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Hypertension and Stroke Prevention

Hypertension and Stroke Prevention. Henry R. Black, MD Clinical Professor of Internal Medicine Director of Hypertension Research New York University School of Medicine New York, New York. 10,000. All causes. 1000. Heart disease. Deaths per 100,000 Population (log scale). Cancer. Stroke.

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Hypertension and Stroke Prevention

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  1. Hypertension and Stroke Prevention Henry R. Black, MD Clinical Professor of Internal Medicine Director of Hypertension Research New York University School of Medicine New York, New York

  2. 10,000 All causes 1000 Heart disease Deaths per 100,000 Population(log scale) Cancer Stroke 100 Unintentional injuries CLRD 10 1950 1960 1970 1980 1985 1990 1995 2002 Year Leading Causes of Death for All Ages, United States CLRD=chronic lower respiratory diseases. Centers for Disease Control and Prevention. Available at: http://www.cdc.gov/nchs/data/hus/ hus05.pdf. Accessed July 4, 2006.

  3. Ezzati M, et al. PLoS Med. 2005;2(5):e133. Global Mortality and Burden of Disease Attributable to CVD and Their Major Risk Factors for People Aged 30 Years CVD=cardiovascular disease.VD

  4. Lopez AD, et al. Lancet. 2006;367:1747-1757. Leading Causes of Premature Death (YLL) and Deaths Worldwide, 2001 Proportion of Deaths or Total Years of Life Lost (%) YLL=years of life lost.

  5. Lopez AD, et al. Lancet. 2006;367:1747-1757. Mortality Due to Leading Global Risk Factors Attributable Deaths in Thousands

  6. Disease Burden (DALYs) 2001: Age Group 70-79 Years15 Leading Causes, Both Sexes, World DALYs=disability-adjusted life-years. Adapted from Mathers CD, et al. Disease Control Priorities Project. Working paper No. 18. Revised January 2005.

  7. 256 256 128 128 64 64 32 32 16 16 8 8 4 4 2 2 1 1 0 0 120 140 160 180 120 140 160 180 Stroke and IHD Mortality vs Usual SBP by Age Age at risk: Age at risk: Stroke 80-89 y IHD 80-89 y 70-79 y 70-79 y 60-69 y 60-69 y 50-59 y 50-59 y IHD Mortality(floating absolute risk and 95% CI) 40-49 y Mortality(floating absolute risk and 95% CI) Usual SBP (mm Hg) Usual SBP (mm Hg) IHD=ischemic heart disease; SBP=systolic blood pressure. Adapted from Lewington S, et al. Lancet. 2002;360:1903-1913.

  8. BP Reductions as Small as 2 mm Hg Reduce the Risk of CV Events by Up to 10% • Meta-analysis of 61 prospective, observational studies • 1 million adults • 12.7 million person-years 7% reduction in risk of IHD mortality 2-mm Hg decrease in mean SBP 10% reduction in risk of stroke mortality Lewington S, et al. Lancet. 2002;360:1903-1913.

  9. CV Mortality Risk Doubles With Each 20/10-mm Hg BP Increment* 8 7 6 5 CV Mortality Risk 4 3 2 1 0 115/75 135/85 155/95 175/105 SBP/DBP (mm Hg) DBP=diastolic blood pressure. *Individuals aged 40-69 years, starting with BP 115/75 mm Hg. Lewington S, et al. Lancet. 2002;360:1903-1913. Chobanian AV, et al. JAMA. 2003;289:2560-2572.

  10. Older ALLHAT ATMH CAPPP EWPHE HEP HOPE HOT L vs H HOT M vs H INSIGHT MIDAS/NICS/VHAS MRC2 NORDIL PART2/SCAT PATS PROGRESS/Per PROGRESS/Com RCT70-80 RENAAL SHEP STONE STOP 1 STOP2/CCBs STOP2/ACEIs -5 0 5 10 15 20 25 Syst-China Syst-Eur UKPDS C vs A UKPDS L vs H Odds Ratio for CV Events and Systolic BP Difference: Recent and Older Trials 1.50 Recent trials Recent Older trials placebo AASK L vs H ABCD/NT L vs H 1.25 Older trials active ALLHAT/Aml ALLHAT/Lis ALLHAT/Lis 65 P<.0001 ALLHAT/Lis Blacks 1.00 ANBP2 CONVINCE Odds Ratio(experimental/reference) DIABHYCAR ELSA MRC1 IDNT2 0.75 LIFE/ALL LIFE/DM NICOLE PREVENT 0.50 SCOPE 0.25 Difference (reference minus experimental) in SBP (mm Hg) Staessen JA, et al. J Hypertens. 2003;21:1055-1076.

  11. 1.50 1.25 1.00 0.75 0.50 0.25 Importance of Lowering BP Meta-Regression Analysis Yellow circles indicate actively controlled trials. Blue circles indicate placebo-controlled studies or trials with an untreated control group. Negative values indicate tighter BP control for control treatment vs reference. CV Mortality MIDAS/NICS/VHAS P=.002 UKPDS C vs A NORDIL INSIGHT HOT L vs H STOP2/ACEIs HOT M vs H MRC1 MRC2 STOP2/CCBs PATS Odds Ratio (experimental/reference) SHEP HEP STONE Syst-Eur EWPHE CAPPP HOPE UKPDS L vs H PROGRESS/Com RCT70-80 Syst-China STOP1 PART2/SCAT ATMH 0 -5 0 5 10 15 20 25 Difference (reference treatment minus experimental treatment) in SBP (mm Hg) Staessen JA, et al. Hypertens Res. 2005;28:385-407.

  12. 1.50 1.25 1.00 0.75 0.50 0.25 -10 -8 -6 -4 -2 0 2 4 BP-Lowering Treatment Trialists Stroke CHD 1.50 Relative Risk of Stroke 1.25 1.00 Relative Risk of CHD 0.75 0.50 0.25 4 -10 -8 -6 -4 -2 0 2 SBP Difference Between Randomized Groups (mm Hg) SBP Difference Between Randomized Groups (mm Hg) Turnbull F, et al. Lancet. 2003;362:1527-1535.

  13. BP Results by Treatment Group Chlorthalidone Amlodipine Lisinopril 90 150 85 145 mm Hg BP 80 140 mm Hg BP 75 135 70 130 0 1 2 3 4 5 6 0 1 2 3 4 5 6 Years Years Compared tochlorthalidone: SBP significantly higher in theamlodipinegroup (1 mm Hg) and thelisinoprilgroup (2 mm Hg). Compared tochlorthalidone: DBP significantly lower in theamlodipinegroup (1 mm Hg). Furberg CD, et al. JAMA. 2002;288:2981-2997.

  14. Stroke—Subgroup Comparisons—RR (95% CI) Total 0.93 (0.82, 1.06) Total 1.15 (1.02, 1.30) Age <65 y 0.93 (0.73, 1.19) Age <65 y 1.21 (0.97, 1.52) Age 65 y 0.93 (0.81, 1.08) Age 65 y 1.13 (0.98, 1.30) Men 1.00 (0.85, 1.18) Men 1.10 (0.94, 1.29) Women 0.84 (0.69, 1.03) Women 1.22 (1.01, 1.46) Black 0.93 (0.76, 1.14) Black 1.40 (1.17, 1.68) Non-Black 0.93 (0.79, 1.10) Non-Black 1.00 (0.85, 1.17) Diabetic 0.90 (0.75, 1.08) Diabetic 1.07 (0.90, 1.28) Non-Diabetic 0.96 (0.81, 1.14) Non-Diabetic 1.23 (1.05, 1.44) 0.50 1 2 0.50 1 2 Amlodipine Better Chlorthalidone Better Lisinopril Better ChlorthalidoneBetter P=.01 for interaction. Furberg CD, et al. JAMA. 2002;288:2981-2997.

  15. VALUE: Fatal and Non-fatal Stroke 6 5 4 3 2 1 0 Valsartan-based regimen Amlodipine-based regimen Proportion of Patients With First Event (%) HR=1.15; 95% CI=0.98-1.35; P =.08 0 6 12 18 24 30 36 42 48 54 60 66 Time (months) Number at risk Valsartan 7649 7494 7448 7312 7170 7022 6877 6692 6093 3859 1516 6515 7596 Amlodipine 7499 7455 7334 7195 7055 6918 6744 6163 3846 1532 6587 VALUE=Valsartan Antihypertensive Long-term Use Evaluation. Julius S, et al. Lancet. 2004;363:2022-2031.

  16. VALUE: Outcome and SBP Differencesat Specific Time Periods: Stroke STROKE Time Interval  SBP (months) (mm Hg) Odds Ratios and 95% CIs Overall study 2.2 0–3 3.8 3–6 2.3 6–12 2.0 12–24 1.8 24–36 1.6 36–48 1.4 Study end 1.7 0.25 0.5 1.0 2.0 4.0 Favors Valsartan Favors Amlodipine Julius S, et al. Lancet. 2004;363:2022-2031.

  17. VALUE: SBP in Study Sitting SBP by Time and Treatment Group 155 Valsartan (N=7649) Amlodipine (N=7596) 150 mm Hg 145 140 135 1 2 3 4 6 12 18 24 30 36 42 48 54 60 66 Baseline Months (or final visit) Difference in SBP Between Valsartan and Amlodipine 5.0 4.0 3.0 mm Hg 2.0 1.0 0 1 2 3 4 6 12 18 24 30 36 42 48 54 60 66 Months (or final visit) Julius S, et al. Lancet. 2004;363:2022-2031.

  18. VALUE: Analysis of Results Based on BP Control at 6 Months Patients Treated With Valsartan Patients Treated With Amlodipine Odds Ratio Odds Ratio Fatal/Non-fatal cardiac events 0.76 (0.66–0.88) ** 0.73 (0.63–0.85) ** Fatal/Non-fatal stroke 0.60 (0.48–0.74) 0.50 (0.39–0.64) ** ** ** 0.79 (0.69–0.92) ** 0.79 (0.69–0.91) All-cause death 0.91 (0.71–1.17) 0.83 (0.66–1.03) Myocardial infarction Heart failure hospitalizations 0.62 (0.50–0.77) ** 0.64 (0.52–0.79) ** 0.4 0.6 0.8 1.0 1.2 0.4 0.6 0.8 1.0 1.2 Controlled Patients* (n=5253) Non-controlled Patients (n=2396) Controlled Patients* (n=5502) Non-controlled Patients (n=2094) Hazard Ratio 95% CI Hazard Ratio 95% CI *SBP<140 mm Hg by 6 months. **P<.05. Weber MA, et al. Lancet. 2004;363:2049-2051.

  19. VALUE: Analysis of Results Based on BP Control at 6 Months Conclusions: • Regardless of the class of agent used, rigorous and prompt BP control provides powerful cardiovascular benefits—these data validate guidelines recommendations Weber MA, et al. Lancet. 2004;363:2049-2051.

  20. 2.0 1.0 0.5 Hazard Ratio PROGRESSCombination (ACEI + Diuretic) Lowered BP by 12/5 mm Hg Single drug (ACEI) Lowered BP by 5/3 mm Hg Events (No.) Risk reduction Favors Active Favors Placebo Active Placebo (95% CI) Stroke Combination 150 255 43% (30%-54%) 5% (-19%-23%) Single drug 157 165 Total 307 420 28% (17%-38%) Major vascular events Combination 231 367 40% (29%-49%) Single drug 227 237 4% (-15%-20%) Total 458 604 26% (16%-34%) PROGRESS=Perindopril Protection Against Recurrent Stroke Study. Tests for homogeneity (combination vs single drug): both <.001. MacMahon S, et al. Lancet. 2001;358:1033-1041.

  21. Algorithm for Treatment of Hypertension Lifestyle Modifications Not at Goal BP (<140/90 mm Hg) (<130/80 mm Hg for those with diabetes or chronic kidney disease) Initial Drug Choices Without Compelling Indications With Compelling Indications Stage 1 Hypertension(SBP 140–159 or DBP 90–99 mm Hg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination Stage 2 Hypertension (SBP >160 or DBP >100 mm Hg) 2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB) Drug(s) for the compelling indications Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed Not at Goal BP Optimize dosages or add additional drugs until goal BP is achieved.Consider consultation with hypertension specialist

  22. Goal of Antihypertensive Therapy • <140 mm Hg and <90 mm Hg for most patients • <130 mm Hg and <80 mm Hg for patients with • Diabetes • Heart failure • Chronic kidney disease • Ischemic heart disease • Goal is not dependent on age, gender, or comorbidity

  23. Elliott, Jonsson, and BlackCirculation. 2006;113:2754.

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