Browsing by Author "Kundu, Suman"

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    Associations of HIV and Depression With Incident Diabetes Mellitus: Veterans Aging Cohort Study
    (Oxford University Press, 2022-02-03) Bourgi, Kassem; Kundu, Suman; Stewart, Jesse C.; So-Armah, Kaku; Freiberg, Matthew; Gupta, Samir K.; Medicine, School of Medicine
    Background: Persons with HIV (PWH) are at increasingly higher risk for metabolic complications, including diabetes mellitus (DM). Additionally, depression is highly prevalent among PWH and has been associated with increased risk for DM in the general population. However, the association of HIV and depression with incident DM has not been well established. Methods: Using the Veterans Aging Cohort Study (VACS), we selected adults with and without HIV who did not have DM at baseline. Prevalent depression was defined as having a Patient Health Questionnaire-9 (PHQ-9) score of ≥10. Incident DM was identified using validated Kelly's criteria. Basic clinical and demographic characteristics were collected, and cox proportional hazards regression models were run to test the association between depression and incident DM stratified by HIV serostatus. Results: A total of 5,722 participants were analyzed, 2,886 (53%) had HIV and 1,124 (20%) had depression at baseline. 1,235 (22%) participants developed incident DM during follow-up, with 26% of HIV-negative participants developing DM compared to 17% of participants with HIV. Depression was significantly associated with increased risk of incident DM among HIV-negative participants (adjusted HR [aHR] = 1.31; p-value 0.003), but not among participants with HIV (aHR 1.09; p-value 0.44). However, among participants with HIV with baseline viral load < 500 copies/mL, we noted a stronger association between depression and incident DM. Conclusions: Incident DM in the VACS cohort is significantly higher for HIV-negative participants compared to veterans with HIV. A significant association between depression and incident DM was noted among HIV-negative participants but not among those with HIV.
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    Associations of Total, Cognitive/Affective, and Somatic Depressive Symptoms and Antidepressant Use With Cardiovascular Disease–Relevant Biomarkers in HIV: Veterans Aging Cohort Study
    (Wolters Kluwer, 2020) Stewart, Jesse C.; Polanka, Brittanny M.; So-Armah, Kaku A.; White, Jessica R.; Gupta, Samir K.; Kundu, Suman; Chang, Chung-Chou H.; Freiberg, Matthew S.; Psychology, School of Science
    Objective We sought to determine the associations of total, cognitive/affective, and somatic depressive symptoms and antidepressant use with biomarkers of processes implicated in cardiovascular disease in HIV (HIV-CVD). Methods We examined data from 1546 HIV-positive and 843 HIV-negative veterans. Depressive symptoms were assessed using the Patient Health Questionnaire-9, and past-year antidepressant use was determined from Veterans Affair pharmacy records. Monocyte (soluble CD14 [sCD14]), inflammatory (interleukin-6 [IL-6]), and coagulation (D-dimer) marker levels were determined from previously banked blood specimens. Linear regression models with multiple imputation were run to estimate the associations between depression-related factors and CVD-relevant biomarkers. Results Among HIV-positive participants, greater somatic depressive symptoms were associated with higher sCD14 (exp[b] = 1.02, 95% confidence interval [CI] = 1.00–1.03) and D-dimer (exp[b] = 1.06, 95% CI = 1.00–1.11) after adjustment for demographics and potential confounders. Further adjustment for antidepressant use and HIV factors slightly attenuated these relationships. Associations were also detected for antidepressant use, as selective serotonin reuptake inhibitor use was related to lower sCD14 (exp[b] = 0.95, 95% CI = 0.91–1.00) and IL-6 (exp[b] = 0.86, 95% CI = 0.76–0.96), and tricyclic antidepressant use was related to higher sCD14 (exp[b] = 1.07, 95% CI = 1.03–1.12) and IL-6 (exp[b] = 1.14, 95% CI = 1.02–1.28). Among HIV-negative participants, total, cognitive/affective, and somatic depressive symptoms were associated with higher IL-6, and tricyclic antidepressant use was related to higher sCD14. Conclusions Our novel findings suggest that a) monocyte activation and altered coagulation may represent two pathways through which depression increases HIV-CVD risk and that b) tricyclic antidepressants may elevate and selective serotonin reuptake inhibitors may attenuate HIV-CVD risk by influencing monocyte and inflammatory activation.
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    Depression and All-Cause Mortality Risk in HIV-infected and HIV-uninfected U.S. Veterans: A cohort study
    (Wiley, 2019-03-29) So-Armah, Kaku; Gupta, Samir K.; Kundu, Suman; Stewart, Jesse C.; Goulet, Joseph L.; Butt, Adeel A.; Sico, Jason J.; Marconi, Vincent C.; Crystal, Stephen; Rodriguez-Barradas, Maria C.; Budoff, Matthew; Gibert, Cynthia L.; Chang, Chung-Chou H.; Bedimo, Roger; Freiberg, Matthew S.; Medicine, School of Medicine
    Objectives: The contribution of depression to mortality in adults with and without HIV infection is unclear. We hypothesized that depression increases mortality risk and that this association is stronger among those with HIV infection. Methods: Veterans Aging Cohort Study (VACS) data were analysed from the first clinic visit on or after 1 April 2003 (baseline) to 30 September 2015. Depression definitions were: (1) major depressive disorder defined using International Classification of Diseases, Ninth Revision (ICD-9) codes; (2) depressive symptoms defined as Patient Health Questionnaire (PHQ)-9 scores ≥ 10. The outcome was all-cause mortality. Covariates were demographics, comorbid conditions and health behaviours. Results: Among 129 140 eligible participants, 30% had HIV infection, 16% had a major depressive disorder diagnosis, and 24% died over a median follow-up time of 11 years. The death rate was 25.3 [95% confidence interval (CI) 25.0-25.6] deaths per 1000 person-years. Major depressive disorder was associated with mortality [hazard ratio (HR) 1.04; 95% CI 1.01, 1.07]. This association was modified by HIV status (interaction P-value = 0.02). In HIV-stratified analyses, depression was significantly associated with mortality among HIV-uninfected veterans but not among those with HIV infection. Among those with PHQ-9 data (n = 7372), 50% had HIV infection, 22% had PHQ-9 scores ≥ 10, and 28% died over a median follow-up time of 12 years. The death rate was 27.3 (95% CI 26.1-28.5) per 1000 person-years. Depressive symptoms were associated with mortality (HR 1.16; 95% CI 1.04, 1.28). This association was modified by HIV status (interaction P-value = 0.05). In HIV-stratified analyses, depressive symptoms were significantly associated with mortality among veterans with HIV infection but not among those without HIV infection. Conclusions: Depression was associated with all-cause mortality. This association was modified by HIV status and method of depression ascertainment.
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    Depression as a Risk Factor for Incident Ischemic Stroke Among HIV‐Positive Veterans in the Veterans Aging Cohort Study
    (American Heart Association, 2021-07-06) Sico, Jason J.; Kundu, Suman; So-Armah, Kaku; Gupta, Samir K.; Chang, Chung-Chou H.; Butt, Adeel A.; Gibert, Cynthia L.; Marconi, Vincent C.; Crystal, Stephen; Tindle, Hilary A.; Freiberg, Matthew S.; Stewart, Jesse C.; Medicine, School of Medicine
    Background: HIV infection and depression are each associated with increased ischemic stroke risk. Whether depression is a risk factor for stroke within the HIV population is unknown. Methods and Results: We analyzed data on 106 333 (33 528 HIV-positive; 72 805 HIV-negative) people who were free of baseline cardiovascular disease from an observational cohort of HIV-positive people and matched uninfected veterans in care from April 1, 2003 through December 31, 2014. International Classification of Diseases, Ninth Revision (ICD-9) codes from medical records were used to determine baseline depression and incident stroke. Depression occurred in 19.5% of HIV-positive people. After a median of 9.2 years of follow-up, stroke rates were highest among people with both HIV and depression and lowest among those with neither condition. In Cox proportional hazard models, depression was associated with an increased risk of stroke for HIV-positive people after adjusting for sociodemographic characteristics and cerebrovascular risk factors (hazard ratio [HR], 1.18; 95% CI: 1.03-1.34; 0.014). The depression-stroke relationship was attenuated by alcohol use disorders, cocaine use, and baseline antidepressant use, and unaffected by combined antiretroviral therapy use or individual antiretroviral agents. A numerically higher HR of depression on stroke was found among those younger than 60 years. Conclusions: Depression is associated with an increased risk of stroke among HIV-positive people after adjusting for sociodemographic characteristics, traditional cerebrovascular risk factors, and HIV-specific factors. Alcohol use disorders, cocaine use, and baseline antidepressant use accounted for some of the observed stroke risk. Depression may be a novel, independent risk factor for ischemic stroke in HIV, particularly among younger people.
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    Insomnia as an Independent Predictor of Incident Cardiovascular Disease in HIV: Data from the Veterans Aging Cohort Study
    (Wolters Kluwer, 2019-02) Polanka, Brittanny M.; Kundu, Suman; So-Armah, Kaku A.; Freiberg, Matthew S.; Gupta, Samir K.; Bedimo, Roger J.; Budoff, Matthew J.; Butt, Adeel A.; Chang, Chung-Chou H.; Gottlieb, Stephen S.; Marconi, Vincent C.; Womack, Julie A.; Stewart, Jesse C.; Psychology, School of Science
    Background: Insomnia is associated with increased cardiovascular disease (CVD) risk in the general population and is highly prevalent in people with HIV. The CVD risk conferred by insomnia in the HIV population is unknown. Methods: Using the Veterans Aging Cohort Study-Survey Cohort, insomnia symptoms were measured and dummy coded with the item, “Difficulty falling or staying asleep?” (5-point scale from no difficulty to bothers a lot). Incident CVD event ICD-9 codes (acute myocardial infarction, stroke, or coronary artery revascularization) were identified with VA and Medicare administrative data and VA fee-for-service data. Those with baseline CVD were excluded. Results: HIV-infected (N=3,108) veterans had a median follow-up time of 10.8 years, during which 267 CVD events occurred. Compared to HIV-infected veterans with no difficulty falling or staying asleep, HIV-infected veterans bothered a lot by insomnia symptoms had an increased risk of incident CVD after adjusting for demographics (HR=1.64, 95%CI=1.16-2.31, p=.005), CVD risk factors (HR=1.62, 95%CI=1.14-2.30, p=.007), additional potential confounders (hepatitis C infection, renal disease, anemia, alcohol use, cocaine use; HR=1.70, 95%CI=1.19-2.43, p=.003), and HIV-specific factors (HIV-1 RNA, CD4+ T-cell count, ART; HR=1.66, 95%CI=1.16-2.37, p=.005). Additional adjustment for non-benzodiazepine sleep medication (HR=1.62, 95%CI=1.13-2.32, p=.009) did not attenuate the association; however, it fell short of significance at p < .01 after adjustment for depressive symptoms (HR=1.51, 95%CI=0.98-2.32, p=.060) or antidepressant medication (HR=1.51, 95%CI=1.04-2.19, p=.031). Conclusion: Highly bothersome insomnia symptoms were significantly associated with incident CVD in HIV-infected veterans, suggesting that insomnia may be a novel, modifiable risk factor for CVD in HIV.
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    Insomnia symptoms and biomarkers of monocyte activation, systemic inflammation, and coagulation in HIV: Veterans Aging Cohort Study
    (PLOS, 2021-02-09) Polanka, Brittanny M.; Kundu, Suman; So-Armah, Kaku A.; Freiberg, Matthew S.; Gupta, Samir K.; Zapolski, Tamika C. B.; Hirsh, Adam T.; Bedimo, Roger J.; Budoff, Matthew J.; Butt, Adeel A.; Chang, Chung-Chou H.; Gottlieb, Stephen S.; Marconi, Vincent C.; Womack, Julie A.; Stewart, Jesse C.; Medicine, School of Medicine
    Background: Insomnia may be a risk factor for cardiovascular disease in HIV (HIV-CVD); however, mechanisms have yet to be elucidated. Methods: We examined cross-sectional associations of insomnia symptoms with biological mechanisms of HIV-CVD (immune activation, systemic inflammation, and coagulation) among 1,542 people with HIV from the Veterans Aging Cohort Study (VACS) Biomarker Cohort. Past-month insomnia symptoms were assessed by the item, "Difficulty falling or staying asleep?," with the following response options: "I do not have this symptom" or "I have this symptom and…" "it doesn't bother me," "it bothers me a little," "it bothers me," "it bothers me a lot." Circulating levels of the monocyte activation marker soluble CD14 (sCD14), inflammatory marker interleukin-6 (IL-6), and coagulation marker D-dimer were determined from blood specimens. Demographic- and fully-adjusted (CVD risk factors, potential confounders, HIV-related factors) regression models were constructed, with log-transformed biomarker variables as the outcomes. We present the exponentiated regression coefficient (exp[b]) and its 95% confidence interval (CI). Results: We observed no significant associations between insomnia symptoms and sCD14 or IL-6. For D-dimer, veterans in the "Bothers a Lot" group had, on average, 17% higher D-dimer than veterans in the "No Difficulty Falling or Staying Asleep" group in the demographic-adjusted model (exp[b] = 1.17, 95%CI = 1.01-1.37, p = .04). This association was nonsignificant in the fully-adjusted model (exp[b] = 1.09, 95%CI = 0.94-1.26, p = .27). Conclusion: We observed little evidence of relationships between insomnia symptoms and markers of biological mechanisms of HIV-CVD. Other mechanisms may be responsible for the insomnia-CVD relationship in HIV; however, future studies with comprehensive assessments of insomnia symptoms are warranted.