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Systolic Blood Pressure Goals to Reduce Cardiovascular Disease Among Older Adults

      Abstract

      The 2014 Evidence-Based Guideline for the Management of High Blood pressure in Adults Report From the panel Members Appointed to the Eighth Joint National Committee (JNC 8) was recently published. This guideline recommended that older adults (≥60 years) without diabetes or chronic kidney disease with systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg be initiated on antihypertensive medication with a treatment goal SBp/DBP <150/90 mm Hg. In contrast, the previous 3 JNC guidelines recommended treatment for these individuals be initiated at SBP/DBP ≥140/90 mm Hg with goal SBP/DBP <140/90 mm Hg. In this article, we review randomized trials of antihypertensive medication and observational data on SBP and DBP with cardiovascular outcomes among older adults, possible explanations underlying the different findings from these randomized trials and observational studies, and contemporary antihypertensive treatment patterns among older U.S. adults. In closing, we highlight future research needs related to hypertension and outcomes among older adults.

      Key Indexing Terms

      High blood pressure (BP) is one of the most important risk factors for cardiovascular disease (CVD), the leading cause of mortality among U.S. adults.
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      Elevated systolic blood pressure and risk of cardiovascular and renal disease: overview of evidence from observational epidemiologic studies and randomized controlled trials.
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      Blood pressure, systolic and diastolic, and cardiovascular risks. US population data.
      The U.S. population is aging, and it is projected that the number of U.S. adults aged ≥60 years will double by 2050.
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      The incidence and prevalence of hypertension increase with age.
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      Ethnic differences in hypertension incidence among middle-aged and older adults: the multi-ethnic study of atherosclerosis.
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      Therefore, the impact of high BP among older adults on morbidity and mortality is expected to grow over the coming decades.
      For several decades, U.S. adults without diabetes or chronic kidney disease with systolic blood pressure (SBP) ≥140 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg were recommended the initiation of antihypertensive medication.
      • Frohlich E.D.
      Detection, evaluation, and treatment of hypertension: JNC-5 (Joint National Committee on detection, evaluation, and treatment of high blood pressure).
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      The seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report.
      The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure.
      Additionally, once on antihypertensive medication, health care providers were recommended to treat these patients to achieve an SBP < 140 mm Hg and a DBP <90 mm Hg. Based on evidence from randomized controlled trials, the 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8) recently recommended a higher SBP threshold (150 mm Hg) for treatment initiation and goal attainment for adults aged ≥60 years without diabetes or chronic kidney disease.
      • James P.A.
      • Oparil S.
      • Carter B.L.
      • et al.
      2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8).
      Although randomized controlled trials are considered the gold standard of evidence for making treatment decisions, they often include select populations with limited generalizability.
      • Antman K.
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      • Wood W.
      • et al.
      Selection bias in clinical trials.
      This is particularly relevant for older adults, a population comprised of individuals with a broad distribution of health status and a high prevalence of frailty. Therefore, high quality observational data may complement randomized trials for understanding the benefits and risks of antihypertensive treatment among older adults and generating new hypotheses.
      In this review, first, we provide context for the 2014 Guideline recommendation for a higher SBP goal. We provide a brief overview of the new high BP guideline, as it relates to SBP and DBP goals for older U.S. adults. Second, we provide an overview of findings from randomized controlled trials on the benefits and risks of antihypertensive medication among older adults. Additionally, we will discuss 2 ongoing randomized trials testing different treatment goals for older adults. Third, we review observational studies on the association between SBP and outcomes among older adults. Fourth, we reconcile the findings from the randomized trials and observational studies by reviewing data on the impact frailty may have on the association between SBP and DBP with outcomes. Finally, to provide context for the new treatment goals, we review contemporary treatment patterns among older U.S. adults with hypertension.

      GUIDELINE RECOMMENDATIONS

      The 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults Report From the Panel Members Appointed to JNC 8 was published online on December 18, 2013.
      • James P.A.
      • Oparil S.
      • Carter B.L.
      • et al.
      2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8).
      This guideline focused on 3 questions related to BP management and published 9 recommendations. of relevance to older adults, this guideline recommended for the general population aged ≥60 years that antihypertensive treatment be initiated at SBP ≥150 mm Hg or DBP ≥90 mm Hg and treat to a goal SBP < 150 mm Hg and goal DBP <90 mm Hg (Table 1). Lower recommendations were made for individuals with diabetes or chronic kidney disease; discussion of these populations is beyond the scope of this article. The JNC 8 panel members found strong evidence from randomized controlled trials on the benefits of older adults achieving a SBP <150 mm Hg on antihypertensive medications. However, there was little evidence from randomized controlled trials supporting the benefit of achieving SBP <140 mm Hg on outcomes among older adults taking antihypertensive medications. The panel members acknowledged a lack of consensus regarding the appropriate SBP target (<140 mm Hg or <150 mm Hg) for adults aged ≥60 years.
      Table 1Treatment recommendations for older adults in published guidelines and scientific statements
      SBP/DBP treatment goal
      OrganizationPublication dateDefinition of elderlyGeneral recommendationExceptions
      JNC 8
      2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8).9
      201460 yrSBP/DBP <150/90 mm HgSBP/DBP <140/90 mm Hg for those with chronic kidney disease or diabetes
      ESH/ESC
      2013 ESH/ESC Guidelines for the Management of Arterial Hypertension.11
      201380 yrSBP 140–149 mm HgSBP <140 mm Hg if well tolerated. For frail individuals, treatment decision left to physician
      ACCF/AHA
      ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus documents.12
      201165–79 yrSBP/DBP <140/90 mm HgSBP/DBP ≥80 yr treated to 140–145/<90 mm Hg if well tolerated
      SBP, systolic blood pressure; DBP, diastolic blood pressure; JNC, Joint National Committee; ESH, European Society of Hypertension; ESC, European Society of Cardiology; ACCF, American College of Cardiology Foundation; AHA, American Heart Association.
      a 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8).
      • James P.A.
      • Oparil S.
      • Carter B.L.
      • et al.
      2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8).
      b 2013 ESH/ESC Guidelines for the Management of Arterial Hypertension.
      • Mancia G.
      • Fagard R.
      • Narkiewicz K.
      • et al.
      2013 ESH/ESC guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).
      c ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus documents.
      • Aronow W.S.
      • Fleg J.L.
      • Pepine C.J.
      • et al.
      ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents.
      The 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults is not the first guideline to suggest a higher SBP treatment goal for older adults (Table 1). The 2013 European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines for the management of hypertension emphasized that the available randomized trials of antihypertensive treatment in the elderly showed a reduction in CVD events through lowering of BP; however, the average achieved SBP in trials was never <140 mm Hg.
      • Mancia G.
      • Fagard R.
      • Narkiewicz K.
      • et al.
      2013 ESH/ESC guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).
      Therefore, they suggested that elderly individuals with hypertension should be treated to SBP levels of 140 to 149 mm Hg. In “fit” persons, aged less than 80 years, an SBP goal <140 mm Hg may be considered, whereas in frail elderly individuals, they recommended that SBP goals be adapted to individual tolerability. Also, the American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) 2011 Expert Consensus Document on Hypertension in the Elderly suggested that a target SBP/DBP <140/90 mm Hg in persons aged 65 to 79 years with a target SBP of 140 to 145 mm Hg, if tolerated, in persons aged 80 years and older.
      • Aronow W.S.
      • Fleg J.L.
      • Pepine C.J.
      • et al.
      ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents.
      The authors of each of these guidelines have emphasized that very limited data exist to make definitive recommendations on target BP levels in the elderly.

      RANDOMIZED TRIAL EVIDENCE IN THE ELDERLY—ANTIHYPERTENSIVE TREATMENT AND SBP GOALS

      A number of randomized controlled trials have evaluated the risks and benefits of antihypertensive medications in older adults (Table 2).
      Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group.
      • Staessen J.A.
      • Fagard R.
      • Thijs L.
      • et al.
      Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.
      • Beckett N.S.
      • Peters R.
      • Fletcher A.E.
      • et al.
      Treatment of hypertension in patients 80 years of age or older.
      • Verdecchia P.
      • Staessen J.A.
      • Angeli F.
      • et al.
      Usual versus tight control of systolic blood pressure in non-diabetic patients with hypertension (Cardio-Sis): an open-label randomised trial.
      • Ogihara T.
      • Saruta T.
      • Rakugi H.
      • et al.
      Valsartan in Elderly Isolated Systolic Hypertension Study Group. Target blood pressure for treatment of isolated systolic hypertension in the elderly: valsartan in elderly isolated systolic hypertension study.
      • JATOS Study Group
      Principal results of the Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients (JATOS).
      Some of these trials evaluated the benefits of antihypertensive treatment and certain drug classes on reducing CVD risk and delaying mortality, whereas others have evaluated the benefits and risks of achieving SBP goals. One of the earlier studies, the Systolic Hypertension in the Elderly Program (SHEP), included 4,736 participants aged ≥60 years with SBP ≥160 mm Hg who were randomized to chlorthalidone to achieve a 20-mm Hg reduction in SBP to <160 mm Hg or placebo.
      Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group.
      Over a mean of 4.5 years of follow-up, the reduction in the incidence of stroke, nonfatal myocardial infarction plus coronary death and major CVD events associated with treatment was 36%, 27% and 32%, respectively. SHEP has been followed by several other randomized trials including the Systolic Hypertension in Europe (Syst-Eur), which demonstrated the benefits of calcium channel blockers among adults aged ≥60 years and the HYpertension in the Very Elderly Trial (HYVET), which demonstrated the benefits of antihypertensive treatment for individuals aged ≥80 years with SBP ≥160 mm Hg.
      • Staessen J.A.
      • Fagard R.
      • Thijs L.
      • et al.
      Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.
      • Beckett N.S.
      • Peters R.
      • Fletcher A.E.
      • et al.
      Treatment of hypertension in patients 80 years of age or older.
      Although these studies demonstrated clear benefits of antihypertensive treatment in older adults, the goal SBP in each of these studies was <160 mm Hg or <150 mm Hg, and the benefits of lower SBP goals were not tested.
      Table 2Randomized controlled trials of antihypertensive medication among older adults
      TrialPublication dateSample sizeAge range, yrFollow-up durationRandomization armsPrimary outcome (results)Secondary outcome (results)Limitations
      SHEP19914,73660Mean: 4.5 yrSBP reduction by ≥20 mm Hg to <160 mm Hg vs. placeboStroke (lower risk with treatment)CVD and CHD, all- cause mortality (lower risk with treatment)Lower SBP targets were not evaluated
      Syst-Eur19974,69560Median: 2 yrTreatment to reduce SBP by 20 mm Hg to <150 mm Hg vs. placeboStroke (lower risk with treatment)Death, myocardial infarction, heart failure, dissecting aortic aneurysm, renal insufficiency (lower risk but not statistically significant)Lower SBP targets were not evaluated
      HYVET20083,84580Median: 1.8 yrTreatment to reduce SBP/DBP to <150/80 mm Hg vs. placeboStroke (lower risk with treatment but not significant, P = 0.06)Death, death from CVD, death from cardiac causes, stroke death (lower risk for all-cause and stroke death, benefits for other outcomes not statistically significant)Lower SBP targets were not evaluated; Healthier than general population aged ≥80 yr
      JATOS20084,41870–843.07SBP <140 mm Hg vs. 140–159 mm HgComposite CVD (no benefit of SBP <140 mm Hg)Death, all-cause and cause-specific (no benefit of SBP <140 mm Hg)Trial not adequately powered
      CARDIO-SIS20091,11155Median: 2 yrSBP <130 mm Hg vs. <140 mm HgLeft ventricular hypertrophy (lower SBP associated with lower risk)Composite CVD (lower SBP associated with lower risk)Surrogate primary outcome, included participants aged <60 yr
      VALISH20103,26065–85Up to 2 yrSBP <140 mm Hg vs. 140–149 mm HgComposite CVD (no benefit of SBP <140 mm Hg)Individual components of primary outcome (no benefit of SBP <140 mm Hg)Trial not adequately powered
      SHEP, Systolic Hypertension in the Elderly Program; SBP, systolic blood pressure; CHD, coronary heart disease; CVD, cardiovascular disease; Syst-Eur, Systolic Hypertension in Europe; HYVET, HYpertension in the Very Elderly Trial; DBP, diastolic blood pressure; JATOS, Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients; CARDIO-SIS, Cardiovascolari del Controllo della Pressione Arteriosa Sistolica; VALISH, VALsartan in Elderly Isolated Systolic Hypertension.
      Three recent randomized trials have compared different SBP goals on CVD outcomes among elderly patients. In the Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients (JATOS), the effect of SBP reduction to <140 mm Hg (strict control) versus 140 to 159 mm Hg (mild-treatment) on the composite outcome of CVD and renal failure was determined in 4418 individuals aged 65 to 84 years with SBP ≥160 mm Hg at baseline.
      • JATOS Study Group
      Principal results of the Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients (JATOS).
      The mean SBP/DBP at the end of follow-up was 136/75 mm Hg among participants in the strict control group and 146/78 mm Hg in the mild-treatment group. However, differences in outcomes over 2 years of follow-up were not statistically significant; 9% of participants in the strict treatment group and 8% in the mild-treatment group experienced the primary outcome. Differences in mortality across randomization arms in JATOS were also small and not statistically significant. Similarly, in the VALsartan in Elderly Isolated Systolic Hypertension (VALISH) study, no differences in cardiovascular morbidity and mortality were present between participants randomized to SBP <140 mm Hg versus 140 to 149 mm Hg.
      • Ogihara T.
      • Saruta T.
      • Rakugi H.
      • et al.
      Valsartan in Elderly Isolated Systolic Hypertension Study Group. Target blood pressure for treatment of isolated systolic hypertension in the elderly: valsartan in elderly isolated systolic hypertension study.
      VALISH enrolled 3,079 participants aged 70 to 84 years with SBP ≥160 mm Hg at baseline. After 3 years of follow-up, mean SBP/DBP was 137/75 mm Hg and 142/77 mm Hg in the strict control and moderate control groups, respectively. The incidence of the primary outcome, composite of sudden death, fatal or nonfatal stroke, fatal or nonfatal myocardial infarction, heart failure death, other CVD death, unplanned hospitalization for CVD and renal dysfunction was 10.6 and 12.0 per 1,000 person-years in the strict and moderate control groups, respectively (P = 0.38). None of the individual components of the primary outcome were statistically significantly different across randomization arms (all P values >0.2). The rates of events in both JASTOS and VALISH were lower than planned, potentially resulting in inadequate statistical power to detect benefits of the lower SBP goals. In the Studio Italiano Sugli Cardiovascolari del Controllo della Pressione Arteriosa Sistolica (CARDIO-SIS) trial, 1111 patients, aged ≥55 years (mean age 67 years) without diabetes and with SBP ≥150 mm Hg, were randomized to SBP <130 mm Hg (tight control) or <140 mm Hg (moderate control).
      • Verdecchia P.
      • Staessen J.A.
      • Angeli F.
      • et al.
      Usual versus tight control of systolic blood pressure in non-diabetic patients with hypertension (Cardio-Sis): an open-label randomised trial.
      After 2 years of follow-up, 27.3% and 72.2% of participants in the moderate and tight SBP control groups, respectively, had achieved SBP <130 mm Hg. At 2 years, 17.0% and 11.4% of those in the moderate and tight control groups, respectively, had the primary outcome of left ventricular hypertrophy (P = 0.013). The secondary end point was a composite of CVD and renal disease and occurred in 9.4% in the moderate SBP control group and 4.8% in the tight control group (P = 0.003).
      Despite the tremendous knowledge gained from each of these studies, the optimal on-treatment SBP goal for older adults remains unknown. Previous randomized trials have been limited by short follow-up, limited sample size and selected populations. Additionally, studies have not assessed frailty. Many studies may have excluded frail individuals, resulting in limited generalizability. Two large ongoing studies (Systolic Blood Pressure Intervention Trial [SPRINT] and the Stroke in Hypertension Optimal Treatment Trial of the European Society of Hypertension and the Chinese Hypertension League [ESH-CHL-SHOT]) may provide important new information for older adults.

      Optimal blood pressure and cholesterol targets for preventing recurrent stroke in hypertensives (esh-chl-shot). Available at: http://clinicaltrials.gov/show/nct01563731. Accessed December 20, 2013.

      SPRINT, which was launched in 2010 by the U.S. National Institute of Health, is designed to determine whether maintaining SBP/DBP <120/80 mm Hg versus <140/90 mm Hg will reduce the risk of CVD and kidney disease, as well as age-related cognitive decline in 9250 adults aged ≥55 years. Age ≥75 years is an a priori defined subgroup in SPRINT. ESH-CHL-SHOT is a prospective, randomized trial comparing 3 SBP targets (<125, 125–134 and 135–144 mm Hg). The trial is being conducted in 7,500 adults aged ≥65 years with hypertension from Europe (n = 2,500) and China (n = 5,000). Participants will be followed for the primary outcome of stroke and secondary outcomes including a major cardiovascular event and cognitive decline. It is anticipated that both trials will be completed in 2018. SPRINT and ESH-CHL-SHOT may help identify the optimal SBP goal for the elderly with hypertension.

      OBSERVATIONAL DATA ON BP AND OUTCOMES AMONG OLDER ADULTS

      Epidemiology studies have consistently found weaker associations between established risk factors from the general population when studied in older adults.
      • Howard G.
      • Goff Jr., D.C.
      A call for caution in the interpretation of the observed smaller relative importance of risk factors in the elderly.
      The association between SBP and CVD and all-cause mortality is no exception. In 2002, Lewington et al
      • Lewington S.
      • Clarke R.
      • Qizilbash N.
      • et al.
      Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies.
      published data from over 1 million adults from 61 studies on the associations between SBP and DBP and mortality from stroke and coronary heart disease by age. The associations between both SBP and DBP and mortality from stroke, coronary heart disease and other vascular disease were graded and continuous with the lowest risk at SBP of 115 mm Hg and DBP of 75 mm Hg (lower BP levels were not reported) and the highest risk at SBP of 175 mm Hg and DBP of 105 mm Hg (higher levels were not reported). However, these associations were weaker at older age (Figure 1).
      Figure thumbnail gr1
      Figure 1Age-specific hazard ratios for stroke, ischemic heart disease and other vascular disease mortality associated with 20-mm Hg lower systolic blood pressure (A) and 10-mm Hg lower diastolic blood pressure (B).
      • Lewington S.
      • Clarke R.
      • Qizilbash N.
      • et al.
      Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies.
      Not every study has found an association between higher SBP and DBP and increased risk for outcomes among older adults. Using data from the Established Populations for Epidemiologic Studies of the Elderly, Satish et al
      • Satish S.
      • Freeman Jr., D.H.
      • Ray L.
      • et al.
      The relationship between blood pressure and mortality in the oldest old.
      evaluated the association between SBP and DBP and mortality over 6 years of follow-up among 12,802 community-dwelling adults aged 65 to 84 and ≥85 years. Among men and women aged 65 to 84 years, higher SBP was associated with an increased risk for mortality. The multivariable adjusted hazard ratios for mortality associated with 10 mm Hg higher SBP was 1.04 (95% confidence interval [CI]: 1.01–1.07) for men and 1.10 (95% CI: 1.07–1.13) for women. However, higher SBP was associated with a lower risk for death among men aged ≥85 years, and no association was present for women in this age group (hazard ratio each 10 mm Hg higher SBP of 0.92; 95% CI: 0.86–0.99 for men and 1.00; 95% CI: 0.95–1.05 for women). For participants aged 65 to 84 and ≥85 years, higher DBP was associated with a lower mortality risk for men, but no association was present for women. Furthermore, some studies have reported an increased CVD risk at very low SBP levels among older adults.
      • Voko Z.
      • Bots M.L.
      • Hofman A.
      • et al.
      J-shaped relation between blood pressure and stroke in treated hypertensives.
      • Ogihara T.
      • Matsuoka H.
      • Rakugi H.
      Practitioner’s trial on the efficacy of antihypertensive treatment in elderly patients with hypertension II (PATE-hypertension II study) in Japan.
      The weaker, and possibly harmful, association between lower SBP and outcomes at older age has generated hypotheses regarding whether lower treatment targets for older adults with hypertension should be achieved. Given new randomized trial data are not expected until 2018, observational data may be a useful source to better understand the association of SBP treatment targets with CVD outcomes.

      RECONCILING DIFFERENCES BETWEEN CLINICAL TRIALS AND OBSERVATIONAL STUDIES

      An important aspect of interpreting observational studies in older populations is heterogeneity in health status. However, this is often not taken into account in guidelines. As noted over 20 years ago by Harris, among older adults, normal SBP may be found in (1) someone with life-long normal BP, (2) someone whose BP has shown a progressive rise through their adult life but remains in the “normal” range or (3) someone with a history of hypertension and heart failure who has normal SBP due to compromised cardiac function.
      • Harris T.B.
      • Feldman J.J.
      Implications of health status in analysis of risk in older persons.
      CVD risk may be very different in these groups, and the heterogeneity in health status may distort the true SBP-CVD association among older adults.
      Additionally, the prevalence of frailty increases with age, and this phenotype has been associated with adverse health outcomes including hospitalization and mortality.
      • Rockwood K.
      • Stadnyk K.
      • MacKnight C.
      • et al.
      A brief clinical instrument to classify frailty in elderly people.
      Frailty is a syndrome of decreased physiologic reserve across multiple organ systems that results in vulnerability to adverse outcomes.
      • Fried L.P.
      • Tangen C.M.
      • Walston J.
      • Cardiovascular Health Study Collaborative Research Group
      • et al.
      Frailty in older adults: evidence for a phenotype.
      The frailty phenotype has been operationalized as ≥3 of the following: shrinking, weakness, slowness, exhaustion and low activity.
      • Fried L.P.
      • Tangen C.M.
      • Walston J.
      • Cardiovascular Health Study Collaborative Research Group
      • et al.
      Frailty in older adults: evidence for a phenotype.
      Frail patients are often excluded from randomized trials but included in observational research of older adults.
      Previous research suggests that the association between SBP and mortality differs by frailty status. Specifically, a recent analysis of the U.S. National Health and Nutrition Examination Survey (NHANES) Mortality Follow-up Study by Odden et al
      • Odden M.C.
      • Peralta C.A.
      • Haan M.N.
      • et al.
      Rethinking the association of high blood pressure with mortality in elderly adults: the impact of frailty.
      evaluated the association between SBP and mortality among U.S. adults aged ≥65 years by walking speed, a marker of frailty status. This study included 2340 participants who participated in the 1999 to 2000 or 2001 to 2002 NHANES cycles. Participants were asked to complete a 6-m walk test during the NHANES clinic examination and were categorized into 3 groups (faster walkers [≥0.8 m/s], slower walkers [<0.8 m/s] and those who did not complete the walk test). Additionally, SBP and DBP were measured 3 or 4 times by a physician following a standardized protocol. In this sample, 56% of participants were fast walkers, 34% were slow walkers and 10% did not complete the walk test. Over up to 8 years of follow-up, 589 participants died. After adjustment for NHANES survey year, age, gender, race, education, smoking, total cholesterol and having a history of heart disease, heart failure or stroke, the association between SBP and mortality differed by walking speed. For example, the adjusted hazard ratio for all-cause mortality associated with SBP ≥140 mm Hg versus <140 mm Hg was 1.35 (95% CI: 1.03–1.77) for fast walkers, 1.12 (95% CI: 0.87–1.45) for slow walkers and 0.38 (95% CI: 0.23–0.62) for participants who did not complete the walk test (P value for interaction = 0.001). The adjusted hazard ratio for all-cause mortality associated with DBP ≥90 mm Hg versus <90 mm Hg was 0.94 (95% CI: 0.38–2.28), 0.75 (95% CI: 0.32–1.75) and 0.10 (95% CI: 0.01–0.81) for fast walkers, slow walkers and those who did not complete the walk test, respectively (P value for interaction = 0.21). This study highlights the potential differences in the appropriate SBP treatment targets that may exist for many older adults and the limited generalizability of randomized trials of antihypertensive medication among older adults.

      ANTIHYPERTENSIVE TREATMENT AND SBP AND DBP LEVELS AMONG OLDER U.S. ADULTS IN THE GENERAL POPULATION

      Data on mean SBP and DBP, the prevalence of hypertension and BP treatment patterns among older U.S. adults are important for understanding how previous guidelines, recent trials and observational studies have been translated into clinical practice. Analyses of data from serial NHANES provide information on SBP and DBP levels among older U.S. adults. Guo et al
      • Guo F.
      • He D.
      • Zhang W.
      • et al.
      Trends in prevalence, awareness, management, and control of hypertension among United States adults, 1999 to 2010.
      found that the mean SBP declined from 141 mm Hg in 1999 to 2000 to 131 mm Hg in 2009 to 2010 (P value <0.001) among U.S. adults aged ≥60 years. Additionally, mean DBP declined from 71 to 66 mm Hg over this time period. The prevalence of hypertension did not change substantially over time and was 66.7% in 2009 to 2010. Also, in 2009 to 2010, 84.0% of those with hypertension were aware of their diagnosis, 85.3% of those aware were treated and 54.9% of all people with hypertension and 64.4% of those being treated had an SBP/DBP <140/90 mm Hg.
      More recent data have been analyzed for very old U.S. adults. Using serial national cross-sectional samples of U.S. adults aged ≥80 years, Bromfield et al
      • Bromfield S.
      • Bowling C.B.
      • Tanner R.
      • et al.
      Trends in hypertension prevalence, awareness, treatment, and control among US adults 80 years and older, 1988-2010.
      studied mean SBP and DBP levels and the prevalence, awareness, treatment and control of hypertension. Among U.S. adults aged 80 years and older, mean SBP was 147 mm Hg in 1988 to 1994, 148 mm Hg in 1999 to 2004 and 140 mm Hg in 2005 to 2010 (P trend <0.001). Mean DBP decreased from 70 mm Hg in 1988 to 1994 to 61 mm Hg in 1999 to 2004 and was 59 mm Hg in 2005 to 2010 (P trend <0.001). Overall, the prevalence of hypertension was stable over the time periods studied and was 76.5% in 2005 to 2010. Between 1988 to 1994 and 2005 to 2010, awareness of hypertension increased from 59.3% to 79.4%, treatment among those aware increased from 33.7% to 57.4% and SBP/DBP <140/90 mm Hg increased from 14.8% to 39.8% among those with hypertension and from 30.4% to 53.1% among those taking antihypertensive medication. It is important to note that among those with hypertension, the mean number of antihypertensive medication classes being taken doubled between 1988 to 1994 and 2005 to 2010. Additionally, the proportion of U.S. adults aged 80 years and older taking ≥3 classes of antihypertensive medication increased from 7.0% to 30.9% (Figure 2). Given the uncertainty surrounding the optimal SBP target for older adults, the benefits and risks of antihypertensive medication polypharmacy among older adults needs to be investigated in future studies.
      Figure thumbnail gr2
      Figure 2Number of antihypertensive medication classes being taken by U.S. adults aged ≥80 years with hypertension in 1988 to 1994, 1999 to 2004 and 2005 to 2010.

      CONCLUSIONS

      Several randomized trials have demonstrated clear benefits of antihypertensive medication among older adults with SBP ≥160 mm Hg. However, the 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults Report From the Panel Members Appointed to the JNC 8 did not find evidence from randomized trials supporting a SBP treatment goal <140 mm Hg for older adults without diabetes or chronic kidney disease. This guideline highlights several pressing research questions that will provide important new knowledge to help guide the management of hypertension among older adults. First, the optimal SBP treatment target for older adults remains a critical knowledge gap. Whether treating SBP to <140 mm Hg, or perhaps even lower, is appropriate for older adults needs to be determined. Second, the effect of health status and frailty has on SBP treatment targets warrants future investigation. Given the heterogeneity of health status for older adults, how aggressive SBP should be lowered may vary and a single SBP goal may not be appropriate for all older adults. Third, the population- and patient-level benefit and risk of anti- hypertensive medication polypharmacy with respect to the potential harms of low SBP in the elderly should be determined. A high percentage of older adults are taking multiple classes of antihypertensive medication and the real-world implications of these treatment patterns may inform future trials and guidelines. In conclusion, although substantial progress has been made in the treatment and control of hypertension among older adults, it remains an important public health challenge as the U.S. population continues to age.

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