Hypertension in the Elderly John Puxty Division of Geriatrics Center for Studies in Aging and Health, Providence Care
Learning Objectives Review evidence for treatment of hypertension in elderly Consider role for life-style modification Describe potential benefits and sideeffects of common anti-hypertensive treatments
CLASSIFICATION OF BP LEVELS Category Systolic (mm Hg) Diastolic (mm Hg) Normal <120 and <80 Prehypertension 120 39 or 80 89 Hypertension Stage 1 Stage 2 140 159 >160 or 90 99 >100
Percent of Population HYPERTENSION PREVALENCE BY AGE AND GENDER 1 0 0 Men Women 75 50 25 0 35-44 45-54 55-64 65-74 >75 Age Source: NHANES III, 1999-2002, CDC NCHS Data
Physiological Issues 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
Arterial Wall Compliance and Pulse Pressure Wave Elastic Vessel Systole Diastole Stiff Vessel Systole Diastole Stroke Volume Aorta Resistance Arterioles Pressure (Flow) Young Artery Bentley Dw, Izzo JL. J Am Geriatr Soc. 1982; 30:352-359. Arteriosclerotic Artery
Life-Style modification Modification Weight Reduction Adopt DASH eating plan Dietary sodium reduction Physical activity Moderation of alcohol consumption Approximate SBP Reduction (range) 5-10 mmhg/10kg 8-14 mmhg 2-8 mmhg 4-9 mmhg 2 4 mmhg
Effect of 30 minute walk 3 days a week Age 70-79 Exercise Group Systolic Diastolic 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
Trial of Non Pharmacologic Interventions in the Elderly (TONE) Reduction (%) in Incidence of Hypertension or CV Event 0-10 -20-30 -40-31 -30-50 -60-70 -53 Na Reduction Wt Reduction Combined JAMA 1998;279:839-846
Life-Style modification Many 75 year old hypertensive's (Grade 2) continue to be so after attempting: Salt restriction to 2 grams/day Adopting a low red meat/low dairy diet Calcium supplementation reduction to 2 alcoholic drinks or less/day 30 minutes/day of exercise at least 4X/week (Khan NA, et al, Can J Cardiol, 2009:25:287-298)
European Working Party on Hypertension in the Elderly European Working Party on Hypertension in the Elderly, Lancet, 1986 (N=840 patients, 200 over age 80, systolic BP 160-240) demonstrated benefit treating classical hypertension in 65-80 demonstrated no benefit from treatment in persons over 80 Evidence-based treatment of hypertension in the elderly resumed after SHEP study, JAMA 1991, showed small benefit in N=4700 patients 700 over age 80, systolic BP 160-240
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
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.
Hypertension in the Very Elderly Trial (HYVET) The Trial: International, multi-centre, randomised double-blind placebo controlled Inclusion Criteria: Exclusion Criteria: Aged 80 or more, Standing SBP < 140mmHg Systolic BP; 160-199mmHg Stroke in last 6 months + diastolic BP; <110 mmhg, Dementia Informed consent Need daily nursing care Primary Endpoint: All strokes (fatal and non-fatal)
HYVET Trial: International, multi-centre, randomised double-blind placebo controlled Target blood pressure 150/80 mmhg Indapamide SR 1.5 mg + Perindopril 4 mg + Perindopril 2 mg Placebo Placebo + Placebo + Placebo M-2 M-1 M0 M3 M6 M9 M12 M18 M24 M60
4761 Entered into Placebo Run-in 916 not randomised Placebo 1912 Active 1933 3845 randomised; Western Europe (86) Eastern Europe (2144), China (1526), Australasia (19), Tunisia (70) At end of trial; 1882 still in double blind, 17 vital status not known, 220 in open follow-up
Baseline data Placebo (n= 1912) Active (n= 1933) Age (years) 83.5 83.6 Female 60.3% 60.7% Blood Pressure: Sitting SBP (mmhg) 173.0 173.0 Sitting DBP (mmhg) 90.8 90.8 Orthostatic Hypotension 8.8% 7.9% Isolated Systolic Hypertension 32.6% 32.3% Fall in SBP 20mmHg and/or fall in DBP 10mmHg
Baseline Data (Previous Cardiovascular History) Placebo (%) Active (%) Cardiovascular disease 12.0 11.5 Known Hypertension 89.9 89.9 Anti-hypertensive treatment 65.1 64.2 Stroke 6.9 6.7 Myocardial Infarction 3.2 3.1 Heart Failure 2.9 2.9
Baseline data (Cardiovascular Risk factors) Placebo Active Current smoker 6.6% 6.4% Diabetes (Known DM/ DM treatment/glucose>11.1mmo/l) 6.9% 6.8% Total cholesterol (mmol/l) 5.3 5.3 HDL Cholesterol (mmol/l) 1.35 1.35 Serum Creatinine (µmol/l) 89.2 88.6 Uric acid (µmol/l) 279 280 Body Mass Index (kg/m 2 ) 24.7 24.7
Blood pressure separation 180 170 15 mmhg 160 150 Blood Pressure (mmhg) 140 130 120 110 Median follow-up I 1.8 years Placebo Indapamide SR +/- perindopril 100 90 6 mmhg 80 70 0 1 2 3 4 5 Follow-up (years)
All stroke (30% reduction) P=0.055
Total Mortality (21% reduction) P=0.019
Fatal Stroke (39% reduction) P=0.046
Heart Failure (64% reduction) P<0.0001
Per-Protocol HR 95% CI P All stroke - 34% 0.46-0.95 0.025 Total mortality - 28% 0.59-0.88 0.001 Fatal stroke - 45% 0.33-0.93 0.021 Cardiovascular mortality -27% 0.55-0.97 0.029 Heart failure - 72% 0.17-0.48 <0.001 Cardiovascular events - 37% 0.51-0.71 <0.001 NEJM 2008;358(18):1887-1898
Meta-analysis of Hypertension Treatment Trials in People > 80 Years of Age 10 0-10 -20-30 p=ns 6 p=ns -40-50 p=.014 p=.01 Stroke CHD CF Death Lancet 1999;353:793-796
Treatment Goals To achieve maximum mortality reduction in hypertensive persons over 75, the goal of therapy is typically a standing systolic pressure between 130 and 140, and no lower. (Oates, DJ et al, Journal of the American Geriatrics Society, 2007;55:383-388) 4,000 persons 80 and over with hypertension followed over 5 years. Lowest mortality if all diastolic pressures 80 to 89, and all systolic pressures 130 to 139. (J-shaped curve) Any diastolic <80, or systolic <130 associated with significant increase in mortality at 5 year follow-up
Benefits of Treatment Treatment reduces overall mortality, CVD events, heart failure, and stroke Treatment effect is greatest in men, patients older than 70 years, and patients with greater pulse pressure Treatment effect is delayed about 5 years, so drug therapy may not be advisable for very elderly people
Treatment Tips Focus on SBP and pulse pressure In general: SBP 135 to 140 mm Hg DBP 85 to 90 mm Hg Type 2 diabetes: SBP <130 mm Hg If SBP is very high, an intermediate target (eg, 160 mm Hg) may be a better initial goal in the absence of target-organ damage
Treatment Choice Angiotensin converting enzyme (ACE) inhibitors, newer calcium channel blockers, and thiazide diuretics are the first and second- line drugs of choice for mortality reduction Wright JM and Musini VM, Cochrane Database Syst Rev 2009 CD001841
Newer Generation Ca Channel Blockers Amlodipine plus benazepril caused more edema (31 vs 13) than hydrochlorthiazide plus benazepril. But reduced cardiac events and deaths more (11.9 vs 9.6) in 11,000 pts over 3 yrs. (Jamerson K, et al, N Eng J Med 2008:359:2417-2428) Amlodipine/felodipine are good for urge incontinence (1/3 of all persons 75 and over), whereas HCTZ/ chlorthalidone/indapamide tend to make it worse
Centrally acting ACEI* Reduce risk of cognitive decline (Sink KM et Al Arch Int Med 2009:169:1195-1202) Reduce risk of mobility decline (Sumukadas D, et al, Effect of Perindopril on physical function in elderly people with functional impairment: a randomized controlled trial. CMAJ 2007; 177:867-874) * (captopril,fosinopril, lisinopril, perindopril, ramipril, and trandolapril)
Role of Beta-Blockers? atenolol is a cardioselective beta-blocker that doesn't reduce mortality (Psaty BM,JAMA;2006;295:1704-6) Unless a person over 75 has CAD (Ml within 5 years) or CHF, use of other beta-blockers proven to reduce mortality for CAD (timolol, propranolol, metaprolol) or CHF (metaprolol, bisoprolol, carvedilol) won't lower mortality due to hypertension (Wiysonge CS, et al, Cochrane Database Syst Rev 2007 CD002003) If a person over 75 has had an Ml within 5 years, or has systolic CHF (EF <45), then an appropriate beta-blocker is MORE effective than other meds for hypertension at reducing mortality (Law MR, BMJ 2009;338:b1665). Dose needed to reduce resting heart rate by 10 beats per minute is probably sufficient
Ethnic Issues Diuretics and calcium channel blockers work better in young and elderly black and hispanics ACEIs and ARBs less useful in blacks CCB/ACEIs useful in elderly Asians No studies in elderly Native Americans Except for differences above, no interethnic differences in antihypertensive efficacy in the elderly. (Park IU, Ann Fam Med 2007:5:444-452)
Costs Metaprolol SR 100 mg = 14 cents Chlorthalidone 12.5 mg (1/4 pill)=3 cents HCTZ 12.5 mg (1/2 pill) = 2 cents Indapamide 1.25 mg = 15 cents All ACE inhibitors are between 27 cents (lisinopril) and 50 cents (ramipril) a day regardless of dose Felodipine (23-69 cents/day), arnlodipine (33-99 cents/ day), depending on dose All of the above costs are for generic version. All ARBs/DRIs are $1.15/day or higher
HTN in Long Term Care HTN affects about 33% to 66% of residents of long-term care (LTC) facilities Postural hypotension Affects about 33% of residents Independent risk factor for falls, syncope, stroke, mortality
Management of HTN in LTC No well-designed trials have studied antihypertensive treatment in the LTC setting Risk-benefit ratio of treatment is unclear in: Patients older than 80 years Patients with multiple comorbidities, taking multiple medications Antihypertensive medications are a risk factor for falls, so assess postural BP
Summary Treatment of HTN reduces adults the risk of CVD events and mortality in older A trial of lifestyle modification is recommended for nondiabetic patients with stage 1 HTN A low-dose thiazide-type diuretic is the preferred first-line drug therapy. Consider combination Tx (HTN, ACEI, Ca.CB) Start low and go slow monitor for falls, postural hypotension, and other adverse event