Latent Tuberculosis Infection and Elevated Incidence of Hypertension

The global prevalence of latent tuberculosis infection (LTBI) exceeds 1.7 billion.1 Clinically, tuberculosis is categorized as either active or latent. Active tuberculosis is characterized by persistent infection and clinical symptoms such as chronic cough, weight loss, night sweats, and fatigue and has significant associated acute and subacute morbidity.1,2 Conversely, LTBI is characterized by chronic, clinically asymptomatic infection in the setting of robust inflammatory signaling, marked by production of tumor necrosis factor-α, interferons, and interleukins.2 Despite clear evidence from clinical and experimental models on the role of amplified and dysregulated inflammation in the pathogenesis of cardiovascular disease (CVD) and associated risk factors,3,4 data relating LTBI to CVD risk factors and overt CVD are sparse. Given the link between LTBI and proinflammatory immune dysregulation, the role of inflammation in CVD and its risk factors, and recent cross-sectional evidence suggesting heightened myocardial infarction risk among people with LTBI,5 we investigated associations of LTBI with major CVD risk factors: diabetes mellitus (DM) and hypertension. Our study was exempt by institutional board review. Data were de-identified by the Northwestern Medicine Enterprise Data Warehouse team before our access. The data that support our findings in this study are available from the corresponding author upon reasonable request. Using the Northwestern Medicine Enterprise Data Warehouse, a comprehensive data repository on over 6.6 million patients in a large metropolitan healthcare system, adults aged 18 to 75 with LTBI and frequency-matched on age, sex, race, and geographic region with non-LTBI controls were identified. Patients meeting these conditions who received care (defined as at least 1 face-to-face encounter every 2 years between baseline and censoring date) between January 1, 2000 and January 1, 2020 were included. Of 7298 total patients, 5185 had neither hypertension nor DM at baseline and were eligible for analyses (2679 LTBI and 2506 LTBI-free controls). LTBI was defined by both diagnosis of LTBI and either a positive tuberculin skin test and/or interferon-γ release assay (T Spot, QuantiFERON). Comorbid conditions were identified based on International Classification of Diseases, Ninth Revision and Tenth Revision (ICD-9 and ICD-10) codes. Multivariable Cox regression analysis, adjusting for age, sex, and race, was performed to evaluate the incidence of DM and hypertension. A sensitivity analysis was performed with additional adjustment for baseline body mass index, total cholesterol level, and HIV serostatus. Smoking status was not widely available, precluding additional adjustment for smoking. Statistical significance was defined as P<0.05. Statistical analyses were performed using R (https://R-proje ct.org/) survival and mice packages.