Influence of Hypertension on 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 and Results: We estimated the risk of prevalent hypertension with incident respiratory diseases over mean 8 follow-up 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.107,310 (30%) participants had hypertension at UK Biobank enrollment, and 9,969 (3%) developed a pneumonia during follow-up. Prevalent hypertension was independently associated with increased risk for incident pneumonia (HR: 1.36; 95% CI: 1.29 to 1.43; P<0.001), as well as other incident respiratory diseases. Genetic predisposition to a 5-mmHg increase in blood pressure was associated with increased risk of incident pneumonia for systolic blood pressure (HR: 1.08; 95% CI: 1.04 to 1.13; P<0.001) and diastolic blood pressure (HR: 1.11; 95% CI: 1.03 to 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 strongly suggest that elevated blood pressure increases risk for pneumonia. Maintaining adequate blood pressure control, in addition to other measures, may reduce risk for pneumonia.