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HYPERTENSION 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. 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 25% Prevalence of Obesity among US Adults, 1991 and 2001 Obesity 1991 2001 Mokdad AH, et al., JAMA, 2003:289;76-80. No Data 10% Prevalence of Diabetes among US Adults, 1991 and 2001 Diabetes 1991 2001 Mokdad AH, et al., JAMA, 2003:289;76-80. Hyperglycemia Dyslipidemia Hyperinsulinemia Hypertension Insulin resistance Obesity Insulin deficiency Metabolic Syndrome (mg/dL) Diagnostic 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 + IGTIFG 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;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 0 5 10 15 20 25 30 35 40 45 20-29 30-39 40-49 50-59 60-69 ?70 Men (n=4265) Women (n=4559) Hypertension l Hyperinsulinemia can enhance renal sodium reabsorption and vascular reactivity l Angiotensinogen from fat cells can increase angiotensin II and thus blood pressure l Both systolic and diastolic blood pressure increase with increasing body mass index Subcutaneous Fat Abdominal Muscle Layer Intra-abdominal Fat Visceral Adiposity: The Critical Adipose Depot Heart Disease Insulin Resistance Metabolic Syndrome Adipocytokines + Fatty Acids Liver 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 IIAngiotensinogen 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 Enhanced Lipolysis FreeFA IL- 6, TNF- , and RAS Activation Reduced Adiponectin Atherosclosis Large (Insulin resistant) Fat Cells RR .66, 95% Cl .46 - .94 RR .66, 95% Cl .55 - .79 DiabetesNondiabetes 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;276:1886-1892. 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 12.4 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 Better *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 | | | | Tight Glucose Control Tight BP Control *P 160 or DBP 100 mmHg) 2-drug combination for most (usually thiazide-type diuretic 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 achieved. 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, chronic 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 AADiuretic JNC 7 Compelling Indications for Specific 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 n 140/90 mmHg for uncomplicated hypertension n 130/80 mmHg for patients with diabetes or nondiabetic renal disease and proteinuria 1 g/d n Combination antihypertensive therapy if SBP 15 mmHg or DBP 10 mmHg above target n 1g/24 h (Consider for All High-Risk Patients) Goal BP: 130/80 mmHg Hypertension and Diabetes American Diabetes Association “There 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 et al. Diabetes Care. 2003;26(suppl):S80S82. ADA Guidelines For Management of Hypertension in Adults With Diabetes Systolic Diastolic Goal (mmHg) 130 80 Behavioral therapy alone 130139 8089 (maximum 3 months) then add pharmacologic treatment Behavioral therapy + 140 90 pharmacologic treatment Arauz-Pacheco C et al. Diabetes Care. 2003;26(suppl):S80S82. UKPDS Mean Blood Pressures Less tight control 160/94 154/87 Tight control 161/94 144/82 Difference 1/0 10/5 P 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;317:703-713. 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 Cases 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 = 55) LIFE Study: Results P .001 P .05 Dahlf B et al. Lancet. 2002;359:995-1003. 25% decrease in RR 40* 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 new 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. 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 Clin 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 titrate or combine medications, despite knowing the pa