Very Good rev of HTN

1. Treatment Of The Elderly: Is There Anything New? Joel Handler, MD Clinical Hypertension Leader Care Management Institute Kaiser Permanente

3. Prevalence of High BP in Americans Aged 20 Years and Older by Age and Gender (NHANES IV: 1999-2000)

4. Does elderly hypertension have specific characteristics?

5. Characteristics of Hypertension in the Elderly Increased Systolic blood pressure and pulse pressure Left ventricular mass and wall thickness Arterial stiffness Calculated total peripheral resistance Decreased Cardiac output and heart rate Renal blood flow, plasma renin activity, and angiotensin II levels Arterial compliance and blood volume Diastolic blood pressure Black H. JCH 2003; 5:12

6. Men, Age (y) Women, Age (y) Pulse pressure Pulse pressure Mean Systolic and Diastolic BP by Age and Race/Ethnicity for Men and Women (US Population ³Age 18 Years, NHANES III) Burt VI, et al. Hypertension . 1995;25:305-313. 18-29 30-39 40-49 50-59 60-69 70-79 80+ 0 70 80 110 130 150 18-29 30-39 40-49 50-59 60-69 70-79 80+ 0 70 80 110 130 150 0 70 80 110 130 150 0 70 80 110 130 150 DBP (mm Hg) SBP (mm Hg) DBP (mm Hg) SBP (mm Hg) DBP (mm Hg) SBP (mm Hg) DBP (mm Hg) SBP (mm Hg) Non-Hispanic Black Non-Hispanic White Mexican American

7. Control to SBP goal, DBP goal, or both by age group among 1189 treated subjects with hypertension. Open columns represent subjects ≤60 years old (n=295); gray bars, subjects 61 to 75 years old (n=533); filled columns, subjects >75 years old (n=361). Age ≤60 Age 61-75 Age >75 Lloyd-James et al. Hypertens 2000; 36:594-599

8. Bentley Dw, Izzo JL. J Am Geriatr Soc . 1982; 30:352-359. Stroke Volume Aorta Resistance Arterioles Pressure (Flow) Young Artery Systole Diastole Elastic Vessel Arteriosclerotic Artery Stiff Vessel Systole Diastole Arterial Wall Compliance and Pulse Pressure Wave

9. A representative central arterial waveform with pulse pressure indicated.

10. Relationship between basal supine systolic blood pressure and postural change in systolic blood pressure for aggregate data from older subjects. Postural change in systolic blood pressure (mm Hg) Clin Sci 1985;69:337-341

11. “ If the standing blood pressure is consistently much lower than the sitting blood pressure, the standing blood pressure should be used to titrate drug dosages during treatment.” National High Blood Pressure Education Program Working Group Report on Hypertension in the Elderly.

12. Cerebral Blood flow Percent of Control Strandgaard et al. Lanset 1987; 2:658-661

13. What are the measurement issues?

15. 2-year Incidence of Cardiovascular End Points Staessen et al. JAMA 1999; 282:544

16. Number of Strokes per 100 Patient Years Fagard et al. Circulation 2000; 102:1139-1144

17. Relative Risk Adjusted estimated relative risk for cardiovascular disease by diastolic blood pressure (DBP) goal cutoff categories. Relative Risk 95% Confidence Interval p (trend) <.001 DBP cutoff, mm Hg Somes GW et al. Arch Intern Med 1999; 2004-2009

18. 200 140 160 120 180 20 40 60 80 100 0 A softer blowing sound A sharp thump A softer thump A blowing or whooshing sound K1 K2 K3 K4 K5

20. Do lifestyle measures really work for elderly hypertension?

21. Lifestyle Modifications 4-9 mmHg Physical activity 2–4 mmHg Moderation of alcohol consumption 2-8 mmHg Dietary sodium reduction 8-14 mmHg Adopt DASH eating plan 5-10 mmHg/10kg Weight Reduction Approximate SBP Reduction (range) Modification

22. Bar graph shows change in mean arterial blood pressure used to define salt responsivity as a function of age in normotensive [open bars] and hypertensive [color bars] subjects. Change in Mean Arterial Blood Pressure Weinberger M. Hypertens 1991; 18:69

23. Effect of 30 minute walk 3 days a week Age 70 - 79 Systolic Diastolic Exercise Group Baseline 156 ± 10 mm Hg  86 ± 8 mm Hg 3 months 151 ± 15 mm Hg 80 ± 6 mm Hg Control Group Baseline 153 ± 7 mm Hg 85 ± 8 mm Hg 3 months 156 ± 10 mm Hg 85 ± 6 mm Hg Conone et al. Med Scl in Sports and Exercise. 1991

24. Free End of Point, % Time after Withdrawal, mo TONE Study. JAMA 1998;279:844

25. What is the effect of drug therapy related to age? Are the recommendations different?

26. 5 Year NNTs (Number Necessary to Treat) Age <60 Age ≥60 12 trials, n = 33,000 13 trials, n = 16,564 Stroke NNT = 168 Stroke NNT = 43 CHD event NNT = 184 CHD event NNT = 61 Stroke, CHD NNT = n. a. Stroke, CHD NNT = 18 CV mortality NNT = 205 CV mortality NNT = 52 Mulrow et al. JAMA 1994; 272:1932-1938

27. Trials Examining Treatment of Hypertension in the Elderly EWPHE MRC-Elderly SHEP STOP-H Syst-China Syst-Eur (N = 840) (N = 4396) (N = 4736) (N = 1627) (N = 2394) (N = 4695) Stroke reduction, % -36 -25 -33 -47 -38 -42 CAD change, % -20 -19 -27 -13 +6 -26 CHF reduction, % -22 Not stated -55 -51 -58 -27 % of Patients receiving 35 52 (b-blocker) 44 67 11-26 26-36 combination drug therapy 38 (diuretic) Prisant, Moser M. Arch Int Med 2000; 160:284

28. Major Clinical Trials Showing Benefit of Treating Isolated Systolic Hypertension SHEP Syst-Eur Syst-China (n=4736) (n=4695) (n=2394) Baseline 160-219/ 160-219/ 160-219/ SBP/DBP (mm Hg) <90 <95 <95 BP reduction: 27/9 23/7 20/5 SBP/DBP (mm Hg) Drug therapy Chlorthalidone Nitrendipine Nitrendipine Atenolol Enalapril Captopril HCTZ HCTZ Outcomes (%) Stroke 33 42 38 CAD 27 30 27 CHF 55 29 — All CVR disease 32 31 25 Journal of Clinical Hypertension Vol II, No. 5, page 336, September/October 2000.

30. SHEP stroke subset analysis Ischemic Hemorrhagic Lacunar Atherosclerotic Embolic n = 217 n = 28 n = 66 n = 26 n = 25 0.63 0.47 0.53 0.99 0.55 (0.??-0.83) (0.21-1.04) (0.32-0.88) (0.46-2.31) (0.24-1.25) Davis BR et al. Stroke 1998; 29:1333-1340

31. Comparative Drug Studies: Elderly Hypertension NIC-E : Nicardipine = thiazide SHELL : Lacidipine = thiazide STOP-2 : CCB, ACEI = thiazide, BB

33. So, why aren’t we doing a better job?

35. Independent Predictors of Using Antihypertensives Medications in 2000 Variable Adjusted OR (95% CI) of Using Antihypertensives Comorbid conditions Asthma/COPD 0.43 (0.40-0.47) Depression 0.50 (0.45-0.55) GI disorders 0.59 (0.54-0.64) Osteoarthritis 0.63 (0.59-0.67) Cardiovascular conditions Coronary artery disease 1.31 (1.23-1.40) Cerebrovascular disease 1.03 (.97-1.10) Congestive heart failure 1.05 (0.99-1.11) Diabetes 1.16 (1.10-1.22) Wang PS et al. Hypertension 2005; 46:273-279

36. HDFP 5 Year Incidence ADR’s 29.1 60 – 69 38.0 50 – 59 36.8 40 – 49 34.1 30 – 39 ADR’s/100/5 Years Age

37. Barriers to Optimal Control of Hypertension Inaccurate measurement of blood pressure (BP) Focusing on diastolic BP rather than systolic BP goal Failure to consider absolute global risk Failure to advocate lifestyle modifications Failure to use polypharmacy Failure to use effective drug combinations Failure to titrate doses upward Fear of reaching excessively low diastolic BP The patient with truly resistant hypertension Behavioral barriers Franklin S. JCH 2006; 8:524

38. Prevalence of Renal Arterial Lesions in Normotensive and Hypertensive Patients Age, Normotensive Hypertensive Years Normal Lesion Normal Lesion 31-40 7 3 6 10 41-50 26 8 14 22 51-60 99 35 28 50 60+ 69 56 15 48 Eyler WR, Clark MD, Garman JE, et al. Radiology 1962; 78:879-892.

39. What is the systolic blood pressure goal?

40. Blood Pressure in SHEP and Syst-Eur (mm Hg) SHEP Syst-Eur Entry 160-219/<90 160-219/<95 Goal (SBP) <160 + ≥20  <150 + ≥20  Baseline 170/77 174/86 Achieved: Rx 143/68 151/79 Achieved: Placebo 155/72 161/84 Difference: Rx-Placebo 12/4 10/5 Journal of Clinical Hypertension, Vol II, No. 5, page 336. March/April 2000.

41. IHD mortality (floating absolute risk and 95% CI) Usual SBP (mm Hg) IHD, ischemic heart disease. Prospective Studies Collaboration. Lancet . 2002;360:1903-1913. Ischemic Heart Disease Mortality Rate in Each Decade of Age 120 140 160 180 256 128 64 32 16 8 4 2 1 SBP 40-49 y Age at risk: 70-79 y 60-69 y 50-59 y 80-89 y Usual DBP (mm Hg) 70 80 90 110 100 256 128 64 32 16 8 4 2 1 DBP

42. What have we learned from ALLHAT?

43. Number at Risk: Chlorthalidone 15,255 14,477 13,820 13,102 11,362 6,340 2,956 209 Amlodipine 9,048 8,576 8,218 7,843 6,824 3,870 1,878 215 Lisinopril 9,054 8,535 8,123 7,711 6,662 3,832 1,770 195 Cumulative Event Rates for the Primary Outcome (Fatal CHD or Nonfatal MI) by ALLHAT Treatment Group Chlorthalidone Amlodipine Lisinopril Years to CHD Event 0 1 2 3 4 5 6 7 Cumulative CHD Event Rate 0 .04 .08 .12 .16 .2 0.81 0.99 (0.91-1.08) L/C 0.65 0.98 (0.90-1.07) A/C p value RR (95% CI) ALLHAT

44. Nonfatal MI + CHD Death – Subgroup Comparisons – RR (95% CI) ALLHAT Amlodipine Better Chlorthalidone Better 0.50 1 2 Non-Diabetic 0.97 (0.86, 1.09) Diabetic 0.99 (0.87, 1.13) Non-Black 0.97 (0.87, 1.08) Black 1.01 (0.86, 1.18) Women 0.99 (0.85, 1.15) Men 0.98 (0.87, 1.09) Age>=65 0.97 (0.88, 1.08) Age <65 0.99 (0.85, 1.16) Total 0.98 (0.90, 1.07) Lisinopril Better Chlorthalidone Better 0.50 1 2 Non-Diabetic 0.99 (0.88, 1.11) Diabetic 1.00 (0.87, 1.14) Non-Black 0.94 (0.85, 1.05) Black 1.10 (0.94, 1.28) Women 1.06 (0.92, 1.23) Men 0.94 (0.85, 1.05) Age >= 65 1.01 (0.91, 1.12) Age < 65 0.95 (0.81, 1.12) Total 0.99 (0.91, 1.08)

45. Cumulative Event Rates for Heart Failure by ALLHAT Treatment Group Chlorthalidone Amlodipine Lisinopril Number at risk: Chlor 15,255 14,528 13,898 13,224 11,511 6,369 3,016 384 Amlo 9,048 8,535 8,185 7,801 6,785 3,775 1,780 210 Lisin 9,054 8,496 8,096 7,689 6,698 3,789 1,837 313 Cumulative CHF Rate Years to HF 0 1 2 3 4 5 6 7 0 .03 .06 .09 .12 .15 <.001 1.19 (1.07-1.31) L/C <.001 1.38 (1.25-1.52) A/C p value RR (95% CI) ALLHAT

46. Heart Failure – Subgroup Comparisons – RR (95% CI) ALLHAT Amlodipine Better Chlorthalidone Better 0.50 1 2 Non-Diabetic 1.33 (1.16, 1.52) Diabetic 1.42 (1.23, 1.64) Non-Black 1.33 (1.18, 1.51) Black 1.47 (1.24, 1.74) Women 1.33 (1.14, 1.55) Men 1.41 (1.24, 1.61) Age >= 65 1.33 (1.18, 1.49) Age < 65 1.51 (1.25, 1.82) Total 1.38 (1.25, 1.52) Lisinopril Better Chlorthalidone Better 0.50 1 2 Non-Diabetic 1.20 (1.04, 1.38) Diabetic 1.22 (1.05, 1.42) Non-Black 1.15 (1.01, 1.30) Black 1.32 (1.11, 1.58) Women 1.23 (1.05, 1.43) Men 1.19 (1.03, 1.36) Age >= 65 1.20 (1.06, 1.35) Age < 65 1.23 (1.01, 1.50) Total 1.20 (1.09, 1.34)