Hypertension incidence among individuals successfully treated for pulmonary tuberculosis

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Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Hypertension incidence among individuals successfully treated for pulmonary tuberculosis Victoria C Ontiveros , Maia Kipiani , Teona Avaliani , Sara C Auld , Mariam Gujabidze , Russell R Kempker , Hardy Kornfeld , Cassandra Bryan , Moises A Huaman , Matthew J Magee , Argita D Salindri doi: https://doi.org/10.1101/2024.06.24.24309432 Victoria C Ontiveros 1 Department of Epidemiology, Emory University Rollins School of Public Health , Atlanta, GA, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Maia Kipiani 2 National Center for Tuberculosis and Lung Diseases , Tbilisi, Georgia 3 David Tvildiani Medical University , Tbilisi, Georgia 4 The University of Georgia , Tbilisi, Georgia Find this author on Google Scholar Find this author on PubMed Search for this author on this site Teona Avaliani 2 National Center for Tuberculosis and Lung Diseases , Tbilisi, Georgia Find this author on Google Scholar Find this author on PubMed Search for this author on this site Sara C Auld 1 Department of Epidemiology, Emory University Rollins School of Public Health , Atlanta, GA, USA 5 Division of Pulmonary and Critical Care Medicine, Emory University School of Medicine , Atlanta, GA, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Mariam Gujabidze 2 National Center for Tuberculosis and Lung Diseases , Tbilisi, Georgia Find this author on Google Scholar Find this author on PubMed Search for this author on this site Russell R Kempker 6 Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine , Atlanta, GA, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Hardy Kornfeld 7 Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, UMass Chan Medical School , Worcester, MA, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Cassandra Bryan 8 Hubert Department of Global Health, Emory University Rollins School of Public Health , Atlanta, GA, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Moises A Huaman 9 Department of Internal Medicine, University of Cincinnati College of Medicine , Cincinnati, OH, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Matthew J Magee 1 Department of Epidemiology, Emory University Rollins School of Public Health , Atlanta, GA, USA 8 Hubert Department of Global Health, Emory University Rollins School of Public Health , Atlanta, GA, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Argita D Salindri 8 Hubert Department of Global Health, Emory University Rollins School of Public Health , Atlanta, GA, USA 10 Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, USA 11 Department of Population Health Sciences, Georgia State University School of Public Health , Atlanta, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: adsalind{at}stanford.edu Abstract Full Text Info/History Metrics Data/Code Preview PDF ABSTRACT We reported a cumulative incidence of hypertension of 28% among individuals successfully treated for pulmonary tuberculosis (TB) with no prior hypertension indication at TB treatment initiation (i.e., prevalent hypertension). The cumulative incidence of hypertension among those with ≥1 cavitary lesion was twice the cumulative incidence among those without cavitary lesions. INTRODUCTION Emerging evidence suggests that tuberculosis (TB) disease increases the risk of cardiovascular events during and after TB treatment. 1 A systematic review conducted by Romanowski et al. also suggested that cardiovascular disease (CVD) is the most frequent cause of long-term mortality in people treated for TB. 2 Furthermore, cross-sectional studies have shown that people with TB have a high prevalence of risk factors for CVD among people with active TB. 3 , 4 However, prospective studies assessing the CVD risk trajectories among people after they have completed TB treatment are scarce as it may require a long follow-up period. Hypertension, a key mediator in CVD pathophysiology, has been shown to increase the risk of mortality in individuals treated for TB. 5 A systematic review found that up to an estimated 38.2% of people with active TB have hypertension. 6 However, most epidemiologic studies to date are cross-sectional or examine the impact on hypertension on TB outcomes while the impact of TB disease on incident hypertension post-TB treatment completion is not well described. Furthermore, little is known which TB-related factors could increase the risk of incident hypertension. As 11% of patients with active TB are estimated to have a cardiovascular disease 7 and post-TB mortality rates are nearly three times that of the general population, 2 there have been calls to understand the directionality of the relationship between active TB and hypertension 6 and to integrate TB and cardiovascular health care. 8 – 10 Targeting non-communicable disease (NCD) prevention efforts like hypertension control may be critical to reducing the chronic impacts of TB. In this study, we aimed to estimate the prevalence of hypertension at TB treatment initiation and the cumulative incidence of hypertension during and within 12 months post-treatment completion. We also estimated the relationship between TB disease severity and incident hypertension. METHODS Study Design, Setting, and Participants We conducted a prospective cohort study among adults successfully treated (i.e., those who received microbial cure or completed treatment) for pulmonary TB at the National Center for Tuberculosis and Lung Diseases in Tbilisi, Georgia, from 2020 to 2022. Eligible participants included adults (≥16 years) with laboratory confirmed (by smear, culture, or rapid molecular test [Xpert]) pulmonary TB. Individuals with a history of lung cancer, prior pulmonary TB treatment, HIV co-infection, and pregnant women were excluded. Participants were recruited at the time of TB treatment completion and followed prospectively at 6- and 12-months post-treatment. Study Measures Our primary outcome of interest was hypertension and data were available from 4 time points: TB treatment initiation (abstracted from medical charts), treatment completion, and at 6- and 12-months post-treatment completion. Prevalent hypertension was defined as 1) a single reading of either systolic blood pressure (SBP) ≥130mmHg or diastolic blood pressure (DBP) ≥80mmHg; or 2) a self-reported history of hypertension diagnosis by healthcare providers at TB treatment initiation. Among those without prevalent hypertension, incident hypertension was defined as ≥2 readings of either SBP ≥130mmHg, DBP ≥80mmHg, or a self-reported hypertension diagnosis at separate follow-up study visits (end of TB treatment, 6- and 12-months post-treatment). Participants were required to have ≥2 blood pressure measurements during follow-up to be considered eligible in hypertension incidence analyses. A sensitivity analysis was performed to evaluate whether measures of association changed substantially when using the WHO-defined hypertension cut-off (i.e., ≥140/90mmHg). To describe changes in SBP, we subtracted SBP absolute values measured at the 12 months post-TB treatment from SBP values measured at treatment initiation. Indicators of TB severity were determined by chest computed tomography (CT) findings (i.e., presence of cavitary lesions, ≥1 pulmonary lobes with severe [>75%] involvement, and high total lung severity score [i.e., ≥10]). Other covariates included age, gender, drug-susceptibility profile (i.e., drug-susceptible and isoniazid monoresistant TB [DS/Hr TB] vs. rifampicin-resistant and multidrug/extensively drug-resistant TB [RR/MDR TB+]), body mass index (BMI) and BMI changes during TB treatment (BMI increase ≥5% vs. less), glycated hemoglobin (HbA1c), visceral adipose index (VAI) 11 , low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides. BMI was categorized as underweight (BMI <18.5 kg/m 2 ), normal (BMI 18.5–24.9 kg/m 2 ), and overweight/obese (BMI ≥25 kg/m 2 ). 12 Statistical Analyses We used chi-square or Fisher’s exact tests to assess unadjusted associations between participants’ characteristics and hypertension incidence (p-values were not shown). We used robust Poisson regression models 13 to estimate cumulative incidence ratios (CIR) of incident hypertension, comparing individuals with ≥1 cavitary lesion vs. no lesions. Covariates included in the final model were based on bivariate association, confounders identified in published literature, and directed acyclic graph. A final multivariable model was determined by selecting a model with the lowest Akaike Information Criterion ( Table S1 ). Mann-Whitney U tests were used to compare median changes of SBP among individuals with hypertension (n=26). We characterized these changes in boxplots produced by using ggplot2 package. 14 All analyses were perfomed in R (v.4.2.2; R Core Team 2023) 15 with p-values <0.05 considered significant in all analyses. RESULTS From 2020-2022, we enrolled 140 participants; 122 had complete blood pressure data from TB treatment initiation and were included in our analyses. Study participants were mostly male (57%), <40 years (64%), and had DS/Hr TB (75%). Prevalence of hypertension at TB treatment intiation was 20% (24/122, 95% confidence interval [CI] 14–28). Among 98 participants without prevalent hypertension, 94 had ≥2 follow-up BP readings for incident hypertension classification. Of these, 26 developed hypertension during treatment or within 12 months of treatment completion (26/94, cumulative incidence=28%, 95%CI 20–37). The unadjusted cumulative incidence of hypertension was significantly higher among participants ≥40 years (CIR=2.8, 95%CI 1.3–6.0), males (CIR=2.6, 95%CI 1.1– 7.1), and those with ≥1 cavitary lesion (CIR=2.4, 95%CI 1.1–5.1) or VAI ≥2.60 (CIR=2.2, 95%CI 1.2–7.7) ( Table 1 ). Although non-significant, the cumulative incidence of hypertension among those with ≥1 cavitary lesion was 2.3 times (95%CI 0.9–6.2) the incidence among those without cavitary lesion after adjusting for age, sex, drug-susceptibilty profile, 5% relative BMI increase during TB treatment, and lipid profile. The CIR estimated with the WHO-defined hypertension cut-off was similar to the more sensitive cut-off used in our primary analyses ( Table S2 ). View this table: View inline View popup Table 1. Factors associated with incident hypertension among adults successfully treated for confirmed pulmonary tuberculosis in the country of Georgia, 2020–2022 (n=94) Among participants included in the incidence analyses and available SBP levels at TB treatment initiation (n=91), the median change in SBP was 10mmHg (IQR 0–19), 5mmHg (IQR −2.0–10.0mmHg) among participants without incident hypertension, and 20mmHg (IQR 10.2–30.0mmHg) among participants with incident hypertesion. Among those with incident hypertension, the median change in SBP was slightly higher among those with ≥1 cavitary lesions ( Figure 1A ) or ≥1 severe lobe involvement ( Figure 1B ) compared to those without. Download figure Open in new tab Figure 1 Median change in systolic blood pressure (SBP) from tuberculosis treatment initiation to 12-month post-tuberculosis treatment completion among individuals with incident hypertension, Tbilisi, Georgia 2020–2022 (N=26) Boxes represent the interquartile range (IQR), whiskers represent data falling within 1.5 times IQR, and points represent outliers (>1.5 times IQR). Panel A) presence of cavitary lesions (No cavity median: 17.0mmHg vs. ≥1 cavity median: 27.5mmHg, median difference=10.5mmHg), and Panel B) presence of severe lobe(s) (No severe lobe median: 15.0mmHg vs. ≥1 severe lobe(s) median: 25.0mmHg, median difference=10.0mmHg). DISCUSSION In our cohort, one-fifth had hypertension at TB treatment initiation, and more than one-quarter of participants without prevalent hypertension developed incident hypertension during or within 12 months of completing treatment. Our study is the first to assess the association between cavitary lesions and hypertension incidence, highlighting the need for larger prospective cohort studies to comprehensively assess the impact of TB-severity factors on hypertension or CVD risks post-TB treatment. Our study suggested that the cumulative incidence risk of hypertension among participants with ≥1 cavitary lesion may be twice the risk among participants without cavitary lesions (adjusted CIR was non-significant). More severe TB manifestations (e.g., marked by lung cavitation) may lead to a prolonged or greater degree of systematic inflammation, a key factor in the development of hypertension. 16 , 17 Individuals with severe manifestations of TB may benefit from routine screening for hypertension to monitor of cardiovascular risk trajectories while in TB care. Our preliminary findings highlight an important relationship between TB and hypertension. Although our study sample was small and from a single site, our findings suggest that it is critical to improve our understanding of the hypertension burden and trajectories of CVD risks post-TB treatment. Routinely measuring blood pressure levels during and at the end of TB treatment could be an inexpensive way to identify individuals with early signs of CVD and determine whether referrals to other clinics are needed. Future studies should aim to measure how integrating post-TB treatment care and NCD programs (e.g., NCD screening, referral to NCD clinics) impacts post-TB morbidity and mortality. DECLARATIONS AND ACKNOWLEGEMENTS Potential Conflicts of Interest We have no conflict of interest to declare. Patient Consent Statement The study was submitted to, reviewed, and approved by the Institutional Review Boards (IRBs) at Emory University, Atlanta, USA, and the ethics committee at the National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia (FWA000020831). All participants provided written informed consent prior to study participation. Funding This work was supported in part by grants from the National Institutes of Health (NIH) including the National Institute of Allergy and Infectious Diseases (NIAID) [R03AI133172 to MJM, R03AI139871 to RRK, R01AI153152 to MJM], the National Heart, Lung, and Blood Institute (NHLBI) [R01HL156779 to MAH], and the Fogarty International Center (FIC) [R21TW011157 to MK and MJM]. ADS was supported by a Vanderbilt Emory Cornell Duke (VECD) Global Health Fellowship, funded by the NIH FIC (D43TW009337). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Authors Contributions MJM, ADS and VCO conceived the study design. MK, TA, MG and ADS collected the data. VCO performed the analyses. VCO, MJM, and ADS interpreted the results. VCO and ADS wrote the first draft of the manuscript. MJM assisted with further drafting and revisions of manuscripts. All authors reviewed and approved the final version of the manuscript. Data Availability Statement The data that support the findings of this study are available from the corresponding author, ADS, upon reasonable request. SUPPLEMENTAL MATERIALS View this table: View inline View popup Download powerpoint Table S1. Comparison of Akaike Information Criterion (AIC) values across multivariable models View this table: View inline View popup Download powerpoint Table S2. Factors associated with incident hypertension (BP≥140/90) among adults successfully treated for confirmed pulmonary tuberculosis in the country of Georgia, 2020–2022 Acknowledgments The authors thank the study doctors (Leila Goginashvili, Sergo Vashakidze, Nino Jakobia, Manana Rekhviashvili, Khatuna Guchmazashvili, Marine Gachechiladze, Liana Tsivtsivadze, Tamar Natriashvili) who helped the participant enrollment process at the National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia. 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Feb 2021 ; 19 : 92 – 98 . doi: 10.1016/j.cophys.2020.09.016 OpenUrl CrossRef View the discussion thread. Back to top Previous Next Posted June 25, 2024. Download PDF Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Hypertension incidence among individuals successfully treated for pulmonary tuberculosis Message Subject (Your Name) has forwarded a page to you from medRxiv Message Body (Your Name) thought you would like to see this page from the medRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. 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