The 'Timing Hypothesis' states that the benefits and harms of hormone replacement therapy (HRT) are related to the proximity with which it is begun following the onset of menopause. The primary aim of this analysis was to test for heterogeneity of treatment effect for HRT using Chi2 and I2 tests for younger versus older initiators of HRT. The secondary aim was to perform a meta-regression with mean age at trial baseline as the covariate for various outcomes. Younger initiation trials were defined as those with mean age of participants <60 years and older initiation trials were those with mean age >60 years. The primary endpoints included all-cause mortality, cardiac mortality, coronary heart disease (CHD) events (a composite of cardiac mortality and nonfatal myocardial (MI)), and a composite of stroke, transient ischemic attack (TIA) and systemic embolism. Thirty-one RCTs were identified comparing HRT users to nonusers (n = 40,521). There was significant heterogeneity of treatment effect between younger versus older HRT initiators for all-cause mortality (Chi2 = 9.74, p = 0.002, I2 = 89.7%), cardiac mortality (Chi2 = 4.04, p = 0.04, I2 = 75.2%), and CHD events (Chi2 = 3.06, p = 0.08, I2 = 67.3%). Both groups experienced an increase in stroke, TIA and systemic embolism (1112/18,774 in the HRT group versus 734/18,070 in the control group; OR = 1.52; 95% confidence interval (CI) = 1.38–1.67). When performing the meta-regression, as age increased the treatment effect of HRT was increased for stroke, TIA and systemic embolism (point estimate 0.006 with a standard error of 0.002) (p = 0.0003). Younger initiation of HRT may be effective in reducing death and cardiac events. However, younger HRT initiators remained at an increased risk of stroke, TIA and systemic embolism and this risk increased as average age increased. Younger menopausal women using HRT to treat vasomotor symptoms do not appear to be at an increased risk of dying or experiencing CHD events.
Background: In heart failure (HF) patients, remote monitoring of hemodynamics using implantable devices may be used to predict and reduce HF exacerbations. Methods: A meta-analysis of randomized controlled trials (RCTs) testing remote monitoring versus standard of care for management of HF patients was performed. Endpoints included all-cause mortality and Cardiovascular (CV)/HF hospitalizations. Risk Ratios (RR) and 95% confidence intervals (CI) were calculated for each endpoint. A secondary analysis tested for heterogeneity of treatment effect (HTE) using Chi 2 and I 2 tests comparing implanted right ventricular/pulmonary pressure monitoring versus impedance-based monitoring on HF hospitalization. Results: 10 RCTs (n=6,020) were identified with a mean follow-up of 1.74 years. The mean age and reported ejection fraction were 64.1 and 27.1%, respectively. Remote monitoring did not reduce mortality (RR 0.88, [95% CI 0.76, 1.03]) or CV/HF hospitalizations (RR 0.99, [0.81, 1.20]) (Figure 1). When performing the test of subgroup differences, there was significant HTE for HF hospitalization between those studies that used implanted right ventricular/pulmonary pressure monitoring versus impedance-based monitoring (Chi 2 = 7.92, p = 0.005, I 2 = 87.4%). Conclusions: Compared to standard of care, remote monitoring of physiologic markers of HF did not reduce mortality and CV or HF hospitalization. However, right ventricular/pulmonary pressure monitoring may reduce HF hospitalization compared to impendence-based monitoring. Further studies are necessary to evaluate the role of remote monitoring in patients with heart failure.
Background: Evidence linking social isolation to cardiovascular disease morbidity and mortality has grown in recent years. Still, information on how this may manifest in real world settings and its implications for screening practices is limited. In 2019, our large national integrated health care system implemented screening for social isolation as part of a broader universal social risk assessment. This repository of screening data was joined to administrative claims to test these associations in real world data and explore differences by demographic and medical factors. Methods: Social isolation responses recorded from 2019-2022 were included for a cohort of adult health plan members with documented atherosclerotic cardiovascular disease (ASCVD). We selected a single random assessment for each member and retained any other responses for sensitivity analyses. Cohort members had at least 10 months of enrollment surrounding assessment date for use as the baseline period and were followed for 365 days. We used cox proportional hazards regression with right censoring for coverage gaps to estimate the risk of all-cause mortality conferred by social isolation. We used Poisson regression to model the rate of inpatient stays. Results: There were 881 deaths among 7,484 members (18% of those with social isolation; 11% of those without). The isolated group skewed less male (54% vs. 65%, p <0.001) and older (68.4 [SD 12.7] vs. 67.5 [SD 12.6] years, p <0.05) than those not isolated. At baseline, the isolated group had higher rates of mean inpatient stays (2.3 [SD 1.9] vs. 1.9 [SD 1.6], p <0.001), ED visits (1.2 [SD 1.9] vs. 0.9 [SD 1.6], p < 0.001), and smoking (50% vs. 44%, p < 0.05), and a higher mean Charlson Comorbidity Index (CCI) (3.6 [SD 2.6] vs. 3.0 [SD 2.4], p < 0.001). Adjusted survival models suggested an independent 33% increase in all-cause mortality risk among those screening positive for social isolation (1.33 HR 95% CI 1.10, 1.62). Adjusted Poisson models found a similar increase in inpatient stays (1.36 IRR 95% CI 1.14, 1.62). Conclusions: Our findings corroborate the association between social isolation and morbidity and mortality among those with known ASCVD. The effect for social isolation was similar in magnitude to clinical comorbidities and smoking, suggesting that routine screening for social isolation may provide valuable information for assessing and managing the risk of death among patients with ASCVD.
Introduction: Recent evidence suggests colchicine may prevent adverse outcomes from cardiovascular disease (CVD). The objective of this study is to perform a meta-analysis of randomized controlled trials (RCTs) testing colchicine’s effect on CVD adverse events and mortality among participants with known CVD. Methods: All RCTs testing colchicine versus control were identified and included in the analysis. The endpoints of interest included CVD adverse events (a composite of acute coronary syndrome, cardiac arrest, acute heart failure and hospitalization, stroke, revascularization, and recurrent myocardial infarction), mortality, and gastrointestinal (GI) adverse events. The primary analysis calculated the summary odds ratio (OR) and 95% confidence intervals (CI) for each endpoint. A secondary analysis tested CVD adverse events for heterogeneity of treatment effect (HTE) using Chi 2 and I 2 tests. Results: 9 RCTs (N = 7,031, mean follow-up 9 months) were identified comparing colchicine to control. Colchicine decreased the risk of CVD adverse events [OR 0.64, 95% CI 0.45-0.91]. Colchicine did not reduce all-cause mortality [OR 0.84, 95% CI 0.61-1.15]. GI adverse events were more likely in the colchicine group [OR 3.03, 95% CI 1.60-5.75, p = 0.0007; I 2 = 83%] but with significant HTE. When performing the test for subgroup differences, there was significant HTE between placebo and open-label trial for CVD events [Chi 2 = 10.55, p = 0.001, I 2 = 90.5%]. After excluding two open-label trials, colchicine reduced the risk of CVD events [OR 0.77, 95% CI 0.63-0.93]. Conclusion: Colchicine was associated with reduced CVD adverse events, but not with reduced mortality, among patients with underlying CVD. Colchicine use was associated with increased GI adverse events. Further studies with longer follow-up times are needed to better understand colchicine’s role in the long-term prevention of CVD adverse events.
The objective of this study was to evaluate whether increased serum 25-hydroxyvitamin D3 (25OHD3) concentrations, in response to calcium/vitamin D (CaD) supplementation, are associated with improved lipids in postmenopausal women.
