Outcomes of Treated Hypertension at Age 80 and Older

Cohort Analysis of 79,376 Individuals

João Delgado, PhD; Jane A. H. Masoli, MBChB; Kirsty Bowman, MPH; W. David Strain, MD; George A. Kuchel, MD; Kate Walters, PhD; Louise Lafortune, PhD; Carol Brayne, MD; David Melzer, PhD; Alessandro Ble, MD

Disclosures

J Am Geriatr Soc. 2017;65(5):995-1003. 

In This Article

Discussion

A large cohort of the oldest adults in primary care taking antihypertensive medication over the long term was studied to estimate prognosis according to attained BP level in routine primary care practice working under national guidance to achieve a SBP less than 150 mmHg in older adults with hypertension. Individuals with major comorbidities at baseline that might have posed specialist treatment challenges or confounded estimates were excluded. The analysis included 49.7% of individuals aged 80 and older in the complete population-based analysis. It was found, as expected, that all-cause mortality and risk of cardiovascular disease rose with increasing SBP above 145 to 154 mmHg. Linearly increasing risk of myocardial infarction was found with increasing SBP, although greater mortality was also found in those with SBP of less than 135 mmHg. Confounding is typically evident in the first few years of follow-up, but the excess mortality at SBP less than 135 mmHg was consistent, even over the longest follow-up period (8–11.9 years) Table S4. The sensitivity analyses on comorbidity, BMI, major weight loss, incident cancer, and exclusion of those seen by practice staff in residential or nursing homes also had little effect on estimates. Results were also similar in individuals with diabetes mellitus (Table S2).

These results reflect outcomes of individuals aged 80 and older receiving ongoing treatment for hypertension under currently recommended targets; at the time the data were recorded in electronic clinical records, intensive treatment to reduce SBP below 140 mmHg in individuals aged 80 and older was not indicated. Observational studies of prognosis in the above context are not comparable with studies that randomize participants to intensive treatment to achieve lower target BP. If intensive treatment were instituted to achieve SBP substantially lower than 150 mmHg, those with low SBP might be expected to be taking more antihypertensive medications than those with higher attained BP, but the group with lower attained SBP (<125 mmHg) had slightly fewer prescribed medications (mean 1.84) than the reference group (mean 1.99 for SBP 145–154 mmHg). Also, the participants being in routine care, the medications prescribed may have differed from those used in recent trials aiming to achieve lower SBP. This analysis has other limitations, including inaccuracies in routine data recording. Although routine practice is to measure BP more than once for each clinical review, the available data contain only one recorded BP at each consultation, although it seems likely that the BPs recorded in clinical records are those used as a basis for management. Inaccuracies in estimated BPs were minimized by using median of recorded BPs across consultations during a 3-year lead-in period, avoiding "outliers" (perhaps recorded during acute events) that might distort mean values, and the mean number of measurements studied varied from 7.2 for the group with SBP less than 125 mmHg to 13.4 for those with SBP of 165 to 174 mmHg (Table S3). The studied BPs were used in monitoring antihypertensive treatment and thus have validity for the purpose of estimating prognosis in routine practice. Other aspects of BP, including orthostatic hypotension, have been associated with adverse events and may have contributed to the results observed,[19] alghouth no data are available on orthostatic hypotension in the dataset. Although assessment of orthostatic hypotension is thought to be common, the lack of specific data on these measures limits this analysis. Given the "typical care" rather than etiological context, BP measured during follow-up (e.g., accounting for regression dilution)[20] was not accounted for because subsequent BP measurement were not available at treatment review in practice. Antihypertensive medication data are from real-time prescribing records; no measure of adherence was available,[8] although nonadherence should be associated with higher BP and was unlikely to bias estimates of greater mortality at low SBP. Cause-specific mortality was not studied, because death certification is thought to lack precision in the oldest adults, especially for cardiac outcomes. Records of lower SBP were more common in the later part of the period (2000–2014), with shorter mean follow-up times for individuals with low SBP ( Table 1 ). This may have been the result of incentive payments to improve hypertension management introduced from 2004, but adjusting for year of baseline BP measurement did not significantly alter results.[21] Elaborate adjustment of models was also avoided, with potentially confounding conditions excluded instead and easily interpretable estimates of prognosis in routine primary care provided. It is also possible that there was some undiagnosed disease at baseline that reduced BP and increased mortality, but low SBP was associated with excess mortality even in the 8 years to the end of follow-up (ignoring the first 8 years of follow-up), making this explanation less likely. The Charlson Comorbidity Index was used to account for comorbidities, but this does not fully capture functional status or frailty in this population; better measurement of functional status or frailty (e.g., gait speed) might correlate with the poor outcomes in the lower SBP group, although the study subjects were selected to be free of dementia, cancer, stroke, heart failure, coronary heart disease, and end-stage renal disease, and adjustment for Charlson comorbidities altered the results only slightly, as did any of the other sensitivity analyses.

In the United Kingdom, 98% of the population are registered with a GP, and the CPRD sample was found to be broadly representative of English population based on the 2011 Census, particularly in older age groups.[8] Longer follow-up was included than in existing studies in adults aged 80 and older.[22] Randomized trials provide the most robust evidence of causation by tested treatments, observational population representative studies are also useful for estimating overall clinical prognosis (combination of antihypertensive effects and all other factors, measured and unmeasured). Observational studies are useful for investigating applicability to typical patient groups, longer follow-up times, and adverse outcomes.[23,24]

Comparison With Previous Evidence

These results are restricted to the oldest adults undergoing antihypertensive treatment and focus on clinical prognosis in routine care. The finding of J-shaped associations for some outcomes is broadly consistent with previous evidence for individuals aged 80 and older in studies of individuals with high cardiovascular risk.[25–27] The Clinical research using LInked Bespoke studies and Electronic health Records (CALIBER) study also used CPRD GP medical records and linked data to study cardiovascular outcomes in individuals taking antihypertensive medications. In their subgroup aged 80 to 95 taking antihypertensive medications (with no exclusions for non-CVD comorbidities, Table S15), increasing SBP was similarly associated with a linear increase in incident myocardial infarction, plus a J-shaped association for heart failure and a flat association with ischemic stroke for SBP less than 159 mmHg.[23] CALIBER did not study all-cause mortality or fragility fracture outcomes. CALIBER reported "unheralded" CHD mortality based on death certification in people without a history of cardiovascular disease and found markedly higher mortality at low SBP in those aged 80 to 95 (SBP 100–115 mmHg: HR = 1.27, 95% CI = 1.09–1.48; SBP 140–159 mmHg: HR = 0.60, 95% CI = 0.43–0.84). The Prospective Studies Group pooled volunteer cohorts from the 1960s to the 1980s and found a linear association between BP (irrespective of treatment) and vascular and overall mortality in adults aged 80 and older (published 2002), but it is uncertain how these findings relate to older adults with treated hypertension in the current treatment era.[24]

The observational data of outcomes in routine care focus on a different concern and are not comparable with data from randomized controlled trials, although the HYpertension in the Very Elderly Trial—a randomized controlled trial of hypertension management in adults aged 80 and older—showed lower all-cause mortality[28] with a target BP of 150/80 mmHg and an achieved mean sitting BP of 145.0/76.6 mmHg in the active treatment group at the start of the open-label extension. The Systolic Blood Pressure Intervention Trial in Patients Age 75 and Older (SPRINT 75+) aimed "To evaluate the effects of intensive (<120 mmHg) compared with standard (<140 mmHg) SBP targets in persons aged 75 years or older with hypertension but without diabetes".[29] SPRINT included 1,317 cases and 1,319 controls aged 75 and older (37.9% female) free of diabetes mellitus, stroke, a recent cardiovascular event or heart failure, dementia, medical conditions limiting life expectancy to less than 3 years (including cancer), and factors that the clinic team judged to be likely to limit adherence to therapy, or residence in a nursing home. SPRINT 75+ concluded that "intensive treatment resulted in significantly lower rates of fatal and nonfatal major cardiovascular events" over a median follow-up of 3.14 years. There were also nonsignificant trends toward higher rates of some adverse events, except for injurious fracture, which was nonsignificantly less common in the intensive treatment group (4.9% vs 5.5%).

More work is needed to include measures of orthostatic hypotension and to identify the reasons for the apparently poor prognosis of individuals with SBP less than 135 mmHg in routine care. It may be that unplanned low attained SBP may be a useful clinical sign to trigger general clinical review of all comorbidities. Better measurement of frailty and functioning may be informative.

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