Systolic Blood Pressure Trajectory, Frailty, and All-Cause Mortality >80 Years of Age

Abstract

BACKGROUND:Clinical trials show benefit from lowering systolic blood pressure (SBP) in people ≥80 years of age, but nonrandomized epidemiological studies suggest lower SBP may be associated with higher mortality. This study aimed to evaluate associations of SBP with allcause mortality by frailty category >80 years of age and to evaluate SBP trajectories before death. METHODS:A population-based cohort study was conducted using electronic health records of 144 403 participants ≥80 years of age registered with family practices in the United Kingdom from 2001 to 2014. Participants were followed for ≤5 years. Clinical records of SBP were analyzed. Frailty status was classified using the e-Frailty Index into the categories of fit, mild, moderate, and severe. All-cause mortality was evaluated by frailty status and mean SBP in Cox proportionalhazards models. SBP trajectories were evaluated using person months as observations, with mean SBP and antihypertensive treatment status estimated for each person month. Fractional polynomial models were used to estimate SBP trajectories over 5 years before death. RESULTS:During follow-up, 51 808 deaths occurred. Mortality rates increased with frailty level and were greatest at SBP <110 mm Hg. In fit women, mortality was 7.7 per 100 person years at SBP 120 to 139 mm Hg, 15.2 at SBP 110 to 119 mm Hg, and 22.7 at SBP <110 mm Hg. For women with severe frailty, rates were 16.8, 25.2, and 39.6, respectively. SBP trajectories showed an accelerated decline in the last 2 years of life. The relative odds of SBP <120 mm Hg were higher in the last 3 months of life than 5 years previously in both treated (odds ratio, 6.06; 95% confidence interval, 5.40-6.81) and untreated (odds ratio, 6.31; 95% confidence interval, 5.30-7.52) patients. There was no evidence of intensification of antihypertensive therapy in the final 2 years of life. CONCLUSIONS:A terminal decline of SBP in the final 2 years of life suggests that nonrandomized epidemiological associations of low SBP with higher mortality may be accounted for by reverse causation if participants with lower blood pressure values are closer, on average, to the end of life. 2358 B lood pressure increases with age, and older people have a higher prevalence of hypertension. 1,2 Elevated systolic blood pressure (SBP) may be the most important risk factor for cardiovascular disease in older people. 3 Recently, several large clinical trials 4-9 have suggested that use of antihypertensive medications to lower blood pressure may reduce cardiovascular events and mortality in older adults. In HYVET (Hypertension in the Very Elderly Trial) 6 of antihypertensive therapy >80 years of age, lowering blood pressure was associated with 30% reduction in stroke, 21% reduction in all-cause mortality, and 64% reduction in heart failure. In SPRINT (Systolic Blood Pressure Intervention Trial), 7 in people ≥75 years of age, management of SBP to a target of <120 mm Hg was associated with 34% reduction in cardiovascular events and 33% reduction in all-cause mortality. Th...

Systolic Blood Pressure and Mortality: Role of Reverse Causation

“…A recent observational cohort study that tracked SBP trajectories for the 5 years before death in 144,403 individuals aged 80 older provides a compelling example of this limitation. 9 Consistent with Wu and colleagues and other observational studies, mortality was greatest in those with SBP less than 110 mmHg, although there was a decline in the SBP trajectory noted in the last 3 months of life in individuals undergoing treatment for hypertension and those not undergoing treatment. This terminal decline in SBP provided the best explanation for the observed association between low SBP and mortality in this and probably other observational studies.…”

Blood Pressure, Arterial Load, and Survival After Transcatheter Aortic Valve Replacement

“…11 In the latter regard, a recently reported United Kingdom population-based cohort study in 144 403 subjects aged >80 years demonstrated a significant association between lower SBP and all-cause mortality, independent of frailty status. 12 The association appeared to be explained, in part, by a terminal decline in SBP in the final 2 years of life. The investigators concluded that reverse causation might have pertained if lower SBP resulted from temporal proximity to death and that the observed (nonrandomized) association between higher SBP O'Gara BP, Arterial Load, and Survival After TAVR and greater longevity could have been confounded.…”

“…12 A single blood pressure determination in elderly patients 30 days after TAVR may not provide enough information from which to draw firm conclusions on causality.…”

“…The investigators concluded that reverse causation might have pertained if lower SBP resulted from temporal proximity to death and that the observed (nonrandomized) association between higher SBP O'Gara BP, Arterial Load, and Survival After TAVR and greater longevity could have been confounded. 12 A single blood pressure determination in elderly patients 30 days after TAVR may not provide enough information from which to draw firm conclusions on causality.…”

“…12 A single blood pressure determination in elderly patients 30 days after TAVR may not provide enough information from which to draw firm conclusions on causality.The current study's observations on the differential effects of total, pulsatile, and resistive arterial loads, and their interactions with SBP, are important reminders of the complex ventricular-valvular-arterial interactions that ensue in an elderly, predominantly hypertensive patient cohort after relief of aortic valve obstruction. [13][14][15] The deleterious effects of increased arterial stiffness and pulsatile load in this population are vastly underappreciated although likely not remediable with medical therapy in advanced age.…”