14%? Guefflier F et al, Lancet 353:793, 1999 Adjusted Hazard Ratios with Active Treatment vs. Placebo in 60+ Year Old Patients with Systolic Hypertension ±Diabetes: Syst Euro Tuomilehto J et al, NEJM, 340: ,

3 Hazard Ratios for 10 Year Risk of CVD Events in 782 Adults >65 Years with Diabetes: Cardiovascular Health Study Risk Factor Basic Model + Biomarkers + Subclinical Measures Systolic BP 1.15 ( ) 1.15 ( ( Total Cholesterol 1.17 ( ) 1.18 ( ) 1.16 ( ) HDL Cholesterol 0.79 ( ) 0.82 ( ) 0.86 ( ) Mukamal KJ et al, Diabetologia 56:275, 2013 Kaplan Meier Estimates of Major CVD Events by Ramipril vs. Placebo In 66 Year Old Hypertensive Subjects: HOPE HOPE Investigators, NEJM, 342:145,

4 Effect of Amlodipine vs. Atenolol + ACEI vs. Thiazide in Patients with Hypertension on CVD Events and Related Outcomes: ASCOT BPLA Dahlof B et al, Lancet, 366: 895, 2005 Age > 65 4

5 RRs and 95% CIs for Amlodipine/Chlorthalidone CVD Outcomes in ALLHAT Participants ± Metabolic Syndrome Black HR et al, Diabetes Care 31:353, 2008 RRs and 95% CIs for Lisinopril/Chlorthalidone CVD Outcomes in ALLHAT Participants ± Metabolic Syndrome Black HR et al, Diabetes Care 31:353,

6 For those without metabolic syndrome, the rate of newly diagnosed type 2 diabetes was: chlorthalidone 7.7% amlodipine 4.2% lisinopril 4.7% (P < 0.05 for both comparisons) Black HR et al, Diabetes Care 31:353, 2008 Circulation Cardiovascular Qual Outcomes 5:153,

7 The findings suggest that thiaziderelated incident diabetes has less adverse long term CVD impact than incident diabetes that develops while on other antihypertensive medications. Barzilay JI et al, Circulation Cardiovascular Qual Outcomes 5:153, 2012 Important Issues Related to Treatment of Lipids/Lipoprotein Disorders to Reduce CVD Risk in Older Patients, Diabetes Included The risk for CVD related to total and LDL C is reduced after age 65 and becomes inversely related after 80. Selection bias (survival)? Declining levels in LDL C in most patients in later years? Subclinical CVD, but a triggering event is needed? Risk for drug related AEs higher Includes statin induced myopathy Statin induced cognitive impairment? Not seen in older patients in PROSPER (age 70 82), HPS (age 70 80) or Jupiter (age range not stated) 7

8 Effect of Pravastatin on Major CVD Events/Death in Year Old Patients ± Diabetes: PROSPER Benefit was for AMI, AMI Death not CVA; and in men not women! Shepherd J et al, Lancet 360:1623, 2002 Simvastatin ±Fenofibrate and CVD Events in Patients with T2DM: ACCORD Lipid Ginsberg HN et al, NEJM, 362:1563,

9 Effect of Fenofibrate on CVD Events in Patients with T2DM: FIELD Keech A et al, Lancet, 366:1849, 2006 CVD Benefit of Rosuvastatin in Primary Prevention (hscrp 2.0 mg/l): Jupiter Ridker PM et al, NEJM, 359:2195,

10 Jupiter, Rosuvastatin and Glucose Intolerance Ridker PM et al, Lancet 380: Jupiter, Rosuvastatin and Glucose Intolerance Ridker PM et al, Lancet 380:

11 Statins and the Incidence of New Onset Diabetes Sattar N et al, Lancet 375:735, 2010 Jupiter: DM Incidence vs. CVD Benefit In analysis limited to the n=486 who developed diabetes during follow up (270 on rosuvastatin vs 216 on placebo. HR 1.25 for T2DM, 95% CI , p=0 01) Point estimate of CVD risk reduction associated with statin therapy (HR 0.63, 95% CI ) Consistent with that for the trial as a whole (0.56, ) 11

12 Siyambalapitiya S et al, Diabetes Care 30:2025, 2007 Age for Statins in Patients with Diabetes Based on Risk: Framingham Heart Study Study population, n = 60,258 patients with diabetes Age range: years From this group, n = 11,005 patients Not taking any lipid lowering agent No ASCVD Thus, eligible for primary CVD prevention Siyambalapitiya S et al, Diabetes Care 30:2025,

13 CVD Risk for Primary Prevention in Men with Diabetes: Framingham Siyambalapitiya S et al, Diabetes Care 30:2025, 2007 CVD Risk for Primary Prevention in Women with Diabetes: Framingham Siyambalapitiya S et al, Diabetes Care 30:2025,

14 Age of Transition in CVD Risk with Diabetes: Framingham Risk Men Women Low Moderate (yr.) Moderate High (yr.) Moderate Risk Cutoff Sensitivity (%) Specificity (%) High Risk Cutoff Sensitivity (%) Specificity (%) Siyambalapitiya S et al, Diabetes Care 30:2025, 2007 Proportional Effects on Major CVD Events per mmol/l Reduction in LDL C by Baseline Risk Factors in Participants with Diabetes: CTTC Meta Analysis Cholesterol Treatment Trialists (CTT) Collaborators, Lancet, 371:117,

15 Issues Related to Diabetes, Hypertension, Dyslipidemia and CVD in Older Adults Diabetes and Hypertension What level of BP elevation should be treated? How much lowering of BP should be accomplished? What drugs should be used? Side effects, how many and how severe? Diabetes and Dyslipidemia How important is a semi aggressive lifestyle intervention? Statins What about age >80 years? Is there an age related cognitive impairment? What about potential beneficial pleiotropic effects? Renal disease progression? Cancer? Infection? What about new onset T2DM? Are triglycerides and HDL C important to treat? Thank You! 15

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