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Hypertension in the Elderly. Debra L. Bynum, MD. 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
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Hypertension in the Elderly Debra L. Bynum, MD
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
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
Systolic Hypertension • Defined as SBP > 140 with DBP <90 • No longer referred to as “Isolated”
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
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
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
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
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)
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
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
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%)
DATA : SHEP trial • Reduction in Heart Failure • 2.3% vs 4.4 % • ARR 2% • NNT 48
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)
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
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
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)
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
Next Question: • Are patients treated for hypertension less likely to develop cognitive impairment or dementia?
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
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
Final Question: • Will treatment of hypertension reduce the risk of developing cognitive impairment or dementia?
RCTs looking at hypertension and dementia • Syst-Eur Trial • SCOPE • SHEP • Progress • HYVET-COG
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
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)
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
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%
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)
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
Lifestyle Modifications • DASH (Dietary Approaches to Stop Hypertension) • Effective in decreasing SBP • ?increased Na responsiveness in older patients
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
Lifestyle Changes: summary • Evidence that weight loss and Na restriction can be effective for mild SH in older patients
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
Which agent? • Calcium channel blockers? • SHELL (SH in Elderly: Lacidipine Long Term Study) • CCB and thiazide equal
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
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
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
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
Specific Groups • Stage 1 HTN • Over 85 age group • Previously “controversial” treatment groups
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
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…
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
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
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