TB and increased incidence of cardiovascular disease [TBN 097]

A study investigated whether tuberculosis (TB) increases the risk of incident cardiovascular disease (CVD), while accounting for differences in CVD risk that existed before TB diagnosis. This was a retrospective matched cohort study conducted using large electronic health record databases from the United States and the United Kingdom. The study examined CVD incidence during the two years before and two years after TB diagnosis, allowing replication of findings across two independent healthcare systems.

The analysis included 17,941 people with TB (2,121 in the United States and 15,820 in the United Kingdom) and 130,494 matched individuals without TB. Most participants with TB had at least four matched controls. The median age at TB diagnosis was 59 years in the United States and 44 years in the United Kingdom. Covariates measured two years before TB diagnosis included smoking status, body mass index (BMI), comorbidities, and prescriptions for statins or antihypertensive medications. Incident CVD events were identified from primary care and hospital records using ICD-9 and ICD-10 diagnostic codes in the United States and primary care diagnostic codes together with ICD-10 codes in the United Kingdom. Incidence rates and incidence rate ratios (IRRs) were estimated, with adjustment for demographic and clinical covariates, followed by additional adjustment for baseline differences in CVD incidence before TB diagnosis.

Over the four-year observation period, 462 CVD events occurred among participants with TB in the United States and 622 in the United Kingdom, corresponding to incidence rates of 65 and 11 per 1,000 person-years, respectively. Among matched individuals without TB, CVD incidence rates were lower at 31 and 6 per 1,000 person-years. People with TB already had higher CVD incidence during the two years before diagnosis, but the greatest increase occurred during the acute period surrounding TB diagnosis. During this acute period, CVD incidence reached 127 versus 30 per 1,000 person-years in the United States and 16 versus 6 per 1,000 person-years in the United Kingdom for participants with and without TB, respectively. After adjustment for demographic and clinical factors, TB was associated with a significantly increased risk of CVD during the acute period, with adjusted IRRs of 3.5 (95% CI, 2.7 to 4.4) in the United States and 2.7 (95% CI, 2.2 to 3.3) in the United Kingdom. After further accounting for preexisting differences in CVD incidence before TB diagnosis, the association remained significant but was attenuated, with adjusted relative risks of 3.2 (95% CI, 2.2 to 4.4) in the United States and 1.6 (95% CI, 1.2 to 2.1) in the United Kingdom. Stratified analyses showed similar relative risks between men and women in the United Kingdom, with no consistent differences according to age or race/ethnicity.

Active TB was associated with a substantially increased risk of incident cardiovascular disease, particularly during the period surrounding TB diagnosis, even after accounting for preexisting cardiovascular risk. These findings were consistent across independent cohorts from the United States and the United Kingdom, supporting the robustness of the association. As a retrospective observational study, causal inference is limited, and residual confounding remains possible despite extensive adjustment. The findings suggest that cardiovascular risk assessment and monitoring may be important during and shortly after TB diagnosis.

Source: Critchley JA, Limb ES, Khakharia A, Carey IM, Auld SC, De Wilde S, Harris T, Phillips LS, Cook DG, Rhee MK, Chaudhry UA. Tuberculosis and increased incidence of cardiovascular disease: cohort study using United States and United Kingdom health records. Clinical Infectious Diseases. 2025 Feb 15;80(2):271-9.

BMI trajectories and association with TB risk in Southern Africa [TBN 096]

A study investigated the nutritional status of tuberculosis (TB)-affected households and evaluated the association between baseline body mass index (BMI), changes in BMI over time, and TB risk, while describing longitudinal BMI trajectories. This was a prospective, noninterventional observational household contact cohort study (ERASE-TB) conducted in Zimbabwe, Mozambique, and Tanzania. Recruitment began between March and September 2021, enrolling household contacts aged 10 years or older of individuals with microbiologically confirmed pulmonary TB. Participants were followed every six months for up to 24 months.

The study included 2,107 household contacts from 822 households (699 in Zimbabwe, 710 in Mozambique, and 698 in Tanzania), with a median follow-up of 23.8 months (IQR, 21.8 to 26.3). At enrollment and follow-up visits, investigators collected sociodemographic data, medical and TB history, and anthropometric measurements including height, weight, and mid-upper arm circumference (MUAC). Participants also underwent blood pressure, hemoglobin, and optional HIV testing. TB screening consisted of the World Health Organization symptom questionnaire and chest radiography, followed by Xpert MTB/RIF Ultra and mycobacterial culture when indicated. An independent endpoint review committee classified TB cases, with confirmed or likely TB used as study outcomes. Prevalent TB was defined as diagnosis at baseline, while incident TB was diagnosed more than 30 days after enrollment. Associations between BMI and TB were assessed using adjusted logistic regression, Cox proportional hazards models, restricted cubic spline analyses, Poisson regression with time-varying BMI changes, and growth mixture modeling to identify latent BMI trajectories.

Among participants, 62.2% were female, the median age was 27 years (IQR, 16 to 42), and 29.5% were adolescents. Underweight was common among adolescents (61.8%) but uncommon among adults (9.2%), whereas 36.6% of adults were overweight or obese. A household-level dual burden of malnutrition, with both underweight and overweight individuals, was observed in 14% to 19% of households across the three countries. Twenty-one participants (1.0%) had prevalent TB and 41 (1.9%) developed incident TB, corresponding to an incidence rate of 13.2 per 1,000 person-years (95% CI, 9.5 to 17.9). Baseline underweight alone was not associated with prevalent TB (adjusted odds ratio [aOR], 0.94; 95% CI, 0.28 to 2.73), but underweight combined with anemia was associated with a substantially higher odds of prevalent TB (aOR, 4.83; 95% CI, 1.03 to 16.8). Similarly, baseline underweight alone was not significantly associated with incident TB (adjusted hazard ratio [aHR], 1.06; 95% CI, 0.49 to 2.26), whereas overweight or obesity showed a nonsignificant trend toward lower risk (aHR, 0.42; 95% CI, 0.15 to 1.16). Underweight combined with anemia was associated with a markedly higher hazard of incident TB (aHR, 3.77; 95% CI, 1.50 to 9.51). Restricted cubic spline analysis demonstrated a nonlinear inverse relationship between BMI and TB risk, with sharply increasing risk below a BMI Z-score of 0. The population attributable fraction for underweight was estimated at 17.3% of incident TB. Among participants who developed incident TB and had repeated anthropometric measurements, 64.7% lost weight during follow-up, and 31.8% of these lost more than 10% of baseline BMI. Adults who developed TB generally started with higher BMI and lost weight before diagnosis, whereas adolescents were often underweight from baseline. Time-varying BMI loss of at least 10% was not significantly associated with incident TB (adjusted incidence rate ratio, 2.27; 95% CI, 0.22 to 22.9), likely reflecting limited statistical power. Growth mixture modeling identified four BMI trajectory groups: decreasing, low stable, high stable, and increasing BMI. Participants in the decreasing BMI trajectory had the highest TB incidence (5.8%) compared with the low stable (1.3%), high stable (0.8%), and increasing (0.0%) groups (P = .005). The decreasing BMI group also had the highest baseline median BMI (30.6 kg/m²).

In this East and Southern African household contact cohort, baseline underweight alone was not independently associated with prevalent or incident TB, but underweight combined with anemia identified individuals at substantially higher risk. Declining BMI over time, particularly among adults who were initially overweight or obese, was associated with subsequent TB development, highlighting the value of longitudinal nutritional monitoring. The observational design limits causal inference, and the relatively small number of TB events reduced statistical precision for some analyses. The findings support integrating repeated nutritional assessment, particularly BMI and anemia evaluation, into TB household contact follow-up programs.

Source: Larsson L, Calderwood CJ, Marambire ET, Held K, Banze D, Mfinanga A, Madziva K, Walsh P, Jacob J, Fernandez FT, Lungu P. Body mass index trajectories and association with tuberculosis risk in a cohort of household contacts in Southern Africa. Clinical Infectious Diseases. 2025 Dec 15;81(6):e600-11.