1、HYPERTENSION & DIABETES: “A DANGEROUS DUO”,Thomas D. Giles, M.D. Louisiana State University Medical School New Orleans, Louisiana,METABOLIC SYNDROME DIABETES & HYPERTENSION,Thomas D. Giles, M.D. Louisiana State University Medical School New Orleans, Louisiana,Data from King H et al. Diabetes Care. 1
2、998;21:1414-1431.,Top Three Countries for Diabetes,CV Mortality Risk Doubles with Each 20/10 mm Hg BP Increment*,*Individuals aged 40-69 years, starting at BP 115/75 mm Hg. CV, cardiovascular; SBP, systolic blood pressure; DBP, diastolic blood pressure Lewington S, et al. Lancet. 2002; 60:1903-1913.
3、 JNC VII. JAMA. 2003.,CV mortality risk,SBP/DBP (mm Hg),0,1,2,3,4,5,6,7,8,115/75,135/85,155/95,175/105,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, car
4、diovascular; SBP, systolic blood pressure. Stamler J et al. Diabetes Care. 1993;16:434-444.,200,End Point Hazard Ratios Associated With Increase in SBP,Hazard ratio,Adler A et al. BMJ. 2000;321:412419.,Updated mean SBP (mm Hg),Characteristics of Adults 20 Years With Previously Diagnosed Diabetes,Cha
5、racterisitic,Saydah SH et al. JAMA. 2004;291:335-342.,Mean body mass index Obese (%)HypertensionTaking antihypertensive medicationHypercholesterolemiaTaking lipid-controlling medication,NHANES III,29.9 41.654.877.044.927.7,NHANES 1999-2000,32.3 54.651.485.254.556.1,P,.002 .008.32.05.02.001,Saydah SH
6、 et al. JAMA. 2004;291:335-342.,Percentage of Adults With Recommended Levels of Vascular Disease Risk Factors in NHANES III and NHANES 1999-2000,NHANES III (n=1204),NHANES 1999-2000 (n=370),60,50,40,30,20,10,0,Adults (%),HbA1c Level 7%,BP 130/80 mm Hg,Total Cholesterol Level 200 mg/dL (5.18 mmol/L),
7、Vascular Disease Risk Factors,Metabolic Syndrome: NCEP/ATP III Definition,Presence of at least 3 of 5 risk factors:Abdominal obesityElevated blood pressureElevated fasting glucose Elevated triglyceridesLow HDL-C,Third Report of the National Cholesterol Education Program Expert Panel. Executive Summa
8、ry; May 2001. NIH # 01-3670.,No Data 25%,Prevalence of Obesity among US Adults, 1991 and 2001,Obesity,1991,2001,Mokdad AH, et al., JAMA, 2003:289;76-80.,Prevalence of Diabetes among US Adults, 1991 and 2001,Diabetes,1991,2001,Mokdad AH, et al., JAMA, 2003:289;76-80.,Metabolic Syndrome,(mg/dL),Diagno
9、stic Criteria for Diabetes, IFG, and IGT,3.5,4.5,5.5,6.5,7.5,8.5,2.5,4.5,6.5,8.5,10.5,12.5,14.5,Normal glucose,IGT,IFG + IGT,IFG,2-h Postload Glucose (mmol/L),Fasting Glucose (mmol/L),(mg/dL),140,200,126,110,Diabetes,IFG = impaired fasting glucose. American Diabetes Association. Diabetes Care. 2003;
10、26(suppl 1):S5-S20.,7.0,11.1,Metabolic Syndrome: Prevalence Increases With Age,Prevalence, %,Age, yr,Adapted from: Ford ES, et al. JAMA. 2002;287:356-359.,47 million or 23% of US Adults Have Metabolic Syndrome,Hypertension,Hyperinsulinemia can enhance renal sodium reabsorption and vascular reactivit
11、y Angiotensinogen from fat cells can increase angiotensin II and thus blood pressure Both systolic and diastolic blood pressure increase with increasing body mass index,Visceral Adiposity: The Critical Adipose Depot,Heart Disease,Insulin Resistance,Metabolic Syndrome,Adipocytokines + Fatty Acids,Liv
12、er,Abdominal Adipocytes,Role of Abdominal Adipocytes in Insulin Resistance and Heart Disease, Hepatic Insulin Clearance, Portal FFA, Plasma Insulin, Renal Na+ Reabsorption,Hypertension,Visceral Fat Stores,Fat Cell Products and Hypertension,Vascular Constriction,Angiotensin I,Angiotensin II,Angiotens
13、inogen,Bray GA. Contemp Diagn Obes. 1998.,Cardiometabolic Syndrome:,( Central Fat) (Fatty liver(NASH) (CRP) (Endothelial Dysfunction) Small, dense LDL triglyceridemia HDL Hypertension PAI-1/PA Albuminuria,Visceral Obesity,EnhancedLipolysis FreeFA IL- 6, TNF- , and RAS Activation Reduced Adiponectin,
14、Atherosclosis,Large (Insulin resistant) Fat Cells,RR .66, 95% Cl .46 - .94,RR .66, 95% Cl .55 - .79,Diabetes,Nondiabetes,Systolic Hypertension in the Elderly Program (SHEP): Influence of Diabetes on Cardiovascular Event Rates,RR, relative risk; Cl, confidence interval. Curb JD, et al. JAMA. 1996;276
15、:1886-1892.,35,15,30,25,20,5,0,10,5-Year Cumulative Event Rates for All Major Cardiovascular Events (%),Active treatment,Placebo,Mortality,Mortality and Morbidity in Non-Diabetic Patients,CV Endpoints,Coronary,Stroke,SHEP,SYST-EUR,-15,-18,-34,-30,-38,-39,-19,-22,21.8,21.6,35.8,28.9,15.0,12.3,15.2,12
16、.4,50%,0,-50%,-100%,Placebo Better,*Number of endpoints / 1000 patient years,Rate in Placebo Group*,SHEP,SYST-EUR,Active Better,Mortality,CV Endpoints,Stroke,Coronary,Active Better,SHEP,SYST-EUR,Rate in Placebo Group*,SHEP,SYST-EUR,35.6,45.1,63.0,57.6,28.8,26.6,32.2,21.3,-100%,-50%,0,50%,Placebo Bet
17、ter,*Number of endpoints / 1000 patient years,-25,-55,-34,-59,-22,-73,-56,-57,Mortality and Morbidity in Diabetic Patients,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,
18、|,|,|,|,Tight Glucose Control,Tight BP Control,*P 0.05,-50 -,-40 -,-30 -,0 -,Stroke,Any DM,End Point,DM Death,Microvascular,Complications,Reduction in Risk (%),UKPDS. BMJ. 1998:317;703-712.,-20 -,-10 -,Tight BP Control vs. Tight Glucose Control,Hypertension and Diabetes Reduction in Total Mortality,
19、0%,20%,40%,60%,80%,100%,Captopril (UKPDS)Atenolol(UKPDS)Diuretic (SHEP)Nitrendipine (Syst-Eur)Nitrendipine (Syst-China),JNC 7 Classification and Management of Blood Pressure,SBP, systolic blood pressure; DBP, diastolic blood pressure; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin r
20、eceptor blocker; BB, beta blocker; CCB, calcium channel blocker. *Treatment determined by highest BP category. *Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension. Treat patients with chronic kidney disease or diabetes to BP goal of 130/80 mmHg. Chobanian
21、 AV et al. JAMA. 2003;289:25602572.,No antihypertensive drug indicatedThiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combo2-drug combo for most (usually thiazide-type diuretic and ACEI or ARB or BB or CCB),Drug(s) for compelling indicationsDrug(s) for the compelling indication
22、s Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed,EncourageYesYesYes,and 80or 8089or 9099or 100,120120139140159160,NormalPrehypertensionStage 1 HypertensionStage 2 Hypertension,Category,SBP* mm Hg,DBP* mm Hg,Lifestyle modification,With Compelling Indications,Without Compelling
23、 Indications,Considerations for Initial Therapy,JNC 7 Algorithm for the Treatment of Hypertension,*Compelling IndicationsHeart failurePost-MIHigh coronary artery disease riskDiabetesChronic kidney diseaseRecurrent stroke prevention,Not at Goal Blood Pressure (140/90 mmHg) (130/80 mm Hg for those wit
24、h diabetes or chronic kidney disease),Initial Drug Choices,Drug(s) for the compelling indications* Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed.,Lifestyle Modifications,Stage 2 Hypertension (SBP 160 or DBP 100 mmHg) 2-drug combination for most (usually thiazide-type diureti
25、c and ACEI, or ARB, or BB, or CCB).,Stage 1 Hypertension (SBP 140159 or DBP 9099 mmHg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination.,Without Compelling Indications,Not at Goal Blood Pressure,Optimize dosages or add additional drugs until goal blood pressure is ac
26、hieved. Consider consultation with hypertension specialist.,With Compelling Indications,Chobanian AV et al. JAMA. 2003;289:25602572.,BB, beta blocker; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; AA, aldosterone antagonist; CHF, chro
27、nic heart failure; MI, myocardial infarction; CAD, coronary artery disease; DM, diabetes mellitus Chobanian AV et al. JAMA. 2003;289:25602572.,CHF Post-MI CAD risk Diabetes mellitus Renal disease Recurrent stroke prevention, , ,BB, ,ACEI, ,ARB, ,CCB, ,AA,Diuretic,JNC 7 Compelling Indications for Spe
28、cific Antihypertensive Agents,Based on Favorable Outcome Data From Clinical Trials,Douglas JG et al. Arch Intern Med. 2003;163:525541.,ISHIB Blood Pressure Targets International Society on Hypertension In Blacks,140/90 mmHg for uncomplicated hypertension 130/80 mmHg for patients with diabetes or non
29、diabetic renal disease and proteinuria 1 g/d Combination antihypertensive therapy if SBP 15 mmHg or DBP 10 mmHg above target 140/90 mmHg (eg, 130/80 mmHg) with history of cardiovascular event, stroke, or TIA; or evidence of target organ damage, including microalbuminuria; or CHD or high risk for CHD
30、,ISHIB Algorithm for the Treatment of Hypertension,Douglas JG et al. Arch Intern Med. 2003;163:525541.,Patient With Elevated BP,Assess Cardiovascular Risk Begin Therapeutic Lifestyle Changes Set Target BP,Uncomplicated Hypertension Goal BP: 140/90 mmHg,If BP 155/100 mmHg, Initiate Monotherapy*,If BP
31、 155/100 mmHg, Initiate Combination Therapy,If BP 145/90 mmHg, Initiate Monotherapy or Combination Therapy Including a RAS-Blocking Agent,If BP 145/90 mmHg, Initiate Combination Therapy Including a RAS-Blocking Agent,Not at BP Goal? Intensify Therapeutic and Lifestyle Changes,Not at BP Goal? Intensi
32、fy Therapeutic and Lifestyle Changes,Add a Second Agent From a Different Class or Increase Dose,Increase Dose or Add a Third Agent From a Different Class,Increase Dose or Add a Third Agent From a Different Class,Add a Second Agent From a Different Class or Increase Dose,Not at BP Goal With 3 Agents?
33、 Consider Factors That May Decrease Compliance or Efficacy With Current Regiment Consider Referral to a BP Specialist,Diabetes or Nondiabetic Renal Disease With Proteinuria 1g/24 h (Consider for All High-Risk Patients) Goal BP: 130/80 mmHg,Hypertension and Diabetes American Diabetes Association,“The
34、re is a strong epidemiological connection between hypertension in diabetes and adverse outcomes of diabetes. Clinical trials demonstrate the efficacy of drug therapy versus placebo in reducing these outcomes and in setting an aggressive blood pressurelowering target of 130/80 mmHg.”,Arauz-Pacheco C
35、et al. Diabetes Care. 2003;26(suppl):S80S82.,ADA Guidelines For Management of Hypertension in Adults With Diabetes,Systolic Diastolic Goal (mmHg) 130 80Behavioral therapy alone 130139 8089 (maximum 3 months) then add pharmacologic treatmentBehavioral therapy + 140 90 pharmacologic treatment,Arauz-Pa
36、checo C et al. Diabetes Care. 2003;26(suppl):S80S82.,UKPDS Mean Blood Pressures,Less tight control 160/94 154/87Tight control 161/94 144/82Difference 1/0 10/5P value n.s. 0.0001,Baseline (mm Hg),Mean BP over 9 yrs (mm Hg),UKPDS, United Kingdom Prospective Diabetes Study. UKPDS 38. BMJ. 1998;317:703-
37、713.,CAPPP Study: Results,Data from Hansson L et al. Lancet. 1999;353:611-616.,P .001,13% risk reduction in diabetes,P .04,Conventional,Captopril,SOLVD: Enalapril Reduces New-Onset Diabetes Risk in CHF Patients,P .0001,16.5% absolute risk reduction in development of diabetes,No. of New Diabetes Case
38、s,N = 291,Vermes E et al. Circulation. 2003;107:1291-1296.,SOLVD: Enalapril Reduces Diabetes Risk in CHF Patients With IFG,% Diabetes-Free,1,2,3,4,5,Time (y),Vermes E et al. Circulation. 2003;107:1291-1296.,25,50,75,100,0,Enalapril,Placebo,45% risk reduction P .0001,Patients With IFG at Baseline (n
39、= 55),LIFE Study: Results,P .001,P .05,Dahlf B et al. Lancet. 2002;359:995-1003.,25% decrease in RR,CHARM-Preserved Development of new diabetes,47 77 0.60 0.005 (0.41-0.86),Number of cases HR p-value Candesartan Placebo (CI),ALLHAT: Incidence of New-Onset Diabetes at 4 Years*,*43.2% lower onset of n
40、ew diabetes with lisinopril compared to chlorthalidone (P .001 at 4 y). ALLHAT Officers and Coordinators. JAMA. 2002;288:2981-2997.,Chlorthalidone,Amlodipine,Lisinopril,P .001,P = .04,11.6%,9.8%,8.1%,%,AASK MAP 92,Target BP (mm Hg),Multiple Antihypertensive Agents Are Needed to Achieve Target BP,No.
41、 of antihypertensive agents,1,UKPDS DBP 85,ABCD DBP 75,MDRD MAP 92,HOT DBP 80,Trial,2,3,4,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 C
42、lin Hypertens. 2002;4:393-404.,IDNT SBP 135/DBP 85,ALLHAT SBP 140/DBP 90,JNC VII on Combination Therapy,“When BP is more than 20/10 mm Hg above goal, consideration should be given to initiating therapy with two drugs, either as separate prescriptions or in fixed-dose combinations.” “Failure to titra
43、te or combine medications, despite knowing the patient is not at goal BP, represents clinical inertia and must be overcome.”,JNC VII. JAMA. 2003.,CONCLUSION,Diabetes, the metabolic syndrome and hypertension constitute a particularly dangerous combination as regards cardiovascular morbidity and morta
44、lity. The primary therapeutic goal is to reduce blood pressure. The ACE inhibitors and ARBs may have additional properties that warrant their use in diabetes and the metabolic syndrome, whereas thiazide diuretic monotherapy may not.,Unadjusted Hazard Ratios with 95% CI,Relative Risk of New Diabetes,Verapamil SR Strategy,Atenolol Strategy,HR,CI = confidence interval; HR = hazard ratio,Risk of New Diabetes by Add-on Drug Dose,Reduced Risk,Increased Risk,Trandolapril (mg),Verapamil SR,Atenolol,HCTZ (mg),Verapamil SR,Atenolol,Verapamil SR,Trand/HCTZ (mg),Strategy,Add-On Therapy Dose,Atenolol,HR,
