Epidemiological analyses have linked hypertension to an increased risk of pneumonia. This study from the UK biobank confirmed this correlation and found that there is a genetic predisposition to increased blood pressure. These results suggest that elevated blood pressure may be a causal risk factor for pneumonia.
Blood Pressure and Pneumonia
Hypertension is a common and modifiable risk factor for cardiovascular disease and mortality. Previous epidemiologic analyses have linked hypertension with the risk of developing pneumonia. More recently, it has also been linked to pneumonia resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
However, while epidemiological analyses support a plausible link between blood pressure regulation and respiratory infection, many of these findings are often confounded by co-morbid conditions. Therefore, it is unclear whether hypertension is the direct cause of pneumonia development or whether other factors such as age, diabetes mellitus, air pollution or smoking play a greater role.
Alternatively, Mendelian randomisation is a statistical genetic approach which allows for the unbiased testing for a causal genetic factor. Blood pressure is a highly heritable trait, with several known genomic loci. Therefore, the UK biobank used Mendelian randomisation to test the hypothesis that blood pressure independently influences the risk of pneumonia and reduced pulmonary function.
The study covered 377,143 individuals, and tested whether a genetic predisposition for increased blood pressure was correlated to an increased risk for pneumonia.
Their findings confirmed that hypertension is a risk factor for pneumonia and many other respiratory diseases. They also suggest that there is a genetic predisposition to increased blood pressure, contributed to by at least 75 independent genetic variants. The researchers also completed epidemiological analyses which again revealed an association between hypertension and increased pulmonary obstruction. Mendelian randomisation studies further supported this causal relationship.
Implications for Pneumonia
These findings may have several implications for the prevention of pneumonia. Hypertension has been suggested to promote infection through a variety of mechanisms. Firstly, it may promote the dysregulation of the adaptive immune response, which has been supported by recent Mendelian randomisation studies. Moreover, hypertension can cause endothelial dysfunction, which may promote infection.
Previous studies have also linked hypertension to decreased pulmonary function and increased pulmonary obstruction. Chronic obstructive pulmonary disease (COPD) is also a well-established risk factor for pneumonia, and is co-morbid with several cardiovascular risk factors, including hypertension. This study demonstrated that increased blood pressure may causally lead to increased pulmonary obstruction. This represents a potential mechanism towards an increased risk of pneumonia.
Therefore, blood pressure optimization is likely to reduce the risk of developing pneumonia. The results of this study align with current recommendations to maintain stable, normal blood pressure.
This study involved the analysis of a large, genotyped population-based cohort. They used both high-fidelity phenotyping and included subclinical respiratory phenotypes. Such diverse phenotyping allows more specific and sensitive analyses. The incorporation of mendelian randomisation also allowed a more robust causal inference for the role of hypertension.
The study was conducted among individuals of white British ancestry, therefore the generalisability of these results to other ethnicities and geographic regions remains to be tested. The model used also assumes that genetic factors produce a direct impact and are not confounded by pleiotropy. While analyses were conducted to identify potential confounders, this may limit findings.
The authors also highlight that these outcomes were concluded prior to the COVID-19 pandemic and therefore generalisation of these findings to COVID-19 cases will require further verification.