Key result
Using offspring blood pressure as an instrumental variable, a one standard deviation increase in own systolic blood pressure was causally associated with a 28% increased risk of all-cause mortality (HR 1.28).
Why the study?
Does higher own blood pressure increase mortality from all-causes, CVD, CHD, stroke, and diabetes in adults?
Observational (n=59,762)
Does higher own blood pressure increase mortality from all-causes, CVD, CHD, stroke, and diabetes in adults?
Hazard Ratio: 1.28 (95% CI 1.18–1.39)
p-value: p=<0.0001
Using offspring blood pressure as an instrumental variable amplifies the magnitude of the positive association between own blood pressure and mortality from all-causes, CVD, and CHD compared to conventional observational estimates.
Offspring BP as IV may refine BP-mortality estimates; leaves open causal inference from observational data alone.
Given that observational associations may be inaccurate, we used offspring blood pressure (BP) to provide alternative estimates of the associations between own BP and mortality. Observational associations between BP and mortality, estimated as hazard ratios (HRs) from Cox regression, were compared to HRs obtained using offspring BP as an instrumental variable (IV) for own BP (N = 32,227 mother-offspring and 27,535 father-offspring pairs). Observationally, there were positive associations between own BP and mortality from all-causes, cardiovascular disease (CVD), coronary heart disease (CHD), stroke and diabetes. Point estimates of the associations between BP and mortality from all-causes, CVD and CHD were amplified in magnitude when using offspring BP as an IV. For example, the HR for all-cause mortality per standard deviation (SD) increase in own systolic BP (SBP) obtained in conventional observational analyses increased from 1.10 (95% CI: 1.09-1.12; P < 0.0001) to 1.31 (95% CI: 1.19-1.43; P < 0.0001). Additionally, SBP was positively associated with diabetes and cancer mortality (HRs: 2.00; 95% CI: 1.12-3.35; P = 0.02 and 1.20; 95% CI: 1.02-1.42; P = 0.03, respectively), and diastolic BP (DBP) with stroke mortality (HR: 1.30; 95% CI: 1.02-1.66; P = 0.03). Results support positive associations between BP and mortality from all-causes, CVD, and CHD, SBP on cancer mortality, and DBP on stroke mortality.
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Wade et al. (2015) conducted an observational in Hypertension and Mortality (n=59,762). Elevated own systolic blood pressure (instrumented by offspring blood pressure) vs. Lower systolic blood pressure (per standard deviation increase) was evaluated on All-cause mortality per standard deviation increase in own systolic blood pressure (HR 1.28, 95% CI 1.18-1.39, p=<0.0001). Using offspring blood pressure as an instrumental variable, a one standard deviation increase in own systolic blood pressure was causally associated with a 28% increased risk of all-cause mortality (HR 1.28).
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