Influence of blood pressure on pneumonia risk: Epidemiological association and Mendelian randomisation in the UK Biobank

Abstract

ObjectivesTo determine whether elevated blood pressure influences risk for respiratory infection. DesignProspective, population-based epidemiological and Mendelian randomisation studies. SettingUK Biobank. Participants377,143 self-identified British descent (54% women; median age 58 years) participants in the UK Biobank. Main outcome measuresFirst incident pneumonia over an average of 8 follow-up years. Results107,310 (30%) participants had hypertension at UK Biobank enrolment, and 9,969 (3%) developed a pneumonia during follow-up. Prevalent hypertension at baseline was significantly associated with increased risk for incident respiratory disease including pneumonia (hazard ratio 1.36 (95% confidence interval 1.29 to 1.43), P<0.001), acute respiratory distress syndrome or respiratory failure (1.43 (1.29 to 1.59), P<0.001), and chronic lower respiratory disease (1.30 (1.25 to 1.36), P<0.001), independent of age, age2, sex, smoking status, BMI, prevalent diabetes mellitus, prevalent coronary artery disease, and principal components of ancestry. Mendelian randomisation analyses indicated that genetic predisposition to a 5 mmHg increase in blood pressure was associated with increased risk of incident pneumonia for SBP (1.08, (1.04 to 1.13), P<0.001) and DBP (1.11 (1.03 to 1.20), P=0.005). Additionally, consistent with epidemiologic associations, increase in blood pressure genetic risk was significantly associated with reduced forced expiratory volume in the first second, forced vital capacity, and the ratio of the two (P<0.001 for all). ConclusionsThese results strongly suggest that elevated blood pressure independently increases risk for pneumonia and reduces pulmonary function. Maintaining adequate blood pressure control, in addition to other measures, may reduce risk for pneumonia. Whether the present findings are generalizable to novel coronavirus disease 2019 (COVID-19) require further study. Summary BoxO_ST_ABSSection 1: What is already known on this topicC_ST_ABSO_LIHypertension has been associated with pneumonia in small observational studies. C_LIO_LIBased on early epidemiologic analyses, hypertension is described as a risk factor for SARS-CoV-2 infection and associated novel coronavirus disease 2019 (COVID-19). C_LIO_LIThe influence of hypertension on pneumonia risk is difficult to assess in traditional observational studies. C_LI Section 2: What this study addsO_LIOur pre-COVID-19 analyses are consistent with a causal relationship between increased blood pressure and increased risk for incident respiratory infections, as well as between increased blood pressure and reduced pulmonary function. C_LIO_LIThese results support hypertension as a pneumonia risk factor; efforts to optimize blood pressure may reduce risk for pneumonia. C_LI