Abstract:1 joins a host of other observational studies reporting an inverse relationship between high systolic blood pressure (SBP) and mortality. [2][3][4] The inclusion of measures of grip strength and gait speed in this study provides further evidence that functional status may modify this relationship, but the fundamental limitations inherent in all observational studies that have addressed this relationship compel us to comment. Furthermore, the conclusions derived from two large randomized clinical trials (RCT) o… Show more
“…There is a strong argument that a reduction in systematic BP may worsen cerebral ischemia in relation to altered cerebral autoregulation in the vulnerable penumbral region of AIS [ 33 ], whereas comorbidity and greater neurological severity in those presenting with hypotension, may partly explain the increase in SAEs shown in previous acute stroke trials [ 34 ]. Although low BP in frail older patients might be a harbinger of preterminal decline [ 35 ], we found the increased risk of adverse events in stroke patients with low BP persisted after adjustment for premorbid disability and comorbid heart disease.…”
Objective:
As uncertainties exist over underlying causes, we aimed to define the characteristics and prognostic significance of low blood pressure (BP) early after the onset of acute stroke.
Methods:
Post hoc analyzes of the international Head Positioning in acute Stroke Trial (HeadPoST), a pragmatic cluster-crossover randomized trial of lying flat versus sitting up in stroke patients from nine countries during 2015–2016. Associations of baseline BP and death or dependency [modified Rankin scale (mRS) scores 3–6] and serious adverse events (SAEs) at 90 days were assessed in generalized linear mixed models with adjustment for multiple confounders. SBP and DBP was analysed as continuous measures fitted with a cubic spline, and as categorical measures with low (<10th percentile) and high (≥140 and ≥90 mmHg, respectively) levels compared with a normal range (≥10th percentile; 120–139 and 70–89 mmHg, respectively).
Results:
Among 11 083 patients (mean age 68 years, 39.9% women) with baseline BP values, 7.2 and 11.7% had low SBP (<120 mmHg) and DBP (<70 mmHg), respectively. Patients with low SBP were more likely to have preexisting cardiac and ischemic stroke and functional impairment, and to present earlier with more severe neurological impairment than other patients. Nonlinear ‘J-shaped’ relationships of BP and poor outcome were apparent: compared with normal SBP, those with low SBP had worse functional outcome (adjusted odds ratio 1.27, 95% confidence interval 1.02–1.58) and more SAEs, particularly cardiac events, with adjustment for potential confounders to minimize reverse causation. The findings were consistent for DBP and were stronger for ischemic rather than hemorrhagic stroke.
Conclusion:
The prognostic significance of low BP on poor outcomes in acute stroke was not explained by reverse causality from preexisting cardiovascular disease, and propensity towards greater neurological deficits and cardiac events. These findings provide support for the hypothesis that low BP exacerbates cardiac and cerebral ischemia in acute ischemic stroke.
“…There is a strong argument that a reduction in systematic BP may worsen cerebral ischemia in relation to altered cerebral autoregulation in the vulnerable penumbral region of AIS [ 33 ], whereas comorbidity and greater neurological severity in those presenting with hypotension, may partly explain the increase in SAEs shown in previous acute stroke trials [ 34 ]. Although low BP in frail older patients might be a harbinger of preterminal decline [ 35 ], we found the increased risk of adverse events in stroke patients with low BP persisted after adjustment for premorbid disability and comorbid heart disease.…”
Objective:
As uncertainties exist over underlying causes, we aimed to define the characteristics and prognostic significance of low blood pressure (BP) early after the onset of acute stroke.
Methods:
Post hoc analyzes of the international Head Positioning in acute Stroke Trial (HeadPoST), a pragmatic cluster-crossover randomized trial of lying flat versus sitting up in stroke patients from nine countries during 2015–2016. Associations of baseline BP and death or dependency [modified Rankin scale (mRS) scores 3–6] and serious adverse events (SAEs) at 90 days were assessed in generalized linear mixed models with adjustment for multiple confounders. SBP and DBP was analysed as continuous measures fitted with a cubic spline, and as categorical measures with low (<10th percentile) and high (≥140 and ≥90 mmHg, respectively) levels compared with a normal range (≥10th percentile; 120–139 and 70–89 mmHg, respectively).
Results:
Among 11 083 patients (mean age 68 years, 39.9% women) with baseline BP values, 7.2 and 11.7% had low SBP (<120 mmHg) and DBP (<70 mmHg), respectively. Patients with low SBP were more likely to have preexisting cardiac and ischemic stroke and functional impairment, and to present earlier with more severe neurological impairment than other patients. Nonlinear ‘J-shaped’ relationships of BP and poor outcome were apparent: compared with normal SBP, those with low SBP had worse functional outcome (adjusted odds ratio 1.27, 95% confidence interval 1.02–1.58) and more SAEs, particularly cardiac events, with adjustment for potential confounders to minimize reverse causation. The findings were consistent for DBP and were stronger for ischemic rather than hemorrhagic stroke.
Conclusion:
The prognostic significance of low BP on poor outcomes in acute stroke was not explained by reverse causality from preexisting cardiovascular disease, and propensity towards greater neurological deficits and cardiac events. These findings provide support for the hypothesis that low BP exacerbates cardiac and cerebral ischemia in acute ischemic stroke.
“…4). There is evidence 30,50–52 suggesting reverse causation acting on BP up to three years prior to death, but it is not clear whether chronic, sub-clinical conditions can lower BP earlier than this. Conventional multivariable analyses in which BP is measured at a young age may therefore have limited vulnerability to reverse causation, but we consider offspring BP to be an instrument for lifelong BP in the parents, including in old age when reverse causation is likely to be important in conventional multivariable analyses.Figure 4Directed acyclic graph illustrating potential confounders of the effect of blood pressure (BP) on mortality, when a son’s BP is used as an instrument.…”
High systolic blood pressure (SBP) causes cardiovascular disease (CVD) and is associated with mortality from other causes, but conventional multivariably-adjusted results may be confounded. Here we used a son’s SBP (>1 million Swedish men) as an instrumental variable for parental SBP and examined associations with parents’ cause-specific mortality, avoiding reverse causation. The hazard ratio for CVD mortality per SD (10.80 mmHg) of SBP was 1.49 (95% CI: 1.43, 1.56); SBP was positively associated with coronary heart disease and stroke. SBP was also associated positively with all-cause, diabetes and kidney cancer mortality, and negatively with external causes. Negative associations with respiratory-related mortality were probably confounded by smoking. Hazard ratios for other causes were imprecise or null. Diastolic blood pressure gave similar results to SBP. CVD hazard ratios were intermediate between those from conventional multivariable studies and Mendelian randomization and stronger than those from clinical trials, approximately consistent with an effect of exposure duration on effect sizes. Plots of parental mortality against offspring SBP were approximately linear, supporting calls for lower SBP targets. Results suggest that conventional multivariable analyses of mortality and SBP are not substantially confounded by reverse causation and confirm positive effects of SBP on all-cause, CVD and diabetes mortality.
“…It is unlikely that there is a universal blood pressure goal in this population, and therefore the scientific query should center on how to establish the ideal target for each patient. We appreciate the comments by Supiano et al, 1 yet we disagree with the statement that the findings from our observational study conflict with results from randomized trials. In contrast, we believe that integrating evidence from different types of studies can help us reach our common goal of treating those patients who stand to benefit the most from blood pressure lowering.…”
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