Elevated Blood Pressure Increases Pneumonia Risk: Epidemiological Association and Mendelian Randomization in the UK Biobank

Background Small studies have correlated hypertension with pneumonia risk; whether this is recapitulated in larger prospective studies, and represents a causal association, is unclear. Methods We estimated the risk for prevalent hypertension with incident respiratory diseases over mean follow-up of 8 years among 377,143 British participants in the UK Biobank. Mendelian randomization of blood pressure on pneumonia was implemented using 75 independent, genome-wide significant variants associated with systolic and diastolic blood pressures among 299,024 individuals not in the UK Biobank. Secondary analyses with pulmonary function tests were performed. Findings In total, 107,310 participants (30%) had hypertension at UK Biobank enrollment, and 9,969 (3%) developed pneumonia during follow-up. Prevalent hypertension was independently associated with increased risk for incident pneumonia (HR: 1.36; 95% CI: 1.29–1.43; p < 0.001), as well as other incident respiratory diseases. Genetic predisposition to a 5 mm Hg increase in blood pressure was associated with increased risk for incident pneumonia for systolic blood pressure (HR: 1.08; 95% CI: 1.04–1.13; p < 0.001) and diastolic blood pressure (HR: 1.11; 95% CI: 1.03–1.20; p = 0.005). Additionally, consistent with epidemiologic associations, increased blood pressure genetic risk was significantly associated with reduced performance on pulmonary function tests (p < 0.001). Conclusions These results suggest that elevated blood pressure increases risk for pneumonia. Maintaining adequate blood pressure control, in addition to other measures, may reduce risk for pneumonia. Funding S.M.Z. (1F30HL149180-01), M.H. (T32HL094301-07), and P.N. (R01HL1427, R01HL148565, and R01HL148050) are supported by the National Institutes of Health. J.P. is supported by the John S. LaDue Memorial Fellowship.
Graphical Abstract
Highlights We linked high BP and incident pneumonia in the UK Biobank using epidemiology and genetics Hypertension was associated with increased risk for incident pneumonia Genetically elevated BP increased risk for incident pneumonia Hypertension and genetically elevated BP also reduced pulmonary function
Context and Significance Epidemiologic analyses have correlated hypertension with pneumonia risk. Whether this represents a direct consequence of hypertension or the influence of co-morbid risk factors such as age, diabetes mellitus, or smoking is unclear. Here, across 377,143 individuals from the UK Biobank, we show that hypertension is independently associated with significantly increased risk for incident pneumonia. Additionally, using Mendelian randomization, we show that a genetic predisposition to elevated blood pressure across 75 independent genetic variants is associated with increased risk for incident pneumonia and reduced pulmonary function test performance. These results suggest that elevated blood pressure may be a causal risk factor for pneumonia. Maintaining adequate blood pressure control, in addition to other measures, may reduce risk for pneumonia.
Through epidemiological and genetic association analyses in the UK Biobank (N = 377,143), Zekavat et al. link high blood pressure with increased risk for incident pneumonia and reduced performance on pulmonary function tests. These results suggest that maintaining adequate blood pressure control may reduce risk for pneumonia and improve pulmonary function.