Objectives

This study assessed whether the physical component summary score of the RAND-36 health-related quality-of-life survey was associated with incidence of coronary heart disease, stroke, congestive heart failure, angina, or peripheral arterial disease, and whether baseline chronic conditions modified these associations.

Methods

Analysis was limited to 69,155 postmenopausal women (50-79 years) in the Women's Health Initiative Study who had complete data on the RAND-36, the outcomes, and covariates. Chronic conditions were defined as blood pressure ⩾140/90 mm or self-reported heart disease, diabetes, hypertension, arthritis, asthma, emphysema, cancer, and/or cholesterol-reducing medication use. Outcomes data were ascertained during follow-up (1993-2005) with medical records.

Results

There were 2451 coronary heart disease, 1896 stroke, 1533 congestive heart failure, 1957 angina, and 502 peripheral arterial disease events during follow-up (median 8.2 years). Participants in the lowest physical component summary quintile, compared to the highest, had a significantly higher risk of developing coronary heart disease (hazard ratio (95% confidence interval) 2.0 (1.7, 2.3)), stroke (1.8 (1.5, 2.2)), angina (2.4(2.0, 2.9)), and peripheral arterial disease (3.0 (2.0, 4.4)), irrespective of chronic conditions. Interactions between physical component summary and existing chronic conditions were not significant for any outcome except congestive heart failure (p = 0.005); after adjustment, participants in the lowest physical component summary quintile and with any chronic condition had nearly a twofold higher risk of congestive heart failure (Yes = 4.4 (3.3, 5.8) vs No = 2.4 (1.2, 4.3)).

Conclusion

We found a low physical component summary score was a significant risk factor for individual cardiovascular disease incidence in postmenopausal women.

Introduction

Although individual antiretroviral drugs have been shown to be associated with elevated cardiovascular disease (CVD) risk, data are limited on the role of antiretroviral drug combinations. Therefore, we sought to investigate CVD risk associated with antiretroviral drug combinations.

Methods

Using an administrative health-plan dataset, risk of acute myocardial infarction (AMI) associated with current exposure to antiretroviral drug combinations was assessed among persons living with HIV receiving antiretroviral therapy (ART) across the U.S. from October 2009 through December 2014. To account for confounding-by-indication and for factors simultaneously acting as causal mediators and confounders, we applied inverse probability of treatment weighted marginal structural models to longitudinal data of patients.

Results

Over 114,417 person-years (n = 73,071 persons) of ART exposure, 602 cases of AMI occurred at an event rate of 5.26 (95% CI: 4.86, 5.70)/1000 person-years. Of the 14 antiretroviral drug combinations studied, persons taking abacavir-lamivudine-darunavir had the highest incidence rate (IR: 11/1000; 95% CI: 7.4-16.0) of AMI. Risk (HR; 95% CI) of AMI was elevated for current exposure to abacavir-lamivudine-darunavir (1.91; 1.27-2.88), abacavir-lamivudine-atazanavir (1.58; 1.08-2.31), and tenofovir-emtricitabine-raltegravir (1.35; 1.07-1.71). Tenofovir-emtricitabine-efavirenz was associated with reduced risk (0.65; 0.54-0.78). Abacavir-lamivudine-darunavir was associated with increased risk of AMI beyond that expected of abacavir alone, likely attributable to darunavir co-administration. We did not find an elevated risk of AMI when abacavir-lamivudine was combined with efavirenz or raltegravir.

Conclusion

The antiretroviral drug combinations abacavir-lamivudine-darunavir, abacavir-lamivudine-atazanavir and tenofovir-emtricitabine-raltegravir were found to be associated with elevated risk of AMI, while tenofovir-emtricitabine-efavirenz was associated with a lower risk. The AMI risk associated with abacavir-lamivudine-darunavir was greater than what was previously described for abacavir, which could suggest an added risk from darunavir. The results should be confirmed in additional studies.

Abstract Background Past studies of relationships between alcohol and hip fracture have generally focused on total alcohol consumed and not type of alcohol. Different types of alcohol consist of varying components which may affect risk of hip fracture differentially. This study seeks to examine the relationship between alcohol consumption, with a focus on type of alcohol consumed (e.g. beer, wine, or hard liquor) and hip fracture risk in post-menopausal women. Methods The longitudinal cohort consisted of U.S. post-menopausal women aged 50–79 years enrolled between 1993–1998 in the Women’s Health Initiative Clinical Trials and Observational Study (N=115,655). Results Women were categorized as non-drinkers, past drinkers, infrequent drinkers and drinkers by preference of alcohol type (i.e. those who preferred wine, beer, hard liquor, or who had no strong preference). Mean alcohol consumption among current drinkers was 3.3 servings per week; this was similar among those who preferred wine, beer and liquor. After adjustment for potential confounders, alcohol preference was strongly correlated with hip fracture risk (p = 0.0167); in particular, women who preferred wine were at lower risk than non-drinkers (OR=0.78; 95% CI 0.64-0.95), past drinkers (OR=0.85; 95% CI 0.72-1.00), infrequent drinkers (OR=0.73; 95% CI 0.61-0.88), hard liquor drinkers (OR=0.87; 95% CI 0.71-1.06), beer drinkers (OR=0.72; 95% CI 0.55-0.95) and those with no strong preference (OR=0.89; 95% CI 0.89; 95% CI 0.73-1.10). Conclusions Preference of alcohol type was associated with hip fracture; women who preferentially consumed wine had a lower risk of hip fracture compared to non-drinkers, past drinkers, and those with other alcohol preferences.

Importance

Psychological stress contributes to numerous diseases and may do so in part through damage to telomeres, protective non-coding segments on the ends of chromosomes.

Objective

We conducted a systematic review and meta-analysis to determine the association between self-reported, perceived psychological stress (PS) and telomere length (TL).

Data sources

We searched 3 databases (PubMed, PsycInfo, and Scopus), completed manual searches of published and unpublished studies, and contacted all study authors to obtain potentially relevant data.

Study selection

Two independent reviewers assessed studies for original research measuring (but not necessarily reporting the correlation between) PS and TL in human subjects. 23 studies met inclusion criteria; 22 (totaling 8948 subjects) could be meta-analyzed.

Data extraction and synthesis

We assessed study quality using modified MINORS criteria. Since not all included studies reported PS-TL correlations, we obtained them via direct calculation from author-provided data (7 studies), contact with authors (14 studies), or extraction from the published article (1 study).

Main outcomes and measures

We conducted random-effects meta-analysis on our primary outcome, the age-adjusted PS-TL correlation. We investigated potential confounders and moderators (sex, life stress exposure, and PS measure validation) via post hoc subset analyses and meta-regression.

Results

Increased PS was associated with a very small decrease in TL (n=8724 total; r=-0.06; 95% CI: -0.10, -0.008; p=0.01; α=0.025), adjusting for age. This relationship was similar between sexes and within studies using validated measures of PS, and marginally (nonsignificantly) stronger among samples recruited for stress exposure (r=-0.13; vs. general samples: b=-0.11; 95% CI: -0.27, 0.01; p=0.05; α=0.013). Publication bias may exist; correcting for its effects attenuated the relationship.

Conclusions and relevance

Our analysis finds a very small, statistically significant relationship between increased PS (as measured over the past month) and decreased TL that may reflect publication bias, although fully parsing the effects of publication bias from other sample-size correlates is challenging, as discussed. The association may be stronger with known major stressors and is similar in magnitude to that noted between obesity and TL. All included studies used single measures of short-term stress; the literature suggests long-term chronic stress may have a larger cumulative effect. Future research should assess for potential confounders and use longitudinal, multidimensional models of stress.

Objectives

To evaluate the association between childhood physical activity and incident cardiovascular disease (CVD) during postmenopausal years.

Methods

Proportional hazards and logistic regression were used describe the association between self-reported childhood physical activity and CVD incidence and mortality in 36,741 postmenopausal women.

Results

Older women, African-Americans, or nondrinkers or past drinkers self-reported the highest levels of youth physical activity and women with a history of diabetes, hypertension, overweight or obesity, or current smoking reported the highest youth physical activity dose. Youth physical activity was not associated with CVD incidence (HR=1.11; 0.93, 1.34) or mortality (HR=1.2; 0.9, 1.73).

Conclusions

Self-reported youth activity was not associated with postmenopausal CVD incidence or mortality.

PURPOSE:To investigate whether selected carotid computed tomography angiography (CTA) quantitative features can predict 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores. METHODS:One hundred seventeen patients with calculated ASCVD risk scores were considered. A semiautomated imaging analysis software was used to segment and quantify plaque features. Eighty patients were randomly selected to build models using 14 imaging variables and the calculated ASCVD risk score as the end point (continuous and binarized). The remaining 37 patients were used as the test set to generate predicted ASCVD scores. The predicted and observed ASCVD risk scores were compared to assess properties of the predictive model. RESULTS:Nine of 14 CTA imaging variables were included in a model that considered the plaque features in a continuous fashion (model 1) and 6 in a model that considered the plaque features dichotomized (model 2). The predicted ASCVD risk scores were 18.87% ± 13.26% and 18.39% ± 11.6%, respectively. There were strong correlations between the observed ASCVD and the predicted ASCVDs, with r = 0.736 for model 1 and r = 0.657 for model 2. The mean biases between observed ASCVD and predicted ASCVDs were -1.954% ± 10.88% and -1.466% ± 12.04%, respectively. CONCLUSIONS:Selected quantitative imaging carotid features extracted from the semiautomated carotid artery analysis can predict the ASCVD risk scores.

Understanding the incidence of disease is often crucial for public policy decision-making, as observed during the COVID-19 pandemic. Estimating incidence is challenging, however, when the definition of incidence relies on tests that imperfectly measure disease, as in the case when assays with variable performance are used to detect the SARS-CoV-2 virus. To our knowledge, there are no pragmatic methods to address the bias introduced by the performance of labs in testing for the virus. In the setting of a longitudinal study, we developed a maximum likelihood estimation-based approach to estimate laboratory performance-adjusted incidence using the expectation-maximization algorithm. We constructed confidence intervals (CIs) using both bootstrapped-based and large-sample interval estimator approaches. We evaluated our methods through extensive simulation and applied them to a real-world study (TrackCOVID), where the primary goal was to determine the incidence of and risk factors for SARS-CoV-2 infection in the San Francisco Bay Area from July 2020 to March 2021. Our simulations demonstrated that our method converged rapidly with accurate estimates under a variety of scenarios. Bootstrapped-based CIs were comparable to the large-sample estimator CIs with a reasonable number of incident cases, shown via a simulation scenario based on the real TrackCOVID study. In more extreme simulated scenarios, the coverage of large-sample interval estimation outperformed the bootstrapped-based approach. Results from the application to the TrackCOVID study suggested that assuming perfect laboratory test performance can lead to an inaccurate inference of the incidence. Our flexible, pragmatic method can be extended to a variety of disease and study settings.

Background

Protease-activated receptor-1 antagonism by vorapaxar could facilitate arteriovenous fistula maturation but may increase bleeding risk.

Objective

The primary objective of the Vorapaxar Study for Maturation of arteriovenous fistula for Hemodialysis Access (VorapAccess) was to determine if vorapaxar improves arteriovenous fistula functional maturation in patients with end-stage renal disease.

Methods

VorapAccess was a randomized, placebo-controlled, double-blind pilot trial comparing 2.5 mg vorapaxar per day with placebo for twelve weeks starting on day two after arteriovenous fistula creation. The primary outcome was time to functional maturation defined as successful cannulation for six hemodialysis sessions within three weeks. The planned sample size was 50 participants. The study was terminated early after withdrawal of planned financial support. Given the small number of randomized patients, we performed descriptive analyses without inference testing.

Results

A total of 13 participants were randomly allocated study drug (six vorapaxar and seven placebo). The median age was 56 years and seven participants (54%) were female. The median (minimum-maximum) days to functional maturation were 169 (77-287) days in the vorapaxar group and 145 (48-198) days in the placebo group. Six of the 13 (46%) participants had arteriovenous fistula functional maturation within 180 days; two of six (33%) in the vorapaxar group and four of seven (57%) in the placebo group. There was one bleeding event in the placebo group.

Conclusion

Fewer than half of participants had functional maturation within 180 days after surgery, suggesting a major need for agents or strategies that enhance arteriovenous fistula maturation.

Background

We examined the social and economic factors associated with nursing home (NH) admission in older women, overall and poststroke.

Methods

The Women's Health Initiative (WHI) included women aged 50-79 years at enrollment (1993-1998). In the WHI Extension Study (2005-2010), participants annually reported any NH admission in the preceding year. Separate multivariate logistic regression models analyzed social and economic factors associated with long-term NH admission, defined as an admission on 2 or more questionnaires, overall and poststroke.

Results

Of 103,237 participants, 8904 (8.6%) reported NH admission (2005-2010); 534 of 2225 (24.0%) women with incident stroke reported poststroke NH admission. Decreased likelihoods of NH admission overall were demonstrated for Asian, Black, and Hispanic women (versus whites, adjusted odds ratio [aOR] = .35-.44, P < .001) and women with higher income (aOR = .75, 95% confidence interval [CI] = .63-.90), whereas increased likelihoods of NH admission overall were seen for women with lower social support (aOR = 1.34, 95% CI = 1.16-1.54) and with incident stroke (aOR = 2.59, 95% CI = 2.15-3.12). Increased odds of NH admission after stroke were demonstrated for women with moderate disability after stroke (aOR = 2.76, 95% CI = 1.73-4.42). Further adjustment for stroke severity eliminated the association found for race/ethnicity, income, and social support.

Conclusions

The level of care needed after a disabling stroke may overwhelm social and economic structures in place that might otherwise enable avoidance of NH admission. We need to identify ways to provide care consistent with patients' preferences, even after a disabling stroke.

Background

Evidence suggests that childhood physical activity may play a role in the etiology and prevention of adult chronic diseases. Because researchers must often depend on self-recalled physical activity data many years after the exposure, it is important to understand factors which may influence adult recall of childhood physical activity. This study evaluated the influence of adult characteristics on reported childhood physical activity and the association between adult physical activity and self-recalled childhood physical activity.

Methods

48,066 post-menopausal women from the Women's Health Initiative Observational Study reported their physical activity level during ages 5 - 9, 10 - 14, and 15 - 19.

Results

In this cohort, over 65% of the population reported the same category of physical activity over the three childhood age groups. While higher levels of childhood physical activity were significantly associated with higher adult physical activity, this association varied by race/ethnicity, education, smoking, body mass index, history of diabetes or cardiovascular disease, social support and physical functional status. Women who were consistently highly active reported adult physical activity levels that were 2.82 MET-hr/week (95% C.I. = 2.43, 3.20) higher compared to women who were always physically inactive during childhood.

Conclusions

It is important for researchers to understand the influence of adult characteristics on reported childhood physical activity.