Lower Risk Of All-cause Mortality Research Articles

Association of Oral Microbiome Diversity and All-Cause Mortality in the General US Population and in Individuals With Chronic Diseases: A Prospective Cohort Study.

To investigate whether oral microbiome diversity is associated with all-cause mortality in the general US population and in individuals with chronic diseases. We included 8224 individuals with oral microbiome diversity data from the National Health and Nutrition Examination Survey (2009-2012), representing 164,000,205 US adults, using a survey-weighted analysis method. Cox regression analyses were performed to identify the association between oral microbiome diversity and all-cause mortality. During a survey-weighted mean follow-up period of 8.86 years, 429 all-cause deaths (survey-weighted number: 7,124,920) occurred in 8224 participants. Cox regression analysis revealed that higher oral microbiome diversity was significantly associated with a lower all-cause mortality risk. Significant differences in all-cause mortality risk were observed among the different clusters based on oral microbiome β-diversity (log-rank p < 0.001). Subgroup analyses revealed that the oral microbiome diversity was independently associated with all-cause mortality in individuals with diabetes mellitus and hypertension. A multivariate logistic regression model showed that current smoking and antibiotic use were significantly associated with lower oral microbiome α diversity. Higher oral microbiome diversity was significantly associated with a lower all-cause mortality risk in the general US population and in individuals with diabetes mellitus and hypertension.

Long-term safety and efficacy of glucagon-like peptide-1 receptor agonists in individuals with obesity and without type 2 diabetes: A global retrospective cohort study.

We aimed to investigate the long-term impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on thyroid function, cardiovascular health, renal outcomes and adverse events in individuals with obesity and without type 2 diabetes (T2D). In this observational cohort study, we used propensity score matching to construct comparable cohorts of individuals with obesity and without T2D who were new to GLP-1 RA treatment and those who did not receive glucose-lowering medications. In total, 3,729,925 individuals with obesity were selected from the TriNetX Global Network, with an index event between 1 January 2016 and 31 March 2024. The primary outcomes were safety, cardiovascular, thyroid and clinical biochemical profile outcomes occurring within 5 years following the index event. After propensity score matching, the study included 12,123 individuals in each group. GLP-1 RA treatment was associated with a significantly lower risk of all-cause mortality (hazard ratio 0.23; 95% confidence interval 0.15-0.34) and several cardiovascular complications, including ischaemic heart disease, heart failure, arrhythmias, hypertension, stroke and atrial fibrillation (all p < 0.05). GLP-1 RAs were also associated with a lower risk of acute kidney injury and allergic reactions. These protective effects were consistent across various subgroups and regions. In this large observational study, GLP-1 RAs showed long-term protective effects on cardiovascular health, renal outcomes and adverse events in individuals with obesity and without T2D. Our findings suggest that GLP-1 RAs may offer a comprehensive approach to managing obesity and its related comorbidities, potentially improving overall health and survival in this population.

Percutaneous mechanical circulatory support versus intraaortic balloon counterpulsation in patients with acute myocardial infarction complicated by cardiogenic shock

Abstract Background Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) is a disease process associated with significantly poor clinical prognosis, placing patients at increased risk for morbidity and mortality. Currently, the optimal choice for temporary mechanical circulatory support remains unclear, with studies evaluating use of percutaneous ventricular assist devices (pVAD) yielding conflicting results. Purpose The goal of this meta-analysis is to evaluate the efficacy of pVAD compared to intra-aortic balloon counterpulsation (IABP) in patients presenting with AMI-CS. Methods A database search was performed for studies reporting on the association of pVAD compared to IABP with clinical outcomes in patients with AMI-CS. The primary endpoint of interest was 30-day all-cause mortality. Secondary endpoints included cardiovascular (CV) mortality, and recurrence of AMI. The databases searched included Pubmed, Web of Science, and Embase. The search was not restricted by time or publication status. Registry studies were excluded from this analysis. Subgroup analysis was performed separating randomized controlled trials from retrospective cohort studies. Results A total of 8 studies with 651 participants (322 treated with pVAD, 329 treated with IABP) met inclusion criteria. Mean age was 65 years old, 73.9% were men, mean left ventricular ejection fraction was 28%, mean follow-up was 9.8 months (ranging 1-66 months). Treatment of AMI-CS patients with pVAD was not associated with lower risk of 30-day all-cause mortality compared to IABP (OR 0.90, 95% CI 0.63-1.27; p=0.55). Heterogeneity was low for the RCT subgroup and moderate for the cohort study subgroup (I2=0%; I2=48%). Use of pVAD in patients with AMI-CS was associated with a non-statistically significant trend toward lower CV mortality compared to IABP (OR 0.53, 95% CI 0.29-0.99; p=0.05). The heterogeneity was low (I2=0%). Use of pVAD was not associated with significantly lower risk of recurrent AMI (OR 0.62, 95% CI 0.22-1.74; p=0.37). Heterogeneity was low for this analysis (I2=0%). Test for subgroup differences was not statistically significant for any of the above analyses. Conclusion In patients presenting with AMI-CS, use of pVAD compared to IABP is not associated with lower risk of all-cause mortality or recurrent AMI. However given the apparent trend toward lower risk of CV mortality in patients treated with pVAD, additional high-quality prospective studies are required.Figure 1

The effect of Glucagon-like peptide-1 receptor agonists on cardiovascular outcomes in type 2 diabetes mellitus patients with coronary artery disease

Abstract Background Cardiovascular disease is the primary cause of mortality in patients with type 2 diabetes mellitus (T2DM). Randomized controlled trials (RCT) have shown that Glucagon-like peptide-1 receptor agonists (GLP-1RA) improve cardiovascular outcomes in T2DM patients, with greater therapeutic benefits observed in patients with established atherosclerotic cardiovascular disease. However, the effect of GLP1-RA therapy on cardiovascular outcomes has been inconsistent and the RCT have not been sufficiently powered to examine the effect of GLP1-RA on mortality or their therapeutic effect in different subgroups of T2DM patients. Purpose This study aimed to examine the effect of GLP1-RA therapy on cardiovascular outcomes and mortality in a real-world cohort of T2DM patients with coronary artery disease (CAD). Methods This study included T2DM patients with CAD who were treated with metformin at a daily dose of ≥ 1g for a period of ≥ 180 days. CAD was defined as ≥ 50% luminal stenosis in any coronary artery segment according to a nationwide angiography and angioplasty registry. We performed sequential emulated target trials at monthly intervals between January 1, 2013 and December 31, 2020 to examine the effect of GLP1-RA therapy on major adverse cardiovascular outcomes (MACE), a composite of myocardial infarction, ischemic stroke and all-cause mortality. Secondary outcomes included the individual components of MACE. Marginal structural models were used to compute pooled effect estimates. This was an intention-to-treat analysis with 5 years of follow-up for each emulated target trial. Inverse probability of treatment weighting was used to adjust for confounding due to differences in patient demographics at baseline. Results This study consisted of 26,746 individuals who were treated with GLP1-RA and 74,638 controls. The 5-year cumulative risk of MACE was 27.7 % in the GLP1-RA group and 32.7 % in the control group (risk ratio 0.85 [95% confidence interval 0.82 – 0.88]). GLP1-RA therapy was associated with a lower risk of all-cause mortality (risk ratio 0.76 [95% confidence interval 0.72 – 0.79]) and myocardial infarction (risk ratio 0.95 [95% confidence interval 0.89 – 1.00]). We found little or no effect of GLP1-RA therapy on the risk of ischemic stroke (risk ratio 1.13 [95% confidence interval 0.97 – 1.27]). Conclusions In this large real-world cohort of T2DM patients with established CAD, we observed that GLP1-RA therapy was associated with a lower risk of MACE, myocardial infarction and all-cause mortality.

Association between PCSK9 inhibitor with cause-specific morality amongst cancer survivors

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor has emerged as a novel pharmacotherapy for dyslipidemia and been shown to be effective in reducing the risks of atherosclerotic cardiovascular diseases. PCSK9 is aberrantly expressed in a broad spectrum of cancers and has been demonstrated to contribute to cancer prognosis. However, no prior study has investigated the associations between PCSK9 inhibitors (PCSK9i) with cardiovascular and cancer mortality amongst cancer survivors. Purpose This study investigated the effects of PCSK9i on cause-specific mortality amongst cancer survivors. Methods This retrospective study used data from the Tianjin Coronary Artery Disease Cohort, which included medical data from 71 secondary or tertiary hospitals in Tianjin, China. Adult patients with coronary artery disease (CAD) diagnosed with incident cancer between 2017 and 2023 were enrolled in this study. Propensity score matching with a 1:3 ratio for PCSK9i users versus non-users was performed. The primary outcomes included all-cause mortality, cardiovascular mortality, and cancer mortality. Multivariable Cox regression was used to test associations between PCSK9i with outcomes, adjusting for age, gender, cardiovascular and non-cardiovascular comorbidities, lipid-lowing agents and other medication use, lipid level, as well as cancer characteristics. Multivariable competing risk analysis was used as sensitivity analysis. Results A total of 62,341 incident cancer patients were identified. After matching, 424 PCSK9i users and 1,272 non-users were included in this study. During a median follow-up of 1,009 days, 315 patients died, among which 98 died due to cardiovascular cause, 146 died due to cancer cause. Compared to non-users, cancer patients treated with PCSK9i presented with significantly lower risk of all-cause mortality (hazard ratio [HR], 0.33; 95% confidence interval [CI] 0.23-0.47; p &amp;lt;0.001), after adjusting for potential confounders. In addition, PCSK9i therapy was associated with a 63% lower risk of cardiovascular mortality (HR, 0.37; 95%CI 0.20-0.69; p=0.002) and a 75% lower risk of cancer-related mortality (HR, 0.25; 95%CI 0.14-0.45; p&amp;lt;0.001), in relation to non-PCSK9i group. Sensitivity analysis using multivariable competing risk model also suggested a significant association between PCSK9i treatment with reduced risk of cardiovascular mortality (HR, 0.41; 95%CI 0.22-0.76; p=0.005) and cancer mortality (HR, 0.26; 95%CI 0.15-0.48; p&amp;lt;0.001) among cancer survivors. Conclusion The use of PCSK9i was associated lower risks of all-cause, cardiovascular-related, and cancer-related mortality amongst cancer survivors. These findings potentially indicate benefits of PCSK9i beyond adverse cardiovascular events related to atherosclerosis.

Relative effectiveness of high-dose versus standard-dose quadrivalent influenza vaccine against hospitalizations and mortality according to frailty score: a post-hoc analysis of the DANFLU-1 trial

Abstract Background Frailty is a major risk factor for adverse cardiovascular events. Influenza vaccination has been shown to protect against cardiovascular fatal and nonfatal events. However, limited data exist on the added benefit of high-dose versus standard-dose influenza vaccination according to frailty status. Purpose We sought to assess the relative effectiveness of high-dose (QIV-HD) versus standard-dose (QIV-SD) quadrivalent influenza vaccination according to frailty status in elderly individuals. Methods This is a post-hoc analysis of the randomized controlled feasibility trial of QIV-HD versus QIV-SD conducted during the 2021–2022 influenza season in adults aged 65–79 years. We assessed the following prespecified outcomes: hospitalizations for pneumonia or influenza, cardio-respiratory hospitalizations, cardiovascular hospitalizations, all-cause hospitalizations and all-cause mortality. Level of frailty was defined according to the Hospital Frailty Risk Score based on ICD-10 codes for relevant comorbidities any time prior to vaccination. We divided the participants into two categories according to Frailty Score (FS): low frailty (0-4 points) and intermediate or high frailty (≥5 points). We analyzed outcomes as time to first event using Cox proportional hazards regression. Results Among 12,473 randomly assigned participants to QIV-HD versus QIV-SD (mean age 71.7 years, 47.1% female), 10,711 (85.9%) were categorized as having low frailty and 1,762 (14.1%) had intermediate or high frailty. In total, 38 individuals were hospitalized for pneumonia or influenza during follow-up, 219 were hospitalized for cardiorespiratory illness, 1055 were hospitalized due to any cause and 62 died during follow-up. FS significantly modified the effect of QIV-HD versus QIV-SD for all-cause mortality (P for interaction 0.02). In participants with low frailty, QIV-HD was associated with a lower risk of all-cause mortality (Figure 1: HR 0.26, 95% CI 0.13 to 0.55), whereas there was no evidence of effect among those with intermediate or high frailty (HR 1.68, 95% CI 0.66 to 4.26). QIV-HD versus QIV-SD was associated with a lower incidence of hospitalizations for pneumonia and influenza, this effect was consistent regardless of frailty status (P for interaction 0.88). QIV-HD was not associated with a significantly lower incidence of hospitalizations due to cardiovascular, cardiorespiratory or respiratory disease or any cause regardless of frailty status. Conclusions In this post-hoc analysis of a large-scale pragmatic trial, QIV-HD was similarly associated with a lower incidence of hospitalizations for pneumonia and influenza among older adults irrespective of frailty status. The potential benefit of QIV-HD versus QIV-SD may therefore be applicable regardless of frailty status. However, our results suggest that QIV-HD is associated with a lower risk of all-cause mortality among adults with low frailty only.Figure 1.

Are migrant workers at greater risk of workplace deaths? A systematic review and meta-analysis

Abstract Background Globally, 170 million individuals migrate for work. Yet, evidence on their mortality risk remains unclear. Our aim was to synthesize global evidence on migrant worker mortality risk compared to local workers and to identify the multiple intersecting social determinants of mortality. Methods We conducted a systematic review of peer-reviewed literature which reported on mortality outcome of migrant workers. Studies published between 1 Jan 2000 to 17 Jan 2023 in English were searched in MEDLINE, Embase, PsycINFO, and Ovid Global Health. Meta-analysis using random effects model was used to calculate pooled estimates and narrative synthesis was used to develop a data-driven framework on intersectional social determinants. Results Out of 11,495 identified records, 44 were included, of which 11 were pooled in meta-analyses. The combined migrant worker death count was 44,338, with data from 16 countries, including migrants from agriculture, construction, and service industries. Compared to local workers, migrant workers had a higher risk of fatal occupational injury (pooled RR = 1.71, 95%CI: 1.22-2.38, I² = 99.4%), and a lower risk of all-cause mortality (pooled RR = 0.94, 95%CI: 0.88-0.99, I² = 90.7%). Key social determinants associated with increased mortality risk were either migration-related (e.g. lower language proficiency, undocumented status) or labour-related (e.g. precarious employment, labour migration policies) interacting over migrant workers’ life course. Conclusions As the largest evidence synthesis to date, these findings indicate that migrant workers have higher fatal occupational injury rates than local workers, indicating the need for tailored protections for migrant workers. These data confirm that the all-cause mortality advantage observed in migrant populations applies to the working population. Future interventions should be designed to address both migration- and labour-related determinants of migrant worker health. Key messages • Migrant workers have a higher risk of workplace fatality despite being generally healthier than local workers, explained by structural determinants such as precarious employment. • Future interventions must address migration- and labour-related social determinants of health at structural levels, such as extending labour protection laws to migrant workers.

Temporal trends in treatment patterns, morbidity, and mortality in patients with new-onset heart failure compared to heart failure survivors: a nationwide 23-year perspective

Abstract Background New therapy options have improved the prognosis of heart failure (HF) over recent decades. However, temporal trends in the prognosis and treatment disparities between patients with new-onset HF and HF survivors remain unexplored. Purpose To investigate temporal trends in HF treatment patterns, worsening HF and all-cause mortality, in new-onset HF patients compared to HF survivors. Methods We defined two separate cohorts of patients with HF, using the Danish nationwide registers. One cohort comprised all patients with new-onset HF each year from 1996 to 2018, included at the date of HF diagnosis (new-onset HF patients). The second cohort comprised patients with HF who have survived at least three years since being diagnosed with HF, included on January 1st of each year from 1996 to 2018 (HF survivors). Patients were allowed to contribute in both cohorts. The proportion of patients in guideline recommended therapy and the absolute five-year risk of worsening HF and all-cause mortality were assessed in the two cohorts separately, accounting for competing risks where relevant. Results From 1996 to 2018, the proportion of HF survivors tripled, while the number of yearly new-onset HF patients remained constant (figure 1). The proportion of new-onset HF patients who redeemed a prescription of BB increased from 17.1% in 1996 to 78.2% in 2018, while it increased from 15.9% to 69.4% in HF survivors during the same period. The proportion of patients in ACEi/ARB therapy increased from 49.1% to 81.5% in the new-onset HF patients, while it increased from 37.8% to 69.0% in HF survivors. The proportion of patients in MRA therapy increased from 14.4 to 33.0% in those with new-onset HF, and from 19.1% to 24.8% in HF survivors. The absolute risk (AR)[±95CI] for all-cause mortality decreased from 68.4% [67.9-68.9] in the first year group (1996-2000) to 45.7% [45.0-46.3] in the latest year group (2013-2018) for new-onset HF patients, while it decreased from 58.4% [58.2-58.9] to 39.7% [39.4-40.0] for the HF survivors. Additionally, the AR for worsening HF went from 27.4% [26.9-27.8] in the first year group to 27.8% [27.3-28.2] in the latest year group for the new-onset HF patients, whereas it for the HF survivors decreased from 19.6% [19.3-20.0] to 16.7% [16.4-19.9]. Conclusions Over a 23-year period, the annual number of patients with incident HF has remained constant while the number of HF survivors has increased by 304%. Although HF survivors show a lower prescription redemption prevalence for essential HF medications compared to incident HF patients, they exhibit significantly lower risk of all-cause mortality and worsening HF.Figure 1:OverviewFigure 2:Prescription redememption rates

Bioprosthetic versus mechanical prostheses in patients aged 50 to 70 years undergoing aortic valve replacement surgery: outcomes analysis from propensity score matching

Abstract Introduction Despite increasing use of bioprosthetic surgical aortic valve replacement (bAVR) in patients ≤70 years [1, 2], the relative benefits compared to mechanical valve replacement (mAVR) remain uncertain [3, 4]. Purpose The current study aims to compare mortality and other important clinical endpoints by prosthesis type for patients aged 50-70 years who received an AVR in a well-characterised Australian cohort. Methods A retrospective cohort study was designed utilising the WAVES Patient Registry and incorporating linked administrative outcome data including all patients who had an AVR in Western Australian public hospitals between 2010-2020. The primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular (CV) mortality, separately and combined with non-fatal myocardial infarction and non-fatal stroke (MACE), major bleeding, and days alive and out of hospital (DAOH). Outcomes were compared based on a propensity-matched analysis (including demographics, biometrics, and clinical characteristics). Results Within the initial cohort of 727 patients undergoing surgical AVR (mean age = 63 ± SD 6), a propensity-matched cohort identified 151 patients each with bAVR (mean age = 61 ± 4) and mAVR (mean age = 60 ± 5). Patients who received mAVR versus bAVR had improved all-cause survival (Hazard Ratio [HR] 0.50; 95% CI 0.25-0.99) but increased risk of major bleeding (HR 4.85; 95% CI 1.57-14.98). There were no significant differences in CV mortality (HR 0.58; 95% CI 0.19-1.74), MACE (HR 0.59; 95 % CI 0.32-1.07), or DAOH by prosthesis type (P = 0.452). Conclusions Patients aged 50-70 years who underwent mAVR had lower risk of all-cause mortality compared with bAVR, despite higher bleeding risk. Although risks of CV mortality and MACE were lower in mAVR, statistical significance was not reached, likely due to the small sample size. Larger studies are necessary to confirm these findings, which have important clinical implications.

Early discharge following cardiac implantable electronic device implantation: a systematic review and meta-analysis

Abstract Background As the demand for cardiac implantable electronic device (CIED) placement rises, healthcare expenses, including the post-procedure hospital stay costs, have been on the increase. This systematic review and meta-analysis were undertaken to evaluate the safety and viability of same-day discharge (SDD) following cardiac device implantations. Methods We conducted a systematic searched of PubMed, Embase and Cochrane database during November 2023 for studies comparing SDD versus discharge after overnight stay (OS) after CIED. Outcomes included all-cause mortality and complications after the procedure (lead/device dislodgment, re-hospitalization, pneumothorax, local hematoma and wound complications). Data from each study were combined using the random-effects model to calculate pooled odds ratio (OR) with 95% confidence interval (CI). Results Eleven studies, including two randomized clinical trials, were incorporated, with a total of 64,646 patients, providing 918 pooled death events (74 in SDD and 844 in OS). The meta-analysis revealed that SDD was associated with a significantly lower risk of all-cause mortality compared to OS (pooled HR 0.72; 95% CI: 0.55-0.93; I2=0%) and no difference was found regarding re-hospitalization (pooled HR 0.96; 95% CI: 0.88-1.05; I2 55%). SSD was not associated with higher lead/device dislodgement (pooled HR 0.93; 95% CI: 0.50-1.71; I2=0%), pneumothorax (pooler HR 1.04; 95% CI: 0.31-3.50; I2 0%) and wound complications (pooled HR 0.65; 95% CI 0.22-1.01; I2 0%). SSD was associated with more episodes of local hematoma (pooled HR 0.31; 95% CI 0.09-1.05; I2 0%). Conclusion Our meta-analysis suggests that SDD is associated with a decreased all-cause mortality compared to OS. Although associated with more episodes of local hematoma, SDD was not significantly different regarding lead/device dislodgment, pneumothorax, re-admissions and wound complications. SDD after CIED appears to be a safe and feasible alternative.

Prognostic implications of guideline-directed medical therapy in functional mitral regurgitation: a meta-analysis

Abstract Background Randomized evidence of the role of heart failure medical therapy for patients with functional mitral regurgitation (FMR) is lacking. Purpose The present meta-analysis sought to investigate the independent long-term prognostic impact of the different medical categories recommended in heart failure, for subjects with FMR. Methods A systematic literature review was conducted in electronic databases to identify studies reporting the association of renin angiotensin system inhibitors (RASi), beta-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) with outcomes in FMR. A random-effects meta-analysis was conducted to quantify the unadjusted and adjusted hazard ratios [(a)HRs] for all-cause death and the composite outcome in each medical category. Results The final sample comprised 12 studies with 6,715 FMR patients (Picture 1). The use of RASi and BBs was associated with a significantly lower risk for all-cause mortality (HR 0.52 [0.39-0.68]; p &amp;lt;0.00001, I2 =62 % and HR 0.62 [0.49-0.77]; p &amp;lt;0.0001, I2 =44 % respectively) and for the composite outcome (HR 0.54 [0.44-0.67]; p &amp;lt;0.00001, I2 =33 % and HR 0.62 [0.52-0.75], p &amp;lt;0.00001, I2 =35% respectively) in unadjusted models (Picture 2). Both RASi (aHR 0.73 [0.56-0.95], p =0.02, I2 =52%) and BBs (aHR 0.60 [0.41-0.88], p = 0.009, I2 =55%) retained their association with the composite outcome in pooled adjusted models (Picture 2). The prognostic benefit of using RASi or BBs was retained in subgroup analysis including only patients with moderate of severe FMR. MRAs did not demonstrate a significant association with improved outcomes in FMR. Conclusions RASi and BBs appear to have a favorable prognostic impact in patients with FMR, regardless of regurgitation severity.Study flow chart for study selectionPharmacotherapy and prognosis in FMR

Association of HbA1C with mortality and cardiovascular outcome in patients with type 2 diabetes using drugs with different hypoglycemic risk

Abstract Background Previous clinical trials showed that intensive glucose control did not reduce macrovascular events and mortality. It was speculated that severe hypoglycaemia contributed to these adverse outcomes. More contemporary clinical trials using newer anti-diabetic agents with less hypoglycaemic potential showed a linear relationship between major adverse cardiovascular events (MACE) and HbA1c reduction according to a meta-regression analysis. Purpose The aim of this study was to examine the association between clinical outcomes and HbA1c under different treatment backgrounds in the real-world setting. We hypothesised that when using drugs with minimal hypoglycaemic risk, lower HbA1c would be associated with better outcomes. Methods This was a retrospective population-based cohort study using a multi-centre electronic medical record database. Eligible patients were those diagnosed with type 2 diabetes between 2009 and 2020 who received non-insulin antidiabetic drugs. Patients were stratified into two groups based on the drugs received: drugs with high hypoglycaemic risk (sulphonylurea, meglitinide) and drugs with low hypoglycaemic risk (thiazolidinediones, acarbose, DPP4 inhibitors, GLP1 agonists, SGLT-2 inhibitors). Patients were excluded if they had received these drugs for less than 180 days or had received both high and low hypoglycaemic risk oral drugs simultaneously. HbA1c levels were assessed from the index date to the date of the interested outcome or the end of the study period (31 December 2021), whichever came first. The relationship between HbA1c and clinical outcomes was examined using a Cox proportional hazards model. The outcomes of interest included all-cause mortality and MACE. Results The study population consisted of 6,923 patients, including 3,639 high hypoglycaemic risk drug users and 3,284 low hypoglycaemic risk drug users. Patients with lower HbA1c levels during the follow-up period were older and frailer. After adjusting for baseline covariates, the association between the risk of death and HbA1c presented a U-shaped pattern, and this U-shaped association was similar in the two treatment cohorts (Table 1). On the other hand, the association between the risk of MACE and HbA1c presented a J-shaped pattern. In the high hypoglycaemic risk drug cohort, patients with the highest HbA1c levels (mean HbA1c 9.6%) were associated with a higher risk of MACE compared to the group with a mean HbA1c of 7.2% (hazard ratio [HR] 4.16, 95% confidence interval [CI] 2.07-8.37); lower HbA1c levels were not associated with a lower risk of MACE (Table 2). In contrast, in the low hypoglycaemic risk drug cohort, lower HbA1c levels were associated with a higher risk of MACE (HR 3.82, 95% CI 1.29-11.28). Conclusion Lower HbA1c levels were not associated with a lower risk of all-cause mortality and MACE. Furthermore, this phenomenon was independent of the hypoglycaemic risk of anti-diabetic drugs.

The upfront lipid-lowering combination therapy of statins and ezetimibe vs statin monotherapy in the reduction of cardiovascular outcomes. A meta-analysis.

Abstract Background Despite some data in last few years, there is still some inconsistency concerning the effectiveness and safety of the upfront intensive lipid lowering combination therapy (LLT; of moderate to high intensity statin therapy and ezetimibe) in comparison to high intensity statin therapy and recommended by some guidelines stepwise therapy approach. Purpose We sought to evaluate the efficacy of combination LLT compared with statin monotherapy for cardiovascular outcomes, LDL-C reduction, and associated adverse events. Methods A systematic literature search was conducted using PubMed, Embase, and ClinicalTrial.gov to identify relevant articles published from inception until 29th December 2023. The outcomes were assessed using pooled odds ratio (OR) for categorical data and mean difference (MD) for continuous data, with corresponding 95% confidence intervals (95% CI). Results A total of 11 studies (8 randomized controlled trials and 3 cohort studies) with 106,358 were involved in the analysis. The mean age of the patients in the combination LLT and statin monotherapy group was 65.3 and 65.7 years, respectively. Pooled analysis shows that combination LLT significantly reduces the LDL-C level from the baseline (MD, -12.13 mg/dl [0.31 mmol/l] (95%CI: -18.26 to -5.99 mg/dl), p&amp;lt;0.001), all-cause mortality (ACM) (OR, 0.75, 95%CI: 0.62 to 0.92, p=0.01), cardiovascular mortality (CVM) (OR 0.75, 95%CI: 0.66 to 0.84, p&amp;lt;0.001), major adverse cardiovascular events (MACE) (OR, 0.72 95%CI: 0.63 to 0.82, p&amp;lt;0.001), non-significant reduction in the incidence of stroke (OR 0.82, 95%CI: 0.66 to 1.01, p=0.06) when compared with statin monotherapy alone. Similarly, the therapy discontinuation rate was comparable between combination LLT and statin monotherapy groups (OR, 0.87 (95%CI: 0.53 to 1.40), p=0.56). The risk of adverse events related to the gastrointestinal tract (OR, 1.12 (95%CI: 0.93 to 1.36), p=0.23) and musculoskeletal system (OR, 0.88 (95%CI: 0.52 to 1.50), p=0.65) was comparable between both the groups of patients. Conclusion Combination LLT was associated with an overall greater reduction in LDL-C, a lower risk of ACM, MACE, and CVM compared to statin monotherapy alone.Forest Plot of desired outcomes.Central illustration with key findings.

Resumption of anticoagulation therapy among Non-Valvular Atrial Fibrillation (NVAF) patients with prior intracranial haemorrhage

Abstract Purpose Resumption of anticoagulation therapy (OAC) in patients with non-valvular atrial fibrillation (NVAF) suffering from intracranial haemorrhage (ICH) is challenging in clinical practice. The aim of this study was to evaluate impact of resumption of OAC on clinical outcomes in NVAF patients with history of ICH. Methods Consecutive patients with NVAF with or without OAC who survived from an index ICH between January 2018 and July 2022 in 16 public hospitals in Hong Kong were identified and analyzed retrospectively. Resumption of OAC was substantiated by new prescription obtained from electronic medical records. Patients were divided into 5 groups: (i) OAC naïve (as reference group); (ii) resume direct oral anticoagulant (DOAC); (iii) resume Vitamin K antagonist (VKA); (iv) discontinue DOAC; (v) discontinue VKA. Risks of ischemic stroke, recurrent ICH and all-cause mortality were estimated for all groups and compared with individuals without OAC, using adjusted sub-distribution hazard ratios (aSHR) derived from Fine and Gray regression models, accounting for death as competing risk, adjusting for components of CHA2DS2VASC and HASBLED scores. Sub-analysis was conducted to compare outcomes between different DOAC agents (i.e, apixaban, dabigatran, edoxaban, rivaroxaban), using VKA as reference among patients who resumed DOAC or VKA. Results Of 982 patients who met inclusion criteria (mean age 77.7±10.9, female 40.9%), 39.1% (n=384) were OAC naive, 32.2% (n=316) resumed DOAC, 12.6% (n=124) resumed VKA, 9.0% (n=88) discontinued DOAC and 7.1% (n=70) discontinued VKA. During a median follow-up period of 2.0 (IQR: 0.7-3.5) years, no statistically significant difference in risk of ischemic stroke was observed among 5 groups. Discontinuation of DOAC was associated with markedly higher risk of ischemic stroke (aSHR=8.32 (1.8-39.3)) only among AF patients with CHA2DS2VASC score ≥ 4, Risk of recurrent ICH was higher in patients who resumed VKA (aSHR=1.6(1.0-2.5)). Sub-analysis demonstrated resumption of apixaban was associated with lowest risk of recurrent ICH (aSHR=0.6(0.4-0.9)). Compared to OAC naïve patients, those who resumed DOAC (aSHR=0.5(0.4-0.7)) had lowest risk of all-cause mortality, whereas discontinuation DOAC (aSHR=1.9(0.4-2.5) and VKA (aSHR=1.6(0.2-2.2)) were both associated with increased mortality. Conclusion Our real-world data revealed among NVAF patients with prior ICH long term discontinuation of OAC was associated with increased risk of ischemic stroke. Recurrent ICH was highest among patients who resumed VKA and lowest with apixaban.

The incidence of death and risk factors for mortality following major bleeding in patients anticoagulated with factor Xa inhibitors: an observational study in the UK clinical setting (AXIOM UK)

Abstract Background Major bleeding (MB) in association with anticoagulant use results in significant mortality. Mortality can be directly attributed to bleeding, or may follow bleeding complications such acute kidney injury, myocardial infarction, stroke and other cardiovascular events. Most real-world data relating to bleeding mortality is derived from cohorts receiving vitamin-K antagonists. We investigated all-cause mortality (ACM) after MB in a large cohort anticoagulated with Factor Xa inhibitors (FXai), e.g. direct oral anticoagulants (DOAC) rivaroxaban, apixaban and low-molecular-weight heparins (LMWH). Purpose To describe incidence rates of and risk factors for ACM following MB in patients receiving FXai. To investigate MB related ACM by bleeding site, treatment indication, treatment subgroups and individual and cumulative time periods. Methods Retrospective cohort analysis of new users of FXai, between 2012-2020, for therapeutic indications including atrial fibrillation (AF), venous thromboembolism, bioprosthetic cardiac valves or adult congenital heart disease was conducted. MB was defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria. Incidence rates were reported per 100 person-years. Sub-distribution hazard ratios with 95% confidence intervals (95% CI) were estimated from Fine and Gray regression models accounting for competing risks. Results In 240,357 new users of FXai, 88% used an oral FXai. The most common FXai indication was AF (72%). There were 10,163 patients (4.2%) hospitalised for bleeding events during FXai use. Of these, 3,873 MB events (38%) fulfilled the ISTH definition of MB and 1312 died during 3,542 person years of follow-up (Table 1). ACM incidence rates varied by time, indication, bleeding subtype, and drug type. ACM occurred in 926 patients (23.9%) in the first month. Mortality rates were highest in the first month 607 (95% CI 568-647) per 100 person years, the rates then decreased over the year but remained elevated throughout the first year compared with subsequent years. Those receiving LMWH had higher ACM than those receiving a DOAC, but this was not significant in the adjusted risk factor analysis. Risk factors for ACM following bleeding included age ≥80, and a history of current smoking, myocardial infarction, congestive heart failure, peripheral artery disease, Stage 4 or 5 kidney disease, metastatic cancer, and intracranial haemorrhage. Age&amp;lt;60, bleeding following major trauma, and a history of anaemia were associated with lower risk of ACM (Table 2). Conclusions There is a significant incidence of ACM following MB among FXai users. The incidence rate of ACM in patients treated with FXai was highest in the first month after FXai initiation, declined during the first year and then plateaued. Multiple risk factors associated with ACM have been recognised and these could guide urgent therapies such as antidotes.

A novel risk score based on exercise capacity to predict all-cause mortality in adults with congenital heart disease

Abstract Background Impaired exercise capacity in adults with congenital heart disease is associated with mortality. Thus, exercise capacity is a potential tool for predicting risk in this population. The present study attempts to further explore the usefulness of exercise capacity in risk assessment of all-cause mortality, together with a limited number of easily accessible clinical variables. Methods The national register of congenital heart disease was searched for adults (18-60 years of age) with at least one bicycle ergometer exercise test and follow up in the register. The exercise capacity was classified based on percent of predicted exercise capacity (EC%pred); normal (&amp;gt; 70%), moderately impaired (50-70%) or severely impaired (&amp;lt;50%). All patients were followed for 10 years or until death, if occurring earlier than 10 years after the exercise test. Data were analyzed using logistic regression modelling. A risk evaluation model was constructed based on percent of predicted exercise capacity, age, and complexity of the heart lesion. Finally, the model was converted into a 5-point (p) risk score used to predict 10-year mortality (EC%pred &amp;gt;70%=0p, 50-70=1p, &amp;lt;50%=2p, age &amp;lt;25=0p, 25-40=1p, 40-60=2p, simple lesion=0p, moderate/severe complexity of heart lesion=1p). Results 1171 patients (mean age at exercise test 30.5 years, 44% women) were included with 70 deaths occurring within 10 years. A score 0-1 corresponded to &amp;lt;1% 10-year all-cause mortality, 2p 5%, 3p 9%, 4p 21% and 5p 33% mortality risk (Table 1). The area under curve for the model was 0.75 (95% CI 0.69-0.81). Conclusion An easily performed risk assessment containing % of predicted exercise capacity, age and complexity of heart lesion performs well in detecting patients at both low and high risk of all-cause mortality within 10 years after an exercise test.

Protective Effect of Extra Virgin Olive Oil on Cancers, Gastrointestinal Cancers, and All-Cause Mortality: A Competing Risk Analysis in a Southern Italian Cohort

Background/Objectives: This study investigates the association between extra virgin olive oil (EVOO) consumption and mortality risk in a cohort of Italian adults adhering to the Mediterranean diet. Methods: In a 17-year follow-up study involving participants from Castellana Grotte, Italy (2005–2023), we analyzed dietary intake and mortality data. Participants were categorized into three EVOO consumption groups: &lt;30 g/day, 30–50 g/day, and &gt;50 g/day. Mortality Hazard Ratios (HR) and Subdistribution Hazard Ratios (SHR) were calculated to assess the relationship between EVOO intake and all-cause and cancer mortality. Results: Higher EVOO consumption was associated with significantly reduced cancer and all-cause mortality. Specifically, the daily intake of 30–50 g of EVOO was linked to a 24% lower risk of all-cause mortality (HR 0.77; 95% CI 0.63–0.93), while the consumption of more than 50 g/day was associated with a 20% reduction (HR 0.80; 95% CI 0.65–0.98). The most pronounced benefit was observed for gastrointestinal cancers, with a 60% lower mortality risk for those consuming over 50 g/day (SHR 0.39; 95% CI 0.21–0.73). A 50% reduction in mortality risk from other cancers was also noted for the highest consumption category (SHR 0.50; 95% CI 0.31–0.81). Conclusions: The findings support the beneficial role of EVOO in reducing cancer mortality, particularly with higher consumption levels. The results underscore EVOO’s potential as a dietary intervention for cancer prevention, aligning with the Mediterranean diet’s overall health benefits. Further research is needed to confirm these findings and explore the underlying mechanisms.

Graded association of muscle strength with all-cause and cause-specific mortality in older adults with diabetes: Prospective cohort study across 28 countries.

The worldwide prevalence of diabetes is increasing, particularly among older adults. Understanding the association between muscle strength and mortality in this population is crucial for developing targeted exercise recommendations. To assess the prospective association of muscle strength with mortality in older adults with diabetes. From the Survey of Health, Ageing and Retirement in Europe (SHARE) study, spanning 28 countries, we included 16 149 diabetic adults aged 50 years and older (mean age 68.2 [standard deviation, SD, 9.2] years). Participants fulfilled two criteria: (1) diabetes diagnosis (ever) and (2) current use of diabetes medication. Muscle strength was assessed using handgrip dynamometry (unit: kg). Using time-varying Cox regression with restricted cubic splines, we determined the prospective association of muscle strength with all-cause and cause-specific mortality, controlling for various confounders. Over a mean follow-up of 5.9 years (SD 3.8), 2754 participants died (17%). Using the median level of muscle strength as reference (30 kg), lower and higher levels were associated in a curvilinear fashion with higher and lower all-cause mortality risk, respectively. The 10th percentile of muscle strength (17 kg) showed a hazard ratio (HR) of 1.65 (95% confidence interval (CI) 1.53-1.79). The 90th percentile (47 kg) of muscle strength showed a HR of 0.55 (95% CI 0.49-0.63). A somewhat similar pattern, with varying strength of associations, was seen for mortality due to cardiovascular disease (CVD), respiratory disease, severe infectious disease, digestive system disease and cancer. Muscle strength is gradually and inversely associated with all-cause and cause-specific mortality risk in older adults with diabetes. As muscle strength is highly adaptable to resistance training at all ages, the present findings highlight the importance of improving muscle strength in older adults with diabetes.

Trends in Transcatheter Versus Surgical Aortic Valve Replacement Outcomes in Patients With Low-Surgical Risk: A Systematic Review and Meta-Analysis of Randomized Trials.

Limited data exist on long-term outcomes after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). This meta-analysis aims to elucidate outcome trends following TAVR versus SAVR in patients with severe aortic stenosis and low-surgical risk. A systematic search was conducted in PubMed, Embase, Scopus, and the Cochrane Library databases from inception until May 2024, to identify studies comparing TAVR versus SAVR in patients with low-surgical risk (Society of Thoracic Surgeons predicted risk of mortality score <4%). The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, stroke, disabling stroke, rehospitalization, myocardial infarction, aortic valve reintervention, permanent pacemaker implantation, and new-onset atrial fibrillation. Binary random-effects models were used to compare the risk of each outcome across various follow-up intervals and the risk of bias was assessed using the Cochrane Collaboration's Risk of Bias-2 tool. The meta-analysis included 6 randomized trials including 4682 patients. TAVR was associated with a lower risk of all-cause mortality than SAVR in the 30-day (hazard ratio [HR: 0.45] [95% CI: 0.26-0.77], I2: 0%) and 30-day to 1-year (HR: 0.55 [95% CI: 0.37-0.81], I2: 16%) follow-ups. However, the risk of all-cause mortality was similar during >1-year follow-ups. TAVR was associated with a significantly lower risk of cardiovascular mortality, disabling stroke, rehospitalization, new-onset atrial fibrillation, and a higher risk of permanent pacemaker implantation compared with SAVR during the 30-day follow-up. TAVR was associated with a lower risk of all-cause mortality within the first year of post-procedural follow-up compared with SAVR. However, the risk of all-cause mortality was similar in >1-year follow-ups.

Niacin intake and mortality (total and cardiovascular disease) in patients with cardiovascular disease: Insights from NHANES 2003–2018

BackgroundCardiovascular disease (CVD) poses a significant challenge to global public health. Dietary intervention therapy offers high cost-effectiveness for treating CVD. Currently, there is limited research on the dietary niacin intake and survival of CVD patients. This study aims to examine the association of dietary niacin intake with long-term survival in people with CVD.MethodsA nationally representative sample of 4,377 diabetes subjects was drawn from the NHANES (National Health and Nutrition Examination Survey) data collected between 2003 and 2018. Dietary niacin intake in this study represents either the average of the two recalls or the value from one recall (if only one recall was available for a participant). Weighted Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% CIs to examine the associations between dietary niacin intake and the risk of all-cause and CVD mortality.ResultsAfter adjustment for multiple covariates, HRs and 95% CIs in model 3 indicated that participants in the highest quartile (Quartile 4) of dietary niacin intake were at lower risk for all-cause mortality (HR = 0.74, 95% CI: 0.60–0.90, P for trend = 0.010) and CVD mortality (HR = 0.67, 95% CI:0.51–0.89, P for trend = 0.020).ConclusionHigher dietary niacin intake may be associated with a reduced risk of all-cause and cardiovascular disease mortality among CVD patients. Additionally, significant interactions were found between dietary niacin intake and BMI as well as vitamin B12 subgroups.