Lower Risk Of All-cause Mortality Research Articles

Association Between use of an Adaptive Cardiac Resynchronization Therapy Algorithm and Healthcare Utilization and Cost

To assess the association between use of adaptive pacing on clinical and economic outcomes of CRT recipients in a real-world analysis. The AdaptivCRTTM algorithm was shown in prior subgroup analyses of prospective trials to achieve clinical benefits, but a large prospective trial showed nonsignificant changes in the endpoint of mortality or heart failure hospitalizations. CRT-implanted patients from the Optum Clinformatics® database with ≥90 days of follow-up were included. Remote monitoring data was used to classify patients based on CRT setting - adaptive biventricular and left ventricular pacing (aCRT) vs. standard biventricular pacing (Standard CRT). Inverse probability of treatment weighting was used to adjust for baseline differences between groups. Mortality, 30-day readmissions, healthcare utilization, and payer and patient costs were evaluated post-implantation. This study included 2,412 aCRT and 1,638 Standard CRT patients (mean follow-up: 2.4 ± 1.4 years), with balanced baseline characteristics after adjustment. The aCRT group was associated with lower all-cause mortality (adjusted hazard ratio = 0.88 [95% confidence interval (CI):0.80, 0.96]), fewer all-cause 30-day readmissions (adjusted incidence rate ratio = 0.87 [CI:0.81, 0.94]), and fewer all-cause and HF-related inpatient, outpatient, and emergency department (ED) visits. The aCRT cohort was also associated with lower all-cause outpatient payer-paid amounts and lower all-cause and HF-related inpatient and ED patient-paid amounts. In this retrospective analysis of a large real-world cohort, use of an adaptive CRT algorithm was associated with lower mortality, reduced healthcare resource utilization, and lower payer and patient costs. While cardiac resynchronization therapy (CRT) improves quality of life and clinical outcomes for certain heart failure patients, some patients do not respond to this therapy. Adaptive CRT algorithms (aCRT), such as AdaptivCRTTM, have been developed with the goal of improving effectiveness of CRT, and consequently, clinical and economic outcomes. This research study used a large database of administrative claims data - which contains information on patient demographics, diagnoses, healthcare services received, mortality, and cost data - to compare clinical and economic outcomes between CRT patients with the aCRT algorithm turned on (aCRT group) and CRT patients with the aCRT algorithm turned off (standard CRT group). Statistical methods were used to adjust for baseline differences between the aCRT group and standard CRT groups. Ultimately, the aCRT group was found to have a lower risk of all-cause mortality, fewer all-cause 30-day readmissions, fewer hospital visits (including inpatient, outpatient, and emergency department visits), and lower costs to payers and patients for specific types of costs.

Outcomes and Hospital Service Use Among Patients With COPD in a Nurse- and Allied Health–Led Clinic

Multidisciplinary disease management efforts enable the improvement in lung function among patients with chronic obstructive pulmonary disease (COPD), but there is little evidence of its association with risks of adverse health outcomes and health care service use. To examine the association between the use of a nurse- and allied health-led primary care clinic for respiratory patients, namely the Nurse and Allied Health Clinic-Respiratory Care (NAHC-Respiratory), and their risks of mortality and morbidity and health care service use. This territory-wide, population-based, propensity-matched, retrospective cohort study used data from the electronic health records of all patients who used public health care services in Hong Kong, China, from January 1, 2010, to December 31, 2019. All patients with COPD treated in public outpatient clinics between January 1, 2010, and December 31, 2014, were included. Patients who attended NAHC-Respiratory and usual care only were propensity score-matched at a 1:2 ratio. Data analyses were conducted between August 2023 and April 2024. Attendance at NAHC-Respiratory. All-cause and cause-specific mortality, incidence of COPD complications, and use of emergency department and inpatient services until the end of 2019 were compared between the NAHC-Respiratory and usual care participants using Cox proportional hazard regression, Poisson regression, and log-link gamma regression models after matching. This study included 9048 eligible patients after matching, including 3093 in the exposure group (2814 [91.0%] men; mean [SD] age, 69.8 [9.5] years) and 5955 in the reference group (5431 [91.2%] men; mean [SD] age, 69.5 [11.7] years). Compared with patients in the usual care-only group (reference), patients in the exposure group had lower risks of all-cause mortality (hazard ratio [HR], 0.84; 95% CI, 0.78-0.90) as well as pneumonia-caused (HR, 0.85; 95% CI, 0.74-0.97), respiratory-caused (HR, 0.86; 95% CI, 0.77-0.96), and cardiovascular-caused (HR, 0.74; 95% CI, 0.59-0.93) mortality. Exposure was associated with reduced rates of emergency department visits (incidence rate ratio [IRR], 0.92; 95% CI, 0.86-0.98) and hospitalization through emergency department (IRR, 0.89; 95% CI, 0.83-0.95). In this cohort study, the use of a nurse- and allied health-led clinic in primary care settings was associated with reduced risks of mortality and use of hospital services among patients with COPD. These findings emphasize the important role of health care workers other than physicians in disease management in the primary care setting. The NAHC-Respiratory model and service components can be used to help improve primary care programs to benefit more patients with COPD.

Association between alcohol consumption and all-cause mortality, cardiovascular disease, and chronic kidney disease: A prospective cohort study.

In recent years, significant progress has been achieved in comprehending the impact of alcohol consumption on adverse health outcomes. However, the quality of evidence remains limited. Our objective was to conduct a prospective study examining the relationship between different types of alcoholic beverages and the risk of all-cause mortality, cardiovascular disease (CVD), and chronic kidney disease (CKD), and identifying the thresholds of safe dose stratified by sex using data from the UK Biobank. 502,490 participants were enrolled. These participants were initially registered between 2006 and 2010, and underwent reassessment between 2012 and 2013. All participants completed a detailed questionnaire on their alcohol consumption, including total alcohol consumption yesterday, weekly consumption of red wine, champagne plus white wine, beer, spirits, and fortified wine. All-cause mortality and the incidence of CVD and CKD were considered as the primary outcomes. 2852 participants reported CKD during a median follow-up period of 11.94 years, while 79,958 participants reported CVD over a median follow-up period of 11.35 years. Additionally, 18,923 participants died over a median follow-up period of 11.89 years. After adjusting for variables such as age, sex, education level, smoking status, diet score, and exercise score, total alcohol consumption showed a U-shaped relationship with the risk of CVD and all-cause mortality, but showed an inverse association with the risk of CKD. Upon further classification of alcoholic beverages, our analysis revealed that red wine, champagne plus white wine, beer, spirits, and fortified wine presented a U-shaped relationship with the risk of all-cause mortality and CKD. However, spirits were positively associated with the risk of CVD, only red wine, champagne plus white wine, beer, and fortified wine showed a U-shaped relationship with the risk of CVD. The safe doses of total alcohol consumption should be < 11 g/d for males and < 10 for females, red wine consumption should be < 7 glasses/week for males and < 6 for females, champagne plus white wine consumption should be < 5 glasses/week, and fortified wine consumption should be < 4 glasses/week. Red wine, champagne plus white wine, beer, and fortified wine below the corresponding thresholds of safe dose in our analysis were significantly associated with a lower risk of all-cause mortality, CVD, and CKD. And these alcoholic beverages under safe doses exhibited a protective effect against conditions like diabetes, depression, dementia, epilepsy, liver cirrhosis, and other digestive diseases, while didn't increase the risk of cancer.

Coffee consumption and cardiometabolic health: a comprehensive review of the evidence.

This review provides a comprehensive synthesis of longitudinal observational and interventional studies on the cardiometabolic effects of coffee consumption. It explores biological mechanisms, and clinical and policy implications, and highlights gaps in the evidence while suggesting future research directions. It also reviews evidence on the causal relationships between coffee consumption and cardiometabolic outcomes from Mendelian randomization (MR) studies. Findings indicate that while coffee may cause short-term increases in blood pressure, it does not contribute to long-term hypertension risk. There is limited evidence indicating that coffee intake might reduce the risk of metabolic syndrome and non-alcoholic fatty liver disease. Furthermore, coffee consumption is consistently linked with reduced risks of type 2 diabetes (T2D) and chronic kidney disease (CKD), showing dose-response relationships. The relationship between coffee and cardiovascular disease is complex, showing potential stroke prevention benefits but ambiguous effects on coronary heart disease. Moderate coffee consumption, typically ranging from 1 to 5 cups per day, is linked to a reduced risk of heart failure, while its impact on atrial fibrillation remains inconclusive. Furthermore, coffee consumption is associated with a lower risk of all-cause mortality, following a U-shaped pattern, with the largest risk reduction observed at moderate consumption levels. Except for T2D and CKD, MR studies do not robustly support a causal link between coffee consumption and adverse cardiometabolic outcomes. The potential beneficial effects of coffee on cardiometabolic health are consistent across age, sex, geographical regions, and coffee subtypes and are multi-dimensional, involving antioxidative, anti-inflammatory, lipid-modulating, insulin-sensitizing, and thermogenic effects. Based on its beneficial effects on cardiometabolic health and fundamental biological processes involved in aging, moderate coffee consumption has the potential to contribute to extending the healthspan and increasing longevity. The findings underscore the need for future research to understand the underlying mechanisms and refine health recommendations regarding coffee consumption.

Associations of metabolic changes and polygenic risk scores with cardiovascular outcomes and all-cause mortality across BMI categories: a prospective cohort study

BackgroundAssociations between metabolic status and metabolic changes with the risk of cardiovascular outcomes have been reported. However, the role of genetic susceptibility underlying these associations remains unexplored. We aimed to examine how metabolic status, metabolic transitions, and genetic susceptibility collectively impact cardiovascular outcomes and all-cause mortality across diverse body mass index (BMI) categories.MethodsIn our analysis of the UK Biobank, we included a total of 481,576 participants (mean age: 56.55; male: 45.9%) at baseline. Metabolically healthy (MH) status was defined by the presence of < 3 abnormal components (waist circumstance, blood pressure, blood glucose, triglycerides, and high-density lipoprotein cholesterol). Normal weight, overweight, and obesity were defined as 18.5 ≤ BMI < 25 kg/m2, 25 ≤ BMI < 30 kg/m2, and BMI ≥ 30 kg/m2, respectively. Genetic predisposition was estimated using the polygenic risk score (PRS). Cox regressions were performed to evaluate the associations of metabolic status, metabolic transitions, and PRS with cardiovascular outcomes and all-cause mortality across BMI categories.ResultsDuring a median follow-up of 14.38 years, 31,883 (7.3%) all-cause deaths, 8133 (1.8%) cardiovascular disease (CVD) deaths, and 67,260 (14.8%) CVD cases were documented. Among those with a high PRS, individuals classified as metabolically healthy overweight had the lowest risk of all-cause mortality (hazard ratios [HR] 0.70; 95% confidence interval [CI] 0.65, 0.76) and CVD mortality (HR 0.57; 95% CI 0.50, 0.64) compared to those who were metabolically unhealthy obesity, with the beneficial associations appearing to be greater in the moderate and low PRS groups. Individuals who were metabolically healthy normal weight had the lowest risk of CVD morbidity (HR 0.54; 95% CI 0.51, 0.57). Furthermore, the inverse associations of metabolic status and PRS with cardiovascular outcomes and all-cause mortality across BMI categories were more pronounced among individuals younger than 65 years (Pinteraction < 0.05). Additionally, the combined protective effects of metabolic transitions and PRS on these outcomes among BMI categories were observed.ConclusionsMH status and a low PRS are associated with a lower risk of adverse cardiovascular outcomes and all-cause mortality across all BMI categories. This protective effect is particularly pronounced in individuals younger than 65 years. Further research is required to confirm these findings in diverse populations and to investigate the underlying mechanisms involved.Graphical abstract

Association between dietary patterns and the risk of all-cause mortality among old adults with obstructive sleep apnea

BackgroundObstructive sleep apnea (OSA) was associated with the increased cardiovascular events and all-cause mortality. And anti-inflammatory dietary has potential to improve the prognosis of OSA. This study aimed to investigate the association of anti-inflammatory dietary patterns with all-cause mortality among individuals with OSA.MethodsThis retrospective cohort study involved 1522 older adults with OSA from 2005 to 2008 in the National Health and Nutrition Examinations Survey (NHANES). Mortality status was determined by routine follow-up through December 31, 2019, using the National Death Index. Anti-inflammatory dietary patterns included Alternate Mediterranean Diet Score (aMED), Healthy Eating Index-2015 (HEI-2015), and Alternate Healthy Eating Index-2010 (AHEI-2010). Weighted Cox proportional hazard regression models were performed to investigate the association between anti-inflammatory dietary pattern and all-cause mortality.ResultsAfter a median follow-up of 131 months, 604 participants were recorded all-cause mortality. The mean age of OSA patients was 68.99 years old, of whom 859 were male (52.34%). Higher adherence of aMED (HR = 0.61, 95%CI: 0.48 to 0.78) and HEI-2015 (HR = 0.75, 95%CI: 0.60 to 0.95) were associated with lower all-cause mortality risk in the elderly with OSA. Conversely, no association was found between AHEI-2010 dietary pattern and all-cause mortality in individuals with OSA. In the component analysis of aMED, it was found that a higher intake of vegetables and olive oil potentially contributes to the reduction all-cause mortality risk in the elderly with OSA (HR = 0.60, 95%CI: 0.48 to 0.76; HR = 0.67, 95%CI: 0.63 to 0.71).ConclusionHigher adherence to the aMED and the HEI-2015 was associated with a lower risk of all-cause mortality in OSA. Future interventions in the elderly with OSA should considering adopting anti-inflammatory dietary patterns.

Distinct Comorbidity Clusters in Patients With Acute HeartFailure: Data From RELAX-AHF-2.

Multimorbidity frequently occurs in patients with acute heart failure (AHF). The co-occurrence of comorbidities often follows specific patterns. This study investigated multimorbidity subtypes and their associations with clinical outcomes. From the prospective RELAX-AHF-2 (Relaxin for the Treatment of Acute Heart Failure-2) trial, 6,545 patients (26% with HF with preserved ejection fraction, defined as LVEF≥50%) were classified into multimorbidity groups using latent class analysis. The association between subgroups and clinical outcomes was examined. Validation of these findings was conducted in the RELAX-AHF trial, which comprised 1,161 patients. Five distinct multimorbidity groups emerged: 1) diabetes and chronic kidney disease (CKD) (often male, high prevalence of CKD and diabetes mellitus); 2) ischemic (ischemic HF); 3) elderly/atrial fibrillation (AF) (oldest, high prevalence of AF); 4) metabolic (obese, hypertensive, more often HF with preserved ejection fraction); and 5) young (fewest comorbidities). After adjusting for confounders, patients in the diabetes and CKD (HR: 1.80; 95%CI: 1.50-2.20), elderly/AF (HR: 1.42; 95%CI: 1.20-1.70), and metabolic (HR: 1.40; 95%CI: 1.20-1.80) groups had higher rates of the composite outcome than patients in the young group, primarily driven by differences in rehospitalization. Treatment allocation (placebo or serelaxin) modified these associations (Pinteraction<0.001). Serelaxin-treated patients in the young group were associated with a lower risk for all-cause mortality (HR: 0.59; 95%CI: 0.40-0.90). Similarly, patients from the RELAX-AHF trial clustered in 5 multimorbidity groups. The clinical characteristics and associations with outcomes could also be validated. Comorbidities naturally clustered into 5 mutually exclusive groups in RELAX-AHF-2, showing variations in clinical outcomes. These data emphasize that the specific combination of comorbidities can influence adverse outcomes and treatment responses in patients with AHF.

Association of Life's essential 8 score with the risk of all-cause mortality and cardio-cerebrovascular mortality in patients with stroke.

A higher Life's Essential 8 (LE8)-based cardiovascular health (CVH) has been reported to be associated with a lower risk of both all-cause mortality and cardio-cerebrovascular diseases (CCVDs) related mortality in adults in the United States. At the same time, multiple studies have shown a significant negative association of CVH with the risk of stroke and CCVDs. Since no research has investigated the applicability of the LE8 in stroke patients, this study aimed to explore the association of LE8 with all-cause mortality and cardio-cerebrovascular mortality in stroke patients. Data of patients were extracted from the National Health and Nutrition Examination Surveys (NHANES) database in 2007-2018 in this retrospective cohort study. Weighted univariate and multivariate COX regression analyses were utilized to investigate the associations of LE8 with all-cause mortality and cardio-cerebrovascular mortality. We further explored these relationships in subgroups of age, gender, body mass index (BMI), cancer, congestive heart failure (CHF), and coronary heart disease (CHD). The evaluation indexes were hazard ratios (HRs) and 95% confidence intervals (CIs). Among the eligible patients, 278 died from all-cause and 89 (8.38%) of them died due to CCVDs. After adjusting for covariates, patients with LE8 score ≥ 58.75 seemed to have both lower risk of all-cause mortality (HR = 0.46, 95%CI: 0.31-0.69) and cardio-cerebrovascular mortality (HR = 0.51, 95%CI: 0.26-0.98), comparing to those with LE8 score < 48.123. Higher LE8 scores were associated with lower risk of all-cause mortality in patients aged < 65years old, without cancer, and whatever the gender, BMI, CHF or CHD conditions (all P < 0.05). The relationships between high LE8 scores and low cardio-cerebrovascular mortality risk were only found in age < 65years old and non-cancer subgroups (all P < 0.05). A higher LE8 score was associated with lower risk of both all-cause mortality and cardio-cerebrovascular mortality in patients with stroke, which may provide some reference for risk management and prognosis improvement in stoke. However, more evidences are needed to verify this beneficial role of high LE8 score in stroke prognosis.

Associations of vitamin D status with all-cause and cause-specific mortality in long-term prescription opioid users.

This study aimed to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) concentrations and mortality in long-term prescription opioid users. The study included 1856 long-term prescription opioid users from the National Health and Nutrition Examination Survey (NHANES, 2001-2018). Mortality status were determined by matching with the National Death Index (NDI) records until December 31, 2019. Multivariable Cox proportional hazard models were constructed to assess the association. Over a median follow-up period of 7.75 years, there were 443 cases of all-cause mortality, including 135 cardiovascular disease (CVD) deaths and 94 cancer deaths. After multivariable adjustment, participants with serum 25(OH)D concentrations within 50.00 to <75.00 nmol/L and ≥ 75 nmol/L had a lower risk of all-cause mortality, with hazard ratios (HRs) of 0.50 (95% confidence interval [CI] 0.29, 0.86) and 0.54 (95% CI 0.32, 0.90), respectively. Nevertheless, no significant association was found between serum 25(OH)D concentrations and the risk of CVD or cancer mortality. The RCS analysis revealed a non-linear association of serum 25(OH)D concentration with all-cause mortality (p for non-linear = 0.01). Per 1-unit increment in those with serum 25(OH)D concentrations <62.17 nmol/L corresponded to a 2% reduction in the risk of all-cause mortality (95% CI 0.97, 1.00), but not changed significantly when 25(OH)D concentrations ≥62.17 nmol/L. In conclusion, a non-linear association existed between serum 25(OH)D concentrations and all-cause mortality in long-term prescription opioid users. Maintaining serum 25(OH)D concentrations ≥62.17 nmol/L may be beneficial in preventing all-cause mortality in this population.

Diuretic prescriptions in the first year of haemodialysis: international practice patterns and associations with outcomes.

The use of diuretics in patients on haemodialysis (HD) is thought to maintain diuresis. However, this assumption and the optimal dose are based on little scientific evidence, and associations with clinical outcomes are unclear. We reported international variations in diuretic use and loop diuretic dose across 27759 HD patients with dialysis vintage <1year in the Dialysis Outcomes and Practice Patterns Study phases 2-5 (2002-2015), a prospective cohort study. Doses of torsemide (4:1) and bumetanide (80:1) were converted to oral furosemide-equivalent doses. Adjusted Cox, logistic and linear regressions were used to investigate the association of diuretic use and dose with outcomes. Diuretic utilization varied widely by country at vintage <3months, ranging from >80% in Germany and Sweden to <35% in the USA, at a median dose ranging from 400-500mg/day in Germany and Sweden to <100mg/day in Japan and the USA. Neither diuretic use nor higher doses were associated with a lower risk of all-cause mortality, a higher risk of hospitalization for fracture or elevated parathyroid hormone levels, but the prescription of higher doses (>200mg/day) was associated with a higher risk of all-cause hospitalization. Substantial international differences exist in diuretic prescriptions, with use and doses much higher in some European countries than the USA. The prescription and higher doses of loop diuretics was not associated with improved outcomes.

Associations between enteral nutrition and outcomes in the SUP-ICU trial: Results of exploratory post hoc analyses.

Enteral nutrition may affect risks of gastrointestinal bleeding, pneumonia and mortality in critically ill patients and may also modify the effects of pharmacological stress ulcer prophylaxis. We undertook post hoc analyses of the stress ulcer prophylaxis in the intensive care unit trial to assess for any associations and interactions between enteral nutrition and pantoprazole. Extended Cox models with time-varying co-variates and competing events were used to assess potential associations, adjusted for baseline severity of illness. Potential interactions between daily enteral nutrition and allocation to pantoprazole on outcomes were similarly assessed. Enteral nutrition was associated with lower risk of clinically important gastrointestinal bleeding (cause-specific hazard ratio [HR]: 0.29, 95% confidence interval: [CI] 0.19-0.44, p < .001), higher risk of pneumonia (HR: 1.44, 95% CI: 1.14-1.82, p = .003), and lower risk of all-cause mortality (HR: 0.22, 95% CI: 0.18-0.27, p < .001). Enteral nutrition with allocation to pantoprazole was associated with a lower risk of mortality (HR: 0.27, 95% CI: 0.21-0.35, p < .001), similar to enteral nutrition with allocation to placebo (HR: 0.17, 95% CI: 0.13-0.23, p < .001). Allocation to pantoprazole with no enteral nutrition had little effect on mortality (HR: 0.83, 95% CI: 0.63-1.09, p = .179), whilst allocation to pantoprazole and receipt of enteral nutrition was mostly compatible with increased all-cause mortality (HR: 1.27, 95% CI: 0.99-1.64, p = .061). The test of interaction between enteral nutrition and pantoprazole treatment allocation for all-cause mortality was statistically significant (p = .024). Enteral nutrition was associated with an increased risk of pneumonia and a reduced risk of gastrointestinal bleeding. The interaction between pantoprazole and enteral nutrition suggesting an increased risk of mortality requires further study.

Complete versus partial revascularization for older adults with acute coronary syndrome: a meta-analysis and systematic review of randomized and multivariable adjusted data.

Evidence from randomized studies support complete over culprit-only revascularization for patients with acute coronary artery syndrome (ACS) and multivessel coronary artery diseases (MVD). Whether these findings extend to elderly patients, however, has not been thoroughly explored. We conducted a systematic review and meta-analysis comparing clinical outcomes of elderly individuals (defined as age ≥75 years) with ACS and MVD submitted to complete vs partial-only percutaneous coronary intervention (PCI). PubMed, Embase, and Cochrane were searched. We computed pooled hazard ratios with 95% confidence intervals (CI) to preserve time time-to-event data. We included 7 studies, of which 2 were RCT and 5 were multivariable adjusted cohorts, comprising a total 10 147, of whom 43.8% underwent complete revascularization. As compared with partial-only PCI, complete revascularization was associated with a lower all-cause mortality (hazard ratio 0.71; 95% CI 0.60-0.85; P < 0.01), cardiovascular mortality (hazard ratio 0.64; 95% CI 0.52-0.79; P < 0.01), and recurrent myocardial infarction (hazard ratio 0.65; 95% CI 0.50-0.85; P < 0.01). There was no significant difference between groups regarding the risk of revascularizations (hazard ratio 0.80; 95% CI 0.53-1.20; P = 0.28). Among elderly patients with ACS and multivessel CAD, complete revascularization is associated with a lower risk of all-cause mortality, cardiovascular mortality, and recurrent myocardial infarction.

Prognosis and Treatment Strategies for Atrial Fibrillation in Heart Failure with Mildly Reduced Ejection Fraction.

The study investigates the prognosis of atrial fibrillation (AF) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Data concerning the prognostic impact of AF in patients with HFmrEF is scarce. Consecutive patients with HFmrEF (i.e., left ventricular ejection fraction 41-49% and signs and/or symptoms of HF) were retrospectively included at one institution from 2016 to 2022. Patients with AF were compared to patients without with regard to the primary composite endpoint of all-cause mortality and HF-related rehospitalization at 30 months (median follow-up). Statistical analyses included Kaplan-Meier analyses, multivariable Cox proportional regression analyses and propensity score matching. 2,148 patients with HFmrEF were included with an overall prevalence of AF of 43%. The presence of AF was associated with higher risk of the primary composite endpoint all-cause mortality and HF-related rehospitalization at 30 months (HR = 2.068; 95% CI 1.802-2.375; p = 0.01), which was confirmed after propensity-score matching (HR = 1.494; 95% CI 1.216-1.835; p = 0.01). AF was an independent predictor of both all-cause mortality (HR = 1.340; 95% CI 1.066-1.685; p = 0.01) and HF-related rehospitalization (HR = 2.061; 95% CI 1.538-2.696; p = 0.01). Finally, rhythm control may be associated with lower risk of all-cause mortality compared to rate control for AF (HR = 0.342; 95% CI 0.199-0.587; p = 0.01). AF affects 43% of patients with HFmrEF and represents an independent predictor of adverse long-term prognosis.

Unveiling the influence of SGLT2 inhibitors on clinical outcomes in patients with cancer with therapy-related cardiac dysfunction: A meta-analysis and systemic review.

e24003 Background: Cancer patients undergoing chemotherapy suffer from a variable degree of cancer therapy–related cardiac dysfunction and heart failure (HF). It is known that sodium glucose co-transporter 2 (SGLT2) inhibitors improve outcomes in patients with HF independent of diabetes mellitus and left ventricular ejection fraction; our study aims to investigate the potential benefits of SGLT2 inhibitory therapy specifically in cancer patients undergoing chemotherapy. Methods: We performed an electronic search on PubMed, Embase, and Cochrane, from the inception of databases till January 29, 2024, to identify all the articles that compared the use of SGLT2 inhibitors in adult (≥18 years) with type 2 diabetes mellitus and exposure to cardiotoxic antineoplastic therapy, subsequently diagnosed with cardiomyopathy, heart failure, or LVEF &lt; 40%. The data was extracted and pooled using a random effects model to calculate the odds ratio (OR) with a respective 95% confidence interval (CI). R software (v.4.3) was used for all statistical analyses. Results: Our search identified three observational studies with a total of 3,164 patients (SGLT2- inhibitor group: 1,550; Control group: 1,614). We found that the use of SGLT2 inhibitors was associated with a lower risk of all-cause mortality (OR: 0.25 [0.20, 0.31]; I2 = 16%; p &lt; 0.001), hospitalizations from heart failure (OR: 0.25 [0.10, 0.62]; I2 = 0%; p = 0.003), and acute exacerbation of heart failure (OR: 0.35 [0.27, 0.47]; I2 = 0%; p &lt; 0.001). Conclusions: Our findings suggest a favorable association between the use of SGLT2 inhibitors and reduced mortality, as well as improved cardiac clinical outcomes in cancer patients undergoing chemotherapy. However, further validation through large-scale studies and randomized controlled trials across diverse malignancies is warranted to establish the efficacy of these drugs. [Table: see text]

Mediterranean Diet Adherence and Risk of All-Cause Mortality in Women

Higher adherence to the Mediterranean diet has been associated with reduced risk of all-cause mortality, but data on underlying molecular mechanisms over long follow-up are limited. To investigate Mediterranean diet adherence and risk of all-cause mortality and to examine the relative contribution of cardiometabolic factors to this risk reduction. This cohort study included initially healthy women from the Women's Health Study, who had provided blood samples, biomarker measurements, and dietary information. Baseline data included self-reported demographics and a validated food-frequency questionnaire. The data collection period was from April 1993 to January 1996, and data analysis took place from June 2018 to November 2023. Mediterranean diet score (range, 0-9) was computed based on 9 dietary components. Thirty-three blood biomarkers, including traditional and novel lipid, lipoprotein, apolipoprotein, inflammation, insulin resistance, and metabolism measurements, were evaluated at baseline using standard assays and nuclear magnetic resonance spectroscopy. Mortality and cause of death were determined from medical and death records. Cox proportional hazards regression was used to calculate hazard ratios (HRs) for Mediterranean diet adherence and mortality risk, and mediation analyses were used to calculate the mediated effect of different biomarkers in understanding this association. Among 25 315 participants, the mean (SD) baseline age was 54.6 (7.1) years, with 329 (1.3%) Asian women, 406 (1.6%) Black women, 240 (0.9%) Hispanic women, 24 036 (94.9%) White women, and 95 (0.4%) women with other race and ethnicity; the median (IQR) Mediterranean diet adherence score was 4.0 (3.0-5.0). Over a mean (SD) of 24.7 (4.8) years of follow-up, 3879 deaths occurred. Compared with low Mediterranean diet adherence (score 0-3), adjusted risk reductions were observed for middle (score 4-5) and upper (score 6-9) groups, with HRs of 0.84 (95% CI, 0.78-0.90) and 0.77 (95% CI, 0.70-0.84), respectively (P for trend < .001). Further adjusting for lifestyle factors attenuated the risk reductions, but they remained statistically significant (middle adherence group: HR, 0.92 [95% CI, 0.85-0.99]; upper adherence group: HR, 0.89 [95% CI, 0.82-0.98]; P for trend = .001). Of the biomarkers examined, small molecule metabolites and inflammatory biomarkers contributed most to the lower mortality risk (explaining 14.8% and 13.0%, respectively, of the association), followed by triglyceride-rich lipoproteins (10.2%), body mass index (10.2%), and insulin resistance (7.4%). Other pathways, including branched-chain amino acids, high-density lipoproteins, low-density lipoproteins, glycemic measures, and hypertension, had smaller contributions (<3%). In this cohort study, higher adherence to the Mediterranean diet was associated with 23% lower risk of all-cause mortality. This inverse association was partially explained by multiple cardiometabolic factors.

Epigenetic Age Mediates the Association of Life's Essential 8 With Cardiovascular Disease and Mortality.

Life's Essential 8 (LE8) is an enhanced metric for cardiovascular health. The interrelations among LE8, biomarkers of aging, and disease risks are unclear. LE8 score was calculated for 5682 Framingham Heart Study participants. We implemented 4 DNA methylation-based epigenetic age biomarkers, with older epigenetic age hypothesized to represent faster biological aging, and examined whether these biomarkers mediated the associations between the LE8 score and cardiovascular disease (CVD), CVD-specific mortality, and all-cause mortality. We found that a 1 SD increase in the LE8 score was associated with a 35% (95% CI, 27-41; P=1.8E-15) lower risk of incident CVD, a 36% (95% CI, 24-47; P=7E-7) lower risk of CVD-specific mortality, and a 29% (95% CI, 22-35; P=7E-15) lower risk of all-cause mortality. These associations were partly mediated by epigenetic age biomarkers, particularly the GrimAge and the DunedinPACE scores. The potential mediation effects by epigenetic age biomarkers tended to be more profound in participants with higher genetic risk for older epigenetic age, compared with those with lower genetic risk. For example, in participants with higher GrimAge polygenic scores (greater than median), the mean proportion of mediation was 39%, 39%, and 78% for the association of the LE8 score with incident CVD, CVD-specific mortality, and all-cause mortality, respectively. No significant mediation was observed in participants with lower GrimAge polygenic score. DNA methylation-based epigenetic age scores mediate the associations between the LE8 score and incident CVD, CVD-specific mortality, and all-cause mortality, particularly in individuals with higher genetic predisposition for older epigenetic age.

Blood urea nitrogen/creatinine ratio in heart failure: Systematic review and meta-analysis.

The meta-analysis is to evaluate the predictive value of the blood urea nitrogen / creatinine ratio (BCR) for long-term outcomes in patients with heart failure (HF). PubMed, EMBASE, the Cochrane library, and Web of Science were searched for relevant studies from inception to October 2023. STATA SE 14.0 software was used for statistical analysis. A total of 2036 reports were identified with 14 studies meeting pre-designed inclusion criteria. Three long-term outcomes were investigated. In patients with HF, the increase of BCR level indicated a greater risk of all-cause mortality (HR = 1.67, 95% CI 1.38-2.00; I2 = 90.8%, P = 0.000). The acute HF (AHF) subgroup demonstrated a higher risk of all-cause mortality (HR = 1.79, 95% CI 1.15-2.79; I2 = 93.9%, P = 0.000) as did the non-AHF subgroup (HR = 1.51, 95% CI 1.34-1.71; I2 = 37.1%, P = 0.122). The subgroup (≤ 70 years old) demonstrated a lower risk of all-cause mortality in patients with HF (HR = 1.62, 95% CI 1.35-1.94; I2 = 68.3%, P = 0.004) as did the subgroup (> 70 years old) (HR = 1.67, 95% CI 1.19-2.34; I2 = 88.3%, P = 0.000). In addition, this study did not support the predictive value of BCR in CVD mortality (HR = 1.48, 95% CI 0.91-2.43; I2 = 63%, P = 0.100) and HF hospitalization (HR = 1.28, 95% CI 0.73-2.24; I2 = 77.5%, P = 0.035). Sensitivity analysis showed that all the results were robust. In summary, the results showed that the blood urea nitrogen / creatinine ratio (BCR) had a significant predictive value for all-cause mortality in patients with heart failure and was a fairly promising predictor obviously. Moreover, more studies are needed to further determine the predictive value of BCR in other long-term outcomes such as CVD mortality, HF hospitalization or aborted cardiac arrest.

Systematic review and meta-analysis comparing cardiac resynchronization therapy with versus without defibrillation in patients with non-ischemic cardiomyopathy

Abstract Background Cardiac resynchronization therapy (CRT) stands as a notable medical breakthrough for individuals with heart failure and electrical desynchrony. This intervention aims to alleviate symptoms, diminish hospitalization rates, and enhance overall survival, both in conjunction with and without implantable cardioverter-defibrillator (ICD) therapy. Despite these advancements, the role of defibrillator therapy in addition with CRT for patients with non-ischemic cardiomyopathy (NICM) remains a topic of debate. Objective To assess and compare the outcomes of individuals diagnosed with NICM who have underwent CRT with implantable cardioverter-defibrillator (CRT-D) against those who received CRT with a pacemaker only (CRT-P). Methods We conducted a systematic search of PubMed, Embase and Cochrane database during August 2023 for studies comparing CRT-P and CRT-D in patients with nonischemic cardiomyopathy. Results Thirteen studies, including two randomized clinical trials, were incorporated, with a total of 61,326 patients providing 16,446 pooled death events (9,108 in CRT-D and 7,338 in CRT-P). The meta-analysis revealed that CRT-D was associated with a significantly lower risk of all-cause mortality compared to CRT-P (pooled HR 0.74; 95% CI: 0.62-0.88; I2=84%). Subgroup analysis focusing on propensity score-matched studies yielded consistent findings (pooled HR 0.82; 95% CI: 0.77-0.87; I² = 0%, P&amp;lt;0.001). However, subgroup analysis for patients older than 75 years suggested no statistically significant difference in mortality risk within this specific age group (pooled HR 0.96; 95% CI: 0.811-1.15; I² = 39%, P&amp;lt;0.001). Regarding the secondary endpoint of cardiovascular mortality, no significant risk reduction with CRT-D was observed (pooled HR 0.70; 95% CI: 0.49-1.01; I² = 92%), albeit with high heterogeneity. Conclusion Our study suggests that the addition of defibrillator therapy significantly reduces all-cause mortality in CRT-eligible patients with NICM, although results were not observed for patients older than 75 years.All-cause MortalityPatients older 75 years old

#853 Kidney-protective medication and risk of adverse clinical outcomes in patients with chronic kidney disease: preliminary findings from DISCOVER CKD

Abstract Background and Aims Renin-angiotensin-system inhibitors (RASi) have been a foundational therapy in chronic kidney disease (CKD) for several decades. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have also emerged as a critical disease-modifying therapy in CKD, with contemporary data from trials showing SGLT2i to significantly improve kidney and cardiovascular (CV) outcomes in patients with or without diabetes. Nonetheless, several studies have revealed sub-optimal prescribing of RASi and/or SGLT2i therapy (both herein referred to as kidney-protective medication) in patients with CKD. Using prospective data from the DISCOVER CKD study, we conducted an exploratory analysis to assess the association of kidney-protective medication real-world use with mortality risk, CV events (fatal and non-fatal), and hospitalisation in patients with CKD. Method DISCOVER CKD (NCT04034992) is a multi-country, non-interventional cohort study designed to characterise the epidemiology of CKD, including describing patient characteristics, disease progression, clinical outcomes, patient journey, practice patterns, and clinical management. In the prospective phase, patients with CKD were recruited from the UK, USA, Spain, Italy, Sweden and Japan between September 2019 and June 2022. Clinical data were extracted manually from patients’ health records into a standardised case report form. The current analysis includes 12 months’ follow-up data. A Cox proportional hazards model was used to compare the risk of all-cause mortality and CV events and a negative binomial regression model was used to compare the risk of all-cause hospitalisation between patients receiving and not receiving kidney-protective medication at baseline, with adjustments for age, sex, CKD stage, diabetes mellitus, hyperkalaemia, and heart failure. DISCOVER CKD received research ethics board approval, and informed consent was obtained from all patients. Results Of the 1052 patients enrolled in DISCOVER CKD, 643 (61.1%) were receiving kidney-protective medication in the form of RASi (n = 618) and SGLT2i (n = 147) at baseline. The mean age of participants receiving and not receiving kidney-protective medication was 62.4 years and 62.7 years, respectively; 34.4% and 40.8%, respectively, were female. Most patients had CKD stage 3A (n = 332, 31.6%) or 3B (n = 308, 29.3%), and 8.4% (n = 88) had ongoing dialysis. Body mass index (30.4 vs 29.4 kg/m2) and blood pressure were similar for those receiving kidney-protective medication versus those who were not. Laboratory assessments were also generally similar, although estimated glomerular filtration rate (eGFR; 40.9 vs 33.7 mL/min/1.73 m2) and haemoglobin (132.0 g/L vs 124.0 g/L) were higher in patients receiving kidney-protective medication versus those not. During the follow-up, patients receiving kidney-protective medication had a 67% lower risk of all-cause mortality (hazard ratio [HR] 0.33; 95% confidence interval [CI] 0.12–0.80, p = 0.019), and a 20% lower risk of all-cause hospitalisation (HR, 0.80; 95% CI 0.64–0.99, p = 0.042) compared with patients not receiving kidney-protective medication. In the population without pre-existing CV disease, a trend towards a lower rate of CV events was observed in patients with kidney-protective medication (CV events rates: 2.2 vs 3.2 per 100 person-years; HR, 0.38; 95% CI 0.12–1.08, p = 0.074 (Figure). Conclusion In this multinational CKD cohort, preliminary analysis indicates that using kidney-protective medication was associated with lower risks of adverse outcomes including death. Further analysis to mitigate potential confounding will be performed to confirm these preliminary findings.

Association of dietary inflammatory indices with sarcopenia and all-cause mortality in COPD patients

BackgroundSarcopenia frequently occurs as a comorbidity in individuals with COPD. However, research on the impact of Appendicular Skeletal Muscle Mass (ASM) on survival in COPD patients is scarce. Moreover, there is a lack of research on the association between dietary pro-inflammatory capacity and sarcopenia in COPD.MethodsWe analyzed data from the National Health and Nutrition Examination Survey (NHANES) covering the years 1999 to 2006 and 2011 to 2018. We aimed to investigate the relationship between the Dietary Inflammatory Index (DII) and sarcopenia prevalence among adults diagnosed with COPD in the United States. Furthermore, we sought to explore the relationship between sarcopenia, ASMI, and all-cause mortality. The study included a total of 1,429 eligible adult participants, divided into four groups based on quartiles of DII, with adjustments for sample weights. Methodologically, we used multivariable logistic regression analyses and to examine the association between DII and sarcopenia. Additionally, we used restricted cubic spline (RCS) tests to evaluate potential non-linear relationships. To assess the effect of sarcopenia on overall all-cause mortality, we used Kaplan–Meier models and Cox proportional hazards models. Moreover, we used RCS analyses to investigate potential non-linear relationships between ASMI and all-cause mortality. Subgroup analyses were conducted to confirm the reliability of our study findings.ResultsIn our COPD participant cohort, individuals with higher DII scores were more likely to be female, unmarried, have lower educational attainment, and show lower ASMI. Using multivariable logistic regression models, we found a positive association between the highest quartile of DII levels and sarcopenia incidence [Odds Ratio (OR) 2.37; 95% Confidence Interval (CI) 1.26–4.48; p = 0.01]. However, analysis of RCS curves did not show a non-linear relationship between DII and sarcopenia. Throughout the entire follow-up period, a total of 367 deaths occurred among all COPD patients. Kaplan–Meier survival curves showed a significantly higher all-cause mortality rate among individuals with concurrent sarcopenia (p &amp;lt; 0.0001). Cox proportional hazards model analysis showed a 44% higher risk of all-cause mortality among COPD patients with sarcopenia compared to those without sarcopenia [Hazard Ratio (HR): 1.44; 95% CI 1.05–1.99; p &amp;lt; 0.05]. Additionally, our final RCS analyses revealed a significant non-linear association between ASMI levels and all-cause mortality among COPD patients, with a turning point identified at 8.32 kg/m2. Participants with ASMI levels above this inflection point had a 42% lower risk of all-cause mortality compared to those with ASMI levels below it (HR 0.58; 95% CI 0.48–0.7).ConclusionWe observed a significant association between concurrent sarcopenia and an increased risk of all-cause mortality in COPD patients within the United States. Moreover, ASMI demonstrated a non-linear association with all-cause mortality, with a critical threshold identified at 8.32 kg/m2. Our findings also revealed an association between DII and the presence of sarcopenia. Consequently, further investigations are warranted to explore the feasibility of dietary DII adjustments as a means to mitigate muscle wasting and enhance the prognosis of COPD.