Depression as a Risk Factor for Incident Ischemic Stroke Among HIV-Positive Veterans in the Veterans Aging Cohort Study.
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SUBMITTER: Sico JJ
PROVIDER: S-EPMC8403311 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPersons 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.MethodsUsing 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.ResultsA 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.ConclusionsIncident 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.
| S-EPMC10874269 | biostudies-literature
Project description:BACKGROUND:Both HIV and depression are associated with increased heart failure (HF) risk. Depression, a common comorbidity, may further increase the risk of HF among adults with HIV infection (HIV+). We assessed the association between HIV, depression, and incident HF. METHODS AND RESULTS:Veterans Aging Cohort Study (VACS) participants free from cardiovascular disease at baseline (n=81?427: 26?908 HIV+, 54?519 without HIV [HIV-]) were categorized into 4 groups: HIV- without major depressive disorder (MDD) [reference], HIV- with MDD, HIV+ without MDD, and HIV+ with MDD. International Classification of Diseases, Ninth Revision codes from medical records were used to determine MDD and the primary outcome, HF. After 5.8 years of follow-up, HF rates per 1000 person-years were highest among HIV+ participants with MDD (9.32; 95% confidence interval [CI], 8.20-10.6). In Cox proportional hazards models, HIV+ participants with MDD had a significantly higher risk of HF (adjusted hazard ratio, 1.68; 95% CI, 1.45-1.95) compared with HIV- participants without MDD. MDD was associated with HF in separate fully adjusted models for HIV- and HIV+ participants (adjusted hazard ratio, 1.21; 95% CI, 1.06-1.37; and adjusted hazard ratio, 1.29; 95% CI, 1.11-1.51, respectively). Among those with MDD, baseline antidepressant use was associated with lower risk of incident HF events (adjusted hazard ratio, 0.76; 95% CI, 0.58-0.99). CONCLUSIONS:Our study is the first to suggest that MDD is an independent risk factor for HF in HIV+ adults. These results reinforce the importance of identifying and managing MDD among HIV+ patients. Future studies must clarify mechanisms linking HIV, MDD, antidepressants, and HF and identify interventions to reduce HF morbidity and mortality in those with both HIV and MDD.
| S-EPMC4624488 | biostudies-literature
Project description:BackgroundInsomnia 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.MethodsUsing 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 the Department of Veterans Affairs (VA) and Medicare administrative data and VA fee-for-service data. Those with baseline CVD were excluded.ResultsHIV-infected (N = 3108) 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 [hazard ratio (HR) = 1.64, 95% confidence interval (CI): 1.16 to 2.31, P = 0.005], CVD risk factors (HR = 1.62, 95% CI: 1.14 to 2.30, P = 0.007), additional potential confounders (hepatitis C infection, renal disease, anemia, alcohol use, and cocaine use; HR = 1.70, 95% CI: 1.19 to 2.43, P = 0.003), and HIV-specific factors (HIV-1 RNA, CD4 T-cell count, and antiretroviral therapy; HR = 1.66, 95% CI: 1.16 to 2.37, P = 0.005). Additional adjustment for nonbenzodiazepine sleep medication (HR = 1.62, 95% CI: 1.13 to 2.32, P = 0.009) did not attenuate the association; however, it fell short of significance at P < 0.01 after adjustment for depressive symptoms (HR = 1.51, 95% CI: 0.98 to 2.32, P = 0.060) or antidepressant medication (HR = 1.51, 95% CI: 1.04 to 2.19, P = 0.031).ConclusionsHighly 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.
| S-EPMC6456378 | biostudies-literature
Project description:BackgroundPulmonary hypertension incidence based on echocardiographic estimates of pulmonary artery systolic pressure in people living with HIV remains unstudied. We aimed to determine whether people living with HIV have higher incidence and risk of pulmonary hypertension than uninfected individuals.MethodsIn this retrospective cohort study, we evaluated data from participants in the Veterans Aging Cohort Study (VACS) referred for echocardiography with baseline pulmonary artery systolic pressure measures of 35 mm Hg or less. Incident pulmonary hypertension was defined as pulmonary artery systolic pressure higher than 35 mm Hg on subsequent echocardiogram. We used Poisson regression to estimate incidence rates (IRs) of pulmonary hypertension by HIV status. We then estimated hazard ratios (HRs) by HIV status using Cox proportional hazards regression. We further categorised veterans with HIV by CD4 count or HIV viral load to assess the association between pulmonary hypertension risk and HIV severity. Models included age, sex, race or ethnicity, prevalent heart failure, chronic obstructive pulmonary disease, hypertension, smoking status, diabetes, body-mass index, estimated glomerular filtration rate, hepatitis C virus infection, liver cirrhosis, and drug use as covariates.FindingsOf 21 314 VACS participants with at least one measured PASP on or after April 1, 2003, 13 028 VACS participants were included in the analytic sample (4174 [32%] with HIV and 8854 [68%] without HIV). Median age was 58 years and 12 657 (97%) were male. Median follow-up time was 3·1 years (IQR 0·9-6·8) spanning from April 1, 2003, to Sept 30, 2017. Unadjusted IRs per 1000 person-years were higher in veterans with HIV (IR 28·6 [95% CI 26·1-31·3]) than in veterans without HIV (IR 23·4 [21·9-24·9]; p=0·0004). The risk of incident pulmonary hypertension was higher among veterans with HIV than among veterans without HIV (unadjusted HR 1·25 [95% CI 1·12-1·40], p<0·0001). After multivariable adjustment, this association was slightly attenuated but remained significant (HR 1·18 [1·05-1·34], p=0·0062). Veterans with HIV who had a CD4 count lower than 200 cells per μL or of 200-499 cells per μL had a higher risk of pulmonary hypertension than did veterans without HIV (HR 1·94 [1·49-2·54], p<0·0001, for those with <200 cell μL and HR 1·29 [1·08-1·53], p=0·0048, for those with 200-499 cells per μL). Similarly, veterans with HIV who had HIV viral loads of 500 copies per mL or more had a higher risk of pulmonary hypertension than did veterans without HIV (HR 1·88 [1·46-2·42], p<0·0001).InterpretationHIV is associated with pulmonary hypertension incidence, adjusting for risk factors. Low CD4 cell count and high HIV viral load contribute to increased pulmonary hypertension risk among veterans with HIV. Thus, as with other cardiopulmonary diseases, suppression of HIV should be prioritised to lessen the burden of pulmonary hypertension in people living with HIV.FundingNational Heart, Lung, and Blood Institute (National Institutes of Health, USA); National Institute on Alcohol Abuse and Alcoholism (National Institutes of Health, USA).
| S-EPMC8294078 | biostudies-literature
Project description:Depression has been associated with an increased risk of coronary heart disease, but prospective data for the association with stroke are limited.We followed-up 80 574 women aged 54 to 79 years in Nurses' Health Study without a history of stroke from 2000 to 2006. Depressive symptoms were assessed at multiple time points by a Mental Health Index score (1992, 1996, and 2000), and clinical significant depressive symptoms were defined as a score?52. Antidepressant medication use was asked biennially beginning in 1996, and physician-diagnosed depression was reported biennially beginning in 2000. Depression was defined as currently reporting or having a history of any of these 3 conditions.During 6 years of follow-up, 1033 incident strokes were documented (538 ischemic, 124 hemorrhagic, and 371 unknown strokes). Having a history of depression was associated with a multivariate-adjusted hazard ratio (HR) of 1.29 (95% confidence interval [CI], 1.13-1.48) for total stroke. Women who used antidepressant medications were at increased risk for stroke, whether they also had a Mental Health Index score?52 or diagnosed depression (HR, 1.39; 95% CI, 1.15-1.69) or not (HR, 1.31; 95% CI, 1.03-1.67). Furthermore, for each cycle, participants who reported current depression had an increased risk of stroke (HR, 1.41; 95% CI, 1.18-1.67), whereas individuals who only had a history of depression were at nonsignificantly elevated risk (HR, 1.23; 95% CI, 0.97-1.56) compared with women who never reported a diagnosis of depression or antidepressant medication use.Our results suggest that depression is associated with a moderately increased risk of subsequent stroke.
| S-EPMC3183155 | biostudies-literature
Project description:BACKGROUND:Proteinuria in human immunodeficiency virus (HIV)-infected individuals has been associated with poorer outcomes. We examined risk factors associated with the development of proteinuria in a national registry of HIV-infected veterans. METHODS:A total of 21,129 HIV-infected veterans of black and white race without preexisting kidney disease were receiving health care in the Veterans' Health Administration (VHA) medical system between 1997 and 2011. Using the VHA electronic record system, we identified kidney-related risk factors (hypertension, diabetes, and cardiovascular disease) and HIV-related risk factors (CD4 lymphocyte count, HIV RNA level, hepatitis C virus, and hepatitis B virus) for developing proteinuria. Proteinuria was defined by 2 consecutive dipstick measures of 1 or higher. The Fine-Gray competing risk model was used to estimate association between clinical variables and incident proteinuria, while accounting for intervening mortality events. RESULTS:During follow-up (median = 5.3 years), 7031 patients developed proteinuria. Overall, black race compared with white race was associated with a higher risk of proteinuria {hazard ratio [95% confidence interval (CI)] = 1.51 [1.43 to 1.59]}, but the association was stronger at younger ages (P interaction <0.001). Age-stratified risk of proteinuria for blacks relative to whites was greatest among veterans <30 years [2.19 (1.66 to 2.89)] and the risk diminished with increasing age [1.14 (0.97 to 1.34) for >60 years]. We found the race difference to be stronger for the outcome of 2 or higher proteinuria [2.13 (1.89 to 2.39)]. Both HIV-related and traditional risk factors were also associated with incident proteinuria (P < 0.05). CONCLUSIONS:Compared with whites, risk of proteinuria was higher in black veterans with HIV infection, particularly at younger ages. In both races, HIV- and kidney-related risk factors were associated with higher proteinuria risk.
| S-EPMC4162813 | biostudies-literature
Project description:Reducing blood pressure (BP) after stroke reduces risk for recurrent events. Our aim was to describe hypertension care among veterans with ischemic stroke including BP control by discharge and over the 6 months after the stroke event.The Office of Quality and Performance Stroke Special Study included a systematic sample of veterans hospitalized for ischemic stroke in 2007. We examined BP control (<140/90 mm Hg) at discharge excluding those who died, enrolled in hospice, or had unknown discharge disposition (n=3640, n=3382 adjusted analysis). The second outcome was BP control (<140/90 mm Hg) within 6-months after stroke, excluding patients who died/readmitted within 30 days, were lost to follow-up, or did not have a BP recorded (n=2054, n=1915 adjusted analysis). The population was 62.7% white and 97.7% men; 46.9% were <65 years of age; and 29% and 37% had a history of cerebrovascular or cardiovascular disease, respectively. Among the 3640 stroke patients, 1573 (43%) had their last documented BP before discharge as >140/90 mm Hg. Black race (adjusted odds ratio, 0.77; 95% confidence interval, 0.65 to 0.91), diabetes (odds ratio, 0.73; 95% confidence interval, 0.62 to 0.86), and hypertension history (odds ratio, 0.51; 95% confidence interval, 0.42 to 0.63) were associated with lower odds for controlled BP at discharge. Of the 2054 stroke patients seen within 6 months from their index event, 673 (32.8%) remained uncontrolled. By 6 months after the event, neither race nor diabetes was associated with BP control, whereas history of hypertension continued to have lower odds of BP control. For each 10-point increase in systolic BP >140 mm Hg at discharge, odds of BP control within 6 months after discharge decreased by 12% (95% confidence interval [8%, 18%]).BP values in excess of national guidelines are common after stroke. Forty-three percent of patients were discharged with an elevated BP, and 33% remained uncontrolled by 6 months.
| S-EPMC3140571 | biostudies-literature
Project description:OBJECTIVE:HIV-positive individuals are at higher risk than healthy persons for aging-related diseases, including myocardial infarction and non-AIDS defining cancers. Recent evidence suggests that HIV infection may modulate changes in the host cell epigenome, and these changes represent a potential mechanism through which HIV infection accelerates aging. We assessed the difference in DNA methylation (DNAm) age, an aging marker involving multiple age-related cytosine-guanine dinucleotide (CpG) sites, among antiretroviral treatment (ART)-naive HIV-positive and HIV-negative individuals in a cohort of veterans from the Veterans Aging Cohort Study. DESIGN:Peripheral blood samples were collected from 19 ART-naive, HIV-positive, and 19 HIV-negative male participants, matched by age and race. Blood samples were collected from HIV-positive participants 7-11 years after ART initiation. METHODS:We compared DNAm age between HIV-positive and HIV-negative groups at baseline and between HIV-positive patients at baseline and follow-up. We also performed an epigenome-wide analysis to identify CpG methylation sites associated with HIV infection. RESULTS:DNAm age in HIV-positive individuals is, on average, 11.2 years higher than HIV study participants at baseline, and two of 10 HIV-positive individuals showed an increase in DNAm age after ART initiation. Epigenome-wide association studies showed an association of HIV infection with one site, in gene VPS37B, which approached statistical significance in our cohort (P?=?3.30?×?10, Bonferroni-corrected threshold?=?1.22?×?10) and was replicated in a second, larger cohort. CONCLUSION:ART treatment-naive HIV-positive individuals have significantly older DNAm age compared to HIV-negative individuals in the Veterans Aging Cohort Study cohort. Longitudinal changes in DNAm age are highly variable across individuals after initiation of antiretroviral therapy.
| S-EPMC5263111 | biostudies-literature
Project description:ObjectivesThe 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.MethodsVeterans 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.ResultsAmong 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.ConclusionsDepression was associated with all-cause mortality. This association was modified by HIV status and method of depression ascertainment.
| S-EPMC6459698 | biostudies-literature
Project description:ImportanceWith the advent of highly effective antiretroviral therapy and improved survival, human immunodeficiency virus (HIV)-infected people are living longer and are now at an increased risk for cardiovascular disease (CVD). There is an urgent need to identify novel risk factors and primary prevention approaches for CVD in HIV. Although depression is prevalent in HIV-infected adults and is associated with future CVD in the general population, its association with CVD events has not been examined in the HIV-infected population.ObjectiveTo examine whether depressive disorders are prospectively associated with incident acute myocardial infarction (AMI) in a large cohort of adults with HIV.Design, setting, and participantsIncluded in this cohort study were 26 144 HIV-infected veterans without CVD at baseline (1998-2003) participating in the US Department of Veterans Affairs Veterans Aging Cohort Study from April 1, 2003, through December 31, 2009. At baseline, 4853 veterans (19%) with major depressive disorder (MDD; International Classification of Diseases, Ninth Revision [ICD-9] codes 296.2 and 296.3) and 2296 (9%) with dysthymic disorder (ICD-9 code 300.4) were identified. The current analysis was conducted from January 2015 to November 2015.Main outcomes and measuresIncident AMI (defined by discharge summary documentation, enzyme/electrocardiography evidence of AMI, inpatient ICD-9 code for AMI (410), or AMI as underlying cause of death [International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code 121]) between the enrollment date and December 31, 2009.ResultsThe mean (SD) age of those with MDD was 47.3 (7.9) years and for those without MDD was 48.2 (9.7) years. During 5.8 years of follow-up, 490 AMI events (1.9%) occurred. Baseline MDD was associated with incident AMI after adjusting for demographics (hazard ratio [HR], 1.31; 95% CI, 1.05-1.62), CVD risk factors (HR, 1.29; 95% CI, 1.04-1.60), and HIV-specific factors (HR, 1.30; 95% CI, 1.05-1.62). Further adjustment for hepatitis C, renal disease, substance abuse, and hemoglobin level (HR, 1.25; 95% CI, 1.00-1.56) and antidepressant use (HR, 1.12; 95% CI, 0.87-1.42) attenuated associations. Baseline dysthymic disorder was not associated with incident AMI.Conclusions and relevanceWe report novel evidence that HIV-infected adults with MDD have a 30% increased risk for AMI than HIV-infected adults without MDD after adjustment for many potential confounders. Our findings raise the possibility that MDD may be independently associated with incident atherosclerotic CVD in the HIV-infected population.
| S-EPMC5621480 | biostudies-literature