Hilary A. Tindle

Optimism, Cynical Hostility, and Incident Coronary Heart Disease and Mortality in the Women’s Health Initiative

Background— Trait optimism (positive future expectations) and cynical, hostile attitudes toward others have not been studied together in relation to incident coronary heart disease (CHD) and mortality in postmenopausal women. Methods and Results— Participants were 97 253 women (89 259 white, 7994 black) from the Women’s Health Initiative who were free of cancer and cardiovascular disease at study entry. Optimism was assessed by the Life Orientation Test–Revised and cynical hostility by the cynicism subscale of the Cook Medley Questionnaire. Cox proportional hazard models produced adjusted hazard ratios (AHRs) for incident CHD (myocardial infarction, angina, percutaneous coronary angioplasty, or coronary artery bypass surgery) and total mortality (CHD, cardiovascular disease, or cancer related) over ≈8 years. Optimists (top versus bottom quartile [“pessimists”]) had lower age-adjusted rates (per 10 000) of CHD (43 versus 60) and total mortality (46 versus 63). The most cynical, hostile women (top versus bottom quartile) had higher rates of CHD (56 versus 44) and total mortality (63 versus 46). Optimists (versus pessimists) had a lower hazard of CHD (AHR 0.91, 95% CI 0.83 to 0.99), CHD-related mortality (AHR 0.70, 95% CI 0.55 to 0.90), cancer-related mortality (blacks only; AHR 0.56, 95% CI 0.35 to 0.88), and total mortality (AHR 0.86, 95% CI 0.79 to 0.93). Most (versus least) cynical, hostile women had a higher hazard of cancer-related mortality (AHR 1.23, 95% CI 1.09 to 1.40) and total mortality (AHR 1.16, 95% CI 1.07 to 1.27; this effect was pronounced in blacks). Effects of optimism and cynical hostility were independent. Conclusions— Optimism and cynical hostility are independently associated with important health outcomes in black and white women. Future research should examine whether interventions designed to change attitudes would lead to altered risk.

Smoking Cessation Behavior Among Intermittent Smokers Versus Daily Smokers

Nondaily intermittent smokers (ITS) are common, but their cessation behavior remains elusive. We examined cessation of native-ITS (n = 2040), converted-ITS (n = 1808), and daily smokers (DS; n = 25 344). All ITS were more likely than were DS to make a quit attempt (native-ITS adjusted odds ratio [AOR] = 1.60, 95% confidence interval [CI] = 1.42, 1.80; converted-ITS AOR = 3.33, 95% CI = 2.93, 3.78). Native-ITS (18%) and converted-ITS (27%) were more likely than were DS (13%) to quit smoking (native-ITS AOR = 1.34, 95% CI = 1.07, 1.67; converted-ITS AOR = 2.36, 95% CI = 2.01, 2.78), but the low cessation rates of ITS challenge their nonaddicted status.

HIV infection, cardiovascular disease risk factor profile, and risk for acute myocardial infarction

Background:Traditional cardiovascular disease risk factors (CVDRFs) increase the risk of acute myocardial infarction (AMI) among HIV-infected (HIV+) participants. We assessed the association between HIV and incident AMI within CVDRF strata. Methods:Cohort—81,322 participants (33% HIV+) without prevalent CVD from the Veterans Aging Cohort Study Virtual Cohort (prospective study of HIV+ and matched HIV− veterans) participated in this study. Veterans were followed from first clinical encounter on/after April 1, 2003, until AMI/death/last follow-up date (December 31, 2009). Predictors—HIV, CVDRFs (total cholesterol, cholesterol-lowering agents, blood pressure, blood pressure medication, smoking, diabetes) used to create 6 mutually exclusive profiles: all CVDRFs optimal, 1+ nonoptimal CVDRFs, 1+ elevated CVDRFs, and 1, 2, 3+ major CVDRFs. Outcome—Incident AMI [defined using enzyme, electrocardiogram (EKG) clinical data, 410 inpatient ICD-9 (Medicare), and/or death certificates]. Statistics—Cox models adjusted for demographics, comorbidity, and substance use. Results:Of note, 858 AMIs (42% HIV+) occurred over 5.9 years (median). Prevalence of optimal cardiac health was <2%. Optimal CVDRF profile was associated with the lowest adjusted AMI rates. Compared with HIV− veterans, AMI rates among HIV+ veterans with similar CVDRF profiles were higher. Compared with HIV− veterans without major CVDRFs, HIV+ veterans without major CVDRFs had a 2-fold increased risk of AMI (HR: 2.0; 95% confidence interval: 1.0 to 3.9; P = 0.044). Conclusions:The prevalence of optimal cardiac health is low in this cohort. Among those without major CVDRFs, HIV+ veterans have twice the AMI risk. Compared with HIV− veterans with high CVDRF burden, AMI rates were still higher in HIV+ veterans. Preventing/reducing CVDRF burden may reduce excess AMI risk among HIV+ people.

Optimism, response to treatment of depression, and rehospitalization after coronary artery bypass graft surgery.

Objective Optimism has been associated with a lower risk of rehospitalization after coronary artery bypass graft (CABG) surgery, but little is known about how optimism affects treatment of depression in post-CABG patients. Methods Using data from a collaborative care intervention trial for post-CABG depression, we conducted exploratory post hoc analyses of 284 depressed post-CABG patients (2-week posthospitalization score in the 9-item Patient Health Questionnaire ≥10) and 146 controls without depression who completed the Life Orientation Test – Revised (full scale and subscale) to assess dispositional optimism. We classified patients as optimists and pessimists based on the sample-specific Life Orientation Test – Revised distributions in each cohort (full sample, depressed, nondepressed). For 8 months, we assessed health-related quality of life (using the 36-item Short-Form Health Survey) and mood symptoms (using the Hamilton Rating Scale for Depression [HRS-D]) and adjudicated all-cause rehospitalization. We defined treatment response as a 50% or higher decline in HRS-D score from baseline. Results Compared with pessimists, optimists had lower baseline mean HRS-D scores (8 versus 15, p = .001). Among depressed patients, optimists were more likely to respond to treatment at 8 months (58% versus 27%, odds ratio = 3.02, 95% confidence interval = 1.28–7.13, p = .01), a finding that was not sustained in the intervention group. The optimism subscale, but not the pessimism subscale, predicted treatment response. By 8 months, optimists were less likely to be rehospitalized (odds ratio = 0.54, 95% confidence interval = 0.32–0.93, p = .03). Conclusions Among depressed post-CABG patients, optimists responded to depression treatment at higher rates. Independent of depression, optimists were less likely to be rehospitalized by 8 months after CABG. Further research should explore the impact of optimism on these and other important long-term post-CABG outcomes.

Association Between HIV Infection and the Risk of Heart Failure With Reduced Ejection Fraction and Preserved Ejection Fraction in the Antiretroviral Therapy Era: Results From the Veterans Aging Cohort Study

Importance With improved survival, heart failure (HF) has become a major complication for individuals with human immunodeficiency virus (HIV) infection. It is unclear if this risk extends to different types of HF in the antiretroviral therapy (ART) era. Determining whether HIV infection is associated with HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), or both is critical because HF types differ with respect to underlying mechanism, treatment, and prognosis. Objectives To investigate whether HIV infection increases the risk of future HFrEF and HFpEF and to assess if this risk varies by sociodemographic and HIV-specific factors. Design, Setting, and Participants This study evaluated 98 015 participants without baseline cardiovascular disease from the Veterans Aging Cohort Study, an observational cohort of HIV-infected veterans and uninfected veterans matched by age, sex, race/ethnicity, and clinical site, enrolled on or after April 1, 2003, and followed up through September 30, 2012. The dates of the analysis were October 2015 to November 2016. Exposure Human immunodeficiency virus infection. Main Outcomes and Measures Outcomes included HFpEF (EF≥50%), borderline HFpEF (EF 40%-49%), HFrEF (EF<40%), and HF of unknown type (EF missing). Results Among 98 015 participants, the mean (SD) age at enrollment in the study was 48.3 (9.8) years, 97.0% were male, and 32.2% had HIV infection. During a median follow-up of 7.1 years, there were 2636 total HF events (34.6% were HFpEF, 15.5% were borderline HFpEF, 37.1% were HFrEF, and 12.8% were HF of unknown type). Compared with uninfected veterans, HIV-infected veterans had an increased risk of HFpEF (hazard ratio [HR], 1.21; 95% CI, 1.03-1.41), borderline HFpEF (HR, 1.37; 95% CI, 1.09-1.72), and HFrEF (HR, 1.61; 95% CI, 1.40-1.86). The risk of HFrEF was pronounced in veterans younger than 40 years at baseline (HR, 3.59; 95% CI, 1.95-6.58). Among HIV-infected veterans, time-updated HIV-1 RNA viral load of at least 500 copies/mL compared with less than 500 copies/mL was associated with an increased risk of HFrEF, and time-updated CD4 cell count less than 200 cells/mm3 compared with at least 500 cells/mm3 was associated with an increased risk of HFrEF and HFpEF. Conclusions and Relevance Individuals who are infected with HIV have an increased risk of HFpEF, borderline HFpEF, and HFrEF compared with uninfected individuals. The increased risk of HFrEF can manifest decades earlier than would be expected in a typical uninfected population. Future research should focus on prevention, risk stratification, and identification of the mechanisms for HFrEF and HFpEF in the HIV-infected population.

Do Biomarkers of Inflammation, Monocyte Activation, and Altered Coagulation Explain Excess Mortality Between HIV Infected and Uninfected People?

Background: HIV infection and biomarkers of inflammation [measured by interleukin-6 (IL-6)], monocyte activation [soluble CD14 (sCD14)], and coagulation (D-dimer) are associated with morbidity and mortality. We hypothesized that these immunologic processes mediate (explain) some of the excess risk of mortality among HIV infected (HIV+) versus uninfected people independently of comorbid diseases. Methods: Among 2350 (1521 HIV+) participants from the Veterans Aging Cohort Study Biomarker Cohort (VACS BC), we investigated whether the association between HIV and mortality was altered by adjustment for IL-6, sCD14, and D-dimer, accounting for confounders. Participants were followed from date of blood draw for biomarker assays (baseline) until death or July 25, 2013. Analyses included ordered logistic regression and Cox Proportional Hazards regression. Results: During 6.9 years (median), 414 deaths occurred. The proportional odds of being in a higher quartile of IL-6, sCD14, or D-dimer were 2–3 fold higher for viremic HIV+ versus uninfected people. Mortality rates were higher among HIV+ compared with uninfected people [incidence rate ratio (95% CI): 1.31 (1.06 to 1.62)]. Mortality risk increased with increasing quartiles of IL-6, sCD14, and D-dimer regardless of HIV status. Adjustment for IL-6, sCD14, and D-dimer partially attenuated mortality risk among HIV+ people with unsuppressed viremia (HIV-1 RNA ≥10,000 copies per milliliter) compared with uninfected people—hazard ratio (95% CI) decreased from 2.18 (1.60 to 2.99) to 2.00 (1.45 to 2.76). Conclusions: HIV infection is associated with elevated IL-6, sCD14, and D-dimer, which are in turn associated with mortality. Baseline measures of these biomarkers partially mediate excess mortality risk among HIV+ versus uninfected people.Supplemental Digital Content is Available in the Text.

Depression and HIV Infection are Risk Factors for Incident Heart Failure Among Veterans: Veterans Aging Cohort Study

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.

Functional Independence in Late-Life: Maintaining Physical Functioning in Older Adulthood Predicts Daily Life Function after Age 80

BACKGROUND We examined physical functioning (PF) trajectories (maintaining, slowly declining, and rapidly declining) spanning 15 years in older women aged 65-80 and protective factors that predicted better current levels and less decline in functional independence outcomes after age 80. METHODS Womens Health Initiative extension participants who met criteria (enrolled in either the clinical trial or observational study cohort, >80 years at the data release cutoff, PF survey data from initial enrollment to age 80, and functional independence survey data after age 80) were included in these analyses (mean [SD] age = 84.0 [1.4] years; N = 10,478). PF was measured with the SF-36 (mean = 4.9 occasions). Functional independence was measured by self-reported level of dependence in basic and instrumental activities of daily living (ADLs and IADLs) (mean = 3.4 and 3.3 occasions). RESULTS Maintaining consistent PF in older adulthood extends functional independence in ADL and IADL in late-life. Protective factors shared by ADL and IADL include maintaining PF over time, self-reported excellent or very good health, no history of hip fracture after age 55, and no history of cardiovascular disease. Better IADL function is uniquely predicted by a body mass index less than 25 and no depression. Less ADL and IADL decline is predicted by better self-reported health, and less IADL decline is uniquely predicted by having no history of hip fracture after age 55. CONCLUSIONS Maintaining or improving PF and preventing injury and disease in older adulthood (ages 65-80) has far-reaching implications for improving late-life (after age 80) functional independence.

Chronic Stress and Endothelial Dysfunction: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND Endothelial dysfunction may represent an important link between chronic stress and cardiovascular disease (CVD) risk. However, few studies have examined the impact of chronic stress on endothelial dysfunction. The purpose of this study was to examine whether chronic stress was associated with flow-mediated dilation (FMD) and 2 biomarkers of endothelial dysfunction (intercellular adhesion molecule-1 (ICAM-1) and E-selectin) in a multiethnic sample of adults (ages 45–84 years). METHODS Data come from the baseline examination of Multi-Ethnic Study of Atherosclerosis participants. Chronic stress was assessed based on self-report of the presence and severity of ongoing problems in 5 domains. FMD was obtained using high-resolution ultrasound; biomarkers were assayed in different subsets of participants. RESULTS Higher chronic stress was associated with lower absolute FMD (mm FMD) in models adjusted for demographic and socioeconomic characteristics (0.169mm in high-stress participants vs. 0.178 and 0.179mm in medium and low-stress participants; P for trend = 0.04). This association remained unchanged with further adjustment for behavioral and biological CVD risk factors. Higher stress was related to higher ICAM-1 in models adjusted for sociodemographic characteristics and biological risk factors (P for trend = 0.005), but this association attenuated with adjustment for cigarette smoking (P for trend = 0.07). Chronic stress was not associated with E-selectin. CONCLUSIONS Our findings suggest chronic stress is related to endothelial dysfunction, possibly in part through other stress-associated CVD risk factors such as cigarette smoking.

Health Characteristics of Postmenopausal Women with Breast Implants

Background: Long-term health characteristics and quality of life in patients with breast implants are important issues in plastic surgery. Methods: The authors evaluated characteristics of women who had breast implant surgery in the Womens Health Initiative observational study between 1993 and 1998. Most women in this study cohort had breast implant surgery 20 or more years before recruitment into the study. The women who were in the study who had not undergone breast implant surgery served as the comparison group. There were 86,686 women in the study who did not have breast implant surgery and an absent history of breast cancer, and 1257 women who had breast implant surgery and no prior breast cancer. Results: Total mortality rates were substantially lower among women with breast implants, as was the incidence of coronary heart disease. Women with breast implants in this study had a lower body mass index throughout adult life and were more physically active than control subjects. After adjustment for these variables, differences in total mortality were no longer statistically significant. Women who had breast implants reported overall poorer quality of life and emotional well-being. These differences were small, but statistically significant. Among women with breast implant surgery, 7 percent of deaths were due to suicide (n = 3) versus 0.4 percent (n = 20) in controls. Conclusions: Significant differences in health characteristics and quality-of-life measures are seen in a cohort of women with breast implants decades after implant surgery. Further longitudinal studies need to focus on both physical and psychological health among women undergoing breast implant surgery.