1. CVD Workshop SDPI CVD Risk Reduction Project Meeting #5 Denver, Colorado

2. Case Study 62 year old woman presents for her scheduled intake visit for your CVD project She has been overweight most of her adult life and has a BMI of ~32 PMHx: HTN, diet controlled diabetes Medication: HCTZ 25 mg Q day

3. Case Study SHx: Walks to the bus every day and occasionally walks with friend on the weekend She smoked ½ pack/day until 2 years ago FHx: Her sister is overweight, and take metformin for diabetes, her father died from a heart attack, her mother has diabetes

4. Case Study: Physical Exam Vitals: Height: 64” Weight: 188 lb BP 140/90 Waist Circumference: 39” Exam: HEENT WNL, Lungs clear, Heart RRR S1/S2 no murmur, GI obese abdomen, Foot exam: monofilament normal in both feet, pulse and skin normal, no pedal edema, nails mild fungal changes

5. Case Study: Initial Laboratory FBS:165 mg/dl, A1c8.1% TC: 220 mg/dl TG: 240 mg/dl HDL-C: 38 mg/dl LDL-C: 134 mg/dl Creatinine: 0.6 mg/dl Urine M/C Ratio:35

6. Cardiovascular Risk Assessment: Modifiable Major Risk Factors Hypertension Hypercholesterolemia Smoking Microalbuminurea Hyperglycemia Contributing Causes Obesity, fat distribution Lack of physical exercise Genetic factors Age Disease duration Garber, AJ American Family Practice December 15 2000

7. Anydiabetes-relatedendpoint Diabetes-relateddeath Micro- vascular endpoints -12% (P<.0001) -10% (P=.34) -25% (P<.01) Stroke -25% (P<.005) -32% (P=.019) -44% (P=.013) -37% (P=.009) Micro-vascularendpoints Anydiabetes-relatedendpoint Diabetes-relateddeath UK Prospective Diabetes Study Group 38. BMJ. 1998;317:703-713. UK Prospective Diabetes Study Group 33. Lancet. 1998;352:837-853. Glucose Control BP Control (144/82 vs 154/87 mm Hg)0-10 -50 -20 -30 -40 United Kingdom Prospective Diabetes Study (UKPDS): Results

8. S TENO-2 Study:Multifactorial Intervention and CVD in Patients with Type 2 Diabetes Denmark Study: NEJM 1/30/2003 160 patients with type 2 diabetes 8 year study with mean age 55 years Two study groups: intensive therapy and conventional therapy Gaede P, et al. N Eng J Med. 2003;348:383-393.

9. S TENO-2 Study:Multifactorial Intervention and CVD in Patients with Type 2 Diabetes Intensive Group: stepwise implementation of behavior modification and pharmacologic therapy targeting: –Hyperglycemia –Hypertension –Dyslipidemia –Microalbuminurea Gaede P, et al. N Eng J Med. 2003;348:383-393.

10. End point: –Death from cardiovascular causes –Nonfatal myocardial infarction –Stroke –Coronary or peripheral artery revascularization –Amputation as a result of ischemia STENO-2 Study:Multifactorial Intervention and CVD in Patients with Type 2 Diabetes Gaede P, et al. N Eng J Med. 2003;348:383-393.

11. STENO-2 Study:Multifactorial Intervention and CVD in Patients with Type 2 Diabetes Macrovascular Complications Conventional Group: 44% of patient had a primary end point event Intensive Group: 24% of patients had a primary end point event Primary composite endpoint: Death from CV causes, nonfatal MI, CABG, PCI, nonfatal stroke, amputation, or surgery for peripheral atherosclerotic artery disease. Adapted from Gaede P, et al. N Eng J Med. 2003;348:383-393.

12. Primary composite endpoint: conventional therapy (44%) and intensive therapy (24%). * Death from CV causes, nonfatal MI, CABG, PCI, nonfatal stroke, amputation, or surgery for peripheral atherosclerotic artery disease. † Behavior modification and pharmacologic therapy. Adapted from Gaede P, et al. N Eng J Med. 2003;348:383-393. Primary Composite Endpoint* (%) Months of Follow-Up 60 40 20 1224364860728496 Conventional Therapy Intensive Therapy † 20% Absolute Risk Reduction N=160; follow-up=7.8 years Aggressive treatment of † : – Microalbuminuria with ACEIs, ARBs, or combination – Hypertension – Hyperglycemia – Dyslipidemia – Secondary prevention of CVD Intensive Multiple Risk Factor Management Patients with Type 2 Diabetes and Macroalbuminuria

13. CVD Risk Reduction Hyperglycemia Hypertension Control Lipid Control Daily Aspirin Lifestyle Changes Weight loss, healthy foods, Increased activity Smoking Cessation

14. Hypertension

15. “Failure to titrate or combine medications, despite knowing the patient is not at goal BP, represents clinical inertia and must be overcome.” Chobanian A, et al. JAMA. 2003;289:2560-2572. JNC 7

16. Treatment of Hypertension in Diabetes Diagnosis of Hypertension BP>130/80 mm Hg Non-Pharmacologic Therapies Drug Therapies ACE based regimes preferred Multi-drug therapy often needed Target BP <130/85

17. ACE & ARBS Limits nephropathy and Lower CVD risk Thiazide  -Blocker*  Blocker Ca++CB Step-wise progression to controlling Blood pressure

18. Average Number of Antihypertensive Agents Needed Per Patient to Achieve Target BP UKPDSDBP<85 ABCDDBP<75 VDRDMAP<92 HOTDBP<80 AASKMAP<92 Number of Antihypertensive AgentsTrailTarget BP mm Hg

19. SUMMARY Treatment of Hypertension in Diabetes Blood pressure goal in diabetes = 130/85 –Level of blood pressure more important that type of therapy –Reduces rates of both micro and macrovascular disease ACE based therapies: 1 st Line Choice –Reduces CVD complication and offers reno- protection Multi-drug therapy often needed Aggressive treat essential, if CVD and renal disease present ideal goal: 125/80 (?) Arch Intern Med, Vol160, Sep 11, 2000, 2447-2452

20. Hypercholesterol

21. Prevalence of Dyslipidemia in Type 2 Diabetes Most common pattern is elevated triglycerides and low HDL TC & LDL concentration is often the same as non-diabetic individuals However, LDL particles are smaller, denser and more atherogenic

22. Goals for Control LDL < 100 HDL> 45* in men, HDL> 55 in women Lipid panel annually Consider direct LDL if TG >250 or if specimen is non-fasting All patients with LDL > 100 need medical, dietary and lifestyle intervention

23. Considerations in Therapy Diet and exercise are key Hyperglycemia itself will lead to increased TG: try to improve sugars first Metformin will decrease LDL Glitazones will decrease TG, increase HDL Check TFTs in initial work-up Metamucil, increased dietary fiber

24. Microalbuminuria and CVD in Diabetes

25. Microalbuminuria and Diabetes Independent risk factor for development of cardiovascular disease Predictor of cardiovascular mortality in the diabetic population Part of the cardiometabolic syndrome

26. Microalbuminuria and Diabetes Test for urine protein yearly If negative, screen for microalbuminurea Dipstick + microalbuminurea should be confirmed on a separate specimen A/C ratio:  30mg/gm Treat with ACE-inhibitor, regardless of BP

27. Smoking Cessation

28. Smoking doubles the risk of CVD in patients with diabetes Attenuates the benefit of gained from modifying other risks Synergistic with  TC, possibly through enhanced oxidation of LDL MRFIT: independent and  ing risk of CVD based on #cigarettes/day

29. Smoking Cessation: Standards of Care Assessment of smoking status and history Counseling on smoking prevention and cessation Referral to program for delivery of smoking cessation

30. Aspirin Therapy

31. Aspirin Therapy in Diabetes “Aspirin - the poor man’s statin” Reduces risk of MI by ~ 15-60% Treat all high risk patients with diabetes over the age of 35 Use 81 – 325mg/day The Lancet

32. Procoagulant State Platelets are overly sensitive to platelet aggregating agents High levels of Thromboxane, a potent vasoconstrictor Decreased fibrinolytic activity Increased levels of Plasminogen Activitor Inhibitor-1 Clot lysis cannot precede normally

33. Goals for treatment Primary Prevention: Strongly consider ASA in patients > 30 with diabetes and high risk for CVD –FHx CVD, smoking, HTN, obese, albuminurea, dyslipidemia Secondary Prevention: ASA for patients with know CVD: MI, stroke, PVD, claudication, angina DOSE: 162mg to 325mg

34. Conclusion: Aggressive modification of all identified CVD risks factor is essential to reduce the macrovascular complications of diabetes