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Cardiovascular Disease and the Patient with Diabetes and Metabolic Syndrome   Nathan D. Wong, PhD, FACC, FAHA Professor an...
Presenter Disclosure <ul><li>Dr. Wong has received research support through Bristol-Myers Squibb, Novartis, and Forest Lab...
Presentation Objectives <ul><li>Review the epidemiology implicating metabolic syndrome and diabetes in cardiovascular risk...
Diagnosed Diabetes in the US: 2008 http://apps.nccd.cdc.gov/brfss/list.asp?cat=DB&yr=2008&qkey=1363&state=All CDC BRFSS: S...
Prevalence of physician-diagnosed diabetes in Adults age 20 and older by race/ethnicity and sex (NHANES: 2005-2006).  Sour...
The Continuum of CV Risk in Type 2 Diabetes Adapted from American Diabetes Association.  Diabetes Care . 2003;26:3160-3167...
Diagnostic Criteria for Metabolic Syndrome: Modified NCEP ATP III AHA/NHLBI Scientific Statement; Circulation 2005; 112:e2...
IDF Criteria: Abdominal Obesity and Waist Circumference Thresholds <ul><li>AHA/NHLBI criteria: ≥ 102 cm (40 in) in men, ≥ ...
Prevalence of the Metabolic Syndrome Among US Adults NHANES 1988-1994 Age (years) Ford E et al.  JAMA . 2002(287):356. 199...
Diabetes and CVD <ul><li>Atherosclerotic complications responsible for  </li></ul><ul><ul><li>80% of mortality among patie...
Risk of Cardiovascular Events in Patients  with   Diabetes:  Framingham Study <ul><li>  Age-adjusted </li></ul><ul><li>  B...
Diabetes as a CHD Risk Equivalent:  Type 2 DM and CHD  7-Year Incidence of Fatal/Nonfatal MI  (East West Study) No Diabete...
Cardiovascular Disease (CVD) and Total Mortality: U.S. Men and Women Ages 30-74 * p<.05, ** p<.01, **** p<.0001 compared t...
Odds of CVD Stratified by CRP Levels in U.S. Persons (Malik and Wong et al., Diabetes Care 2005; 28: 690-3) <ul><li>* p<.0...
Example of Significant Coronary Calcification from Multidetector CT (Siemens Sensation 64) scanner
10-Year CHD Event Rates (per 1000 person years) by Calcium Score by CAC Categories in  Subjects with Neither MetS nor DM, ...
Under-Treatment of Cardiovascular Risk Factors Among U.S. Adults with Diabetes <ul><ul><li>NHANES Survey 2001-2002, 532 (p...
Summary of Care:  ABC's for Providers A A1c Target  Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigare...
Summary of Care:  ABC's for Providers A A1c Target  Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigare...
A1c Target Aspirin Therapy <ul><li>A1c Target : In persons with diabetes, glucose lowering to achieve normal to near norma...
Type 2 Diabetes:  A1C Predicts CHD CHD Mortality Incidence (%) in 3.5 Years All CHD Events Incidence (%) in 3.5 Years A1C=...
UKPDS Relative Risk Reduction  for Intensive vs. Less Intensive Glucose Control % relative risk reduction P=0.03 P<0.01 P<...
UKPDS Metformin Sub-Study:  CHD Events UKPDS 34, Lancet 352: 854, 1998 n= 411 951 342 411 342 #Events 73 139 39 36 16 Myoc...
Recent Trials Show No Reduction in CV Events with  More Intensive Glycemic Control 1 ACCORD Study Group.  N Engl J Med.  2...
Was Intensive Glycemic Control Harmful?  A closer look at ACCORD AND ADVANCE <ul><li>ACCORD was discontinued early due to ...
2009 ADA/AHA/ACC Statement Recommendations <ul><li>Goal of A1c<7% remains reasonable  </li></ul><ul><ul><li>for uncomplica...
Summary of Care:  ABC's for Providers A A1c Target  Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigare...
Prevalence of Hypertension* in Adults with Diabetes: NHANES III 1988-1994 % with Hypertension Geiss LS, et al. Am J Prev M...
HTN Control Rate Remains Poor in US Adults with  MetS and DM from NHANES 2003-2004 (Wong ND et al., Arch Intern Med 2007) ...
UKPDS: Effects of Tight vs. Less-Tight Blood Pressure Control UK Prospective Diabetes Study Group.  BMJ.  1998; 317:703-713.
HOT Trial:  Effect of BP Control on CV Event Rate Hansson L et al.  Lancet . 1998;351:1755-1762. Diastolic Blood Pressure ...
ACCORD: Effects of Intensive BP Control (NEJM 2010: 362: 1575-85) <ul><li>4733 participants with type 2 DM randomly assign...
Scientific Statements:  Diabetes, CV Disease and Hypertension <ul><li>JNC VII Report on Diabetic Hypertension </li></ul><u...
Summary of Care:  ABC's for Providers A A1c Target  Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigare...
LDL-C as a Predictor of CAD  in Patients with Diabetes Hazard ratio LDL-C quartile mean Adapted with permission from Howar...
CARDS: Primary Endpoint Relative Risk Reduction 37%  (95% CI: 17-52) Years 328 305 694 651 1074 1022 1361 1306 1392 1351 A...
HPS Substudy:  First Major Vascular Event by LDL-C and Prior Diabetes Status Simvastatin (10,269) Placebo (10,267) Rate ra...
Reducing CVD Risk with Statin Therapy in Patients with Diabetes <ul><li>Number needed to treat to prevent 1 major CVD even...
Lipid Goals for Persons with Metabolic Syndrome and DM (Grundy et al., 2005) <ul><li>LDL-C targets, ATP III guidelines </l...
<ul><li>Non-HDL:  Secondary Target </li></ul><ul><li>Non-HDL = TC – HDL </li></ul><ul><li>Non-HDL: secondary target of the...
<ul><li>Management of Low HDL </li></ul><ul><li>LDL is primary target of therapy  </li></ul><ul><li>Weight reduction and i...
ACCORD Lipid Study Results (NEJM 2010; 362: 1563-74) <ul><li>5518 patients with type 2 DM treated with open label simvasta...
Summary of Care:  ABC's for Providers A A1c Target  Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigare...
Smoking Cessation <ul><li>What you do does matter. Physicians who intervene influence cigarette smoking behavior. </li></u...
EFFICACY OF SMOKING CESSATION INTERVENTIONS (1 YEAR QUIT RATES) ACUPUNCTURE    ---- HYPNOSIS    ---- PHYSICIAN ADVICE     ...
The 5 “A’s” for Effective  Smoking Intervention <ul><li>ASK  about smoking </li></ul><ul><li>ADVISE  to quit </li></ul><ul...
Summary of Care:  ABC's for Providers A A1c Target  Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigare...
CHD Mortality Rates (by Degree of Glucose Tolerance) Incidence rate/1000 *Indicates patients known to have diabetes prior ...
Most Cardiovascular Patients Have Abnormal Glucose Metabolism 35% 31% 34% 37% 18% 45% 37% 27% 36% GAMI n = 164 EHS n = 192...
D iabetes  P revention  P rogram:  Protocol Design
D iabetes  P revention  P rogram:  Reduction in Diabetes Incidence
Benefit of Comprehensive, Intensive Management: STENO 2 Study <ul><li>Treatment Goals: </li></ul><ul><ul><li>Intensive TLC...
Summary of Care:  ABC's for Providers A A1c Target  Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigare...
Metabolic Syndrome: Lifestyle Management: Obesity / Physical Activity <ul><li>Obesity / weight management :  low fat – hig...
 
Physical Inactivity: A Call to Arms 10,000 Steps Daily 30 minutes most days
Physical Activity  Recommendations <ul><li>Aerobic exercise a minimum of 30 minutes, 5 times weekly </li></ul><ul><li>Opti...
Summary of Care:  ABC's for Providers A A1c Target  Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigare...
ADA Nutritional Guidelines <ul><li>Patients with pre-diabetes should receive individualized Medical Nutrition Therapy (MNT...
Therapeutic Lifestyle Changes Nutrient Composition of TLC Diet <ul><li>Nutrient Recommended Intake </li></ul><ul><li>Satur...
Effect of Mediterranean-Style Diet  in the Metabolic Syndrome <ul><li>180 pts with metabolic syndrome randomized to Medite...
Conclusions <ul><li>Metabolic syndrome and diabetes are associated with increased levels of atherosclerosis and cardiovasc...
Conclusions (cont.) <ul><li>Clinical management emphasizes achievement of BP and lipid goals, glycemic control, and antipl...
Thank you for your attention! Now Published from Informa Healthcare  … For more information visit our website at www.heart...
Question #1 <ul><li>Which of the following statements is true? </li></ul><ul><ul><li>Diabetes prevalence is higher in Afri...
Question #2 <ul><li>What  are the recommended target levels for LDL-C and BP for most uncomplicated patients with DM? </li...
Question #3 <ul><li>Diabetes has been considered a CHD risk equivalent because: </li></ul><ul><ul><li>Nearly all persons w...
Question #4 <ul><li>Recent large clinical trials such as ACCORD and ADVANCE suggest: </li></ul><ul><ul><li>Aggressive glyc...
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Cardiovascular Disease and the Patient with Diabetes and ...

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Cardiovascular Disease and the Patient with Diabetes and ...

  1. 1. Cardiovascular Disease and the Patient with Diabetes and Metabolic Syndrome Nathan D. Wong, PhD, FACC, FAHA Professor and Director Heart Disease Prevention Program Division of Cardiology University of California, Irvine President, American Society for Preventive Cardiology
  2. 2. Presenter Disclosure <ul><li>Dr. Wong has received research support through Bristol-Myers Squibb, Novartis, and Forest Laboratories through the University of California, Irvine </li></ul>
  3. 3. Presentation Objectives <ul><li>Review the epidemiology implicating metabolic syndrome and diabetes in cardiovascular risk </li></ul><ul><li>Discuss the clinical trial evidence for the role of lifestyle management, glycemic, lipid, and blood pressure control. </li></ul><ul><li>Address the ABCs of lifestyle and clinical management of metabolic syndrome and diabetes aimed to reduce cardiovascular disease risk. </li></ul>
  4. 4. Diagnosed Diabetes in the US: 2008 http://apps.nccd.cdc.gov/brfss/list.asp?cat=DB&yr=2008&qkey=1363&state=All CDC BRFSS: Self-Reported Diabetes: 8.2% Nationwide 4 – 6% 6 – 8% 8 – 10% 10 – 12%
  5. 5. Prevalence of physician-diagnosed diabetes in Adults age 20 and older by race/ethnicity and sex (NHANES: 2005-2006). Source: NCHS and NHLBI. NH – non-Hispanic.
  6. 6. The Continuum of CV Risk in Type 2 Diabetes Adapted from American Diabetes Association. Diabetes Care . 2003;26:3160-3167. Tsao PS, et al. Arterioscler Thromb Vasc Biol. 1998;18:947-953. Hsueh WA, et al. Am J Med . 1998;105(1A):4S-14S. American Diabetes Association. Diabetes Care . 1998;21:310-314.
  7. 7. Diagnostic Criteria for Metabolic Syndrome: Modified NCEP ATP III AHA/NHLBI Scientific Statement; Circulation 2005; 112:e285-e290. ≥ 3 Components Required for Diagnosis Components Defining Level Increased waist circumference Men Women ≥ 40 in ≥ 35 in Elevated triglycerides ≥ 150 mg/dL (or Medical Rx) Reduced HDL-C Men Women <40 mg/dL <50 mg/dL (or Medical Rx) Elevated blood pressure ≥ 130 / ≥ 85 mm Hg (or Medical Rx) Elevated fasting glucose ≥ 100 mg/dL (or Medical Rx)
  8. 8. IDF Criteria: Abdominal Obesity and Waist Circumference Thresholds <ul><li>AHA/NHLBI criteria: ≥ 102 cm (40 in) in men, ≥ 88 cm (35 in) in women </li></ul><ul><li>Some US adults of non-Asian origin with marginal increases should benefit from lifestyle changes. Lower cutpoints (≥ 90 cm in men and ≥ 80 cm in women) for Asian Americans </li></ul>Alberti KGMM et al. Lancet 2005;366:1059-1062. | Grundy SM et al. Circulation 2005;112:2735-2752. Men Women Europid ≥ 94 cm (37.0 in) ≥ 80 cm (31.5 in) South Asian ≥ 90 cm (35.4 in) ≥ 80 cm (31.5 in) Chinese ≥ 90 cm (35.4 in) ≥ 80 cm (31.5 in) Japanese ≥ 85 cm (33.5 in) ≥ 90 cm (35.4 in)
  9. 9. Prevalence of the Metabolic Syndrome Among US Adults NHANES 1988-1994 Age (years) Ford E et al. JAMA . 2002(287):356. 1999-2002 Prevalence by IDF vs. NCEP Definitions (Ford ES, Diabetes Care 2005; 28: 2745-9) (unadjusted, age 20+) NCEP : 33.7% in men and 35.4% in women IDF: 39.9% in men and 38.1% in women Prevalence (%) 0 5 10 15 20 25 30 35 40 45 20-29 30-39 40-49 50-59 60-69 > 70 Men Women
  10. 10. Diabetes and CVD <ul><li>Atherosclerotic complications responsible for </li></ul><ul><ul><li>80% of mortality among patients with diabetes </li></ul></ul><ul><ul><li>75% of cases due to coronary artery disease (CAD) </li></ul></ul><ul><ul><li>Results in >75% of all hospitalizations for diabetic complications </li></ul></ul><ul><li>50% of patients with type 2 diabetes have preexisting CAD. (This number may be less now that more younger people are diagnosed with diabetes.)  </li></ul><ul><li>1/3 of patients presenting with myocardial infarction have undiagnosed diabetes mellitus </li></ul>Lewis GF. Can J Cardiol . 1995;11(suppl C):24C-28C Norhammar A, et.al. Lancet 2002;359;2140-2144
  11. 11. Risk of Cardiovascular Events in Patients with Diabetes: Framingham Study <ul><li> Age-adjusted </li></ul><ul><li> Biennial Rate Age-adjusted </li></ul><ul><li> Per 1000 Risk Ratio </li></ul><ul><li>Cardiovascular Event Men Women Men Women </li></ul><ul><li>Coronary Disease 39 21 1.5** 2.2*** </li></ul><ul><li>Stroke 15 6 2.9*** 2.6*** </li></ul><ul><li>Peripheral Artery Dis. 18 18 3.4*** 6.4*** </li></ul><ul><li>Cardiac Failure 23 21 4.4*** 7.8*** </li></ul><ul><li>All CVD Events 76 65 2.2*** 3.7*** </li></ul><ul><li>Subjects 35-64 36-year Follow-up **P<.001,***P<.0001 </li></ul>_________________________________________________________________ _________________________________________________________________
  12. 12. Diabetes as a CHD Risk Equivalent: Type 2 DM and CHD 7-Year Incidence of Fatal/Nonfatal MI (East West Study) No Diabetes Diabetes 3.5% 18.8% 20.2% 45.0% P <0.001 P <0.001 7-year incidence rate of MI CHD=coronary heart disease; MI=myocardial infarction; DM=diabetes mellitus Haffner SM et al. N Engl J Med . 1998;339:229-234.
  13. 13. Cardiovascular Disease (CVD) and Total Mortality: U.S. Men and Women Ages 30-74 * p<.05, ** p<.01, **** p<.0001 compared to none * *** *** *** ** *** *** *** *** *** *** Malik and Wong, et al., Circulation 2004; 110: 1245-1250. (Risk-factor adjusted Cox regression) NHANES II Follow-Up (n=6255) ***
  14. 14. Odds of CVD Stratified by CRP Levels in U.S. Persons (Malik and Wong et al., Diabetes Care 2005; 28: 690-3) <ul><li>* p<.05, **p<.01, **** p<.0001 compared to no disease, low CRP </li></ul><ul><li>CRP categories: >3 mg/l (High) and < 3 mg/L (Low) </li></ul><ul><li>age, gender, and risk-factor adjusted logistic regression (n=6497) </li></ul>* * *** ** *** Odds Rat io
  15. 15. Example of Significant Coronary Calcification from Multidetector CT (Siemens Sensation 64) scanner
  16. 16. 10-Year CHD Event Rates (per 1000 person years) by Calcium Score by CAC Categories in Subjects with Neither MetS nor DM, MetS only, or DM Coronary Heart Disease Coronary Artery Calcium Score 0 1-99 100-399 400+ CHD events per 1000 person years Diabetes MetS Neither MetS/DM Malik and Wong et al. (AHA 2009)
  17. 17. Under-Treatment of Cardiovascular Risk Factors Among U.S. Adults with Diabetes <ul><ul><li>NHANES Survey 2001-2002, 532 (projected to 15.2 million) or 7.3% of adults aged >/=18 years had diabetes </li></ul></ul><ul><ul><li>50.2% not at HbA1c goal <7% </li></ul></ul><ul><ul><li>64.6% not at LDL-C goal <100 mg/dl </li></ul></ul><ul><ul><li>52.3% not at recommended HDL-C >/=40 (M), >/=50 (F) </li></ul></ul><ul><ul><li>48.6% not at recommended triglycerides <150 mg/dl </li></ul></ul><ul><ul><li>53% not at BP goal of <130/80 mg/dl </li></ul></ul><ul><ul><li>Overall, only 5% of men and 12% of women at goal for HbA1c, BP, and LDL-C simultaneously </li></ul></ul>Malik S, Wong ND et al. Diab Res Clin Pract 2007;77:126-33.
  18. 18. Summary of Care: ABC's for Providers A A1c Target Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigarette Smoking Cessation D Diabetes and Pre-Diabetes Management E Exercise F Food Choices
  19. 19. Summary of Care: ABC's for Providers A A1c Target Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigarette Smoking Cessation D Diabetes and Pre-Diabetes Management E Exercise F Food Choices
  20. 20. A1c Target Aspirin Therapy <ul><li>A1c Target : In persons with diabetes, glucose lowering to achieve normal to near normal plasma glucose, as defined by the HbA1c<7% </li></ul><ul><li>Aspirin Daily : Patients with type 2 DM >40 years of age or with prevalent CVD, OR those with metabolic syndrome without DM who are at intermediate or higher risk (e.g., >=10% 10-year risk of CHD) </li></ul>
  21. 21. Type 2 Diabetes: A1C Predicts CHD CHD Mortality Incidence (%) in 3.5 Years All CHD Events Incidence (%) in 3.5 Years A1C=hemoglobin A1C * P <0.01 vs lowest tertile ** P <0.05 vs lowest tertile 0 2 4 6 8 10 12 Low <6% High >7.9% * Middle 6-7.9% 0 5 10 15 20 25 Middle 6-7.9% High >7.9% ** Low <6% Adapted with permission from Kuusisto J et al. Diabetes . 1994;43:960-967.
  22. 22. UKPDS Relative Risk Reduction for Intensive vs. Less Intensive Glucose Control % relative risk reduction P=0.03 P<0.01 P<0.01 P=0.05 P=0.02 UKPDS Group. Lancet. 1998;352:837-853. Over 10 years, HbA 1c was 7.0% (6.2-8.2) in the intensive group (n=2,729) compared with 7.9% (6.9-8.8) in the conventional group (n=1,138).
  23. 23. UKPDS Metformin Sub-Study: CHD Events UKPDS 34, Lancet 352: 854, 1998 n= 411 951 342 411 342 #Events 73 139 39 36 16 Myocardial Infarction 0 5 10 15 20 Incidence per 1000 patient years Conventional Diet Insulin SU’s Metformin p=0.01 NS 39% Reduction Coronary Deaths 0 2 4 6 8 10 p=0.02 50% Reduction Metformin Incidence per 1000 patient years Conventional Diet
  24. 24. Recent Trials Show No Reduction in CV Events with More Intensive Glycemic Control 1 ACCORD Study Group. N Engl J Med. 2008;358:2545-2559. 2 ADVANCE Collaborative Group. N Engl J Med. 2008;358:2560-2572. Number at Risk Intensive 5570 5369 5100 4867 4599 1883 Standard 5569 5342 5065 4808 4545 1921 0 12 24 36 48 60 Cumulative incidence (%) Months of follow-up ADVANCE: Primary Outcome Number at Risk Intensive 5128 4843 4390 2839 1337 475 448 Standard 5123 4827 4262 2702 1186 440 395 Patients with events (%) ACCORD: Primary Outcome 25 20 15 10 5 0 Standard therapy Intensive therapy 0 1 2 3 4 5 6 25 20 15 10 5 0 Years Standard therapy Intensive therapy
  25. 25. Was Intensive Glycemic Control Harmful? A closer look at ACCORD AND ADVANCE <ul><li>ACCORD was discontinued early due to increased total and CVD mortality in the intensive arm. Major hypoglycemia 3-fold higher too. </li></ul><ul><li>And the VA Diabetes Trial did show severe hypoglycemia to be a powerful predictor of CVD events. </li></ul><ul><li>But a more recent analysis of ACCORD just published (Diabetes Care, May 2010) showed deaths to be associated with unsuccessful intensive therapy where A1c remained high . </li></ul><ul><li>However, in both ACCORD AND ADVANCE, the subgroups without macrovascular disease at baseline had an actual benefit in the primary endpoint. </li></ul>
  26. 26. 2009 ADA/AHA/ACC Statement Recommendations <ul><li>Goal of A1c<7% remains reasonable </li></ul><ul><ul><li>for uncomplicated patients </li></ul></ul><ul><ul><ul><li>ACC/AHA Class I (A) </li></ul></ul></ul><ul><ul><li>and for those with macrovascular disease </li></ul></ul><ul><ul><ul><li>ADA Level B; ACC/AHA Class IIb (A) </li></ul></ul></ul><ul><li>Incremental microvascular benefit may be obtained from even lower goals </li></ul><ul><ul><ul><li>ADA Level B; ACC/AHA Class IIa (C) </li></ul></ul></ul><ul><li>Less stringent goals may be appropriate for those with labile glucose control or with advanced micro- or macrovascular disease </li></ul><ul><ul><ul><li>ADA Level C; ACC/AHA Class IIa (C) </li></ul></ul></ul>Circulation 2009; 119: 351-357
  27. 27. Summary of Care: ABC's for Providers A A1c Target Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigarette Smoking Cessation D Diabetes and Pre-Diabetes Management E Exercise F Food Choices
  28. 28. Prevalence of Hypertension* in Adults with Diabetes: NHANES III 1988-1994 % with Hypertension Geiss LS, et al. Am J Prev Med. 2002;22:42-48. *BP ≥130/85 or therapy for hypertension
  29. 29. HTN Control Rate Remains Poor in US Adults with MetS and DM from NHANES 2003-2004 (Wong ND et al., Arch Intern Med 2007) <ul><li>Only 35% of those with DM on treatment for HTN are controlled to a goal of <130/80 mmHg </li></ul><ul><li>Only 47% of those with MetS on treatment for HTN have a blood pressure of <130/85 mmHg </li></ul><ul><li>Thus, JNC-7 recommendations to begin with combination therapy to improve goal attainment should be adhered to, esp. if SBP/DBP exceeds 20/10 mmHg from goal. </li></ul>
  30. 30. UKPDS: Effects of Tight vs. Less-Tight Blood Pressure Control UK Prospective Diabetes Study Group. BMJ. 1998; 317:703-713.
  31. 31. HOT Trial: Effect of BP Control on CV Event Rate Hansson L et al. Lancet . 1998;351:1755-1762. Diastolic Blood Pressure goal Patients without Diabetes Patients with Diabetes Major CV events per 1000 patient-years
  32. 32. ACCORD: Effects of Intensive BP Control (NEJM 2010: 362: 1575-85) <ul><li>4733 participants with type 2 DM randomly assigned to intensive therapy targeting a SBP <120 mmHg vs. standard therapy targeting a SBP<140 mmHg. </li></ul><ul><li>Mean follow-up 4.7 years. </li></ul><ul><li>SBP after 1 year was 119 vs. 133 mmHg. </li></ul><ul><li>No difference in the primary endpoint of nonfatal MI, stroke, or CVD death (annual rate): 1.9% vs. 2.1% (HR=0.88), p=0.20. </li></ul><ul><li>Stroke annual rates significantly lower 0.32% vs. 0.53%, HR=0.59, p=0.01. Thus, overall benefit may be greater in populations with higher stroke risk. </li></ul>
  33. 33. Scientific Statements: Diabetes, CV Disease and Hypertension <ul><li>JNC VII Report on Diabetic Hypertension </li></ul><ul><ul><li>BP goal (<130/80 mm Hg) </li></ul></ul><ul><ul><ul><li>Commonly requiring combinations of ≥2 drugs </li></ul></ul></ul><ul><ul><li>ACEIs, CCBs, Thiazide-diuretics,  -blockers, and ARBs shown to reduce CVD/CVA risk </li></ul></ul><ul><ul><li>ACEIs/ARBs reduce progression of diabetic nephropathy and reduce albuminuria </li></ul></ul><ul><ul><li>ARBS reduce progression of macroalbuminuria </li></ul></ul>Grundy SM, et al. Circulation . 1999;100:1134-1146. Chobanian AV, et al. JAMA . 2003;289:2560-2572.
  34. 34. Summary of Care: ABC's for Providers A A1c Target Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigarette Smoking Cessation D Diabetes and Pre-Diabetes Management E Exercise F Food Choices
  35. 35. LDL-C as a Predictor of CAD in Patients with Diabetes Hazard ratio LDL-C quartile mean Adapted with permission from Howard BV et al. Arterioscler Thromb Vasc Biol . 2000;20:830-835. LDL=low-density lipoprotein cholesterol; CAD=coronary artery disease.
  36. 36. CARDS: Primary Endpoint Relative Risk Reduction 37% (95% CI: 17-52) Years 328 305 694 651 1074 1022 1361 1306 1392 1351 Atorva Placebo 1428 1410 Placebo 127 events Atorvastatin 83 events Cumulative Hazard (%) 0 5 10 15 0 1 2 3 4 4.75 P = 0.001 Colhoun HM et al. Lancet 2004;364:685-96.
  37. 37. HPS Substudy: First Major Vascular Event by LDL-C and Prior Diabetes Status Simvastatin (10,269) Placebo (10,267) Rate ratio (95% CI) Statin better Placebo better LDL-C and diabetes status <116 mg/dL With diabetes 191 (15.7%) 252 (20.9%) No diabetes 407 (18.8%) 504 (22.9%)  116 mg/dL With diabetes 410 (23.3%) 496 (27.9%) No diabetes 1,025 (20.0%) 1,333 (26.2%) All patients 2,033 (19.8%) 2,585 (25.2%) 24% reduction ( P <0.0001) 0.4 0.6 0.8 1.0 1.2 1.4 HPS Collaborative Group. Lancet . 2003;361:2005-2016.
  38. 38. Reducing CVD Risk with Statin Therapy in Patients with Diabetes <ul><li>Number needed to treat to prevent 1 major CVD event </li></ul><ul><ul><li>From HPS and 4S </li></ul></ul><ul><ul><ul><li>Without coronary disease 14 </li></ul></ul></ul><ul><ul><ul><li>With coronary disease 4 </li></ul></ul></ul><ul><ul><li>From meta-analysis </li></ul></ul><ul><ul><ul><li>Without vascular disease 39 </li></ul></ul></ul><ul><ul><ul><li>With vascular disease 19 </li></ul></ul></ul>HPS Collaborative Group. Lancet . 2003;361:2005-2016. Pyorala K, et al. Diabetes Care . 1997;20:614-620 Kearney PM Lancet;2008:371:227-239
  39. 39. Lipid Goals for Persons with Metabolic Syndrome and DM (Grundy et al., 2005) <ul><li>LDL-C targets, ATP III guidelines </li></ul><ul><ul><li>– High Risk: CHD, CHD risk equivalents ( incl. DM or >20% 10-year risk ): <100 mg/dL (option <70 mg/dl if CVD present) </li></ul></ul><ul><ul><li>– Moderately High Risk (10-20%) 2 RF: <130 mg/dL, option <100 mg/dL </li></ul></ul><ul><ul><li>– Moderate Risk (2+ RF, <10%) <130 mg/dL </li></ul></ul><ul><ul><li>-- Low Risk: 0-1 RF: <160 mg/dL </li></ul></ul><ul><li>HDL-C : >40 mg/dL (men) </li></ul><ul><ul><ul><li>>50 mg/dL (women) </li></ul></ul></ul><ul><li>TG : <150 mg/dL </li></ul>
  40. 40. <ul><li>Non-HDL: Secondary Target </li></ul><ul><li>Non-HDL = TC – HDL </li></ul><ul><li>Non-HDL: secondary target of therapy when serum triglycerides are  200 mg/dL (esp. 200-499 mg/dl) </li></ul><ul><li>Non-HDL goal: LDL goal + 30 mg/dL </li></ul>Specific Dyslipidemias: Elevated Triglycerides
  41. 41. <ul><li>Management of Low HDL </li></ul><ul><li>LDL is primary target of therapy </li></ul><ul><li>Weight reduction and increased physical activity (if the metabolic syndrome is present) </li></ul><ul><li>Non-HDL is secondary target of therapy (if triglycerides  200 mg/dL) </li></ul><ul><li>Consider nicotinic acid or fibrates (for patients with CHD or CHD risk equivalents) </li></ul>Specific Dyslipidemias: Low HDL Cholesterol
  42. 42. ACCORD Lipid Study Results (NEJM 2010; 362: 1563-74) <ul><li>5518 patients with type 2 DM treated with open label simvastatin randomly assigned to fenofibrate or placebo and followed for 4.7 years. </li></ul><ul><li>Annual rate of primary outcome of nonfatal MI, stroke or CVD death 2.2% in fenofibrate group vs. 1.6% in placebo group (HR=0.91, p=0.33). </li></ul><ul><li>Pre-specified subgroup analyses showed possible benefit in men vs. women and those with high triglycerides and low HDL-C. </li></ul><ul><li>Results support statin therapy alone to reduce CVD risk in high risk type 2 DM patients. </li></ul>
  43. 43. Summary of Care: ABC's for Providers A A1c Target Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigarette Smoking Cessation D Diabetes and Pre-Diabetes Management E Exercise F Food Choices
  44. 44. Smoking Cessation <ul><li>What you do does matter. Physicians who intervene influence cigarette smoking behavior. </li></ul><ul><li>How do you get your patients to quit smoking? </li></ul><ul><ul><li>Identify i.e.: in vitals signs </li></ul></ul><ul><ul><li>Interventions as brief as 3 minutes can significantly increase quit rates </li></ul></ul><ul><ul><li>Dose dependent changes in behavior </li></ul></ul><ul><ul><li>5-10% may quit within 1 year with MD advice alone </li></ul></ul><ul><li>Smoking cessation aids </li></ul>
  45. 45. EFFICACY OF SMOKING CESSATION INTERVENTIONS (1 YEAR QUIT RATES) ACUPUNCTURE ---- HYPNOSIS ---- PHYSICIAN ADVICE 6% SELF-HELP METHODS 14% NICOTINE PATCH 11-15% PHYSICIAN ADVICE/SELF-HELP PAMPHLETS 22% AVERSIVE SMOKING (RAPID PUFFING) 25% PHARMACOTHERAPY/BEHAVIORAL THERAPY 25% BEHAVIORAL STRATEGIES (GROUP PROG.) 40%
  46. 46. The 5 “A’s” for Effective Smoking Intervention <ul><li>ASK about smoking </li></ul><ul><li>ADVISE to quit </li></ul><ul><li>ASSESS willingness to make a quit attempt </li></ul><ul><li>ASSIST if ready - offer therapy and consultation for quit plan and if not, then offer help when ready </li></ul><ul><li>ARRANGE follow up visits </li></ul>
  47. 47. Summary of Care: ABC's for Providers A A1c Target Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigarette Smoking Cessation D Diabetes and Pre-Diabetes Management E Exercise F Food Choices
  48. 48. CHD Mortality Rates (by Degree of Glucose Tolerance) Incidence rate/1000 *Indicates patients known to have diabetes prior to the study. CHD=coronary heart disease; NGT=normal glucose tolerance; IGT=impaired glucose tolerance Adapted with permission from Eschwege E et al. Horm Metab Res Suppl . 1985;15:41-46.
  49. 49. Most Cardiovascular Patients Have Abnormal Glucose Metabolism 35% 31% 34% 37% 18% 45% 37% 27% 36% GAMI n = 164 EHS n = 1920 CHS n = 2263 GAMI = Glucose Tolerance in Patients with Acute Myocardial Infarction study; EHS = Euro Heart Survey; CHS = China Heart Survey Prediabetes Normoglycemia Type 2 Diabetes Anselmino M, et al. Rev Cardiovasc Med . 2008;9:29-38.
  50. 50. D iabetes P revention P rogram: Protocol Design
  51. 51. D iabetes P revention P rogram: Reduction in Diabetes Incidence
  52. 52. Benefit of Comprehensive, Intensive Management: STENO 2 Study <ul><li>Treatment Goals: </li></ul><ul><ul><li>Intensive TLC </li></ul></ul><ul><ul><li>HgbA1c <6.5% </li></ul></ul><ul><ul><li>Cholesterol <175 </li></ul></ul><ul><ul><li>Triglycerides <150 </li></ul></ul><ul><ul><li>BP <130/80 </li></ul></ul>0 0 10 20 40 50 60 Conventional Therapy Intensive Therapy 30 Months of Follow Up Primary End Point=CV events (%) 12 24 36 48 60 72 84 96 n =80 n =80 Gaede, P. et al, NEJM 2003;348:390-393
  53. 53. Summary of Care: ABC's for Providers A A1c Target Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigarette Smoking Cessation D Diabetes and Pre-Diabetes Management E Exercise F Food Choices
  54. 54. Metabolic Syndrome: Lifestyle Management: Obesity / Physical Activity <ul><li>Obesity / weight management : low fat – high fiber diet resulting in 500-1000 calorie reduction per day to provide a 7-10% reduction on body weight over 6-12 mos, ideal goal BMI <25 </li></ul><ul><li>Physical activity : at least 30, pref. 60 min moderate intensity on most or all days of the week as appropriate to individual </li></ul>Grundy SM, Hansen B, Smith SC, et al. Clinical management of metabolic syndrome. Report of the American Heart Association / National Heart, Lung, and Blood Institute / American Diabetes Association Conference on Scientific Issues Related to Management. Circulation 2004; 109: 551-556
  55. 56. Physical Inactivity: A Call to Arms 10,000 Steps Daily 30 minutes most days
  56. 57. Physical Activity Recommendations <ul><li>Aerobic exercise a minimum of 30 minutes, 5 times weekly </li></ul><ul><li>Optimal physical activity is at least 30 minutes daily </li></ul><ul><li>Resistance exercise training using free weights or machines 2 days a week in the absence of contraindications </li></ul>
  57. 58. Summary of Care: ABC's for Providers A A1c Target Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigarette Smoking Cessation D Diabetes and Pre-Diabetes Management E Exercise F Food Choices
  58. 59. ADA Nutritional Guidelines <ul><li>Patients with pre-diabetes should receive individualized Medical Nutrition Therapy (MNT) </li></ul><ul><li>Weight loss recommended for all overweight or obese individuals who have or are at risk for diabetes </li></ul><ul><li>Physical activity and behavior modification effective for weight loss and maintenance </li></ul><ul><li>Fiber 14 g/1000 kcal intake </li></ul><ul><li>Saturated fat 7% with minimal trans fat </li></ul>
  59. 60. Therapeutic Lifestyle Changes Nutrient Composition of TLC Diet <ul><li>Nutrient Recommended Intake </li></ul><ul><li>Saturated fat Less than 7% of total calories </li></ul><ul><li>Polyunsaturated fat Up to 10% of total calories </li></ul><ul><li>Monounsaturated fat Up to 20% of total calories </li></ul><ul><li>Total fat 25–35% of total calories </li></ul><ul><li>Carbohydrate 50–60% of total calories </li></ul><ul><li>Fiber 20–30 grams per day </li></ul><ul><li>Protein Approximately 15% of total calories </li></ul><ul><li>Cholesterol Less than 200 mg/day </li></ul><ul><li>Total calories (energy) Balance energy intake and expenditure to maintain desirable body weight/ prevent weight gain </li></ul>
  60. 61. Effect of Mediterranean-Style Diet in the Metabolic Syndrome <ul><li>180 pts with metabolic syndrome randomized to Mediterranean-style vs. prudent diet for 2 years </li></ul><ul><li>Those in intervention group lost more weight (-4kg) than those in the control group (+0.6kg) (p<0.01), and significant reductions in CRP and Il-6 </li></ul>Esposito K et al. JAMA 2004; 292(12): 1440-6.
  61. 62. Conclusions <ul><li>Metabolic syndrome and diabetes are associated with increased levels of atherosclerosis and cardiovascular disease event risk </li></ul><ul><li>Lifestyle measures focusing on weight reduction, dietary, and physical activity guidance are crucial in initial management. </li></ul>
  62. 63. Conclusions (cont.) <ul><li>Clinical management emphasizes achievement of BP and lipid goals, glycemic control, and antiplatelet therapy. </li></ul><ul><li>Multidisciplinary programs including primary care physicians, specialists (endocrinologists and cardiologists), dietitians, and exercise specialists are key for the successful management of these conditions. </li></ul>
  63. 64. Thank you for your attention! Now Published from Informa Healthcare … For more information visit our website at www.heart.uci.edu
  64. 65. Question #1 <ul><li>Which of the following statements is true? </li></ul><ul><ul><li>Diabetes prevalence is higher in African Americans and Hispanics compared to Caucasians </li></ul></ul><ul><ul><li>The prevalence of diabetes is approaching the prevalence of obesity </li></ul></ul><ul><ul><li>The impact of diabetes on CVD is similar in men and women </li></ul></ul><ul><ul><li>All of the above </li></ul></ul>
  65. 66. Question #2 <ul><li>What are the recommended target levels for LDL-C and BP for most uncomplicated patients with DM? </li></ul><ul><ul><li>LDL-C <100 mg/dl and 120/80 mmHg </li></ul></ul><ul><ul><li>LDL-C <100 mg/dl and 130/80 mmHg </li></ul></ul><ul><ul><li>LDL-C <70 mg/dl and 140/90 mmHg </li></ul></ul><ul><ul><li>None of the above </li></ul></ul>
  66. 67. Question #3 <ul><li>Diabetes has been considered a CHD risk equivalent because: </li></ul><ul><ul><li>Nearly all persons with CHD also have diabetes </li></ul></ul><ul><ul><li>Persons with diabetes have a similar risk of developing CHD than those who already have CHD (e.g., myocardial infarction) </li></ul></ul><ul><ul><li>Both a and b </li></ul></ul>
  67. 68. Question #4 <ul><li>Recent large clinical trials such as ACCORD and ADVANCE suggest: </li></ul><ul><ul><li>Aggressive glycemic control significantly reduces the risk of future CVD events in high risk persons with diabetes </li></ul></ul><ul><ul><li>The HbA1c target should be set closer to 6% than the conventional target of <7% </li></ul></ul><ul><ul><li>A less stringent goal than <7% for HbA1c might be considered in more complicated patients with diabetes (e.g., those difficult to control, with known macrovascular disease, or with long-standing diabetes) </li></ul></ul>

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