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Item Association Between Depressive Disorders and Incident Acute Myocardial Infarction in Human Immunodeficiency Virus–Infected Adults(American Medical Association, 2016-11-01) Khambaty, Tasneem; Stewart, Jesse C.; Gupta, Samir K.; Chang, Chung-Chou H.; Bedimo, Roger J.; Budoff, Matthew J.; Butt, Adeel A.; Crane, Heidi; Gibert, Cynthia L.; Leaf, David A.; Rimland, David; Tindle, Hilary A.; So-Armah, Kaku A.; Justice, Amy C.; Freiberg, Matthew S.; Psychology, School of ScienceIMPORTANCE With 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. OBJECTIVE To examine whether depressive disorders are prospectively associated with incident acute myocardial infarction (AMI) in a large cohort of adults with HIV. DESIGN, SETTING, AND PARTICIPANTS Included 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 MEASURES Incident 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. RESULTS The 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 RELEVANCE We 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.Item Associations between affective traits and endothelial function in depressed adults(2018) Berntson, Jessica; Stewart, Jesse C.; Cyders, Melissa A.; Rand, Kevin L.; Gupta, Samir K.Depressed adults are at increased risk of developing atherosclerotic cardiovascular disease (CVD). However, heterogeneity in the depressed population engenders a key question: Are there subgroups of depressed adults at greater risk of developing CVD? Because other affective traits – i.e., anxiety, hostility/anger, and low trait positive affect – have also been associated with increased CVD risk, depressed adults with higher levels of these co-occurring affective traits may have an elevated risk of developing CVD. Consequently, the present study’s first aim was to examine, in depressed adults, which affective traits (depression, anxiety, hostility/anger, or low positive affect) are associated with endothelial function, a marker of cumulative CVD risk. In addition, because the other affective traits overlap with depressive symptom severity, this study’s second aim was to investigate which components of pairs of affective traits (shared versus unique) are related to endothelial function. Finally, given that the mechanisms underlying affective trait-endothelial function relationships in depressed adults are unknown, this study’s third aim was to explore traditional CVD risk status as a candidate mediator of observed relationships. To achieve these aims, I combined pre-treatment, cross-sectional data from three randomized controlled trials involving 138 depressed primary care patients with no history of clinical CVD. Assessments included validated self-report questionnaires for affective traits, brachial artery flow-mediated dilation (FMD) for endothelial function, and 10-year Framingham risk score for traditional CVD risk status. I conducted structural equation modeling (SEM) with confirmatory factor analysis to examine the relationships of interest after adjusting for age, sex, race/ethnicity, education, and baseline arterial diameter. Although the shared variance between each affective trait pair could not be modeled due to poor fit, adequate fitting models revealed that hostility/anger and the unique components of hostility/anger were associated with poorer endothelial function (standardized coefficients = -.18 and -.22, respectively). All of the other affective traits and their components (depression, anxiety, positive affect, unique depression, unique anxiety, and unique positive affect) were not related to endothelial function (all ps > .08). Traditional CVD risk status did not partially explain the relationship between the unique components of hostility/anger and endothelial function (standardized coefficient for the indirect effect = .00; p = .89). If my results are supported by future findings, it would suggest that depressed adults with hostility/anger (a) may be a subgroup of the depressed population at greater risk of developing CVD and (b) may be in need of earlier, more intense, and/or different CVD primary prevention efforts. Future studies are needed to confirm this relationship and identify underlying mechanisms.Item Capsaicin and TRPV1 Channels in the Cardiovascular System: The Role of Inflammation(MDPI, 2021-12) Munjuluri, Sreepadaarchana; Wilkerson, Dru A.; Sooch, Gagandeep; Chen, Xingjuan; White, Fletcher A.; Obukhov, Alexander G.; Pharmacology and Toxicology, School of MedicineCapsaicin is a potent agonist of the Transient Receptor Potential Vanilloid type 1 (TRPV1) channel and is a common component found in the fruits of the genus Capsicum plants, which have been known to humanity and consumed in food for approximately 7000–9000 years. The fruits of Capsicum plants, such as chili pepper, have been long recognized for their high nutritional value. Additionally, capsaicin itself has been proposed to exhibit vasodilatory, antimicrobial, anti-cancer, and antinociceptive properties. However, a growing body of evidence reveals a vasoconstrictory potential of capsaicin acting via the vascular TRPV1 channel and suggests that unnecessary high consumption of capsaicin may cause severe consequences, including vasospasm and myocardial infarction in people with underlying inflammatory conditions. This review focuses on vascular TRPV1 channels that are endogenously expressed in both vascular smooth muscle and endothelial cells and emphasizes the role of inflammation in sensitizing the TRPV1 channel to capsaicin activation. Tilting the balance between the beneficial vasodilatory action of capsaicin and its unwanted vasoconstrictive effects may precipitate adverse outcomes such as vasospasm and myocardial infarction, especially in the presence of proinflammatory mediators.Item Clinical characteristics and 12-month outcomes of patients with valvular and non-valvular atrial fibrillation in Kenya(PLOS, 2017-09-21) Temu, Tecla M.; Lane, Kathleen A.; Shen, Changyu; Ng'ang'a, Loise; Akwanalo, Constantine O.; Chen, Peng-Sheng; Emonyi, Wilfred; Heckbert, Susan R.; Koech, Myra M.; Manji, Imran; Vatta, Matteo; Velazquez, Eric J.; Wessel, Jennifer; Kimaiyo, Sylvester; Inui, Thomas S.; Bloomfield, Gerald S.; Biostatistics, School of Public HealthBackground Atrial fibrillation (AF) is a major contributor to the global cardiovascular disease burden. The clinical profile and outcomes of AF patients with valvular heart diseases in sub-Saharan Africa (SSA) have not been adequately described. We assessed clinical features and 12-month outcomes of patients with valvular AF (vAF) in comparison to AF patients without valvular heart disease (nvAF) in western Kenya. Methods We performed a cohort study with retrospective data gathering to characterize risk factors and prospective data collection to characterize their hospitalization, stroke and mortality rates. Results The AF patients included 77 with vAF and 69 with nvAF. The mean (SD) age of vAF and nvAF patients were 37.9(14.5) and 69.4(12.3) years, respectively. There were significant differences (p<0.001) between vAF and nvAF patients with respect to female sex (78% vs. 55%), rates of hypertension (29% vs. 73%) and heart failure (10% vs. 49%). vAF patients were more likely to be taking anticoagulation therapy compared to those with nvAF (97% vs. 76%; p<0.01). After 12-months of follow-up, the overall mortality, hospitalization and stroke rates for vAF patients were high, at 10%, 34% and 5% respectively, and were similar to the rates in the nvAF patients (15%, 36%, and 5%, respectively). Conclusion Despite younger age and few comorbid conditions, patients with vAF in this developing country setting are at high risk for nonfatal and fatal outcomes, and are in need of interventions to improve short and long-term outcomes.Item A Critical Dialogue: Communicating with Type 2 Diabetes Patients about Cardiovascular Risk(2005-12) Roach, Paris; Marrero, David G.Patients with type 2 diabetes mellitus (DM) are at increased risk for cardiovascular disease (CVD), and many patients are inadequately treated for risk factors such as hyperglycemia, hyperlipidemia, hypertension, and smoking. Providing individualized risk information in a clear and engaging manner may serve to encourage both patients and their physicians to intensify risk-reducing behaviors and therapies. This review outlines simple and effective methods for making CVD risk infomation understandable to persons of all levels of literacy and mathematical ability. To allow the patient to understand what might happen and how, personal risk factors should be clearly communicated and the potential consequences of a CVD event should be presented in a graphic but factual manner. Risk calculation software can provide CVD risk estimates, and the resulting information can be made understandable by assigning risk severity (eg, “high”) by comparing clinical parameters with accepted treatment targets and by comparing the individual's risk with that of the “average” person. Patients must also be informed about how they might reduce their CVD risk and be supported in these efforts. Thoughtful risk communication using these techniques can improve access to health information for individuals of low literacy, especially when interactive computer technology is employed. Research is needed to find the best methods for communicating risk in daily clinical practice.Item Depressive Symptom Severity, Stressful Life Events, and Subclinical Atherosclerosis in African American Adults(2015) Berntson, Jessica; Stewart, Jesse; Cyders, Melissa Anne; Rand, Kevin L.; Grahame, Nicholas J.Prospective epidemiologic evidence indicates that both stressful life events (SLEs) and depression are associated with an increased risk of subclinical atherosclerosis and cardiovascular disease (CVD) events. Even though stressful life events (SLEs) and depression co-occur and may act together to influence cardiovascular disease (CVD) risk, these psychosocial factors have been mainly examined in isolation. For instance, depression may moderate the relationship between SLEs and CVD outcomes. I hypothesized that depressive symptoms would potentiate the deleterious effect of SLEs on subclinical atherosclerosis. This hypothesis is plausible, given that depressed adults exhibit exaggerated and prolonged sympathetic nervous system, hypothalamic-pituitary-adrenal (HPA) axis, and inflammatory responses to stress, which in turn could promote atherosclerosis. As compared to their nondepressed counterparts, depressed individuals may also be more likely to engage in maladaptive methods to cope with SLEs (e.g., increased tobacco use, alcohol use, and consumption of low-nutrient, energy dense foods), which could also promote atherosclerosis. I examined cross-sectional data from 274 to 279 (depending on the outcome measure) older, African American adults (mean age = 66 years, 67% female) with no evidence of clinical CVD or dementia who participated in the St. Louis African American Health-Heart study (2009–2011). Number of SLEs was assessed using the Life Events Calendar, a structured interview. From this interview, a continuous SLEs variable was computed (number of adult SLEs: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11+). Severity of depression symptoms was measured using the 17-item Hamilton Rating Scale for Depression (HAM-D). Two measures of subclinical atherosclerosis were obtained: carotid intima-media thickness (CIMT; assessed by ultrasonography) and coronary artery calcification (CAC; assessed by multi-detector computerized tomography). I conducted linear (CIMT) and logistic (CAC) regression models, first adjusted for demographics (age, sex, education) and then fully-adjusted (demographics; mean arterial pressure; low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C); hemoglobin A1c; BMI; tobacco use; diabetes diagnosis; and use of antihypertensitve, lipid lowering, antidiabetic, and antidepressant medications). No main effects of SLEs or HAM-D were found for CIMT or CAC. There were also no SLEs by HAM-D interactions for CIMT or CAC. Because the current results are largely inconsistent with prior literature and there is a paucity of studies utilizing African American samples, future research is needed to examine the independent and interactive associations of SLEs and depressive symptoms with measures of subclinical atherosclerosis. If the present results are replicated, it may suggest that SLEs, depressive symptoms, and their interactive effect are not cardiotoxic among African American adults.Item Depressive Symptoms are Associated with Poor Adherence to Some Lifestyle but not Medication Recommendations to Prevent Cardiovascular Disease: National Health and Nutrition Examination Survey (NHANES) 2005-2010(Office of the Vice Chancellor for Research, 2013-04-05) Berntson, Jessica; Stewart, Kendra Ray; Vrany, Elizabeth; Khambaty, Tasneem; Stewart, Jesse CDepression has been linked to poor medical adherence; however, most studies have involved persons with preexisting conditions, such as cardiovascular disease (CVD). Our aim was to examine relationships between depressive symptoms and adherence to medication and lifestyle recommendations intended to prevent CVD in a community sample. We selected adults ≥18 years (53%-56% female, 47%-52% non-white) with a history of hypertension and/or hypercholesterolemia, but free of CVD, who participated in 2005-2010 waves of NHANES – a survey of a large probability sample representative of the U.S. population. The Patient Health Questionnaire-9 (PHQ-9) was used to assess depressive symptoms (converted to z-scores). The NHANES Blood Pressure and Cholesterol questionnaire was used to assess self-reported adherence to five medication and lifestyle recommendations: take antihypertensive medication (N=3313), take lipid-lowering medication (N=2266), control/lose weight (N=2177), eat fewer high fat/cholesterol foods (N=2924), and increase physical activity (N=2540). Logistic regression models (adjusting for age, sex, race-ethnicity, education, body mass, diabetes, smoking status, daily alcohol intake and NHANES sample design) revealed that a 1-SD increase in PHQ-9 total score was associated with a 14% lower likelihood of adherence to the control/lose weight recommendation (OR=0.86, 95% CI: 0.75-0.98, p=.02) and a 25% lower likelihood of adherence to the increase physical activity recommendation (OR=0.75, 95% CI: 0.65-0.86, p<.001). PHQ-9 total score was not associated with the likelihood of adherence to antihypertensive medication (OR, 0.93, 95% CI: 0.82-1.05, p=0.21), lipid-lowering medication (OR=0.99, 95% CI: 0.86-1.14, p=0.90), or eat fewer high fat/cholesterol foods recommendations (OR=0.94, 95% CI: 0.82-1.08, p=0.40). Adherence rates for depressed verses nondepressed adults to the control/lose weight recommendation were 75% and 85% and the increase physical activity recommendation were 63% and 79%, respectively. Our findings suggest that poor adherence to weight and activity recommendations, but not medication and diet recommendations, may partially explain the excess CVD risk of depressed persons.Item Double Depression is Associated with Greater Risk of Incident Cardiovascular Disease than Major Depression: Data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC)(Office of the Vice Chancellor for Research, 2013-04-05) Case, Stephanie M; Sawhney, Manisha; Stewart, Jesse CEvidence suggests depressive disorders are risk factors for cardiovascular disease (CVD), however, little attention has been given to double depression (major depressive disorder (MDD) superimposed on dysthymia). The current study sought to determine if double depression is a stronger predictor of incident CVD due to greater duration of exposure and severity of depression in adults initially free of CVD. We analyzed data from 29,581 adults (mean age = 45 years, 58% female, 42% non-white) from Waves 1 (2001-2002) and 2 (2004-2005) of the NESARC study. At Wave 1, the Alcohol Use Disorder and Associated Disabilities Interview Schedule was administered to assess lifetime history of DSM-IV MDD and/or dysthymia. A 4-level variable was created for depression: no depression history (n=24,339), lifetime MDD only (n=4,028), lifetime dysthymia only (n=246), lifetime MDD and dysthymia (double depression; n=968). At Wave 2, participants who reported being diagnosed with myocardial infarction, stroke, angina, or arteriosclerosis in the past year were coded as having incident CVD; those diagnosed with myocardial infarction or stroke were coded as having had a hard CVD event. There were 1,380 CVD events and 365 hard CVD events. Logistic regression models adjusted for demographics (age, sex, race-ethnicity, education) and CVD risk factors (hypertension, hypercholesterolemia, diabetes, smoking, BMI) revealed that lifetime double depression (OR=1.72, 95% CI: 1.31-2.25, p<.001) and MDD only (OR=1.26, 95% CI: 1.06-1.49, p=.01), but not dysthymia only (OR=1.45, 95%, CI: 0.88-2.40, p=.15), predicted incident CVD. Double depression was a stronger predictor than MDD only (p=.04). In models predicting hard CVD events, double depression remained a predictor (OR=1.86, 95% CI: 1.10-3.16, p=.02) but MDD and dysthymia only did not (both ps>.43). Our findings partially support our hypothesis and suggest that persons with double depression may have a stronger connection to an elevated CVD risk in which prevention efforts should be intensified.Item Effect of Depression Treatment on Health Behaviors and Cardiovascular Risk Factors Among Primary Care Patients with Depression: Data from the eIMPACT Trial(2023-12) Schuiling, Matthew D.; Stewart, Jesse; Hirsh, Adam; Wu, WeiBackground. Although depression is a risk factor for cardiovascular disease (CVD), few clinical trials in people without CVD have examined the effect of depression treatment on CVD-related outcomes. It’s unknown if successful depression treatment improves indicators of CVD risk, such as CVD-relevant health behaviors, traditional CVD risk factors, and CVD events. Methods. We examined data from eIMPACT trial, a phase II randomized controlled trial conducted from 2015-2020. Depressive symptoms, CVD-relevant health behaviors (self-reported CVD prevention medication adherence, sedentary behavior, and sleep quality) and traditional CVD risk factors (blood pressure and lipid fractions) were assessed. Incident CVD events over four years were identified using a statewide health information exchange. Results. The intervention group exhibited greater improvement in depressive symptoms (p < 0.01) and sleep quality (p < 0.01) than the usual care group, but there was no intervention effect on systolic blood pressure (p = 0.36), low-density lipoprotein cholesterol (p = 0.38), high-density lipoprotein cholesterol (p = 0.79), triglycerides (p = 0.76), CVD prevention medication adherence (p = 0.64), or sedentary behavior (p = 0.57). There was an intervention effect on diastolic blood pressure that favored the usual care group (p = 0.02). CVD-relevant health behaviors did not mediate any intervention effects on traditional CVD risk factors. Twenty-two participants (10%) experienced an incident CVD event. The likelihood of an CVD event did not differ between the intervention group (12.1%) and the usual care group (8.3%; HR = 1.45, 95% CI: 0.62-3.40, p = 0.39). Conclusions. Successful depression treatment alone improves self-reported sleep quality but is not sufficient to lower CVD risk of people with depression. Alternative approaches may be needed reduce CVD risk in depression. Trial Registration: ClinicalTrials.gov Identifier: NCT02458690Item EFFECTS OF PORPHYROMONAS GINGIVALIS TREATED WITH VARIOUS CIGARETTE CONSTITUENTS ON HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS(Office of the Vice Chancellor for Research, 2012-04-13) Gupta, Vinayak; Windsor, L. Jack; Gregory, Richard L.Tobacco use affects the cardiovascular system and increases the rate of cardiovascular disease among smokers. However, the effects of tobacco on the endothelial cells that line blood vessels are not yet fully understood. Thus, the objective of this study was to examine some of the effects that a periodontal pathogen such as Porphyromonas gingivalis (P. gingivalis) treated with cigarette smoke condensate (CSC), nicotine, and dissolvable tobacco strips (DST) have on human umbilical vein endothelial cells (HUVECs). P.gingivalis was grown in an anaerobic environment at 37oC with and without CSC, DST, and nicotine. The cells and supernatants were harvested 96 hours later. A Bradford protein assay was conducted to determine the protein amounts of the cells and in the supernatant. The HUVEC will be cultured in Endothelial Basal Medium-2 and plated in 6 well plates and exposed to the P. gingivalis cells and supernatants and after 72 hours, lactate dehydrogenase (LDH) assays will be used to cytotoxicity. Non-toxic amounts of the cells and supernatants will then be used to treat HUVEC cells for 72 hours before the media is collected and analyzed for cytokine/growth factor expression by protein arrays. It is believed that the treated bacteria will increase the levels of the pro-inflammatory cytokines and growth factors expressed by the HUVECs, which could play roles in vascular diseases. The protein assays showed that only the protein amount in the supernatant from the CSC treated bacteria was decreased.