Lower All-cause Mortality Research Articles

A higher adherence to perindopril-based anti-hypertensive therapy is associated with a reduced risk of cardiovascular outcomes and all-cause mortality in real clinical practice in Italy

Abstract Background Therapeutic management of hypertension is a landmark of cardiovascular (CV) risk prevention. Combined therapies with at least 2 anti-hypertensive agents are required in many patients in whom monotherapy and lifestyle interventions failed in blood pressure control. It is well-known that poor medication adherence remains a major barrier to achieving the therapeutic targets for all CV drugs, including anti-hypertensives. Purpose We evaluated the relationship between adherence to perindopril (PER)-based therapeutic regimen prescribed as single-pill combination (SPC) or free-pill and CV outcomes and all-cause mortality in a large Italian population. Methods A retrospective analysis was performed using administrative databases corresponding to around 6.7 million health-assisted residents. Hypertensive adults were first identified through hospitalization discharge diagnosis or exemption codes for hypertension between 2010 and 2021. Patients prescribed PER-based therapies were screened for all combinations of PER with amlodipine (AML) and/or indapamide (IND) (all formulations, single-pill or free-pill). Time of the first prescription of a PER-based regimen during the inclusion period was considered the index-date. The analysis included all hypertensive subjects prescribed a PER-based therapy, having available data at least 12 months before and 24 months after the index-date, respectively. Since the analysis was focused on the possible associations between adherence level and CV outcomes and all-cause mortality, adherence was assessed during the first year of follow-up on alive patients and outcomes were assessed during the second year. Adherence was assessed using the proportion of days covered (PDC) approach on 1-year follow-up, and considering a PDC<80% as poor-to-moderate adherence, and PDC ≥80% as good adherence. The Cox’s proportional hazard model was applied to estimate Hazard Ratio (HR) adjusting for baseline covariates, including comorbidity profile and pill burden. Results The included cohort (N=24,476) was divided into sub-groups according to adherence in poor-to-moderate (N=6,781) and good adherent patients (N=17,695) with a mean age of 64.8±13.3 and 64.6±11.9 years old, respectively. The Cox’s proportional hazard model showed that good adherence was associated with a relative risk reduction of 23% in all-cause mortality (Table 1A), 21% in all CV events (Table 1B), 17% in ischemic heart disease (Table 1C), 33% in cerebrovascular events (Table 1E), and 22% in the composite outcome of CV events/all-cause mortality (Table 1G). Conclusions The present analysis provided evidence from the Italian real clinical practice that good adherence to PER-based anti-hypertensive therapy results in significantly lower cardiovascular risk and all-cause mortality. These data further emphasize the importance of promoting cost-effective measures to increase medication adherence in patients on anti-hypertensive treatment.

SGLT2 inhibitors in patients with amyloidosis and heart failure: a worldwide retrospective cohort study

Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the combined risk of death and hospitalization in patients with heart failure with reduced or preserved left ventricular ejection fraction. However, evidence of their impact on patients with heart failure due to amyloidosis is lacking. Purpose To evaluate the effects of SGLT2 inhibitors on mortality and hospitalization in patients with amyloidosis and heart failure. Methods In this retrospective cohort study, we used real-world data from 108 healthcare organizations worldwide from the global health research collaborative network TriNetX. We identified 24,619 patients with amyloidosis and heart failure without exposure to SGLT2 inhibitors (control group) and 2,988 patients with amyloidosis and heart failure under treatment with SGLT2 inhibitors (SGLTi group). We performed propensity score matching for demographic and clinical characteristics and Kaplan–Meier plots, log-rank tests, and Cox proportional hazard models were calculated. The outcomes were 12-month all-cause death and 12-month hospitalization. Results After propensity score matching, 2,237 patients were analyzed in each group. During the 12-month follow-up, 198 (8.8%) patients died in the SGLT2i group, and 431 (19.2%) patients died in the control group (hazard ratio 0.51, 95% CI 0.43-0.61). In the SGLT2i group, 974 (44.5%) patients were hospitalized, and in the control group, 1508 (53.5%) patients were hospitalized (hazard ratio 0,79, 95% CI 0.72-0.86). The Kaplan-Meier curves are shown in Figure 1. Conclusions In conclusion, in this retrospective cohort study with a large number of patients with amyloidosis and heart failure, SGLT2 inhibitors were associated with a lower 12-month all-cause mortality and hospitalization. Further evidence from randomized controlled studies are needed to confirm the efficacy of SGLT2 inhibitors in patients with cardiac amyloidosis.Figure 1.Kaplan-Meier curves

Comparison of ventricular tachyarrhythmias in HF patients on dapagliflozin versus empagliflozin

Abstract Background Ventricular tachycardia (VT) and ventricular fibrillation (VF) are devastating tachyarrhythmias that can cause sudden cardiac death in patients with heart failure (HF) if not anticipated or treated promptly. Although post-hoc analysis in DAPA-HF showed promise in their benefit, Sodium-glucose transport protein 2 inhibitors (SGLT2i) have not yet been evaluated for their effect on these tachyarrhythmias. This retrospective analysis aims to compare the 2 most commonly used SGLT2i agents, dapagliflozin and empagliflozin, and the incidence of VT in patients with HF. Methods The TriNetX Research network was used for this study. The two initial patient cohorts were created using ICD-10 codes and medication codes from the TriNetX platform. Both cohorts consisted of patients over age 60 with a history of heart failure and either VF or VT. One cohort was on treatment with dapagliflozin and the other with empagliflozin. The cohorts were balanced by propensity score matching and the greedy nearest neighbor algorithm for age, gender, race, ethnicity, hyperkalemia, and the current use of spironolactone, amiodarone, metoprolol, and carvedilol, resulting in 9,841 patients in each arm. The cohorts were then evaluated for the development of VF or VT over the subsequent five years as well as all-cause mortality. Additional cohorts were created to evaluate dapagliflozin vs empagliflozin in diabetics, nondiabetics, and patients with ejection fractions less than 35% Results Dapagliflozin was associated with an increased risk of ventricular arrhythmia in heart failure patients compared to empagliflozin (46.0% vs. 40.8%, RR 1.13, 95% CI (1.09,1.16), P value < 0.0001). It was also associated with higher mortality at five years (RR 1.10, 95% CI (1.03,1.18), P value 0.0034). Conclusions In comparisons between dapagliflozin and empagliflozin in heart failure patients with previously documented ventricular arrhythmias, empagliflozin had 13% less risk of recurrence of ventricular arrhythmias. Secondarily, the empagliflozin cohort also exhibited lower all-cause mortality (14.8% vs 16.3%) at five years from starting the drug. Our analysis does not disprove findings in DAPA-HF, but rather may support the potential class effect of SGLT2 inhibitors in their ability to suppress VT.(1) Importantly, the overall incidence of ventricular tachyarrhythmias is high in both cohort, given we selected a high-risk population. Notably, our documented recurrence rate is similar to past reports of recurrence after VT ablation, the gold standard for treatment of VT. (2) SGLT2 inhibitors have shown clear benefit in multiple placebo-controlled studies in terms of heart failure outcomes like mortality and readmission, but their effect on arrhythmias is one more additional benefit this class may have. (3) Given these associations, empagliflozin may be a more favorable options for HF patients who have already had VT or VF.

The prognosis evaluation of guideline-directed medical therapy for type 2 acute myocardial infarction patients with acute respiratory failure

Abstract Backgrounds Type 2 myocardial infarction (T2MI) arises from an imbalance between myocardial oxygen supply and demand during acute illness such as tachyarrhythmia, hypoxia, or hypotension without acute atherothrombosis. The efficacy of guideline-directed medical therapy (GDMT) in T2MI complicated by acute respiratory failure remains uncertain. Purposes This study was aimed to assess the impact of GDMT (including dual antiplatelet therapy, statins and β-blockers) on the prognosis of patients with T2MI and acute respiratory failure. Methods The data for this study were derived from a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals between 2010 and 2023. Inclusion criteria included patients with a discharge diagnosis of T2MI and acute respiratory failure. GDMT was defined according to the ACC/AHA Class I recommendations. Patients were divided into GDMT and N-GDMT groups, with differences in clinical characteristics adjusted using propensity score matching (PSM). Primary outcome indicators were major adverse cardiac and cerebrovascular events (MACCE), while secondary outcome indicators included in-hospital mortality, cardiac mortality, non-lethal myocardial infarction, recurrent ischemic stroke, bleeding events and revascularization. Results This study comprised 898 patients in the GDMT group and 3,777 in the N-GDMT group, resulting in 888 matched pairs after PSM. Baseline data showed that patients in the GDMT group had a higher burden of pre-existing comorbidities. In terms of treatment, the GDMT group had a higher proportion of patients undergoing Percutaneous Coronary Intervention (PCI) (4.84% vs. 1.80%, p= 0.001). In-hospital mortality was significantly lower in the GDMT group (12.4% vs. 26.4%, p< 0.001).Over amedian follow-up of 1,304 days, the incidence of MACCE within 1 month was significantly lower in the GDMT group (23.1% vs. 41.3%, p< 0.001). Furthermore, the GDMT group exhibited lower all-cause mortality (52.4% vs. 60.1%, p＜0.01) and cardiac mortality (41.3% vs. 50.3%, p< 0.001) compared to the N-GDMT group, with higher rates of revascularization (3.15% vs. 1.24%, p＜0.01). There were no statistically significant differences in the incidence of bleeding BARC3 (0.45% vs. 0.45%, p=1), recurrent non-lethal myocardial infarction (0.23% vs. 0%, p =0.5) and recurrent stroke (1.46% vs. 0.79%, p =0.261). GDMT at discharge was associated with a lower risk of MACCE in unadjusted analysis (HR=0.51, 95%CI= 0.44-0.59, p＜0.01) and after adjusting for age, gender, Killip classification and comorbidities in multivariate Coxregression analysis (aHR = 0.49, 95%CI= 0.41-0.58). Conclusions Adherence to GDMT was associated with a lower incidence of MACCE during 1-month follow-up, suggesting the importance of GDMT in this patient population.Clinical characteristics of patients

Catheter ablation vs medical management for atrial fibrillation in patients with heart failure: a systematic review and metanalysis

Abstract Background Current guidelines recommend a class IIa recommendation for catheter ablation in Atrial Fibrillation [AFIB]. Traditionally, catheter ablation has been known to be more effective in maintaining sinus rhythm than pharmacological management. However, there is sparse evidence to suggest that this translates to improved clinical outcomes in patients with heart failure. We did a systematic review and meta-analysis of randomized trials to compare the efficacy of ablation vs medical management for AFIB in heart failure. Methods A systematic search was conducted for randomized trials from inception to Jan 2024 for studies comparing the outcomes of catheter ablation vs medical management for AFIB in heart failure. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular (CV) mortality, heart failure hospitalizations, change in LV ejection fraction (LVEF), AF recurrence rate, 6-minute walk test (6MWT), change in MLHFQ scores and cerebrovascular events. Random-effects models were used to calculate the pooled incidence, mean difference (MD), and risk ratios (RRs) with 95% confidence intervals (CIs). Results A total of 10 RCTs with 2,348 patients were included in this study. Pulmonary vein isolation was the mainstay ablation strategy used. Compared with medical management, Ablation was associated with a significant reduction in all-cause mortality (RR- 0.61; 95% CI, 0.48-0.78; P<0.0001). Ablation was also associated with lower cardiovascular (CV) mortality (RR- 0.52; 95% CI, 0.36-0.75; P<0.0004), heart failure hospitalizations (RR- 0.67; 95% CI, 0.54-0.82; P<0.0001) and AF recurrence rate (RR- 0.43; 95% CI, 0.25-0.75; P<0.003). The study showed an improvement in LVEF (RR - 6.05; 95% CI, 3.35-8.75; P<0.0001), 6MWT (RR- 13.99; 95% CI, 4.18-23.81; P<0.005) and in MLHFQ score (RR -6.98; 95% CI, -12.03 to -1.93; P<0.007. There was a statistically significant difference between the 2 cohorts in the rates of cerebrovascular events (RR- 0.68; 95% CI, 0.35-1.30; P<0.24). Conclusion Randomized trials have shown clear benefits with catheter ablation compared to medical management for AFIB in heart failure. Ablation has demonstrated significantly lower all-cause mortality, reduced CV mortality, HF hospitalizations, AFIB recurrence rate, and improvement in LVEF. Patients who underwent catheter ablation showed improvement in functional outcomes like 6MWT and MLHFQ scores. There was no difference in the incidence of cerebrovascular events compared to medical management. This study adds to the growing evidence in the literature for ablation therapy; however, more trials are needed to identify patients for optimal benefits across the spectrum of heart failure patients.Forest PlotsForest Plots

Microaxial Flow Pump Use and Renal Outcomes in Infarct-Related Cardiogenic Shock - a Secondary Analysis of the DanGer Shock Trial.

In the Danish-German Cardiogenic Shock (DanGer Shock) trial, use of a microaxial flow pump (mAFP) in patients with ST-segment elevation myocardial infarction (STEMI)-related CS led to lower all-cause mortality but higher rates of renal replacement therapy (RRT). In this prespecified analysis, rates and predictors of acute kidney injury (AKI) and RRT were assessed. In this international, randomized, open label, multicenter trial, 355 adult patients with STEMI-CS were randomized to mAFP (N=179) or standard care alone (N=176). AKI was defined according to Risk, Injury, and Failure, sustained Loss and End-stage kidney disease (RIFLE) criteria and assessed using logistic regression models. Use of RRT was assessed accounting for the competing risk of death using Fine-Gray subdistribution hazard models. AKI (RIFLE≥1) was recorded in 110 patients (61%) in mAFP group and 79 (45%) in control group (p<0.01); RRT was used in 75 (42%) and 47 (27%) patients, respectively (p<0.01). About 2/3 of the RRTs were initiated within the first 24h from admission (n=48 (64%) in mAFP group, n=31 (66%) in control group). Occurrence of AKI and RRT were associated with higher 180-day mortality in both study arms. At 180 days, all patients alive were free of RRT. mAFP use was associated with higher rates of RRT, even when accounting for competing risk of death (subdistribution hazard: 1.67 [1.18-2.35]). This association was largely consistent among prespecified subgroups. Allocation to mAFP was associated with lower 180-day mortality irrespective of AKI or RRT (p=0.8 for interaction). Relevant predictors of AKI in both groups comprised reduced left ventricular ejection fraction, baseline kidney function, shock severity, bleeding events, and positive fluid balance. In addition, predictors of AKI specific to mAFP were suction events, higher pump speed, and longer duration of support. Shock severity, allocation to mAFP, and device-related complications were associated with an increased risk of AKI. AKI was generally associated with higher mortality, but the allocation to mAFP consistently led to lower mortality rates at 180 days irrespective of the occurrence of AKI with or without RRT initiation.

Ticagrelor versus Clopidogrel in Patients with left main Coronary Artery Stenting.

The left main (LM) coronary artery disease poses high risks for its special anatomical characteristics. Optimal antiplatelet therapy is still controversial in this disease. We aimed to investigate the efficacy and safety of ticagrelor and clopidogrel in patients with stent implantation in the LM coronary artery. We analyzed 3221 patients with stent implantation in the LM coronary artery from January 2011 to June 2022. Patients were separated into two groups: the ticagrelor group (n = 1550) and the clopidogrel group (n = 1671). Baseline data were balanced by propensity score matching. The primary endpoint was all-cause mortality, and secondary endpoints included cardiovascular death, myocardial infarction, stroke, stent thrombosis, or target vessel revascularization. The primary safety endpoint was major bleeding, defined as BARC 3, 5 bleeding. After propensity score matching (n = 1228 in each group), ticagrelor was linked to a lower incidence of all-cause mortality compared with clopidogrel after a three-year follow-up (5.7% vs. 8.5%; HR:0.728; 95%CI:0.537-0.985, P = 0.040). Ticagrelor treatment reduced target lesion revascularization (3.3% vs. 6.4%; HR: 0.542; 95%CI: 0.371-0.791, P = 0.001) and stent thrombosis (1.6% vs. 3.7%; HR: 0.459; 95%CI: 0.271-0.776, P = 0.004). There was no significant difference in major bleeding between the two groups. Multivariate COX analysis suggested that age, heart rate, diabetes, prior myocardial infarction, hemoglobin, serum creatinine, ticagrelor, DAPT duration, LM true-bifurcation, LM stent diameters, and IVUS were independent predictive parameters of all-cause death. Ticagrelor was associated with lower all-cause mortality and no increased risk of major bleeding compared to clopidogrel in LM stenting patients. Thus, ticagrelor can be considered a viable substitute for clopidogrel in LM disease.

Hepatic steatosis estimated by VCTE-derived CAP scores was associated with lower risks of liver-related events and all-cause mortality in patients with chronic liver disease.

The Controlled Attenuated Parameter (CAP) score derived from vibration-controlled transient elastography (VCTE, i.e. Fibroscan®) is a well-validated marker of hepatic steatosis. It is unclear if CAP scores are associated with risks of liver-related outcomes or all-cause mortality. In this retrospective cohort study, we identified 7,587 U.S. Veterans (2,689 with cured hepatitis C [HCV], 1,523 with alcohol-associated liver disease [ALD], 3,375 with metabolic dysfunction-associated steatotic liver disease [MASLD]) who underwent VCTE between 5/2015-12/2021. We followed patients for new hepatic decompensation, hepatocellular carcinoma (HCC), and death from the VCTE date until 1/1/2022. Multivariable Cox-proportional hazards regression was used to assess for the associations between CAP measurements and clinical outcomes, adjusting for age, sex, race/ethnicity, body mass index, Charlson Comorbidity Index, diabetes, liver disease etiology, liver stiffness measurements, and FIB-4, and was reported separately by disease etiology and advanced fibrosis status. Over a median follow-up time of ∼1.9 years, hepatic steatosis (grades 1-3 vs. 0) was associated with a lower risk of death (aHR 0.70, 95% CI: 0.57-0.85). Among patients with MASLD, hepatic steatosis was associated with a lower risk of decompensation (aHR 0.54, 95% CI: 0.32-0.90) and death (aHR 0.52, 95% CI: 0.37-0.73). These associations persisted in subgroup analyses of patients with advanced fibrosis and without cirrhosis. Among patients who underwent VCTE in clinical practice, the presence of substantial hepatic steatosis estimated by the CAP score was associated with lower all-cause mortality among all patients and lower risk of decompensation and death among those with MASLD.

Insurance remains a major source of disparity for patients with testicular cancer: call for advocacy.

To evaluate the effects of socioeconomic factors, including insurance status, on treatment and survival for patients with testicular cancer. We extracted a retrospective cohort from the National Cancer Database that included patients diagnosed with testicular cancer 2004-2020. Competing-risks and Cox regression multivariate models including demographic, pathological, and socioeconomic covariates were constructed to evaluate receipt of treatment and death, respectively. A total of 95 955 patients with testicular cancer were identified. Compared with private insurance, Medicaid (sub-distribution hazard ratio [SHR] 0.70, P < 0.001), Medicare (SHR 0.73, P < 0.001), and uninsured (SHR 0.72, P < 0.001) patients were associated with decreased likelihood of receiving chemotherapy. Compared with private insurance, Medicaid (SHR 0.55, P < 0.001), Medicare (SHR 0.76, P-value <0.001), uninsured (SHR 0.63, P-value < 0.001), and other government insurance (SHR 0.71, P = 0.010) was associated with decreased likelihood of receiving radiation. Medicaid insurance status (reference private, HR 2.60, P < 0.001) conferred the second largest hazard of death, behind having Stage III disease (reference Stage 0). Compared with private insurance, Medicare (HR 2.20, P < 0.001), no insurance (HR 2.32, P < 0.001), and other government insurance (HR 1.53, P = 0.027) statuses had higher risk of death. Patients diagnosed in Medicaid-expansion states had lower all-cause mortality (11.4% vs 13.6%, P < 0.001). Testicular cancer care relies on early diagnosis and treatment. It is critically important to have a healthcare system where individuals have access to insurance and are served equitably.

Characteristics, Predictors, and Clinical Outcomes in Heart Failure With Reduced Ejection Fraction According to a 1-Year Left Ventricular Ejection Fraction Following Sacubitril/Valsartan Treatment.

Optimal medical treatment can lead to improvement in left ventricular ejection fraction (LVEF) in patients with heart failure with reduced EF (HFrEF). We investigated the characteristics, predictors, and outcomes of HFrEF according to the 1-year LVEF following angiotensin receptor-neprilysin inhibitors therapy (ARNI). Using the STRATS-HF-ARNI (Strain for Risk Assessment and Therapeutic Strategies in Patients With Heart Failure Treated With Angiotensin Receptor-Neprilysin Inhibitor) registry, we identified 1074 patients with HFrEF who took ARNI and underwent baseline and 1-year echocardiography. Patients were classified as HF with improved ejection fraction (HFimpEF) and persistent HFrEF (perHFrEF) (1-year LVEF >40% and ≤40%). The primary and secondary outcomes were all-cause and cardiac mortality from the 1-year follow-up. Among 1074 included patients, 498 (46.4%) had HFimpEF, and 576 (53.6%) had perHFrEF. Older age, male sex, and large LV end-diastolic volumes were positive predictors of perHFrEF, whereas atrial fibrillation and high systolic blood pressure were identified as inverse predictors. Patients with HFimpEF showed lower all-cause and cardiac mortality rates (both log-rank P<0.001). In the multivariable analysis, perHFrEF (hazard ratio, 2.402 [95% CI, 1.251-4.610]; P=0.008) was an independent predictor of poor outcomes. The risk of all-cause mortality decreased as the 1-year LVEF increased up to 40%; however, no additional risk reduction was observed beyond 40%. Compared with patients taking renin-angiotensin-aldosterone system inhibitors in the STRATS-AHF (Strain for Risk Assessment and Therapeutic Strategies in Patients With Acute Heart Failure) registry, those in the STRATS-HF-ARNI registry demonstrated better outcomes in both HFimpEF and perHFrEF. Patients with HFimpEF had better prognosis than those with perHFrEF, and ARNI treatment in HFrEF could be more beneficial than renin-angiotensin-aldosterone system inhibitors for both HFimpEF and perHFrEF. URL: https://www.who.int/clinical-trials-registry-platform; Unique identifier: KCT0008098.

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.

Meta-analysis of improved mitral regurgitation after aortic valve replacement.

This meta-analysis aimed to compare survival outcomes among patients experiencing improvement in untreated significant mitral regurgitation (MR) following surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) for severe aortic stenosis, in contrast to those without improvement. We conducted a comprehensive search through February 2024. Pooled hazard ratios (HR) with 95% confidence intervals (CI) were computed. Kaplan-Meier curves depicting all-cause mortality were reconstructed using individual patient data derived from the included studies. A systematic review identified twelve non-randomized studies encompassing 4040 patients. The pooled all-cause mortality of the meta-analysis demonstrated a significant reduction in patients whose MR improved compared to those with persistent MR after aortic valve replacement (AVR) (HR [95% CI] = 0.55 [0.47-0.64], p < .01). The hazard ratio, derived from reconstructed time-to-event data, indicated lower all-cause mortality in patients with improved MR after AVR relative to the other cohort (HR [95% CI] = 0.50 [0.40-0.62], p < .01 in all patients, 0.48 [0.34-0.68], p < .01 in patients undergoing SAVR, and 0.58 [0.42-0.80], p < .01 in those receiving TAVR). In conclusion, this meta-analysis revealed that improved MR after AVR, whether surgically or by transcatheter approach, correlates with superior survival. The benefits of simultaneous or staged intervention on the mitral valve in individuals undergoing AVR warrant validation in future investigations.

Ischemic stroke incidence in intermediate or high-risk patients undergoing transcatheter aortic valve replacement versus surgical aortic valve replacement: a comparative systematic review and meta-analysis

Background and purposeThis comparative systematic review and meta-analysis investigated the incidence of ischemic stroke in intermediate-to-high-risk patients undergoing transcatheter aortic valve replacement versus surgical aortic valve replacement.MethodsWe conducted a systematic review and meta-analysis following the PRISMA guidelines, searching PubMed, Google Scholar, Embase, Web of Science, and Cochrane CENTRAL databases from their inception to December 2023. The evaluated outcomes were primarily incidence of stroke and transient ischemic attack (TIA), along with other secondary safety end-points at 30 days and 1 year post-procedure. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized for each study, employing a random-effects model for data synthesis irrespective of heterogeneity. Statistical heterogeneity was assessed using I2 statistics. All statistical analyses were conducted using Review Manager.ResultsWe screened 8028 articles and included 8 studies consisting of 5 randomized controlled trials and 3 observational studies. The studies examining 30-day and 1-year stroke incidence found no significant difference between TAVR and SAVR patients (OR 0.83, 95% CI 0.59 to 1.17, p = 0.30, OR 0.92, 95% CI 0.64 to 1.33, p = 0.67, respectively). Both TAVR and SAVR also had a comparable risk of having a transient ischemic attack within 30 days (OR 0.93, 95% CI 0.24 to 3.63, p = 0.92, I2 52%) and 1 year (OR 1.15, 95% CI 0.72 to 1.82, p = 0.56, I2 0%) following the procedure. Regarding safety endpoints, TAVR had lower rates of all-cause mortality and acute kidney injury at 1 year post-procedure, but a higher incidence of major vascular complications at both 30 days and 1 year compared with SAVR.ConclusionThe results suggest that TAVR and SAVR have comparable outcomes for both TIA and stroke incidence at 30 days and 1 year post-procedure, but display varying safety profiles in intermediate-to-high surgical risk patients.

Brighter nights and darker days predict higher mortality risk: A prospective analysis of personal light exposure in >88,000 individuals

Light enhances or disrupts circadian rhythms, depending on the timing of exposure. Circadian disruption contributes to poor health outcomes that increase mortality risk. Whether personal light exposure predicts mortality risk has not been established. We therefore investigated whether personal day and night light, and light patterns that disrupt circadian rhythms, predicted mortality risk. UK Biobank participants (N = 88,905, 62.4 ± 7.8 y, 57% female) wore light sensors for 1 wk. Day and night light exposures were defined by factor analysis of 24-h light profiles. A computational model of the human circadian pacemaker was applied to model circadian amplitude and phase from light data. Cause-specific mortality was recorded in 3,750 participants across a mean (±SD) follow-up period of 8.0 ± 1.0 y. Individuals with brighter day light had incrementally lower all-cause mortality risk (adjusted-HR ranges: 0.84 to 0.90 [50 to 70th light exposure percentiles], 0.74 to 0.84 [70 to 90th], and 0.66 to 0.83 [90 to 100th]), and those with brighter night light had incrementally higher all-cause mortality risk (aHR ranges: 1.15 to 1.18 [70 to 90th], and 1.21 to 1.34 [90 to 100th]), compared to individuals in darker environments (0 to 50th percentiles). Individuals with lower circadian amplitude (aHR range: 0.90 to 0.96 per SD), earlier circadian phase (aHR range: 1.16 to 1.30), or later circadian phase (aHR range: 1.13 to 1.20) had higher all-cause mortality risks. Day light, night light, and circadian amplitude predicted cardiometabolic mortality, with larger hazard ratios than for mortality by other causes. Findings were robust to adjustment for age, sex, ethnicity, photoperiod, and sociodemographic and lifestyle factors. Minimizing night light, maximizing day light, and keeping regular light-dark patterns that enhance circadian rhythms may promote cardiometabolic health and longevity.

Combined associations of physical activity, diet quality and their changes over time with mortality: findings from the EPIC-Norfolk study, United Kingdom

BackgroundPhysical activity (PA) and diet quality have each been shown to be inversely associated with mortality but their combined impact on longevity has been less explored, particularly when considering their changes over time. This study aimed to examine the separate and combined associations of PA, diet quality and their changes over time with mortality outcomes.MethodsA prospective cohort study was performed on 9349 adults aged 40 to 79 years from the population-based European Prospective Investigation into Cancer in Norfolk Study, with repeated measurements of PA and diet (from 1993 till 2004) and subsequent follow-up till 2022 (median follow-up 18.8 years). Validated questionnaires were used to derive physical activity energy expenditure (PAEE) as a proxy of total PA and adherence to the Mediterranean diet score (MDS, range 0–15 points) as an indicator of overall diet quality, and their changes over time (∆PAEE and ∆MDS). Cox regression models adjusted for potential confounders and mediators were used to estimate hazard ratios (HRs) and 95% CIs.ResultsOver 149,681 person-years of follow-up, there were 3534 deaths. In adjusted models, for each 1-SD difference in baseline PAEE (4.64 kJ/kg/day), ∆PAEE (0.65 kJ/kg/day per year), baseline MDS (1.30 points) and ∆MDS (0.32 points per year), HRs (95% CI) for all-cause mortality were 0.90 (0.86 to 0.94), 0.89 (0.85 to 0.93), 0.95 (0.91 to 0.99) and 0.93 (0.90 to 0.97), respectively. Compared with participants with sustained low PAEE (< 5 kJ/kg/day) and low MDS (< 8.5 points), those with sustained high PAEE and high MDS had lower all-cause mortality (HR 0.78; 95% CI: 0.68–0.91), as did those who improved both PAEE and MDS (0.60; 0.44–0.82). There was no evidence of interaction between PA and diet quality exposures on mortality risk. Population impact estimates suggested that if all participants had maintained high levels of PA and diet quality consistently, cumulative adjusted mortality rate would have been 8.8% (95% CI: 2.4 to 15.3%) lower.ConclusionsThese findings suggest that adopting and maintaining higher levels of PA and diet quality are associated with lower mortality. Significant public health benefits could be realised by enabling active living and healthy eating through adulthood.

Mediation effect analysis of lipoprotein levels on BMI and cardiovascular outcomes in patients with heart failure

BackgroundAmong heart failure patients with obesity, the prognosis is better than those with normal weight, a phenomenon known as the obesity paradox. However, it is unclear whether lipoprotein levels play a mediating role in the machine of the obesity paradox.MethodsThe study included 1663 heart failure patients hospitalized from January, 2019 through August, 2022. Kaplan-Meier survival analysis and Log-rank tests were performed for three endpoints in order to determine cumulative event-free survival. We investigated the correlation between Body Max Index (BMI) and outcomes by multifactorial Cox models. Mediation analysis was applied to study the presence and magnitude of mediation effects of triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 and apolipoprotein B, with the association between BMI and endpoints.ResultsIn MACCEs, the median follow-up period was 679 days. In Cox model, compared with the underweight group, a high BMI level was significantly associated with lower all-cause mortality (HR=0.47, 95%CI 0.31~0.69, p<0.001, obese vs underweight), cardiovascular mortality (HR=0.46, 95%CI 0.30~0.73, p<0.001, obese vs underweight) and the incidence of MACCEs (HR=0.68, 95%CI 0.53~0.88, p=0.003, obese vs underweight). Mediation analysis revealed that TG was the strongest mediator between BMI and endpoints, with proportions of mediated effects of 6.6% (95%CI 2.2%~18.0%, p=0.0258, in all-cause death),7.0% (95%CI 2.3%~18.9%, p=0.0301, in cardiovascular death) and 10.2% (95%CI 3.3%~27.4%, p=0.0185, in MACCEs).ConclusionsThere is an "obesity paradox" in patients with heart failure, and lipoprotein levels especially triglyceride mediate the association between BMI and cardiovascular outcomes.

Comparative Outcomes of Transcatheter Versus Surgical Aortic Valve Replacement in Elderly Patients With Severe Symptomatic Aortic Stenosis: A Systematic Review.

Aortic stenosis is the most common valvular heart disease globally; while transcatheter aortic valve replacement (TAVR) has proven to be a competitive alternative to surgical aortic valve replacement (SAVR) and revolutionized treatment, its safety and efficacy has yet to be comprehensively assessed against SAVR for certain subsets of aortic stenosis patients; therefore, this study aims to systematically analyze all the available clinical evidence from randomized clinical trials on TAVR versus SAVR among intermediate and low-risk patients with severe symptomatic aortic stenosis. We performed a systematic review of the randomized controlled trials (RCT), studies comparing TAVR and SAVR in low- and intermediate-risk patients were identified by a comprehensive search of the major databases. Mortality, stroke, length of stay, and other perioperative outcomes were assessed. A comprehensive screening of 14,384 records identified 9 studies, encompassing 8884 patients with a mean age of 77.76 years and 49.47% male. TAVR demonstrated a significantly lower all-cause mortality at both 30 days and 1 year compared to SAVR, with comparable outcomes at 2 years, underscoring its potential for enhanced survival. Stroke incidence was markedly lower with TAVR at both 30 days and 1 year, highlighting its favorable neurological safety profile. Additionally, TAVR showed a reduced rate of myocardial infarction within the initial 30 days post-procedure. Prosthetic valve endocarditis rates remained low and comparable between the two approaches at both 30 days and 1 year. Notably, TAVR was associated with a significantly shorter hospital stay, suggesting a faster recovery trajectory and improved patient throughput. These findings collectively emphasize the superior efficacy and safety profile of TAVR over SAVR. TAVR may serve as a viable therapeutic option for intermediate and low-risk patients with severe symptomatic aortic stenosis. Future research should focus on long-term outcomes and TAVR device durability, especially in younger, lower-risk populations.

Association between statin usage and mortality outcomes in aging U.S. cancer survivors: a nationwide cohort study

BackgroundThe population of Aging cancer survivors in the United States has surged to over 16.9 million. Research on the relationship between statin usage and post-cancer survival rates remains limited.AimsThis study aims to investigate the association between statin use and various causes of mortality among aging cancer survivors.MethodsWe analyzed NHANES data from 1999 to 2018, Statin usage, both hydrophilic and lipophilic, was derived from NHANES prescription records. We utilized Cox proportional hazards models to associate statin utilization with mortality, differentiating causes of death according to statin type and patterns of use.ResultsWithin a cohort of 2,968 participants, statin usage was categorized into non-users (1,738), hydrophilic statin users (216), and lipophilic statin users (982). Compared to those who did not use statins, individuals prescribed hydrophilic statins did not show a reduced risk of all-cause mortality (adjusted hazard ratio [HR] 1.01; 95% confidence interval [CI] 0.72–1.41; P = 0.960), as outlined in Model 3. In contrast, the group receiving lipophilic statins exhibited a notable decrease in all-cause mortality risk (adjusted HR, 0.77; P = 0.003). Nonetheless, both hydrophilic and lipophilic statins were effective in diminishing the risk associated with cancer from its onset until death, with hydrophilic statins showing a greater level of efficacy.DiscussionThe potential of statins to reduce cancer-related mortality may provide avenues for targeted clinical interventions and management strategies.ConclusionsOur study reveals that the use of lipophilic statins is significantly associated with lower all-cause and cancer-cause mortality risks among aging cancer survivors.

Timely Follow-Up After a First Diagnosis of Cirrhosis is Associated With Reduced Mortality but No Impact on Rehospitalisations: A Population-Based Cohort of 8852 Patients.

Timely transition of care amongst patients with a first diagnosis of cirrhosis in a hospital to an outpatient visit is important. We evaluated rates of outpatient follow-up after a first diagnosis of cirrhosis during an inpatient setting, and its association with subsequent rates of rehospitalisation and mortality. We conducted a population-based cohort study identifying all hospitalised patients in Sweden diagnosed with cirrhosis between 2002 and 2020 from the Swedish National Patient Register. The primary outcome was any outpatient visit related to cirrhosis within 90 days after hospital discharge. Secondary outcomes were rates of rehospitalisation and mortality within 1 year of discharge in patients receiving outpatient follow-up within 90 days or not. Cox regression was used for all analyses, and incidence rates per 1000 person-years were calculated for mortality and rehospitalisation. Of 8852 patients, 3759 (42%) had outpatient follow-up within 90 days of discharge. Patients who received follow-up within 90 days of discharge were younger, had a higher level of education and were more likely to have liver decompensation or hepatocellular carcinoma compared to those without timely follow-up. We found that follow-up within 90 days was associated with lower rates of all-cause mortality within 1 year (aHR = 0.86, 95%CI = 0.78-0.96) but with no significant impact on rehospitalisations (aHR = 0.97, 95%CI = 0.91-1.03). In Sweden, 42% of hospitalised patients with newly diagnosed cirrhosis receive outpatient follow-up within 90 days of their hospital discharge. These patients may experience lower mortality but no change in rehospitalisations within 1 year.

S1689 Use of Sodium-Glucose Transport Protein 2 Inhibitors and Dipeptidyl Peptidase 4 Inhibitors in Patients with MASLD in a Real-World Setting is Associated with Lower All-Cause Mortality

S1689 Use of Sodium-Glucose Transport Protein 2 Inhibitors and Dipeptidyl Peptidase 4 Inhibitors in Patients with MASLD in a Real-World Setting is Associated with Lower All-Cause Mortality