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Hyper tension and diabetes the two terrorists together

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Hyper tension and diabetes the two terrorists together

  1. 1. Hot Topic in Cardiology 2014 HYPERTENSION AND DIABETES: THE TWO TERRORISTS TOGETHER Kyaw Soe Win MBBS, MMedSc (Int Med), MRCPUK, FRCP (Edin), FAsCC, FAPSIC Sedona Hotel 23rd March 2014
  2. 2. The Two Terrorists in Cardiovascular World The ENORMITY of the problem - compounded
  3. 3. How Common is this deadly Duo? HTN is twice HTN is twice aass ccoommmmoonn iinn DDMM NNeeww oonnsseett DDMM iiss 22..55 ttiimmeess iinn HHTTNN 2200 ttoo 4400%% ooff IIGGTT ppttss hhaavvee HHTTNN 4400 ttoo 5500%% ooff TTyyppee 22 DDMM hhaavvee HHTTNN OOnnllyy 11//44 ooff HHTTNN iinn DDMM iiss ccoonnttrroolllleedd DDMM ++ HHTTNN ––  CCVV RRiisskk 33 ffoolldd long-term survivors of diabetes tend to have lower BP
  4. 4. HTN in DM: Prevalence Hypertension in Type 1 and 2 Diabetes Type 1 Develop after several years of DM Ultimately affects ~30% of patients With macroalbuminaemia-65- 88% Type 2 Mostly present at diagnosis Ultimately affects at least 60% of patients With macroalbuminaemia->90%
  5. 5. Slide 26 PPeerrcceenntt CChhaannccee ooff CCaarrddiioovvaassccuullaarr EEvveenntt iinn 55 YYeeaarrss NNoo DDiiaabbeetteess >>2200%% 1155%%--2200%% 1100%%--1155%% 55%%--1100%% 22..55%%--55%% <<22..55%% MMeenn NNoonnssmmookkeerr SSmmookkeerr TToottaall CChhooll..::HHDDLL--CChhooll.. WWoommeenn NNoonnssmmookkeerr SSmmookkeerr TToottaall CChhooll..::HHDDLL--CChhooll.. 44 55 66 77 88 44 55 66 77 88 44 55 66 77 88 44 55 66 77 88 AAggee 7700 AAggee 6600 AAggee 5500 118800//110055 116600//9955 114400//8855 112200//7755 118800//110055 116600//9955 114400//8855 112200//7755 118800//110055 116600//9955 114400//8855 112200//7755
  6. 6. Slide 27 PPeerrcceenntt CChhaannccee ooff CCaarrddiioovvaassccuullaarr EEvveenntt iinn 55 YYeeaarrss DDiiaabbeetteess MMeenn NNoonnssmmookkeerr SSmmookkeerr TToottaall CChhooll..::HHDDLL--CChhooll.. WWoommeenn NNoonnssmmookkeerr SSmmookkeerr TToottaall CChhooll..::HHDDLL--CChhooll.. 44 55 66 77 88 44 55 66 77 88 44 55 66 77 88 44 55 66 77 88 AAggee 7700 AAggee 6600 AAggee 5500 118800//110055 116600//9955 114400//8855 112200//7755 118800//110055 116600//9955 114400//8855 112200//7755 118800//110055 116600//9955 114400//8855 112200//7755 >>2200%% 1155%%--2200%% 1100%%--1155%% 55%%--1100%% 22..55%%--55%% <<22..55%%
  7. 7. The EVIDENCE BASE How and Why DM + HT is dangerous?
  8. 8. Cardiovascular Mortality Risk Doubles With Each 20/10 mm Hg BP Increment* Cardiovascular Mortality Risk 2x 4x 8x 115/75 135/85 155/95 175/105 SBP/DBP (mm Hg) 8 7 6 5 4 3 2 1 0 SBP = systolic blood pressure; DBP = diastolic blood pressure. *Individuals aged 40-69 years, starting at blood pressure 115/75 mm Hg Chobanian AV et al. JAMA. 2003;289:2560-2572. Lewington S et al. Lancet. 2002;360:1903-1913.
  9. 9. Association of SBP and CV Mortality in Men With Type 2 Diabetes 250 200 150 100 50 0 <120 120-139 140-159 160-179 180-199 SBP (mm Hg) CV mortality rate/ 10,000 person-yr Nondiabetic Diabetic CV, cardiovascular; SBP, systolic blood pressure. Stamler J et al. Diabetes Care. 1993;16:434-444. ≥200
  10. 10. End Point Hazard Ratios Associated With Increase in SBP Hazard ratio 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 Any end point related to diabetes (P<0.0001) Death related to diabetes (P<0.0001) All-cause mortality (P<0.0001) Adler A et al. BMJ. 2000;321:412–419. Updated mean SBP (mm Hg) 0 110 120 130 140 150 160 170
  11. 11. HOT Study: Risk of Morbidity and Mortality in Diabetic Hypertensive Patients Myocardial Infarction Major CV Events Stroke CV Mortality Total Mortality 90 mmHg 80 mmHg | | | | 0 1 2 3 4 Lancet 1998; 351: 1755–62
  12. 12. Each Perpetuates the Other
  13. 13. HTN in DM: PARTNERS IN CRIME DDiiaabbeetteess HHyyppeerrtteennssiioonn HTN vs No HTN DM vs No DM 2.4 x ↑ in DM 2.0 x ↑ in HTN  NEJM 2000; 342:905 Diabetes Care 2005; 28:310
  14. 14. HTN in DM: PARTNERS IN CRIME DDiiaabbeetteess HHyyppeerrtteennssiioonn  CCaauussee:: HHyyppeerrtteennssiioonn iiss uussuuaallllyy rreennooppaarreenncchhyymmaall iinn oorriiggiinn ccaauusseedd bbyy OOrr ppooiinnttiinngg ttoo uunnddeerrllyyiinngg ddiiaabbeettiicc nneepphhrrooppaatthhyy  OOnnsseett:: TTyyppiiccaallllyy bbeeccoommeess mmaanniiffeesstt aabboouutt tthhee ttiimmee tthhaatt ppaattiieennttss ddeevveelloopp mmiiccrrooaallbbuummiinnuurriiaa.. AAmmeerriiccaann DDiiaabbeettiicc AAssssoocciiaattiioonn.. DDiiaabb CCaarree 22000044  CCaauussee:: MMaaiinnllyy dduuee iinnssuulliinn rreessiissttaannccee ((aass aa ffaacceett ooff MMSS)) BBuutt mmaayy bbee dduuee ttoo uunnddeerrllyyiinngg DDNN oorr ootthheerr ccaauusseess.. American Diabetic Association. Diab Care 2004  OOnnsseett:: UUssuuaallllyy pprreecceeddeess tthhee oonnsseett ooff nneepphhrrooppaatthhyy aanndd eevveenn tthhee oonnsseett ooff ttyyppee 22 ddiiaabbeetteess bbyy yyeeaarrss oorr ddeeccaaddee  RRiittzz eett aall.. JJ IInntt MMeedd.. 22000011 ;; 224499:: 221155--222233 DM-1 DM-2
  15. 15. Progression of DM - Nephropathy
  16. 16. Microalbuminuria as a Risk Factor for Death in Type 2 Diabetes 1. 0 0. 8 0. 6 Survival 0. 4 UAC £15 mg/mL 0. UAC 16-40 mg/mL 2 UAC 41-200 mg/mL 0. 0 Years after Diagnosis 0 1 2 3 4 5 6 7 8 9 10 11 UAC, urinary albumin concentration. Adapted from Schmitz A et al. Diabetes Med. 1988;5:126-134.
  17. 17. Proteinuria & Risk of CV Mortality, Stroke, & CHD Events in Type 2 Diabetes 1.0 0.9 0.8 0. 7 0.6 0.5 0 40 30 20 10 0 10 20 30 40 50 60 7080 90 Stroke CHD Events* A: UPC <150 mg/L B: UPC 150-300 mg/L C: UPC >300 mg/L CCHHDD,, ccoorroonnaarryy hheeaarrtt ddiisseeaassee;; UUPPCC,, uurriinnaarryy pprrootteeiinn ccoonncceennttrraattiioonn.. ** DDeeffiinneedd aass CCHHDD ddeeaatthh oorr nnoonnffaattaall MMII.. AAddaapptteedd ffrroomm MMiieettttiinneenn HH eett aall.. SSttrrookkee.. 11999966;;2277::22003333--22003399.. P<.001 for trends Incidence (%) Reduction in Survival due to CV Mortality Months A B C P-values: Overall <.001 A vs B =.013 A vs C <.001 B vs C <.001 0
  18. 18. HTN in DM: PARTNERS IN CRIME DDiiaabbeetteess HHyyppeerrtteennssiioonn  The risk of diabetes associated with antihypertensive-drug therapy appears to be explained by the presence of hypertension.  Among the subjects who had hypertension, the risk among those not taking medication was similar to that among those taking one or more agents.  Among the subjects who were not taking any antihypertensive medication, the risk of diabetes was much higher among hypertensive Pts. than in non hypertensive. 15 10 5 0 11.6% 9.8% 8.1% Chlorthalidone Amlodipine Lisinopril ALLHAT: Incidence of New-Onset Diabetes at 4 Years JAMA 2002;288:2981-2997 Role of Antihypertensive Drugs
  19. 19. HTN in DM: PARTNERS IN CRIME DDiiaabbeetteess HHyyppeerrtteennssiioonn Role of Antihypertensive Drugs  TTaakkiinngg aa tthhiiaazziiddee ddiiuurreettiicc,, AACCEE iinnhhiibbiittoorr,, oorr CCCCBB ccaarrrryy nnoo ggrreeaatteerr rriisskk ffoorr tthhee ssuubbsseeqquueenntt ddeevveellooppmmeenntt ooff DDMM..  DDMM wwaass 2288 ppeerrcceenntt mmoorree lliikkeellyy ttoo ddeevveelloopp iinn ssuubbjjeeccttss ttaakkiinngg BBBB tthhaann iinn tthhoossee ttaakkiinngg nnoo mmeeddiiccaattiioonn..  TThhiiss aaddvveerrssee eeffffeecctt ooff BBBB mmuusstt bbee wweeiigghheedd aaggaaiinnsstt tthhee pprroovveenn bbeenneeffiittss ooff tthhiiss ddrruugg iinn rreedduucciinngg tthhee rriisskk ooff ccaarrddiioovvaassccuullaarr eevveennttss
  20. 20. b-Blockers and the risk of new-onset diabetes mellitus 28% Increased Risk 0.91 1.28 1.0 Prospective study of 12 550 patients w/o DM, aged 45-64, followed for 6 y. Multivariate analysis of 3804 who had HT at baseline. 25% Increased Risk 17.4 13.0 20 15 10 5 0 Atenolol Losartan LIFE1 New Cases Per 1000 Person-Years (%) 1.5 Ratio 1.0 Hazard .5 Prospective study of 9193 hypertensives, aged 55-80, followed for 4.8 y. Analysis of 7998 w/o DM at baseline. 1. Lancet 2002;359:995–1003. 2. N Engl J Med 2000;342:905–12. ARIC2 0 Atenolol RR 1.25 (1.12-1.37) P<.001 b-blocker RR 1.28 (1.04-1.57) P<.05 Thiazide b-blocker None 1.17 CCB 0.98 ACEI
  21. 21. HTN in DM: PARTNERS IN CRIME The TThhee HIPERFRE HHIIPPEERRFFRREE study, ssttuuddyy,, 2008 22000088 1,724 hypertensive patients, 35 physicians, 14 Primary Care Units Association between refractory hypertension and cardiometabolic risk
  22. 22. HTN in DM: PARTNERS IN CRIME  The RAS itself plays imp. role in the development of DDiiaabbeetteess HHyyppeerrtteennssiioonn diabetes.  Over activity of RAS appears to be linked to reduced Hypertensive patients without diabetes tend to be resistant to insulin and are hyperinsulinaemic compared with normotensive controls. insulin and glucose delivery to the peripheral skeletal muscle and Pollare impaired T et al. Metabolism glucose 1990, 39(transport 2):167-174. and response to insulin signalling pathways, thus increasing insulin resistance. About 20% of patients with hypertension will develop type 2 diabetes in a three year Jandeleit-period. Dahm KA et al. J Hypertens 2005, 23(3):463-473. Bosch J et al. N Engl J Med 2006, 355(15):1551-1562.  Activation of a local pancreatic RAS, in particular within the islets, may represent an independent mechanism for the progression of islet cell damage in diabetes. Fasting glucose levels increase in older adults with hypertension regardless of treatment type. BarzilayJ I et al. Arch Intern Med. 2006;166:2191- 2201 Ferrannini E et al. Diabetologia 2003, 46(9):1211-1219.
  23. 23. The Compound Jeopardy !! 2 x 4 x Reilly MP et al – Circulation 2003; 108: 1546-1551
  24. 24. Plasma Glucose as Independent Risk Factor Andersson, DK et al. Diabetes Care 18: 1534-1543
  25. 25. Effect of Hypertension on mortality in DM Mortality vs systolic blood pressure 70 60 50 40 30 20 10 0 110 120 130 140 150 160 Systolic Blood pressure (mmHg) Ten Year Mortality (per 1000) Non-diabetic Diabetic
  26. 26. Effect of Cholesterol on Mortality in DM Serum cholesterol vs Mortality 70 60 50 40 30 20 10 0 4 5 6 7 s-Cholesterol (mmol/L) Ten Year Mortality (per 1000) Non-diabetic Diabetic
  27. 27. D E A T H HTN in DM: PARTNERS IN CRIME Insulin Resistance Hyper-insulinemia Triglycerides LDL HDL Visceral Fat Angiotensin II Sympathetic Activity + Hypertension LDL=low-density lipoprotein; HDL=high-density lipoprotein; MI=myocardial infarction; CHD=congestive heart failiure; HF=heart failure; ESRD=end-stage renal disease Adapted from Arch Intern Med. 2000; 160:1277-1283. Diabetes CHD Stroke MI HF ESRD Metabolic Syndrome Morbid States
  28. 28. Perpetuating Circus CKD Diabetes  BP  Lipids CAD ED
  29. 29. HTN in DM: Accelerates Vascular Age  Diabetes promotes both the development and adverse impact of cardiovascular disease (CVD) risk factors (e.g. hypertension, dyslipidemia, renal dysfunction) and, as a consequence, accelerates cardiovascular age.  Persons with diabetes generally have a cardiovascular age 10 to 15 years in advance of their chronological age.  Advanced cardiovascular age substantially increases both the proximate and lifetime risk for CVD events, resulting in a reduced life expectancy of approximately 12 years. 2013 Canadian Diabetes Association guidelines
  30. 30. HTN in DM: Facts •Hypertension in diabetes : – it accelerates macrovascular disease – it accelerates microvascular disease Glycemic control only is not enough VASCULAR PROTECTION IS IMPORTANT
  31. 31. Vascular Protection for CAD and CKD in DM Hypertension Dyslipidemia Dysglycemia
  32. 32. The EVIDENCE BASE MANAGEMENT Guide
  33. 33. Diabetes Guideline Management  2 main sets of guidelines utilized in U.S.  American Diabetes Association (ADA)  American Association of Clinical Endocrinology (AACE) (Lots of overlap, Evidence based, well accepted, clinically relevant and can be easily incorporated into clinical practice)  Canadian Diabetes Association 2013 Clinical Practice Guidelines (September 2013)  ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD ( August 2013 )
  34. 34. Canadian Diabetes Association 2013 Clinical Practice Guidelines The Essentials Presentation by Dr. Tessa Laubscher Clinical Associate Professor, Family Medicine Saskatoon Sept 2013 guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association
  35. 35. STANDARDS OOFF MMEEDDIICCAALL CCAARREE IINN DDIIAABBEETTEESS——2200114
  36. 36. HTN in DM: Therapy 1. Blood Pressure Goal 2. Life Style Modification 3. Phamacological Therapy
  37. 37. UKPDS Mean Blood Pressures Baseline (mm Hg) Mean BP over 9 yrs (mm Hg) Less tight control 160/94 154/87 Tight control 161/94 144/82 Difference 1/0 10/5 P value n.s. <0.0001 UKPDS, United Kingdom Prospective Diabetes Study. UKPDS 38. BMJ. 1998;317:703-713.
  38. 38. Tight BP Control vs. Tight Glucose Control Any DM End Point DM Death TTiigghhtt GGlluuccoossee CCoonnttrrooll TTiigghhtt BBPP CCoonnttrrooll 0 - Stroke -10 - -20 - -30 - -40 - -50 - **PP << 00..0055 Microvascular Complica tions Reduction in Risk (%) UKPDS. BMJ. 1998:317;703-712.
  39. 39. Comparisons of More Intensive Blood Pressure Lowering Strategies With Less Intensive Strategies
  40. 40. Comparisons of More Intensive Blood Pressure Lowering Strategies With Less Intensive Strategies
  41. 41. HOT Study(Diabetic Subgroup): Significant Benefit From Intensive Treatment in the DBP 25 20 15 10 5 0 Events/1000 pt-years <90 <85 <80 Target diastolic BP DM non-DM Lancet 1998; 351: 1755–62
  42. 42. HTN in DM: Therapy GGooaall BBlloooodd PPrreessssuurree Less Than 130/80  HOT (Hypertension Optimal Treatment).  ABCD-NT (Appropriate Blood Pressure Control in Diabetes)  UKPDS (UK Prospective Diabetes Study)  IDNT (Irbesartan in Diabetic Nephropathy Trial)  INVEST (International Verapamil-Trandolapril)  ADA (American Diabetic association)  ISHIB (International Society of Hypertension in Blacks)  CHEP (Canadian Hypertension Education Program)  BHS (British Hypertension Society)  JNC 7 (Joint National Committee 7)
  43. 43. BP Targets in DM ( before 2013) Ideal Blood Pressure Without proteinuria < 130/80 With proteinuria < 125/75 Goal BP maximum for DM < 130/80 Almost all DM pts require > 1 drug for HTN Identify the co-morbidity – CAD, CKD, CVD
  44. 44. HTN in DM: Therapy GGooaall BBlloooodd PPrreessssuurree Less Than 130/80 Can We Go to More Lower Target ?  National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis. 2000;36(3):646-661.  American Association of Clinical Endocrinologist, 2006  Target BP 125/75 If Proteinuria > 1gm IDNT JASN 2005;16(7):2170–2179
  45. 45. ACCORD trial  ACCORD trial , >4700 patients were assigned to intensive- ( achieved mean SBP 119mmHg) or standard treatment ( mean SBP 134mmHg) over a mean follow-up of 4.7 years.  The proportion of patients with serious side-effect-such as hypotension and declining renal function_ increased from 1.3 to 3.3% with aggressive treatment.  Since the risk-benefit ratio tipped towards harm, this study does not support a reduction of systolic BP below 130mmHg.
  46. 46. HTN in DM: Therapy GGooaall BBlloooodd PPrreessssuurree Less Than 130/80 Can We Go to More Lower Target ? 20,358 individuals studied, 1549 (7.6%) had CKD HR of Stroke vs SBP  Lowest Systolic Blood Pressure Is Associated with Stroke in Stages 3 to 4 Chronic Kidney Disease J Am Soc Nephrol 18: 960–966, 2007
  47. 47. Can We Go to More Lower Target ? GGooaall BBlloooodd PPrreessssuurree Less Than 130/80  Bangalore et al. reported a meta-analysis of 13 RCTs with 37 736 patients with DM,IFG or IGT who, in the intensive group, had a systolic pressure ≤135 mm Hg and, in the standard group, ≤140 mmHg.  The more intensive control related to a 10% reduction in all-cause mortality (95% CI 0.83–0.98), a 17% reduction in stroke but a 20% increase in serious adverse events. Systolic BP ≤130 mmHg was related to a greater reduction in stroke but did not affect other cardiovascular events.
  48. 48. Rethinking Lower Blood Pressure Goals for Diabetic Patients with Coronary Artery Disease – Findings from the INternational VErapamil SR – Trandolapril STudy (INVEST) Rhonda M. Cooper-DeHoff, Yan Gong, Eileen M. Handberg, Anthony A. Bavry, Scott J. Denardo, George L. Bakris and Carl J. Pepine on behalf of the INVEST Investigators University of Florida Gainesville, FL
  49. 49. Methods
  50. 50. Results: Outcome Rates INVEST Follow Up n=6400 Tight Control n=2,255 Usual Control n=1,970 Not Controlled n=2,175 p value Outcome # of Events (Event Rate %) Primary Outcome 286 (12.7) 249 (12.6) 431 (19.8) < 0.0001 Nonfatal MI 29 (1.3) 33 (1.7) 67 (3.1) 0.008 Nonfatal Stroke 22 (1.0) 26 (1.3) 52 (2.4) 0.001 Total MI 108 (4.8) 100 (5.0) 185 (8.5) < 0.0001 Total Stroke 34 (1.5) 33 (1.7) 70 (3.2) 0.0001 All Cause Mortality 248 (11.0) 201 (10.2) 334 (15.4) < 0.0001 Extended Follow Up n=4370 Tight Control n=1,389 Usual Control n=1,423 Not Controlled n=1,558 p value Outcome # of Events (Event Rate %) All Cause Mortality 270 (19.4) 259 (18.2) 370 (23.7) 0.01
  51. 51. Results: Outcomes – Tight Control Group (n=2,255) Reference
  52. 52. Summary
  53. 53. Recommendations: Hypertension/Blood Pressure Control AADDAA 22001144 Goals  People with diabetes and hypertension should be treated to a systolic blood pressure goal of <140 mmHg  Lower systolic targets, such as <130 mmHg, may be appropriate for certain individuals, such as younger patients, if it can be achieved without undue treatment burden  Patients with diabetes should be treated to a diastolic blood pressure <80 mmHg ADA. VI. Prevention, Management of Complications. Diabetes Care 2014;37(suppl 1):S36
  54. 54. Recommendations: Hypertension/Blood Pressure Control AADDAA 22001144 Treatment  Patients with blood pressure >120/80 mmHg should be advised on lifestyle changes to reduce blood pressure  Patients with confirmed blood pressure higher than 140/80 mmHg should, in addition to lifestyle therapy, have prompt initiation and timely subsequent titration of pharmacological therapy to achieve blood pressure goals ADA. VI. Prevention, Management of Complications. Diabetes Care 2014;37(suppl 1):S36
  55. 55. Hypertension / BP control • Screening and diagnosis – BP should be measured at every diabetes related visit and at least twice a year. – Patients found to have elevated BP should have high BP confirmed on a separate day. – Threshold for diagnosing hypertension in person with diabetes is BP ≥130/80 mmHg (may consider SBP up to 140 in elderly). – Target for treating BP is <130/80. • Lifestyle therapy for elevated BP – Weight loss if overweight – DASH-style diet with reduced sodium and increased potassium intake – Moderation of alcohol intake – Increased physical activity guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association
  56. 56. The EVIDENCE BASE FOR Non- Pharmaco and Pharmacotherapy
  57. 57. IInntteerrvveennttiioonn TTaarrggeett RReedduuccee ffooooddss wwiitthh aaddddeedd ssooddiiuumm << 22330000 mmgg //ddaayy WWeeiigghhtt lloossss BBMMII <<2255 kkgg//mm22 AAllccoohhooll rreessttrriiccttiioonn LLeessss oorr eeqquuaall ttoo 22 ddrriinnkkss//ddaayy PPhhyyssiiccaall aaccttiivviittyy aatt lleeaasstt 3300 mmiinnuutteess 44 ttiimmeess//wweeeekk DDiieettaarryy ppaatttteerrnnss DDAASSHH ddiieett SSmmookkiinngg cceessssaattiioonn SSmmookkee ffrreeee eennvviirroonnmmeenntt WWaaiisstt CCiirrccuummffeerreennccee -- EEuurrooppiidd,, SSuubb--SSaahhaarraann AAffrriiccaann,, MMiiddddllee EEaasstteerrnn -- SSoouutthh AAssiiaann,, CChhiinneessee -- JJaappaanneessee MMeenn WWoommeenn <<9944 ccmm <<8800 ccmm <<9900 ccmm <<8800 ccmm <<8855 ccmm <<9900 ccmm HTN in DM: Therapy LLiiffee SSttyyllee MMooddiiffiiccaattiioonnss
  58. 58. DASH Diet Plan Type of Food Servings (1600 K cal) Grains (whole grains) 6 per day Vegetables 3 per day Fruits (not tinned juices) 4 per day Low fat milk 2 per day Lean meat, poultry 3 per day Nuts, seeds (dry roast, soak) 3 per week Fats and oils 2 per day Sweets and pastries 0 per day Salt at table & salted foods None
  59. 59. HTN – Lifestyle modifications
  60. 60. Hypertension In Diabetes Does choice of Antihepertensive Drug matter? Yes
  61. 61. Pathophysiology of hypertension in DM Type 1 DM Secondary to nephropathy Activation of the RAAS Type 2 DM Hyperinsulinemia Secondary to insulin resistance Activation of the sympathetic nervous system
  62. 62. Ideal anti HTN drug in DM  Must decrease blood pressure to £ 140/80  Must reduce the RAAS activity, improve ED  Must prevent, improve or arrest proteinuria  Must prevent and protect from CAD, CKD, CHF  Must be favourable on glycemic control  Must improve the dyslipidemia – not worsen it  Must not worsen peripheral arterial disease  Must improve ED and not cause impotence  Must not decrease eGFR and  serum creatinine  Must not raise uric acid, serum potassium
  63. 63. Management Options Diuretics NDHP - CCBs MNT Exercise New BB ACEi, ARB
  64. 64. ACEi or ARB – A must for VP  Antihypertensive, vasoprotective, anti-thrombotic and anti-inflammatory  Inevitable in DM more so in DM + HT/CVD  Reduce CV events, Reduce atherosclerosis  Reduce renal disease - a strong CV risk factor  Metabolically ‘friendly’ drugs in DM  They prevent new onset DM, Nephropathy  Well-tolerated with few side effects
  65. 65. Vascular Protection ACE inhibitor Trials
  66. 66. Heart Outcomes Prevention Evaluation Study A large, simple, randomized trial of Ramipril and vitamin E in patients at high risk for cardiovascular events
  67. 67. Primary Outcome - Ramipril vs Placebo 0.2 0.15 0.1 0.05 0 0 500 1000 1500 Days of Follow-up Kaplan-Meier Rates Ramipril Placebo RR=0.78 (0.70-0.86) P=0.000002
  68. 68. Prespecified Subgroups – Ramipril vs Placebo 0.6 0.8 1.0 1.2 RR (95% CI) CVD+ CVD-Diabetes + Diabetes - No. Of Pts. 8160 1137 3578 5719 Placebo Rate 18.7 10.1 19.8 16.5
  69. 69. Conclusions: Ramipril vs Placebo There is overwhelming evidence that Ramipril prevents:  CV death, strokes and MI  Heart Failure, Revascularization  Development of diabetes  Diabetic microvascular complications and Nephropathy These benefits are consistently observed in a very broad range of high risk patients and in addition to other effective therapies The only adverse event is a 5% excess of cough
  70. 70. SSttuuddyy eennddppooiinnttss PPrriimmaarryy eennddppooiinntt  CCVV mmoorrttaalliittyy ++ nnoonn ffaattaall MMII ++ ccaarrddiiaacc aarrrreesstt SSeeccoonnddaarryy eennddppooiinnttss  TToottaall mmoorrttaalliittyy ++ nnoonn ffaattaall MMII ++ uunnssttaabbllee aannggiinnaa ++ ccaarrddiiaacc aarrrreesstt  HHeeaarrtt ffaaiilluurree  RReevvaassccuullaarriissaattiioonn ((PPCCII//CCAABBGG))  SSttrrookkee
  71. 71. RRiisskk ffaaccttoorrss PPeerriinnddoopprriill ((%%)) PPllaacceebboo ((%%)) HHyyppeerrtteennssiioonn 2277..00 2277..22 DDiiaabbeetteess mmeelllliittuuss 1111..88 1122..88 HHyyppeerrcchhoolleesstteerroollaaeemmiiaa 6633..33 6633..33 CCuurrrreenntt ssmmookkeerr 1155..44 1155..11
  72. 72. PPrriimmaarryy eennddppooiinntt %% CCVV ddeeaatthh,, MMII oorr ccaarrddiiaacc aarrrreesstt RRRRRR:: 200%% 1144 1122 1100 88 66 44 22 PPllaacceebboo aannnnuuaall eevveenntt rraattee:: 22..44%% PPllaacceebboo PPeerriinnddoopprriill pp == 00..00000033 YYeeaarrss 00 00 11 22 33 44 55
  73. 73. Fatal aanndd nnoonn ffaattaall MMII PPllaacceebboo PPeerriinnddoopprriill 1100 88 66 44 22 00 RRRRRR:: 2244%% 00 11 22 33 44 55 YYeeaarrss ((%%)) pp << 00..000011
  74. 74. HHeeaarrtt FFaaiilluurree PPllaacceebboo PPeerriinnddoopprriill RRRRRR:: 3399%% pp == 00..000022 00 11 22 33 44 55 YYeeaarrss ((%%)) 22..00 11..55 11..00 00..55 00..00
  75. 75. SSuubb--ggrroouuppss aannaallyyssiiss 00..55 11..00 2..00 HHyyppeerrtteennssiioonn PPeerriinnddoopprriill PPllaacceebboo RRRRRR ((%%)) bbeetttteerr bbeetttteerr NNoo hhyyppeerrtteennssiioonn DDiiaabbeetteess mmeelllliittuuss NNoo ddiiaabbeetteess mmeelllliittuuss SSttrrookkee//TTIIAA NNoo ssttrrookkee//TTIIAA 1188..66 1199..99 1188..99 1199..00 1155..88 1199..99
  76. 76. The Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial  A double-blind, placebo-controlled, randomized trial  Sponsored by the National Heart, Lung, and Blood Institute  Study medication and additional support provided by Abbott Laboratories/Knoll Marc Pfeffer, MD, Ph.D
  77. 77. Patient Flow T r a n d o l a p r il ( n = 4 1 5 8 ) Target dose 4 mg/day L o s t t o f o l l o w - u p n = 6 6 ( 1 . 6 % ) V i t a l s t a t u s u n k n o w n n = 2 5 ( 0 . 6 % ) P l a c e b o ( n = 4 1 3 2 ) L o s t t o f o l l o w - u p n = 6 8 ( 1 . 6 % ) V it a l s t a t u s u n k n o w n n = 2 0 ( 0 . 5 % ) R a n d o m i z e d ( n = 8 2 9 0 ) Nov 1996 to June 2000 Median follow-up time = 4.8 years Followed until December 31, 2003
  78. 78. Baseline Medical History Characteristic, % Trandolapril Placebo Documented MI 54 56 CABG or PCI 72 72 Diabetes 18 16 Hypertension 46 45 Stroke or TIA 7 6 Current cigarette use 14 15
  79. 79. 1º Outcome and its Components Outcome Trandolapri l n=4158 % Placebo n=4132 % Hazard Ratio (95% CI) P-value CV death, MI, CABG or PCI 21.9 22.5 0.96 (0.88-1.06) NS CV death 3.5 3.7 0.95 (0.76-1.19) NS Non-fatal MI 5.3 5.3 1.00 (0.83-1.20) NS Revasc 17.8 18.0 0.98 (0.88-1.08) NS
  80. 80. Other Outcomes Outcome Trandolap ril n=4158 % Placebo n=4132 % Hazard Ratio (95% CI) P-value CHF hospitalization 2.5 3.2 0.77 (0.60-1.00) 0.048 CHF hospitalization or CHF death 2.8 3.7 0.75 (0.59-0.95) 0.018 Stroke 1.7 2.2 0.76 (0.56-1.04) 0.09 New diabetes 9.8 11.5 0.83 (0.72-0.96) 0.014 Death (any 7.2 8.1 0.89 (0.76-1.04) 0.13 cause)
  81. 81. Onset of New Diabetes1 The PEACE trial investigators. Angiotensin-Converting-Enzyme Inhibition in Stable Coronary Artery Disease (the PEACE trial). N Engl J Med 2004;351:2-58-68 †The analysis included 3432 patients in the trandolapril group and 3472 patients in the placebo group and excluded patients with diabetes at baseline. Patients (%) Placebo (absolute incidence 399/3472) Trandolapril (absolute incidence 336/3432) p=0.01 9.8% 11.5% 12 10 8 6 4 2 0 Risk Reduction 17%
  82. 82. CHF as a primary cause of hospitalization or death1 Risk Reduction 25% p=0.02 3.7% Placebo (absolute incidence 1529/4132) 2.8% Trandolapril (absolute incidence 115/4158) Patients (%) 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 The PEACE trial investigators. Angiotensin-Converting-Enzyme Inhibition in Stable Coronary Artery Disease (the PEACE trial). N Engl J Med 2004;351:2-58-68
  83. 83. Role of AACCEE iinnhhiibbiittoorrss iinn VVaassccuullaarr HHeeaalltthh MMaannaaggeemmeenntt && PPrreevveennttiioonn
  84. 84. IDNT & RENAAL: Study Design IIDDNNTT†† RREENNAAAALL‡‡ PPaattiieennttss:: 11,,771155 HHTTNN ppaattiieennttss wwiitthh ttyyppee 2 11,,551133 HHTTNN ppaattiieennttss wwiitthh ddiiaabbeetteess && nneepphhrrooppaatthhyy ttyyppee 2 ddiiaabbeetteess && SeCr, serum creatinine; EESSRRDD,, eenndd--ssttaaggee rreennaall ddiisseeaassee.. †† LLeewwiiss EEJJ eett aall.. NN EEnnggll JJ MMeedd.. 22000011;;334455::885511--886600.. ‡‡ BBrreennnneerr BBMM eett aall.. NN EEnnggll JJ MMeedd.. 22000011;;334455::886611--886699.. nneepphhrrooppaatthhyy TTrreeaattmmeenntt aarrmmss:: iirrbbeessaarrttaann,, aammllooddiippiinnee,, lloossaarrttaann,, ppllaacceebboo ppllaacceebboo TTaarrggeett BBPP:: 113355//8855 mmmm HHgg 114400//9900 mmmm HHgg AAddjjuunnccttiivvee tthheerraappyy:: PPeerrmmiitttteedd eexxcceepptt AARRBBss,, PPeerrmmiitttteedd iinncclluuddiinngg AACCEE iinnhhiibbiittoorrss,, oorr CCCCBBss CCCCBBss,, eexxcceepptt AARRBBss oorr AACCEE iinnhhiibbiittoorrss PPrriimmaarryy oouuttccoommee:: CCoommppoossiittee ooff ddoouubblliinngg ooff CCoommppoossiittee ooff ddoouubblliinngg ooff SSeeCCrr,, EESSRRDD,, oorr ddeeaatthh SSeeCCrr,, EESSRRDD,, oorr ddeeaatthh SSeeccoonnddaarryy oouuttccoommeess:: CCVV eevveennttss CCVV eevveennttss
  85. 85. IDNT and RENAAL Trial Results Comparison of Major Endpoints RENAAL IDNT Losartan vs control RRR (%) Irbesartan vs control Irbesartan vs amlodipine Amlodipin e vs control Doubling of Creat, 16 (P=0.02) 20 (P=0.02) 23 (P=0.006)- 4 (P=0.69) ESRD, or death Doubling of Creat 25 (P=0.006) 33 (P=0.003) 37 (P<0.001)- 6 (P=0.60) ESRD 28 (P=0.002) 23 (P=0.07) 23 (P=0.07) 0 (P=0.99) Death -2 (P=0.88) 8 (P=0.57) -4 (P=0.8) 12 (P=0.4) CV Morbidity 10 (P=0.26) 9 (P=0.4) -3 (P=0.79) 12(P=0.29) & Mortality Lewis EJ et al. N Engl J Med 2001;345:851-860. Brenner B et al. N Engl J Med 2001;345:861-869.
  86. 86. HTN in DM: Therapy Most Hypertensive Patients Need Multiple Drugs Trial Target BP (mm Hg) 2 3 4 AASK MAP <92 No. of antihypertensive agents 1 UKPDS DBP <85 ABCD DBP <75 MDRD MAP <92 HOT DBP <80 IDNT SBP <135/DBP <85 ALLHAT SBP <140/DBP <90 DBP, diastolic blood pressure; MAP, mean arterial pressure; SBP, systolic blood pressure. Bakris GL et al. Am J Kidney Dis. 2000;36:646-661. Lewis EJ et al. N Engl J Med. 2001;345:851-860. Cushman WC et al. J Clin Hypertens. 2002;4:393-404.
  87. 87. Other Effects of HTN Drugs
  88. 88. •Largest study in Type 2 diabetes patients •The first study to evaluate everyday, real life diabetic patients over a broad range of BP: normotensive and hypertensive •Very well treated patient with a lower rate of cardiovascular events compared to previous studies
  89. 89. How to differentiate AADDVVAANNCCEE :: PPaattiieennttss pprrooffiillee  ADVANCE is different • From UKPDS: diabetic hypertensive patients with SBP at study end > 145 mm Hg and HbA1C= 8.3 • From Micro HOPE: higher risk profile, CAD, diabetes • From HOT and other hypertension studies: no BP target • From LIFE-diabetes: a subgroup with hypertension+LVH • From diabetes studies with ARBS in nephropathy: renal endpoints
  90. 90. Main results Blood pressure
  91. 91. Blood pprreessssuurree rreedduuccttiioonn Δ 5.6 mmHg (95% CI 5.2-6.0); p<0.001 Δ 2.2 mmHg (95% CI 2.0-2.4); p<0.001 Systolic Diastolic Placebo Perindopril-Indapamide Mean Blood Pressure (mmHg) 165 155 145 135 125 115 105 95 85 75 65 R 6 12 18 24 30 36 42 48 54 60 Follow-up (Months) Average BP during follow-up 140.3 mmHg 134.7 mmHg 77.0 mmHg 74.8 mmHg
  92. 92. AAllll--ccaauussee mmoorrttaalliittyy Placebo Perindopril-Indapamide Follow-up (months) 10 0 0 6 12 18 24 30 36 42 48 54 60 Cumulative incidence (%) Relative risk reduction 14%: 95% CI 2-25% p=0.025 5
  93. 93. DDeeaatthhss CCaarrddiioovvaassccuullaarr 6 12 18 24 30 36 42 48 54 60 Follow-up (months) Placebo Perindopril-indapamide NNoonn--ccaarrddiioovvaassccuullaarr 6 12 18 24 30 36 42 48 54 60 Follow-up (months) Placebo Perindopril-indapamide Relative risk reduction 18%; p=0.027 Relative risk reduction 8%; p=0.41 5% 5% Cumulative incidence (%)
  94. 94. Combined pprriimmaarryy oouuttccoommeess MMaajjoorr mmaaccrroo oorr mmiiccrroovvaassccuullaarr eevveenntt 20 10 0 Placebo Perindopril-Indapamide Relative risk reduction 9%: 95% CI: 0 to 17% 0 6 12 18 24 30 36 42 48 54 60 Follow-up (months) p=0.041 Cumulative incidence (%)
  95. 95. PPrriimmaarryy oouuttccoommeess MMaajjoorr mmaaccrroo oorr mmiiccrroovvaassccuullaarr Number of events Per-Ind Placebo (n=5,569) (n=5,571) Relative risk reduction (95% CI) Favours Per-Ind Favours Placebo Combined macro+micro 861 938 9% (0 to 17) Macrovascular 480 520 8% (-4 to 19) Microvascular 439 477 9% (-4 to 20) 0.5 1.0 2.0 Hazard ratio * *2P=0.04 eevveenntt
  96. 96. CCoorroonnaarryy eevveennttss All coronary heart disease 468 535 14% (2 to 24) Major coronary heart disease† 265 294 11% (-6 to 24) Other coronary heart disease‡ 283 324 14% (-1 to 27) *2P=0.02 0.5 1.0 2.0 †Non-fatal MI or death from coronary heart disease ‡Unstable angina requiring hospitalization, coronary revascularization or silent MI * Number of events Per-Ind Placebo (n=5,569) (n=5,571) Relative risk reduction (95% CI) Favours Per-Ind Favours Placebo Hazard ratio
  97. 97. Cerebrovascular eevveennttss Number of events Per-Ind Placebo (n=5,569) (n=5,571) All cerebrovascular disease 286 303 6% (-10 to 20) Major cerebrovascular disease† 215 218 2% (-18 to 19) Other cerebrovascular disease‡ 79 99 21% (-6 to 41) 2.0 * *2P=0.40 0.5 1.0 †Non-fatal stroke or death from Cerebrovascular disease ‡Transient ischaemic attack or subarachnoid haemorrhage Relative risk reduction (95% CI) Favours Per-Ind Favours Placebo Hazard ratio
  98. 98. RReennaall eevveennttss Total renal events 1243 1500 21% (15 to 27)* New or worsening nephropathy 181 216 18% (-1 to 32) New microalbuminuria 1094 1317 21% (14 to 27) 2.0 0.5 1.0 Hazard ratio *2P=<0.01 Number of events Per-Ind Placebo (n=5,569)(n=5,571) Relative risk reduction (95% CI) Favours Per-Ind Favours Placebo
  99. 99. SSuummmmaarryy  Routine treatment of type 2 diabetic patients with Perindopril-indapamide resulted in: • 14% reduction in total mortality • 18% reduction in cardiovascular death • 9% reduction in major vascular events • 14% reduction in total coronary events • 21% reduction in total renal events Benefits appeared to be similar in all major subgroups. Treatment was very well tolerated, with few side effects and adherence similar to that with placebo.
  100. 100. HTN in DM: Therapy WWhhiicchh ccoommbbiinnaattiioonn ?? ACE-I + Thiazide like Diuretics: Excellent 1st line agent  • Increased HTN control  • Reduced hypokalemia  • Cardioprotective  • Increased adherence ADVANCE trial
  101. 101. HTN in DM: Therapy WWhhiicchh ccoommbbiinnaattiioonn ?? ACCOMPLISH trial  The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial indicated that the calcium channel antagonist amlodipine is superior to hydrochlorothiazide in combination treatment with an ACE-I.  In 6946 patients with DM, the number of primary events was 307 in the group treated with amlodipine and 383 in the group treated with hydrochlorothiazide as the add-on to benazepril (P = 0.003), despite a similar reduction of blood pressure in both groups.
  102. 102. ACCOMPLISH trial
  103. 103. Cardiovascular mmoorrttaalliittyy PPeerriinnddoopprriill 44--88mmgg
  104. 104. Total ccoorroonnaarryy eenndd ppooiinntt PPeerriinnddoopprriill 44--88mmgg
  105. 105. Fatal and nnoonn ffaattaall ssttrrookkeess PPeerriinnddoopprriill 44--88mmgg
  106. 106. New oonnsseett ooff ddiiaabbeetteess PPeerriinnddoopprriill 44--88mmgg
  107. 107. SBP aanndd DDBBPP oovveerr ttiimmee PPeerriinnddoopprriill 44--88mmgg
  108. 108. HTN in DM: Therapy AACCEE--II ++ AARRBBss:: LLiimmiitteedd UUttiilliittyy ONTARGET trial  Theoretically attractive: more complete RAAS blockade  Limited BP ↓ and ↓ CVD events vs ACE-I at max dose  ONTARGET RCT: 25,620 with CVD ± Stroke ± DM  Ramipril vs Telmisartan vs R Å T  Minimal BP ↓: 2.4/1.4 mm Hg  No ↓ CVD events  More side effects  ↓ Albuminuria 30-40% vs monoRx with ACE-I or ARB  ? Effects on ESRD?  NKF, 2007: consider if albumin/cr > 500 mg/g on monoRx NEJM 2008; 358:1547 Am J Kid Dis 2007; 49(Suppl 2):S74
  109. 109. HTN in DM: Therapy WWhhiicchh ccoommbbiinnaattiioonn ?? ALTITUDE trial  In the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) trial, the addition of aliskiren to RAAS blockade in patients with T2DM at high risk for cardiovascular and renal events did not result in a decrease in cardiovascular events and may even have been harmful.
  110. 110. β -Blockers and their Effects ββ11 β1 β2 ββ11
  111. 111. b-Blockers and the risk of new-onset diabetes mellitus 28% Increased Risk 0.91 1.28 1.0 Prospective study of 12 550 patients w/o DM, aged 45-64, followed for 6 y. Multivariate analysis of 3804 who had HT at baseline. 25% Increased Risk 17.4 13.0 20 15 10 5 0 Atenolol Losartan LIFE1 New Cases Per 1000 Person-Years (%) 1.5 Ratio 1.0 Hazard .5 Prospective study of 9193 hypertensives, aged 55-80, followed for 4.8 y. Analysis of 7998 w/o DM at baseline. 1. Lancet 2002;359:995–1003. 2. N Engl J Med 2000;342:905–12. ARIC2 0 Atenolol RR 1.25 (1.12-1.37) P<.001 b-blocker RR 1.28 (1.04-1.57) P<.05 Thiazide b-blocker None 1.17 CCB 0.98 ACEI
  112. 112. Name of β B Receptor ISA Comment Acebutolol β 1 Yes Not Good Penbutolol β 1, β 2 Yes Bad Pindolol β 1, β 2 Yes Bad Propranolol β 1, β 2 No No Good Nadolol β 1, β 2 No No Good Timolol β 1, β 2 No No Good Atenolol β 1 No OK Metoprolol β 1 No Very Good Nebivolol β 1 No Excellent Bisoprolol β 1 No Excellent Labetalol a, β 1, β 2 No Emergency
  113. 113. Advantages of Carvedilol  Neutral on glycemic control  Improves insulin resistance, metabolic syndrome and lipid neutral  Add on to RAAS blockade in DM  Improves MAU/ ACR and ED  First β blockade approved for CHF GEMINI trial and OPTIMIZE-HF Study
  114. 114. RReeccoommmmeennddaattiioonnss:: HHyyppeerrtteennssiioonn//BBlloooodd PPrreessssuurree CCoonnttrrooll Treatment (3) • Pharmacological therapy for patients with diabetes and hypertension C – A regimen that includes either an ACE inhibitor or angiotensin II receptor blocker; if one class is not tolerated, substitute the other • Multiple drug therapy (two or more agents at maximal doses) generally required to achieve blood pressure targets B • Administer one or more antihypertensive medications at bedtime A ADA. VI. Prevention, Management of Complications. Diabetes Care 2014;37(suppl 1):S36
  115. 115. Who Should Receive ACEi or ARB Therapy? • Clinical Macrovascular disease [grade A, level A] or • ≥55 years of age [grade A, level A for those with additional CVD risk factors or end organ damage; grade D, consensus for all others] or • Microvascular disease [grade D, consensus] At doses that have shown vascular protection [perindopril 8 mg daily (EUROPA), ramipril 10 mg daily (HOPE), telmisartan 80 mg daily (ONTARGET)] Among women with childbearing potential, ACEi or ARB should only be used in the presence of proper preconception counseling & reliable contraception. Stop ACEi or ARB either prior to conception or immediately upon detection of pregnancy guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association 2013 EUROPA Investigators, Lancet 2003;362(9386):782-788. HOPE study investigators. Lancet. 2000;355:253-59. ONTARGET study investigators. NEJM. 2008:358:1547-59
  116. 116. HTN Rx. Algorithm in DM BP > 140/80 (2 readings) No TOD / MAU ACE/ARB + TLC 1 M TLC cont. Yes Goal BP £140/80 No Add thiazide like Diuretic Add Amlodipine Verapamil/ Diltizem Yes Yes No >140/90/MAU/TOD 1 Month Add new bB /aB No No No Yes Yes 1 Month 1 Month 1 Month ?
  117. 117. Drug therapy in Hypertension with Diabetes 1st potion ACEIs Monotherapy OR 2nd option ARBs + Combination  Thiazide like diuretic (low dose→Indapamide) Long acting calcium channel blockers (amlodipine) B blocker (cardioselective-e.g. Carvedilol, metoprolol)
  118. 118. Take home Message  HTN in DM is serious; So manage aggressively ( new Target <140/80mmHg)  TLC, Lipid control, Glycemic targets – VP is a must  drugs that act on the RAA axis are recommended for first-line use  ACE inhibitor should be considered first, but ARB should be substituted if ACE inhibitor not tolerated  MAU/ACR must for all DM – Predict CAD, CKD  Typically 2 or more drugs are needed for HTN Rx.  use a diuretic, and in a dosage, which has been shown effective in clinical endpoint trials  New b B, Carvedilol, CCBs are add-on drugs
  119. 119. Vascular Protection in DM 1. Atorvastatin (Lipid management) 2. ASA (Acetyl Salicylic Acid) – (enteric coated) 3. ACE inhibitors or ARBs for BP goal (140/80 as well as Control of Nephropathy, Proteinuria (MAU) 4. A1c control 7%(Glycemic control) 5. Cigarette smoking cessation 6. Weight and waist management 7. Physical Activity – at least 2 km/d x 5 d
  120. 120. Thank you
  121. 121. Highest Percentage Reduction of the Risk of Diabetic Complications in People with Type 2 Diabetes shown in Recent Studies Strategy Complication Reduction of Complication Lipid control · Coronary heart disease mortality · Major coronary heart disease event · Any atherosclerotic event · Cerebrovascular disease event ↓36%¹ ↓55%¹ ↓37%¹ ↓62%¹ Blood Pressure Control · Cardiovascular disease · Heart failure · Stroke · Diabetes-related deaths ↓51%² ↓56%³ ↓44%³ ↓32%³ Blood Glucose Control · Heart Attack ↓37%³ 1 The 4S Study 2 Hypertension Optimal Treatment (HOT) Randomised Trial 3 UKPDS

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