Cardiovascular Outcomes In Adults Research Articles

Revisiting Race and the Benefit of RAS Blockade in Heart Failure: A Meta-Analysis of Randomized Clinical Trials.

Concerns have arisen that renin-angiotensin system (RAS) blockers are less effective in Black patients than non-Black patients with heart failure and reduced ejection fraction (HFrEF). To determine whether the effects of RAS blockers on cardiovascular outcomes differ between Black patients and non-Black patients with HFrEF. MEDLINE and Embase databases through December 31, 2023. Randomized trials investigating the effect of RAS blockers on cardiovascular outcomes in adults with HFrEF that enrolled Black and non-Black patients. Individual-participant data were extracted following Preferred Reporting Items for Systematic Reviews and Meta-analyses Independent Personal Data (PRISMA-IPD) reporting guidelines. Effects were estimated using a mixed-effects model using a 1-stage approach. The primary outcome was first hospitalization for HF or cardiovascular death. The primary analysis, based on the 3 placebo-controlled RAS inhibitor monotherapy trials, included 8825 patients (9.9% Black). Rates of death and hospitalization for HF were substantially higher in Black than non-Black patients. The hazard ratio (HR) for RAS blockade vs placebo for the primary composite was 0.84 (95% CI, 0.69-1.03) in Black patients and 0.73 (95% CI, 0.67-0.79) in non-Black patients (P for interaction = .14). The HR for first HF hospitalization was 0.89 (95% CI, 0.70-1.13) in Black patients and 0.62 (95% CI, 0.56-0.69) in non-Black patients (P for interaction = .006). Conversely, the corresponding HRs for cardiovascular death were 0.83 (95% CI, 0.65-1.07) and 0.84 (95% CI, 0.77-0.93), respectively (P for interaction = .99). For total hospitalizations for HF and cardiovascular deaths, the corresponding rate ratios were 0.82 (95% CI, 0.66-1.02) and 0.72 (95% CI, 0.66-0.80), respectively (P for interaction = .27). The supportive analyses including the 2 trials adding an angiotensin receptor blocker to background angiotensin-converting enzyme inhibitor treatment (n = 16 383) gave consistent findings. The mortality benefit from RAS blockade was similar in Black and non-Black patients. Despite the smaller relative risk reduction in hospitalization for HF with RAS blockade in Black patients, the absolute benefit in Black patients was comparable with non-Black patients because of the greater incidence of this outcome in Black patients.

Effect of Intradialytic Exercise on Cardiovascular Outcomes in Maintenance Hemodialysis: A Systematic Review and Meta-Analysis.

Cardiovascular disease is the leading cause of death among people with kidney failure on hemodialysis, for whom improving cardiovascular health is a research priority. Intradialytic myocardial stunning is common and associated with adverse cardiovascular events. Intradialytic exercise may mitigate intradialytic myocardial stunning and improve cardiovascular structure and function. This systematic review investigated the effect of intradialytic exercise on cardiovascular outcomes in adults undergoing maintenance hemodialysis (PROSPERO #CRD42018103118). Following PRISMA guidelines, we systematically searched MEDLINE, EMBASE, Cochrane CENTRAL, SportDiscus, and PEDro databases from 1960 until June 2022, for randomized and non-randomized studies investigating the effect of intradialytic exercise programs on objective cardiovascular outcomes, pre-specified as primary or secondary outcomes. The primary outcome was arterial resistance. Of 10837 references identified, 32 met eligibility criteria. These studies investigated the effect of intradialytic exercise on arterial resistance (8 studies), blood pressure (20 studies), myocardial structure and function (7 studies), endothelial function (2 studies), sympathetic overactivity (9 studies), biomarkers of cardiac injury (3 studies), cardiovascular hospitalization and mortality (2 studies). Most studies used aerobic exercise as the intervention and usual care (no exercise) controls. Meta-analysis of intradialytic exercise versus usual care resulted in a statistically significant reduction in arterial resistance measured by pulse wave velocity (PWV) with mean difference -1.63 m/sec (95% CI -2.51, -0.75). Meta-analyses for diastolic blood pressure, left ventricular ejection fraction (LVEF), and low-frequency/high-frequency (LF/HF ratio) measure of heart rate variability also showed statistically significant improvements with exercise. There was no significant difference in change in systolic blood pressure, augmentation index, and left ventricular mass index between groups. Intradialytic exercise programming resulted in a clinically meaningful improvement to PWV, a component of arterial resistance. Sseveral physiologic measures of cardiovascular health, including diastolic blood pressure, LVEF and heart rate variability measured by the LF/HF ratio were also observed. The effects of intradialytic exercise on major adverse cardiovascular events remains uncertain.

Plasma Uromodulin and Cardiovascular Outcomes in Adults with Hypertension and CKD

Plasma Uromodulin and Cardiovascular Outcomes in Adults with Hypertension and CKD

Frailty and Cardiovascular Outcomes in Adults With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Frailty is common in individuals with chronic kidney disease (CKD) and increases the risk of adverse outcomes in adults with kidney failure requiring dialysis. However, this relationship has not been thoroughly evaluated among those with non-dialysis-dependent CKD. Prospective cohort study. 2,539 adults in the Chronic Renal Insufficiency Cohort Study. Frailty status assessed using 5 criteria: slow gait speed, muscle weakness, low physical activity, exhaustion, and unintentional weight loss. Atherosclerotic events, incident heart failure, all-cause death, and cardiovascular death. Cause-specific hazards models. At study entry, the participants' mean age was 62 years, 46% were female, the mean estimated glomerular filtration rate was 45.4mL/min/1.73m2, and the median urine protein was 0.2mg/day. Frailty status was as follows: 12% frail, 51% prefrail, and 37% nonfrail. Over a median follow-up of 11.4 years, there were 393 atherosclerotic events, 413 heart failure events, 497 deaths, and 132 cardiovascular deaths. In multivariable regression analyses, compared with nonfrailty, both frailty and prefrailty status were each associated with higher risk of an atherosclerotic event (HR, 2.03 [95% CI, 1.41-2.91] and 1.77 [95% CI, 1.35-2.31], respectively) and incident heart failure (HR, 2.22 [95% CI, 1.59-3.10] and 1.39 [95% CI, 1.07-1.82], respectively), as well as higher risk of all-cause death (HR, 2.52 [95% CI, 1.84-3.45] and 1.76 [95% CI, 1.37-2.24], respectively) and cardiovascular death (HR, 3.01 [95% CI, 1.62-5.62] and 1.78 [95% 1.06-2.99], respectively). Self-report of aspects of the frailty assessment and comorbidities, which may have led to bias in some estimates. In adults with CKD, frailty status was associated with higher risk of cardiovascular events and mortality. Future studies are needed to evaluate the impact of interventions to reduce frailty on cardiovascular outcomes in this population. Frailty is common in individuals with chronic kidney disease (CKD) and increases the risk of adverse outcomes. We sought to evaluate the association of frailty status with cardiovascular events and death in adults with CKD. Frailty was assessed according to the 5 phenotypic criteria detailed by Fried and colleagues. Among 2,539 participants in the CRIC Study, we found that 12% were frail, 51% were prefrail, and 37% were nonfrail. Frailty status was associated with an increased risk of atherosclerotic events, incident heart failure, and death.

Current Smoking Determines the Levels of Circulating MPO and MMP-9 in Adults with Coronary Artery Disease and Obstructive Sleep Apnea.

(1) Background: Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD), in which a rupture of atherosclerotic plaques and oxidative stress play a role in the initiation and progression of the disorder. Circulating levels of myeloperoxidase (MPO), as an oxidative stress marker, as well as matrix metalloproteinase-9 (MMP-9), as a destabilizer of plaques, are known to be elevated in patients with CAD and are associated with worse prognosis. Some studies have suggested that OSA is associated with MPO and MMP-9, but the effect of OSA on these biomarkers in cardiac cohorts is unknown. (2) Aims: We addressed the determinants of high MPO and MMP-9 in a CAD cohort with concomitant OSA. (3) Materials and Methods: The current study was a secondary analysis of the RICCADSA trial that was conducted in Sweden between 2005 and 2013. A total of 502 revascularized CAD patients with OSA (apnea-hypopnea index [AHI] ≥ 15 events/h; n = 391) or no-OSA (AHI < 5 events/h; n = 101), based on a home sleep apnea test, and who had blood samples at baseline were included in the analysis. The patients were dichotomized into a high or low MPO and MMP-9 groups, based on the median cut-off values. (4) Results: The mean age of the participants was 63.9 (±8.6), and 84% of the study cohort were men. Median values of MPO and MMP-9 levels were 116 ng/mL and 269 ng/mL, respectively. In different multivariate linear and logistic regression models, neither OSA nor OSA severity in terms of AHI and oxygenation indices were associated with the high MPO and MMP-9 levels. Current smoking was significantly associated with both high MPO (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.06-2.84; p = 0.030) and high MMP-9 levels (OR 2.41, 95% CI 1.44-4.03; p < 0.001), respectively. Other significant determinants were revealed as beta blocker use (OR 1.81, 95% CI 1.04-3.16; p = 0.036) for high MPO as well as male sex (OR 2.07, 95% CI 1.23-3.50; p = 0.006) and calcium antagonist use (OR 1.91, 95% CI 1.18-3.09; p = 0.008) for high MMP-9 levels. (5) Conclusions: Current smoking, but not OSA, was significantly associated with high MPO and MMP-9 levels in this revascularized CAD cohort. Smoking status should be seriously taken into consideration while evaluating the effects of OSA and its treatment on long-term adverse cardiovascular outcomes in adults with CAD.

Beyond Acute COVID-19: A Review of Long-term Cardiovascular Outcomes.

Statistics Canada estimated that approximately 1.4 million Canadians suffer from long COVID. Although cardiovascular changes during acute SARS-CoV-2 infection are well documented, long-term cardiovascular sequelae are less understood. In this review, we sought to characterize adult cardiovascular outcomes in the months after acute COVID-19 illness. In our search we identified reports of outcomes including cardiac dysautonomia, myocarditis, ischemic injuries, and ventricular dysfunction. Even in patients without overt cardiac outcomes, subclinical changes have been observed. Cardiovascular sequelae after SARS-CoV-2 infection can stem from exacerbation of preexisting conditions, ongoing inflammation, or as a result of damage that occurred during acute infection. For example, myocardial fibrosis has been reported months after hospital admission for COVID-19 illness, and might be a consequence of myocarditis and myocardial injury during acute disease. In turn, myocardial fibrosis can contribute to further outcomes including dysrhythmias and heart failure. Severity of acute infection might be a risk factor for long-term cardiovascular consequences, however, cardiovascular changes have also been reported in young, healthy individuals who had asymptomatic or mild acute disease. Although evolving evidence suggests that previous SARS-CoV-2 infection might be a risk factor for cardiovascular disease, there is heterogeneity in existing evidence, and some studies are marred by measured and unmeasured confounders. Many investigations have also been limited by relatively short follow-up. Future studies should focus on longer term outcomes (beyond 1 year) and identifying the prevalence of outcomes in different populations on the basis of acute and long COVID disease severity.

The Impact of High Protein Diets on Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

High protein diets have gained increased popularity as a means of losing weight, increasing muscle mass and strength, and improving cardiometabolic parameters. Only a few meta-analyses have addressed their impact on cardiovascular morbidity and mortality and failed to show any significant associations without applying strict values to define high protein intake. Due to the conflicting research background, we conducted a meta-analysis to assess the impact of high protein diets compared to normal protein consumption on cardiovascular outcomes in adults without established cardiovascular disease. Fourteen prospective cohort studies were included. A total of 6 studies, including 221,583 participants, reported data about cardiovascular death, without showing a statistically significant difference in the random effect model (odds ratio: 0.94; confidence interval: 0.60-1.46; I2 = 98%; p = 0.77). Analysis of three studies, which included 90,231 participants showed that a high protein diet was not associated with a lower risk of stroke (odds ratio: 1.02; confidence interval: 0.94-1.10; I2 = 0%; p = 0.66). Regarding the secondary outcome of non-fatal myocardial infarction, stroke, or cardiovascular death, 13 studies that included 525,047 participants showed no statistically significant difference (odds ratio; 0.87; confidence interval: 0.70-1.07; I2 = 97%; p = 0.19). In conclusion, according to our study results, high protein consumption does not affect cardiovascular prognosis.

Abstract P526: Associations of Body Mass Index Variability From Childhood and Midlife Class II and Class III Obesity

Background: Short periods of weight loss followed by weight gain (BMI variability) has been linked to adverse cardiovascular outcomes in adults. However, less is known about the effect of long-term BMI variability from childhood on midlife class II and class III obesity. We identified this effect in a cohort of Black and White midlife adults living in a rural community. Methods: We studied 1,268 midlife participants of the Bogalusa Heart Study (age at baseline 9.5 ± 3.5 years, age at midlife 48.2 ± 5.2 years, 59.5% women, 34.4% Black) with ≥4 measurements of BMI and other traditional cardiovascular risk factors (CVRF) from childhood. Long-term BMI variability was computed as deviation from age-predicted values (DEV). Logistic regression, adjusting for age, sex, race, CVRF, depression, alcohol use, education, and employment status, was conducted to assess associations between long-term BMI variability and midlife obesity (class II and III, BMI ≥35kg/m 2 and ≥40kg/m 2 , respectively). Interactions between race, sex and long-term BMI variability were assessed. Results: Prevalence of midlife class II and class III obesity were 26.81%(n=340) and 12.7%(n=161), respectively. DEV was positively significantly associated with having midlife class II and class III obesity. For class II obesity, no significant interactions between DEV and race or sex were observed. For class III obesity, interactions of DEV with race and sex were significant; the odds of having class III midlife obesity per unit increase in DEV were greater in White participants and in men compared with Black participants and women(see Table 1). Conclusions: We identified associations between long-term BMI variability from childhood and midlife obesity. Race and sex were observed to modify the effect of BMI variability on having midlife obesity. Further studies are needed to elucidate the role of long-term BMI variability as a predictor for increased risk of midlife obesity.

Cardiovascular Outcomes in Adults with Coronary Artery Disease and Obstructive Sleep Apnea with versus without Excessive Daytime Sleepiness in the RICCADSA Cinical Trial.

Rationale: Recent randomized controlled trials did not show cardiovascular benefits of continuous positive airway pressure (CPAP) in adults with coronary artery disease (CAD) and obstructive sleep apnea (OSA) in intention-to-treat analyses. It has been argued that exclusion of patients with OSA with excessive daytime sleepiness (EDS), who may be most likely to benefit from CPAP treatment, may be a reason for the null results. Objectives: We addressed 1) the effect of concomitant EDS on adverse outcomes in patients with CAD and OSA; and 2) whether the cardiovascular benefit of CPAP adherence differs between individuals with versus without EDS. Methods: This was a secondary analysis of the RICCADSA (Randomized Intervention with CPAP in CAD and Obstructive Sleep Apnea) trial, conducted in Sweden between 2005 and 2013. Data were analyzed from 155 patients with CAD with OSA (apnea-hypopnea index ⩾ 15/h) and EDS (Epworth Sleepiness Scale score ⩾ 10), who were allocated to CPAP and 244 patients without EDS (ESS < 10), who were randomized to CPAP or no CPAP. Patients who were allocated to no CPAP or were nonadherent (CPAP usage < 4 h/night) were compared with adherent patients (CPAP usage ⩾ 4 h/night) at 1-year follow-up. Inverse probability of treatment weighting was applied to mimic randomization of EDS. The primary endpoint was the first event of repeat revascularization, myocardial infarction, stroke, or cardiovascular mortality. Results: The median follow-up was 52.2 months. The incidence of the primary endpoint did not differ significantly between the EDS versus no-EDS groups in the entire cohort. Within the adherent group, patients without EDS had a significantly decreased risk compared with patients with EDS (adjusted hazard ratio, 0.41; 95% confidence interval, 0.20-0.85; P = 0.02). Conclusions: Adverse cardiovascular outcomes did not differ by degrees of EDS for patients with CAD with OSA who were untreated or nonadherent to treatment. CPAP use, at least 4 h/night, was associated with reduced adverse outcomes in participants without EDS. Clinical trial registered with www.clinicaltrials.gov (NCT00519597).

Long-Term Associations between Human Cytomegalovirus Antibody Levels with All-Cause Mortality and Cardiovascular Outcomes in an Australian Community-Based Cohort.

Human cytomegalovirus (HCMV) infection has been shown to increase the risk of cardiovascular events and all-cause death among individuals with clinically apparent cardiovascular disease (CVD). Whether this association exists in individuals with no history of CVD remains unclear. Serum levels of HCMV IgG antibody were measured using an ELISA in 2050 participants aged 40-80 years from the 1994/1995 Busselton Health Survey who did not have CVD at baseline. Outcomes were all-cause death, cardiovascular death, acute coronary syndrome (ACS) and major adverse coronary and cerebrovascular events (MACCE, composite of all-cause death, ACS, stroke and coronary artery revascularisation procedures). Cox proportional hazards regression analysis was used to investigate HCMV antibody levels as a predictor of death and cardiovascular outcomes during follow-up periods of 5, 10 and 20 years. At baseline, participants had a mean age of 56 years and 57% were female. During the 20-year follow-up, there were 448 (21.9%) deaths (including 152 from CVD), 139 (6.8%) participants had ACS and 575 (28.0%) had MACCE. In the fully adjusted model, levels of HCMV antibody at 20 years was associated with all-cause death (HR 1.04; 95% CI 1.00, 1.07, p = 0.037) but not with CVD death, ACS or MACCE. Levels of HCMV antibody are associated with all-cause death but not with cardiovascular outcomes in adults without pre-existing CVD.

Association of Bariatric Surgery With Cardiovascular Outcomes in Adults With Severe Obesity and Nonalcoholic Fatty Liver Disease

There are no approved treatments for nonalcoholic fatty liver disease (NAFLD) despite its association with obesity and increased risk of cardiovascular disease (CVD). To examine the association between bariatric surgery and CVD risk in individuals with severe obesity and NAFLD. This large, population-based retrospective cohort study obtained data from the MarketScan Commercial Claims and Encounters database from January 1, 2007, to December 31, 2017. Participants included insured adults aged 18 to 64 years with NAFLD and severe obesity (body mass index ≥40) without a history of bariatric surgery or CVD before NAFLD diagnosis. Baseline characteristics were balanced between individuals who underwent surgery (surgical group) and those who did not (nonsurgical group) using inverse probability of treatment weighting. Data were analyzed from March 2020 to April 2021. Bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy, and other bariatric procedures) vs nonsurgical care. The main outcome was the incidence of cardiovascular events (primary or secondary composite CVD outcomes). The primary composite outcome included myocardial infarction, heart failure, or ischemic stroke, and the secondary composite outcome included secondary ischemic heart events, transient ischemic attack, secondary cerebrovascular events, arterial embolism and thrombosis, or atherosclerosis. Cox proportional hazards regression models with inverse probability treatment weighting were used to examine the associations between bariatric surgery, modeled as time varying, and all outcomes. The study included 86 964 adults (mean [SD] age, 44.3 [10.9] years; 59 773 women [68.7%]). Of these individuals, 30 300 (34.8%) underwent bariatric surgery and 56 664 (65.2%) received nonsurgical care. All baseline covariates were balanced after applying inverse probability treatment weighting. In the surgical group, 1568 individuals experienced incident cardiovascular events compared with 7215 individuals in the nonsurgical group (incidence rate difference, 4.8 [95% CI, 4.5-5.0] per 100 person-years). At the end of the study, bariatric surgery was associated with a 49% lower risk of CVD (adjusted hazard ratio [aHR], 0.51; 95% CI, 0.48-0.54) compared with nonsurgical care. The risk of primary composite CVD outcomes was reduced by 47% (aHR, 0.53 [95% CI, 0.48-0.59), and the risk of secondary composite CVD outcomes decreased by 50% (aHR, 0.50; 95% CI, 0.46-0.53) in individuals with vs without surgery. Results of this study suggest that, compared with nonsurgical care, bariatric surgery was associated with significant reduction in CVD risk in individuals with severe obesity and NAFLD.

Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded-endpoint clinical trial

Studies have suggested that evening dosing with antihypertensive therapy might have better outcomes than morning dosing. The Treatment in Morning versus Evening (TIME) study aimed to investigate whether evening dosing of usual antihypertensive medication improves major cardiovascular outcomes compared with morning dosing in patients with hypertension. The TIME study is a prospective, pragmatic, decentralised, parallel-group study in the UK, that recruited adults (aged ≥18 years) with hypertension and taking at least one antihypertensive medication. Eligible participants were randomly assigned (1:1), without restriction, stratification, or minimisation, to take all of their usual antihypertensive medications in either the morning (0600-1000 h) or in the evening (2000-0000 h). Participants were followed up for the composite primary endpoint of vascular death or hospitalisation for non-fatal myocardial infarction or non-fatal stroke. Endpoints were identified by participant report or record linkage to National Health Service datasets and were adjudicated by a committee masked to treatment allocation. The primary endpoint was assessed as the time to first occurrence of an event in the intention-to-treat population (ie, all participants randomly assigned to a treatment group). Safety was assessed in all participants who submitted at least one follow-up questionnaire. The study is registered with EudraCT (2011-001968-21) and ISRCTN (18157641), and is now complete. Between Dec 17, 2011, and June 5, 2018, 24 610 individuals were screened and 21 104 were randomly assigned to evening (n=10 503) or morning (n=10 601) dosing groups. Mean age at study entry was 65·1 years (SD 9·3); 12 136 (57·5%) participants were men; 8968 (42·5%) were women; 19 101 (90·5%) were White; 98 (0·5%) were Black, African, Caribbean, or Black British (ethnicity was not reported by 1637 [7·8%] participants); and 2725 (13·0%) had a previous cardiovascular disease. By the end of study follow-up (March 31, 2021), median follow-up was 5·2 years (IQR 4·9-5·7), and 529 (5·0%) of 10 503 participants assigned to evening treatment and 318 (3·0%) of 10 601 assigned to morning treatment had withdrawn from all follow-up. A primary endpoint event occurred in 362 (3·4%) participants assigned to evening treatment (0·69 events [95% CI 0·62-0·76] per 100 patient-years) and 390 (3·7%) assigned to morning treatment (0·72 events [95% CI 0·65-0·79] per 100 patient-years; unadjusted hazard ratio 0·95 [95% CI 0·83-1·10]; p=0·53). No safety concerns were identified. Evening dosing of usual antihypertensive medication was not different from morning dosing in terms of major cardiovascular outcomes. Patients can be advised that they can take their regular antihypertensive medications at a convenient time that minimises any undesirable effects. British Heart Foundation.

Does fish oil supplementation improve patient-oriented cardiovascular outcomes in adults with hyperlipidemia?

Does fish oil supplementation improve patient-oriented cardiovascular outcomes in adults with hyperlipidemia?

Association between gout and cardiovascular outcomes in adults with no history of cardiovascular disease: large data linkage study in New Zealand

ObjectiveTo examine the association of gout with cardiovascular outcomes using linked administrative health data in Aotearoa New Zealand.DesignData linkage study.SettingNational registries of pharmaceutical dispensing, hospital admission, and deaths linked to...

PCSK9 inhibitors and ezetimibe with or without statin therapy for cardiovascular risk reduction: a systematic review and network meta-analysis

ObjectiveTo compare the impact of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on cardiovascular outcomes in adults taking maximally tolerated statin therapy or who are statin intolerant.DesignNetwork meta-analysis.Data...

Cardiovascular outcomes in adults with migraine treated with eptinezumab for migraine prevention: pooled data from four randomized, double-blind, placebo-controlled studies

BackgroundPatients with migraine have an increased relative risk of cardio- and cerebrovascular events, and some migraine treatments may exacerbate this risk. The primary objective of this analysis was to determine whether the rate of cardiovascular adverse events was higher for patients with migraine treated with the migraine-preventive eptinezumab, compared with patients receiving placebo.MethodsCardiovascular outcomes in patients with migraine were pooled across four clinical trials (phase 1b, phase 2, and two phase 3 trials) for use of eptinezumab as a preventive migraine treatment for up to 1 year. In all studies, treatment-emergent adverse events (TEAEs) that occurred after the first dose of study treatment (eptinezumab 100 mg, 300 mg, 1000 mg, or placebo) and vital signs were recorded through study completion.ResultsCardiovascular TEAEs were rare across all four clinical trials, and rates were similar between patients receiving eptinezumab and those receiving placebo. Cardiovascular TEAEs that did occur were mild or moderate in severity; there were no serious adverse events as per FDA definition. Vital signs (systolic blood pressure, diastolic blood pressure, and heart rate) were not meaningfully different across treatment groups over the course of 56 weeks, compared to placebo. Treatment with eptinezumab did not result in significant new or changed cardiovascular medications used concomitantly compared to placebo.ConclusionsIn this post hoc analysis of four clinical trials for eptinezumab, doses of 100 mg, 300 mg, and 1000 mg (more than 3 times the highest approved dose) were not associated with clinically relevant changes in vital signs or significant changes in concomitant cardiovascular medication usage, and had low incidences of cardiovascular TEAEs, comparable to placebo.Trial registrationNCT01772524 (Study 2), 01/21/2013; NCT02275117 (Study 5), 10/27/2014; NCT02559895 (PROMISE-1), 09/25/2017; NCT02974153 (PROMISE-2), 11/28/2016

Sodium-Glucose Cotransporter 2 Inhibitors, All-Cause Mortality, and Cardiovascular Outcomes in Adults with Type 2 Diabetes: A Bayesian Meta-Analysis and Meta-Regression.

BackgroundThis study aimed to assess the effectiveness of sodium‐glucose cotransporter 2 inhibitors in reducing the incidence of mortality and cardiovascular outcomes in adults with type 2 diabetes.Methods and ResultsWe conducted a Bayesian meta‐analysis of randomized controlled trials comparing sodium‐glucose cotransporter 2 inhibitors with placebo. We used meta‐regression to examine the association between treatment effects and control group event rates as measures of cardiovascular baseline risk. Fifty‐three randomized controlled trials were included in our synthesis. Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all‐cause mortality (empagliflozin: rate ratio [RR], 0.79; 95% credibility interval [CrI], 0.63–0.97; canagliflozin: RR, 0.86; 95% CrI, 0.69–1.05; dapagliflozin: RR, 0.86; 95% CrI, 0.72–1.01) and cardiovascular mortality (empagliflozin: RR, 0.78; 95% CrI, 0.61–1.00; canagliflozin: RR, 0.83; 95% CrI, 0.63–1.05; dapagliflozin: RR, 0.88; 95% CrI, 0.71–1.08), with a 90.1% to 98.7% probability for the true RR to be <1.00 for both outcomes. There was little evidence for ertugliflozin and sotagliflozin versus placebo for reducing all‐cause and cardiovascular mortality. There was no association between treatment effects for all‐cause and cardiovascular mortality and the control group event rates. There was evidence for a reduction in the incidence of heart failure for empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin versus placebo (probability RR <1.00 of ≥99.3%) and weaker, albeit positive, evidence for acute myocardial infarction for the first 3 agents (probability RR <1.00 of 89.0%–95.2%). There was little evidence of any agent except canagliflozin for reducing the incidence of stroke.ConclusionsEmpagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all‐cause and cardiovascular mortality versus placebo. Treatment effects of sodium‐glucose cotransporter 2 inhibitors versus placebo do not vary by baseline risk.

Meta-analysis for effect modification by sex on the associations between fine particulate matters and cardiovascular outcomes in adults

BACKGROUND AND AIM: Exposure to particulate matter with aerodynamic diameter no larger than 2.5 µm (PM2.5) can cause cardiovascular diseases (CVDs) but evidence for more vulnerable sex remains unclear in aiding clinical recommendations or public health approaches. We systematically reviewed observational studies and conduct meta-analysis to assess whether certain sex/gender is more vulnerable. METHODS: English-written studies published between 1995 and 2020 were searched from 4 databases. Population-based observation studies conducting sex subgroup analysis for the impacts of short-term or long-term ambient PM2.5 exposure on target CVDs were included. Random-effects meta-regression analyses were used to pool risk ratios (RRs) for long-term exposure and percent changes in outcomes for short-term exposure for a 10 µg/m³ increase in PM2.5 concentration. Quality of evidence of risk differences by sex was rated following the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS:Data were synthesized for 5 outcomes. The difference in RRs of all CVD mortality for a 10 µg/m³ in long-term PM2.5 concentration between men and women was not significant (1.02; 95% CI, 0.97 to 1.08). The difference in percent changes in daily mortality associated with a 10 µg/m³ increase in short-term PM2.5 concentration between men and women was not significant (-0.09; 95% CI, -0.38 to 0.19). The differences in percent changes in hospitalization/ER visits between men and women were not significant for ischemic heart disease (0.07; 95% CI, -0.83 to 0.98) and cardiac arrest (1.85; 95% CI, -1.48 to 5.30). The GRADE assessment found that there was low quality of evidence for gender difference for the risks of CVD outcomes from PM2.5 exposure. A major limitation of the studies was the lack of measuring disparities in exposure between sex groups. CONCLUSIONS:This review of observational studies indicates there is currently very limited evidence of effect modification by sex/gender for the effects of PM2.5 on CVD outcomes in adults. KEYWORDS: Environmental disparities, Particulate matter, Long-term exposure, Short-term exposure, Cardiovascular diseases

Association between sepsis survivorship and long-term cardiovascular outcomes in adults: a systematic review and meta-analysis.

We aimed to determine the association between sepsis and long-term cardiovascular events. We conducted a systematic review of observational studies evaluating post-sepsis cardiovascular outcomes in adult sepsis survivors. MEDLINE, Embase, and the Cochrane Controlled Trials Register and Database of Systematic Reviews were searched from inception until April 21st, 2021. Two reviewers independently extracted individual study data and evaluated risk of bias. Random-effects models estimated the pooled crude cumulative incidence and adjusted hazard ratios (aHRs) of cardiovascular events compared to either non-septic hospital survivors or population controls. Primary outcomes included myocardial infarction, stroke, and congestive heart failure; outcomes were analysed at maximum reported follow-up (from 30days to beyond 5years post-discharge). Of 12,649 screened citations, 27 studies (25 cohort studies, 2 case-crossover studies) were included with a median of 4,289 (IQR 502-68,125) sepsis survivors and 18,399 (IQR 4,028-83,506) controls per study. The pooled cumulative incidence of myocardial infarction, stroke, and heart failure in sepsis survivors ranged from 3 to 9% at longest reported follow-up. Sepsis was associated with a higher long-term risk of myocardial infarction (aHR 1.77 [95% CI 1.26 to 2.48]; low certainty), stroke (aHR 1.67 [95% CI 1.37 to 2.05]; low certainty), and congestive heart failure (aHR 1.65 [95% CI 1.46 to 1.86]; very low certainty) compared to non-sepsis controls. Surviving sepsis may be associated with a long-term, excess hazard of late cardiovascular events which may persist for at least 5years following hospital discharge.

Invited Perspective: Metal Mixtures and Child Health: The Complex Interplay of Essential and Toxic Elements.

Invited Perspective: Metal Mixtures and Child Health: The Complex Interplay of Essential and Toxic Elements.