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Slide 1 - Debra L. Bynum, MD Hypertension in the Elderly
Slide 2 - Outline Defining Systolic Hypertension Risks of SH in older persons Preventing stroke, CHF, CV events, dementia Review of major trials Choice of treatment Pulse Pressure Specific treatment groups: Stage 1 SH “Oldest old” : those over age 80
Slide 3 - The History… Systolic Hypertension in the Elderly so common that once considered normal part of aging Previously : “Isolated Systolic Hypertension” 1980: JNC on HTN defined ISH as SBP >160 with DBP <90
Slide 4 - Classification: JNC 7
Slide 5 - Systolic Hypertension Defined as SBP > 140 with DBP <90 No longer referred to as “Isolated”
Slide 6 - How Common is Systolic Hypertension?
Slide 7 - Prevalence: Framingham Data Prevalence of HTN increases with age SH accounts for 75% of HTN in those over 65 Over ½ of people over age 60 and ¾ of those over the age of 70
Slide 8 - PreHypertension People over age 65: 26% four year risk of HTN if BP 120-129/80-84 Those over age 65 with BP 130-139/85-89: 50% four year risk of HTN Patients with BP 130-139/85-89 have twice the risk of CVD events compared to those with normal BP
Slide 9 - Why the emphasis on the Systolic number?
Slide 10 - Importance of SBP Continued increase in SBP with age Level/decrease in DBP with age (after 50-60) Systolic Hypertension most common cause of HTN in patients over age 50 After age 50, SBP is much more important risk factor for CV events than DBP SBP more often poorly controlled than DBP
Slide 11 - SBP Increase in SBP with age likely due to changes in arterial stiffness Framingham data from 1976 and meta-analysis of 60 observational studies: SH major risk factor for stroke Initial concern that SBP lowering would lead to increased stroke in patients over age 80 NOT SHOWN
Slide 12 - Systolic Hypertension JNC 7 clear in report: SH in patients over the age of 60 much more important than DBP SH assoicated with increased risk of CAD, LVH, renal insufficiency, stroke, and CV mortality Pulse Pressure (difference between SBP and DBP) predictor of increased CV risk (likely marker of “stiff “ arteries) SH more closely associated with CV risk than DBP in older patients (even in older patients with diastolic hypertension)
Slide 13 - Systolic Hypertension: summary SH more common in older patients SH more closely correlated with CV and stroke events Pulse Pressure also associated with increased risk of CV events, likely marker of arterial disease
Slide 14 - Risks… Epidemiological Studies: Framingham and Physician’s Health Study: Stage I SH: increased risk of CVD, CAD, and Stroke Large RCTs: demonstrate significant benefits of treating older patients with SH
Slide 15 - DATA SHEP trial : 1991 5000 patients, SBP 160-190, DBP <90, mean age 72 Chlorthalidone (thiazide) vs placebo Second agents: atenolol, reserpine Primary endpoint: stroke Significant decrease in 5 year incidence of all strokes (8% vs 5%, ARR 3%)
Slide 16 - DATA : SHEP trial Reduction in Heart Failure 2.3% vs 4.4 % ARR 2% NNT 48
Slide 17 - DATA: SHEP… 32 % Relative Risk Reduction and 5% Absolute Reduction in total combined CV events (secondary outcome) NNT: need to treat 18 people over 5 years to prevent 1 major cardiovascular or cerebrovascular event ?underestimation: goal BP only reached in 70% treatment group; 44% placebo group also treated (intention to treat analysis)
Slide 18 - Benefits of Treatment: Additional Trials Systolic Hypertension in Europe Systolic Hypertension in China All demonstrated decreased risk of stroke and combined CV events in older patients treated for SH None powered to demonstrate difference in all cause or cardiovascular mortality
Slide 19 - Effect of treating SH on risk of Stroke SHEP data: both hemorrhagic and ischemic strokes decreased Immediate effect on bleeds seen 2 years needed to see full effect of reduction in ischemic stroke
Slide 20 - Summary: Prevention of Cardiovascular Endpoints All trials demonstrated decreased stroke (ischemic and hemorrhagic) Decreased CHF Reduction in combined CV events (26% relative risk reduction in one meta-analysis)
Slide 21 - Will treating hypertension prevent dementia?
Slide 22 - First Question: Is Hypertension a Risk Factor for Dementia? Longitudinal studies (15-20 year followup) demonstrate association between midlife hypertension and later cognitive impairment/dementia 20 year followup study, Hypertentsion 1998 15 year study: blood pressure and dementia, Lancet 1996
Slide 23 - Next Question: Are patients treated for hypertension less likely to develop cognitive impairment or dementia?
Slide 24 - Prospective Cohort Studies Honolulu-Asia Aging Study 1965-1996 3 year Utah study of 3000 patients Swedish study of nearly 2000 patients (average age 82) 1992 African American cohort (1900 patients) 2002
Slide 25 - Prospective studies Patients on antihypertensive treatment have lower risk of developing cognitive impairment/dementia/cerebral atrophy Problems Confounding with no placebo group Reliance on self report of treatment and adherence
Slide 26 - Final Question: Will treatment of hypertension reduce the risk of developing cognitive impairment or dementia?
Slide 27 - RCTs looking at hypertension and dementia Syst-Eur Trial SCOPE SHEP Progress HYVET-COG
Slide 28 - Syst-Eur Trial 2400 patients with ISH, average age 70 3.9 year followup Long term treatment of HTN: reduced risk of dementia from 7.4 to 3.3 cases/1000 patient years Decrease in vascular and alzheimer type dementias Trial stopped early because of stroke risk reduction
Slide 29 - SCOPE: Study of Cognition and Prognosis in the Elderly Nearly 5000 patients Follow up: 44 months Significant decline in strokes No difference in dementia Short follow up 84% “controls” were treated (2003) Inclusion criteria: mild hypertension (160-179/90-99)
Slide 30 - SHEP: systolic hypertension in the elderly program JAMA 1991 5000 patients, 4.5 year follow up 1.6 % treatment patients vs 1.9% placebo patients developed dementia (no sig difference) 44% in placebo group were treated b/c of BP High rate of drop out for cognitive assessment
Slide 31 - PROGRESS: Perindopril Protection against recurrent stroke study 6100 patients, average age 64, hx of stroke or TIA 3.9 year follow up Perindopril and indapamide if tolerated Only 48% in each group had HTN Cognitive decline: 9% treatment group, 11% placebo group (p=.01) Stroke and cognitive decline decreased by 45%
Slide 32 - HYVET-COG Over 3000 patients 2.2 year follow up No significant difference in dementia (total 263 new cases of dementia) Problems Short follow up (trial stopped) Patients over 80 started on treatment (not looking at treatment from 60-70)
Slide 33 - Summary : Dementia and Systolic Hypertension Observational studies suggest less risk of cognitive decline in older patients treated for SH Risk of confounding: more frail patients may be less likely to be treated… May be that treatment in MIDDLE AGE/young older age is most important RCTs mixed, but may need longer followup, more patients
Slide 34 - How to Treat…
Slide 35 - Lifestyle Modifications DASH (Dietary Approaches to Stop Hypertension) Effective in decreasing SBP ?increased Na responsiveness in older patients
Slide 36 - Lifestyle: TONE trial Older patients with SH, BP < 145/85 on 1 med Medication stopped 4 groups: Na restriction, weight reduction, both Na restriction and weight reduction, usual care Outcome: remaining free of HTN or need to restart medication or CV event 25% in usual care group remained “free” 38% in Na restriction, 40% in weight reduction, and 44% in combined treatment did well
Slide 37 - Lifestyle Changes: summary Evidence that weight loss and Na restriction can be effective for mild SH in older patients
Slide 38 - Which agent is best? Thiazide diuretics: first line in large trials ACE inhibitors: LIFE (Losartan Intervention for Endpoint Reduction) Losartan vs beta blocker: Losartan decreased risk CV events HOPE (Heart Outcomes Prevention Evaluation) Patients with DM, over 55, CVD risk Ramipril 10/day decreased morbidity/mortality at 5 years Most pronounced effect seen in those over age 65
Slide 39 - Which agent? Calcium channel blockers? SHELL (SH in Elderly: Lacidipine Long Term Study) CCB and thiazide equal
Slide 40 - Which agent? ALLHAT RCT 45,000 patients Thiazide vs amlodipine, lisinopril, or doxazosin (doxazosin arm stopped due to increase risk CHF) Overall NO difference Trend for thiazide treated patients to have less risk of stroke and CHF
Slide 41 - Which agent? Blood Pressure Lowering Treatment Trialists’ Collaboration: Meta-analysis of RCTs looking at different regimens for HTN BMJ 4/2008 31 trials, over 190,000 patients 1. NO difference between age groups with benefit of treatment; benefits seen in ALL age groups 2. NO differences between classes of drugs
Slide 42 - Treatment Uncontrolled hypertension most often due to difficult to control systolic pressure Systolic hypertension usually requires more than one drug Balance with risk for orthostatic hypotension: need to follow with standing blood pressures
Slide 43 - Which Agent: Summary Overall similar Thiazides considered first line ?concern for beta blockers unless other indication Some evidence to avoid alpha blockers unless other indication for use Need to individualize treatment Most often will require more than one drug for SH
Slide 44 - Specific Groups Stage 1 HTN Over 85 age group Previously “controversial” treatment groups
Slide 45 - Stage 1 HTN Prehypertension and stage 1 HTN clearly associated with increased risk of cerebrovascular events, CHF and CV events, and even dementia Consider other risk factors (DM, CAD, and AGE) Recommendations from JNC: Treat Stage 1 HTN Lifestyle modifications for Prehypertension, added pharmacologic treatment if other vascular risk factors present
Slide 46 - Over 80: concerns Observational data that very old patients with lower BPs have higher mortality JAGS 2007: retrospective cohort study of VA patients over age 80 found lower 5 year survival in patients with lower BPs Risk of confounding…
Slide 47 - HYVET: Hypertension in the Very Elderly Trial RCT of nearly 4000 patients from Europe, China, Australia, Tunisia Age over 80 SBP > 160 Indapamide vs placebo ACE inhibitor (perindopril) or placebo added as second agent when needed Primary endpoint: stroke
Slide 48 - HYVET… Mean age : 83 Mean standing BP: 173/90 Target SBP = 150 12% had hx of CV disease 1.8 year follow up Treatment group: 15/6 lower BP
Slide 49 - HYVET: results
Slide 50 - HYVET: results 30% decrease in rate of fatal or nonfatal stroke 39% decrease in rate of death from stroke 21 % decrease in all cause mortality 23% decrease in CV death 64% decrease in heart failure Fewer adverse events in treatment group
Slide 51 - HYVET: Other points Target SBP of <150 Only 50% treatment group reached target BP Followed standing BP to keep over 140 7.9% in treatment group vs 8.8% in placebo group had orthostatic hypotension
Slide 52 - Summary SH is not benign SH is a risk factor for all cause dementia Treatment is associated with decreased CHF and stroke, and ? Dementia Over 80: Benefits seen with modest tx goal (SBP 150) Follow standing BPs to avoid orthostatic hypotension First Line: thiazides, then calcium channel blockers or ACE inhibitors; Beta blockers only if indication other than HTN.