Risk Of All-cause Mortality Research Articles

Diabetes and the risk of cardiovascular events and all-cause mortality among older adults: an individual participant data analysis of five prospective studies.

Guidelines and studies provide conflicting information on whether type 2 diabetes (T2D) should be considered a coronary heart disease risk (CHD) equivalent in older adults. We synthesized participant-level data on 82,723 individuals aged ≥65 years from five prospective studies in two-stage meta-analyses. We estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of T2D (presence versus absence) on a primary composite outcome defined as cardiovascular events or all-cause mortality. Secondary outcomes were the components of the composite. We evaluated CHD risk equivalence by comparing outcomes between individuals with T2D but no CHD versus CHD but no T2D. The median age of participants was 71 years, 20% had T2D and 17% had CHD at baseline. A total of 29,474 participants (36%) experienced the composite outcome. Baseline T2D was associated with higher risk of cardiovascular events or all-cause mortality versus no T2D (HR 1.44, 95% CI [1.40-1.49]). The association was weaker in individuals aged ≥75 years versus 65-74 years (HR 1.32 [1.19-1.46] vs. 1.56 [1.50-1.62]; p-value for interaction = .032). Compared to individuals with CHD but no T2D, individuals with T2D but no CHD had a similar risk of the composite outcome (HR 0.95 [0.85-1.07]), but a lower risk of cardiovascular events (HR 0.76 [0.59-0.98]). T2D was associated with increased risk of cardiovascular events and all-cause mortality in older adults, but T2D without CHD conferred lower risk of cardiovascular events compared to CHD without T2D. Our results suggest that T2D should not be considered a CHD risk equivalent in older adults.

Race/Ethnicity, Education, and All-Cause Mortality in US Adults: Mediation by Telomere Length

Abstract Background Racial/ethnic inequities in mortality risk are pervasive in the United States even after controlling for socioeconomic status indicators such as educational attainment. Although the mechanisms underlying these inequities remain unclear, telomere length (TL) has emerged as a potential mediator. We aimed to investigate the joint association of race/ethnicity and education with all-cause mortality risk, and the contribution of TL to this relationship. Methods We used data from the U.S. National Health and Nutrition Examination Survey, 1999 to 2002, and 2019 Linked Mortality File (n = 6,526 non-institutionalized adults aged 25 years or older, including 2,166 deaths), a retrospective cohort study with a follow-up period to December 31, 2019. Cox proportional hazards regression and causal mediation analysis were used to address these aims. We reported hazard ratios (HR) and 95 % confidence intervals (CI). Furthermore, for the mediation analysis, we reported the total, direct, and indirect effects measured as HR and 95 % CI. Results After adjusting for age and sex, among White individuals, those with less than a high school education had a 2.26 times higher (95% CI: 1.93, 2.65) rate of all-cause mortality compared to those with some college or higher education. When compared with White adults with at least a college degree, Black adults with at least a college degree had a 1.38 higher rate of dying (95% CI: 1.04, 1.84). There was no significant joint association of race/ethnicity and education on all-cause mortality in Mexican Americans. In the mediation analysis, TL did not significantly contribute to the joint association of race/ethnicity and education with all-cause mortality risk. Discussion These findings underscore the need for a better understanding of the joint relationship of race/ethnicity and education on mortality risk inequities and their potential mechanisms to improve population health ultimately. Key messages • Lower educational attainment was associated with higher mortality rates among White individuals, disparities persisted among the Black population, despite higher education levels. • Our analysis did not find a significant mediation effect of telomere length on the joint effect of race/ethnicity and education-mortality relationship.

Utilizing unsupervised machine learning to uncover novel phenogroups within the broad QRS complex

Abstract Background Conduction disease can manifest as a broad QRS complex on the ECG. Broad QRS is conventionally categorised as left bundle branch block (LBBB) and right bundle branch block (RBBB) or non-specific intraventricular conduction delay (IVCD), based on QRS morphology. These subgroups were coined over a century ago and have been relevant for heart failure with reduced ejection fraction and cardiac resynchronization therapy (CRT). However, there may be more precise phenogroups underlying broad QRS complexes. Purpose Using unsupervised machine learning to define novel broad QRS phenogroups and characterise them using clinical variables and disease outcomes. Methods We extracted 51 relevant features using a Variational Autoencoder from 47,456 median-beat ECGs with broad QRS intervals (QRS ≥ 130ms) from a secondary care cohort. These were input into Discriminative Dimensionality Reduction via Learning a Tree (DDRTree), a clustering method that models the continuum of heterogeneity by projecting the underlying distribution as a tree structure in a low-dimensional space, while assigning distinct branch/cluster labels. Results Six distinct phenogroups were identified within broad QRS morphologies (Figure-1). Two branches were RBBB dominant (Branch 1: more males, high-comorbidity; Branch 6: low-comorbidity/healthy-RBBB). Two branches were LBBB dominant (Branch 4: mixed IVCD with CHB burden; Branch 5: more females, CRT responders). Two branches were IVCD/mixed-phenotype (Branch 2: IVCD-dominant, high risk of future cardiovascular events; Branch 3: average/core branch). Within LBBB, Branch 4 and 5 showed similar trends with improving echocardiography profiles and CRT response when adjusted for covariates, each compared against the core branch. Branch 5 was distinct due its high risk of future HF (HR 1.19 [1.07-1.33] p < 0.01), cardiovascular death (HR 1.35 [1.20-1.50] p < 0.0001), all-cause mortality (HR 1.08 [1.01-1.16] p < 0.05) and CHB (HR 1.35 [1.16-1.56] p < 0.0001) (Figure-2). Conversely within RBBB, Branch 1 and 6 showed stark differences across various traits. Branch 1 captured a high-risk profile associated to higher risk of cardiovascular death (HR 1.37 [1.24-1.52] p < 0.0001), all-cause mortality (HR 1.20 [1.12-1.29] p < 0.0001) and CHB (HR 1.15 [1.01-1.32] p < 0.05) (Figure-2), while Branch 6 retained a low-risk phenotype. The tree dimensions also revealed relevant trends in cardiac anatomy and valvular dysfunction; the top-left region in Figure-1 associated with higher left ventricular ejection fraction and lower left ventricular end-diastolic dimension, lower left ventricular end-systolic dimension and a greater CRT response. Conclusion Through unsupervised methods we have identified conduction disease phenogroups with additive value for disease prognosis and CRT response prediction beyond traditional LBBB and RBBB labels. These novel phenogroups may help guide precision care for patients with a broad QRS complex.Figure-1Figure-2

Circadian heart rate fluctuations predict 21-year cardiovascular and all-cause mortality in type 2 and type 1 diabetes

Abstract Background Alterations in circadian heart rate (HR) fluctuations have been associated with cardiovascular events in the general population. This study aimed at defining their long-term prognostic value for cardiovascular and all-cause mortality in patients with diabetes. Methods We examined a cohort of 349 patients with type 2 or type 1 diabetes (52% women, age 57.1±11.9 years, BMI 29.4±5.9 kg/m2, HbA1c 8.6±2.1%, 81% type 2 diabetes) who underwent 24h ambulatory blood pressure and HR monitoring (ABPM) and assessment of diabetic microvascular complications. The median standard deviation (SD) value of ABPM-derived HR measurements was used to define patients with low daily HR fluctuations (low 24h-HR SD), while a <10% decline in average night-time vs day-time HR identified patients with blunted nocturnal HR dip (n=107, 31%). The clinical features and time-dependent prognostic impact of these conditions were evaluated over a 21-year observational follow-up. Results Low 24h-HR SD and blunted nocturnal HR dip were associated with an adverse cardiometabolic risk profile and high prevalence of cardiac autonomic neuropathy and nephropathy. After 6,251 person-years of follow-up (21.0 [14.0-21.0] years), a total of 136 (39%) deaths occurred, of which 100 (68%) of cardiovascular cause. After adjustment for potential confounders, the low 24h-HR SD group had a higher risk for both cardiovascular (hazard ratio 1.99, 95% CI 1.29–3.06, p=0.002) and all-cause mortality (hazard ratio 1.50, 95% CI 1.03–2.18, p=0.033), compared with high 24h-HR SD. Consistently, patients with blunted nocturnal HR dip had a higher adjusted risk for cardiovascular (1.61, 95% CI 1.07–2.43, p=0.023) and all-cause mortality (1.61, 95% CI 1.11–2.34, p=0.012), compared with those with preserved nocturnal HR dip. Conclusions Impaired circadian HR fluctuations are frequent in patients with long-standing diabetes and are associated with microvascular disease and increased long-term cardiovascular and all-cause mortality. Identifying these conditions via 24h-ABPM may provide a cost-effective risk stratification tool in this high-risk population.Kaplan-Meier curves

Serum homocysteine levels and mortality: a cohort study

Abstract Background Homocysteine, an intermediate metabolite derived from dietary methionine, plays a pivotal role in deoxyribonucleic acid expression and contribute to its antioxidant capabilities. Elevated homocysteine levels can increase the risk of cardiovascular disease (CVD), cancer, and neurological disorder; however, low levels of homocysteine are generally not considered harmful. This study evaluates the association between all levels of homocysteine-both low and high-and the risk of all-cause and cause-specific mortality in Korean adult men. Methods A study involving 221,356 Korean adult men categorized them into quintiles based on their homocysteine levels. The main outcomes examined were mortality from all causes, cardiovascular disease (CVD), cancer, and dementia. Hazard ratios (HRs) were determined using Cox proportional hazards models, and the dose-response relationship between homocysteine levels and mortality risk was further analyzed using a restricted cubic splines model. Results Compared to the reference category (Q2, 8.8-9.9 µmol/L), there was a significant increase in all-cause mortality associated with both low and high homocysteine levels after adjusting for multiple variables (Pinteraction=0.002). Furthermore, spline regression revealed a U-shaped relationship between homocysteine levels and both all-cause and CVD mortality, with an inflection point at 9.1 µmol/L. This U-shaped association was not observed in the subgroup that received vitamin supplements. Conclusions Among young and middle-aged Korean adult men, both low and high homocysteine levels were found to increase the risk of all-cause and CVD mortality, demonstrating a U-shaped relationship. However, this association lost statistical significance with vitamin supplementation. These findings underscore the importance of monitoring both low and high homocysteine levels as potential mortality risk factors in men and suggest a possible protective role of vitamins. Key messages • Both low and high levels of homocysteine in young and middle-aged Korean men are associated with increased risks of all-cause and cardiovascular mortality, demonstrating a U-shaped relationship. • Vitamin supplementation appears to nullify this association, suggesting a potential protective effect against mortality.

Long-term exposure to PM2.5 and mortality among Japanese community-dwelling adults

Abstract Background Long-term exposure to PM2.5 (particulate matter with a diameter of 2.5 μm or smaller) is a risk factor for mortality and cardiovascular disease including stroke. However, there was limited evidence for the association between PM2.5 exposure and stroke in Asia where the major cardiovascular disease is stroke. Additionally, the causal association between PM2.5 and respiratory disease is still unresolved. The aim of this study was to investigate the association between long-term exposure to PM2.5 and all-cause, cardiovascular, and respiratory disease mortality in a Japanese community-based prospective cohort. Methods This study included 46,974 participants (19,707 men; 27,267 women) from the second cohort of the Ibaraki Prefectural Health Study. The participants were followed up from baseline survey (in 2009) to 31 December 2019. We confirmed underlying causes by death certificates. Using the PM2.5 concentrations estimated by the inverse distance weighting methods based on ambient air monitoring data, administrative area level concentrations were assigned to each participant. The hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality using a Cox proportional hazard model were presented. Results We identified 2,789 all-cause deaths during the 470,178 person-years of follow-up. PM2.5 exposure had no significant association with all-cause and cause-specific mortality. The multivariable-adjusted HRs per 1 μg/m3 increase in the PM2.5 concentration were 0.94 (95% CI = 0.80-1.12) for coronary heart disease, 0.92 (95% CI = 0.81-1.04) for stroke and 1.09 (95% CI = 0.97-1.23) for non-malignant respiratory disease. Conclusions We observed little evidence of increased risk of all-cause and cause-specific mortality by long-term exposure to PM2.5 whose concentrations ranged from 8.3 to 13.1 μg/m3. A somewhat increased trend for non-malignant respiratory disease mortality may not be negligible. Key messages • We found little evidence of increased risk of all-cause and cause-specific mortality by long-term exposure to PM2.5. • Somewhat increased tendency for non-malignant respiratory disease mortality associated with PM2.5 exposure was observed.

Sex differences in clinical characteristics, phenotypes, management, and long-term outcomes of myocardial injury: an international cohort study

Abstract Background Several studies have demonstrated sex differences in patients presenting to the emergency department (ED) with myocardial infarction, heart failure or syncope. Whether sex-specific differences in chest pain patients with myocardial injury exist is unknown. Purpose To determine whether sex-specific differences in the clinical characteristics, phenotypes, management, and long-term outcomes of patients with myocardial injury exist. Methods Patients presenting to the ED with chest pain suggestive of MI were consecutively enrolled into a prospective multicenter international diagnostic study. Final diagnoses were centrally adjudicated by two independent cardiologists, applying the fourth universal definition of myocardial infarction, using all available medical records, including serial hs-cTn and cardiac imaging. Follow-ups were performed at 3 months, 1-, 2- and 5-years. The primary outcome was 5-year all-cause mortality. Secondary outcomes included 5-year cardiovascular mortality and non-cardiovascular mortality. Multivariable flexible parametric (Royston-Parmar) models assuming proportional hazards were fitted. Models were adjusted for age, history of coronary artery disease, history of malignancy, diabetes, hypertension, smoking status, history of liver disease, and renal function. Results Among 8046 chest pain patients presenting to the ED, 1158 (14.4%) had myocardial injury, of which 358 (31%) were females and 800 (69%) males. Women were older (79 years, vs. 73 years), had fewer cardiovascular risk factors and comparable non-cardiovascular comorbidities except for lung disease which was more commonly found in men. Myocardial injury phenotypes varied between sexes (Figure). The most common phenotype in both sexes was heart failure, yet it was more common in men (37.2%) than in women (22.3%). The second most common phenotype in women was hypertension (15.4%) and arrhythmia (15.4 %), while in men was myocarditis (17.8 %), followed by arrhythmia (15.8%). Women underwent less invasive coronary angiography (19.8% vs 26.9%) or stress testing (12% vs 21.5%). In the angiographic findings, women presented more often with normal findings (30.4% vs. 19.6%) or mild CAD (20.3% vs. 11.2%) whereas men displayed more frequently 3-vessel disease (14.5% vs. 36.4%), Table. After adjusting for known confounders, women were associated with a lower 5-years risk for all-cause mortality (HR 0.69; 95%CI: 0.56–0.83) and cardiovascular mortality (HR 0.61; 95%CI: 0.46–0.79). No statistically significant difference in non-cardiovascular mortality risk was found (HR 0.79; 95%CI: 0.59-1.04). Conclusions Women presenting with chest pain to the ED and having myocardial injury were less likely than men to undergo coronary angiography or non-invasive cardiac imaging. Long-term risk for all-cause or cardiovascular mortality was lower for women compared to men.Myocardial Injury phenotypesPatient management

Temporal trends in mortality and hospitalisation risk in patients with heart failure according to frailty status

Abstract Background Heart failure (HF) and frailty often coexist, and patients with both conditions have a higher risk of mortality and hospitalisation compared with those who are not frail. Over the past two decades, advances in medication targeting HF have been introduced, prolonging the life of patients with HF, but also resulting in increased comorbidity accumulation and susceptibility to frailty. It remains unknown how the interplay between HF and frailty at HF onset impacts patient prognosis and how this has changed over time. Purpose We investigated the temporal trends in the risk of all-cause mortality and HF hospitalisation in patients with HF from 1999 to 2017 according to their frailty status. Methods From Danish nationwide registers, we included patients with new-onset HF. Patients were categorised into four groups according to the year of HF onset: 1999-2002, 2003-2007, 2008-2012, and 2013-2017. The Hospital Frailty Risk Score was used to classify patients into frailty severity categories: 1) non-frail, 2) moderately frail, and 3) severely frail. The primary outcome was the 5-year cumulative incidence of all-cause mortality, assessed using the Kaplan-Meier estimator. The secondary outcome was the 5-year risk of HF hospitalisation, assessed using the Aalen-Johansen estimator, accounting for the competing risk of death. Moreover, a sensitivity analysis was conducted using a multivariable Cox proportional hazard model, investigating the interaction between year group and frailty status for all-cause mortality, comparing frail patients with non-frail patients. Results Among 131,235 patients with HF (median age 74 years; 39.7% female), 102,635 (78%) were categorised as non-frail, 26,054 (20%) as moderately frail, and 2609 (2%) as severely frail. The proportion of moderately frail patients increased the most, from 13% in 1999 to 25% in 2017. From 1999-2002 to 2003-2017, the 5-year cumulative incidence of all-cause mortality declined from 56.4% (95% CI, 55.8-57.0%) to 33.3% (32.6-34.1%), 79.8% (78.5-81.0%) to 58.6% (57.2-60.1%), and 90.8% (85.6-96.0%) to 79.8% (76.4-83.2%) in the non-frail, moderately frail, and severely frail patient group, respectively (Fig 1). The largest relative improvement was observed in the non-frail patient group. The 5-year cumulative incidence of HF hospitalisation remained fairly constant across the frailty groups (Fig 2). Conclusions From 1999 to 2017, we observed an increase in moderately and severely frail patients. Overall, the mortality risk decreased across all frailty groups. These findings underscore the importance of implementing guidelines directed at frail patients with HF.5-year risk of all-cause mortality5-year risk of HF hospitalisation

Modern epidemiology of heart failure with reduced and preserved ejection fraction in population-wide linked electronic health records: a study of 208815 heart failure patients in England

Abstract Background The modern epidemiology of heart failure (HF) with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) is yet to be studied on a population-wide scale in the United Kingdom, particularly in the post-COVID-19 era. Purpose To explore the post-pandemic epidemiology and outcomes of HFrEF and HFpEF in population-wide electronic health records (EHRs). Methods We accessed data in the National Health Service England’s Secure Data Environment for England via the British Heart Foundation Data Science Centre CVD-COVID-UK/COVID-IMPACT Consortium. We used EHRs for 57 million individuals to identify patients aged ≥18 years, of known sex, who were diagnosed with HF as the primary condition in any inpatient hospital stay from 01 Jan 2020 to 27 Feb 2023. By linking HF admissions with the National Heart Failure Audit, six other National Institute for Cardiovascular Outcomes Research audits, and the General Practice Extraction Service Data for Pandemic Planning and Research, we classified HF into HFrEF and HFpEF based on recorded left ventricular ejection fraction (LVEF; ≤40% and >40% respectively) or documented diagnosis. We compared characteristics of these groups and used Cox proportional hazards models, adjusted for key confounders, to examine differences in cause-specific mortality and hospitalisation outcomes. Results Over 3.2 years, we identified 208815 patients with a HF hospitalisation. 86110 (41%) patients had HFrEF, 65735 (31%) had HFpEF, and 56970 (27%) could not be categorised. Compared to patients with HFrEF, patients with HFpEF were older (mean [SD], 80.5 [10.9] vs 75.6 [13.6] years), more often female (n [%], 35990 [54.8] vs 30835 [35.8]), and less deprived (n [%] in the least-deprived Index of Multiple Deprivation 2019 quintile, 12275 [18.7] vs 15055 [17.5]; Table). Over a median follow-up of 11 months among patients with HFrEF and HFpEF, 99740 patients were re-hospitalised (66%) and 71075 (47%) died. Risks of all-cause, cardiovascular, non-cardiovascular, and heart-failure re-hospitalisations were all higher in patients with HFpEF compared with patients with HFrEF (Figure). The risk of all-cause mortality was modestly higher in patients with HFpEF (HR 1.04, 95% CI 1.02–1.06; Figure). Risks of death due to cardiovascular disease overall, fatal myocardial infarction, and fatal HF were higher among patients with HFrEF. In contrast, risks of death due to non-cardiovascular causes were higher in patients with HFpEF. There were no differences in risk of death due to COVID-19. Conclusions Unlike previous epidemiological surveys of HF, patients with HFpEF appear to face worse prognosis and risk-adjusted disease trajectories compared with those with HFrEF after hospitalisation in this population-wide study. Excess mortality in HFpEF appears driven by higher risk of non-cardiovascular mortality. However, post-discharge survival is poor regardless of LVEF and represents an ongoing target for quality improvement efforts.

Incidence, characteristics, and prognostic impact of cancers in patients with atrial fibrillation: a report from the GLORIA-AF registry

Abstract Background Cancers and atrial fibrillation (AF) are all aging-related diseases. Coexistence of the two conditions makes management complex due to increased risk of both thromboembolism and bleeding. Purpose The aim of the present study was to analyze the incidence and prognostic impact of cancers in patients with AF in the GLORIA-AF registry. Methods GLORIA-AF registry is a prospective multi-centered international multi-centered AF cohort studies. We characterized these patients according to the presence or absence of a cancer diagnosis when enrolled. The primary endpoints were all-cause mortality, cardiovascular mortality, and major bleeding; the secondary endpoints were major adverse cardiovascular events (MACEs) including all-cause mortality, stroke, and major bleeding. Results The prevalence of cancers was 9.7%. The mean CHA2DS2-VASc and HAS-BLED scores in cancer patients were higher than in non-cancer patients (mean CHA2DS2-VASc 3.5 vs. 3.2, P<0.001; mean HAS-BLED score 1.6 vs. 1.3, P<0.001). Patients with cancers had higher oral anticoagulant use than non-cancer patients (84.4% vs. 81.0%, P<0.001) and were more likely to receive NOACs (58.4% vs. 54.0%, P<0.001). During a mean follow up period of 3 years, AF patients with cancers had significantly higher all-cause mortality (15.0% vs. 8.3%, P<0.001), major bleeding rate (5.3% vs. 3.1%, P<0.001), the composite of all-cause mortality, stroke, and major bleeding (20.0% vs. 12.0%, P<0.001), and composite of all-cause mortality, thromboembolism, and major bleeding than non-cancer patients (21.0% vs. 12.0%, P<0.001), but nonsignificant differences in cardiovascular mortality (3.6% vs. 3.1%, P=0.2), any stroke, transient ischemic attack, or non-central nervous system embolism (3.2% vs. 2.7%, P=0.1), and OAC discontinuation (29.0% vs. 28%, P=0.2). Among the cancers, hematological cancer was associated the highest risk of all-cause mortality (HR=3.7, 95%CI 2.69-5.0, P<0.001) while respiratory cancer was associated the highest risk of major bleeding (HR=2.62, 95%CI 1.24-5.5, P=0.011). After multivariable adjustment, cancer was independently associated with increased risk of all-cause mortality (HR=1.30, 95%CI 1.05-1.62, P=0.018), composite of all-cause mortality, stroke, and major bleeding (HR=1.32, 95%CI 1.04-1.68, P=0.022), and composite of all-cause mortality, thromboembolism, and major bleeding (HR=1.29, 95%CI 1.04-1.60, P=0.022), but the risk of major bleeding was nonsignificantly different (HR=1.16, 95%CI 0.71-1.87, P=0.6). Conclusions Cancer is a common comorbidity in patients with AF and is independently associated with increased risk of poor outcomes including all-cause mortality and MACEs. However, cancer did not increase the risk of cardiovascular mortality, major bleeding, and discontinuation of OAC. Cancer in patients with AF should receive appropriate treatments for the cancer itself and appropriate OAC, although strategies may vary between different cancers.Distribution of caners in GLORIA-AFKaplan-Meier curves for the outcomes

Associations between neutrophil-percentage-to-albumin ratio level and all-cause mortality and cardiovascular disease-cause mortality in general population: evidence from nhanes 1999-2010

Abstract Introduction Chronic inflammation is a recognized independent risk factor for cardiovascular disease (CVD), highlighting the need for reliable inflammatory indicators to predict CVD(1). As an inflammatory indicator which has been proved to have predictive value for the prognosis of CVDs, neutrophil percentage-to-albumin ratio (NPAR) has obtained increasing attention(2,3), but further research is needed to confirm the relationship with mortality in general population. Purpose To explore whether NPAR can serve as a predictive inflammatory indicator for CVD-cause and all-cause mortality in general population. Methods This prospective cohort study included 21317 individuals who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. The baseline NPAR level was calculated as Neutrophil percentage (%) * 100/Albumin (g/dl). Data for CVD and all-cause mortality were acquired by linking the cohort database with the National Death Index through December 31, 2019.Weighted Kaplan–Meier curves with log-rank tests were conducted to access cumulative survival differences across different NPAR results. Restricted cubic spline analyses were employed to examine the nonlinear association. Multivariable Cox proportional hazards regression models were used to compute hazard ratios and 95% CIs. Receiver Operating Characteristic (ROC) curves were used to compare predictive value of NPAR with systemic immune inflammation index (SII) and neutrophils percent. Results In this cohort study, during 270014 person-years of follow-up, 4074 all-cause deaths and 1116 CVD-cause deaths were documented. We found significant associations between elevated NPAR and both CVD-cause and all-cause mortality in Kaplan–Meier curves (both P for log-rank test<0.001). Restricted cubic splines revealed non-linear associations between NPAR level and both CVD-cause (P=0.018 for nonlinearity) and all-cause mortality (P<0.001 for nonlinearity) (Figure 1A and 1B). After adjusting for confounding factors, participants in the highest NPAR tertile had a significantly increased risk of all-cause mortality (HR: 1.46, 95% CI: 1.33-1.61) and CVD-cause mortality (HR: 1.54, 95% CI: 1.32-1.80) compared to those in the lowest tertile, while no association was detected for individuals in the middle tertile (Figure 2). The effect of NPAR was consistent across most subgroups, with no significant interaction with most covariates except for high cholesterol (CVD-cause mortality: P=0.014, all-cause mortality: P=0.022). Further ROC analysis confirmed that NPAR had higher predictive value than neutrophil percent and SII. Conclusions Elevated NPAR level was significantly associated with an increased risk of all-cause and CVD-cause mortality in general population.Given its easy-to-calculate nature and high predictive value, NPAR index, with implications in public health, deserves greater attention in inflammatory assessment and cardiovascular prevention.Figure 1 Nonlinear associationFigure 2 Cox regression table

Correlation between short-term quality of life improvement and clinical outcomes - a post-hoc ISCHEMIA trial analysis

Abstract Background Patients with symptomatic coronary artery disease (CAD) exhibit improvement in quality of life (QoL) after invasive management (percutaneous coronary intervention [PCI] and coronary artery bypass grafting [CABG]). However, it is not clear how QoL improvements after intervention are related to clinical outcomes. Purpose Using the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) population, we sought to assess the relationship between short-term QoL improvement and long-term clinical outcomes. Methods All participants in the ISCHEMIA trial who were randomized to the invasive arm and who had QoL scores available were included in the analysis. QoL improvement was calculated using the difference between the Seattle Angina Questionnaire (SAQ) score at baseline and at six months regarding randomization. The primary outcome was the trial-defined composite outcome (cardiovascular death, myocardial infarction, cardiac arrest or hospitalization for unstable angina/heart failure) and all-cause death. The secondary outcome was all-cause mortality. Median follow-up was 3.3 years. Cox proportional hazards models included clinically relevant demographic and angiographic covariates. Results After the exclusion of the conservative treatment arm and patients without QoL follow-up or covariate data, 1,577 patients were selected for the final analysis (Fig.1). The median baseline SAQ score was 74 (interquartile range, IQR: 60-88), the change in score at six months was 14 (IQR: 2-26), and 76.1% of patients experienced improvement in QoL. Six-month QoL improvement was not associated with a lower risk of the primary outcome (hazard ratio [HR]: 0.961, 95% confidence interval [CI], 0.920-1.005, p=0.081 – Table 1), but was associated with all-cause mortality (HR: 0.919, 95% CI, 0.859-0.982, p=0.013 – Table 1). In this population, increased age (HR: 2.370, 95% CI, 1.710-3.287, p<0.001, per 10 years) was also associated with higher risk of all-cause mortality. Conclusions Among invasive treated patients in ISCHEMIA trial, six-month QoL improvement was associated with a lower risk of long-term all-cause mortality, but not with a lower risk of major adverse events.Figure 1.Study population.

Renal hyperfiltration as risk factor of major adverse cardiovascular events in patients with acute myocardial infarction

Abstract Objectives While the interaction between heart and kidney potentially contributes the development of renal hyperfiltration (RHF), its clinical consequence of is not clear in patients with acute myocardial infarction (AMI). Methods A total of 9,561 AMI patients with estimated GFR (eGFR) ≥60 mL/min/1.73 m² were enrolled from a large nationwide, multi-center, prospective, observational cohort between November 2011 and December 2015. RHF was defined as eGFR >90th percentile after multiple adjustments. The primary endpoint was a combination of 3-year major adverse cardiovascular events (MACEs) after AMI treatment. Results The cumulative event rate of MACEs was significantly higher in patients with RHF. In multivariable Cox-regression analysis, RHF increased the 1.34-fold risk of MACE (95% confidence interval [CI] 1.12-1.62) compared to those without RHF. Patients with RHF had a significantly higher risk of all-cause mortality (hazard ratio [HR] 1.64; 95% CI 1.25-2.14) and cardiac death (HR 1.78; 95% CI 1.26-2.51). There was a linear correlation between the adjusted risk of MACEs and eGFR, with the risk increasing as eGFR exceeded approximately 100 mL/min/1.73 m². In the 1:1 propensity-score matched population, the cumulative event rate of MACEs, all-cause mortality, and cardiac death were consistently higher in patients with RHF (all p <0.05). Conclusion RHF was significantly associated with an increased risk of MACEs, all-cause mortality, and cardiac death following AMI compared to patients without RHF. Our study offers new insights into the risk stratification of AMI patients presenting with RHF.

Left ventricular dilatation in patients with significant aortic regurgitation: association with mortality

Abstract Background In aortic regurgitation (AR), left ventricular (LV) dilatation occurs as a response to volume and pressure overload. Current guidelines recommend the use of LV end-systolic diameter index (LVESDi) to give indication for intervention, but recent studies suggested that volumetric measures may be more accurate in identifying LV remodeling in AR as compared to linear dimensions. Purpose To characterize LV dilatation in patients with significant AR (≥moderate), based on linear and volumetric dimensions, and to determine their prognostic value. Methods A total of 1070 patients (56 ± 18 years,65% male) were included. Cut-off values of 20 mm/m2 for LVESDi and 45 ml/m2 for end-systolic volume index (LVESVi) were used to identify the following LV remodeling patterns: No-significant LV dilatation (N=485), when both LVESDi and LVESVi were below the cut-off values; Discordant LV dilatation (N=279) if only one positive criterion was present; and Concordant LV dilatation (N=306) when both LVESDi and LVESVi were enlarged (Figure 1). The primary endpoint was all-cause mortality. Results Baseline characteristics differed across the 3 LV dilatation groups. Compared to patients with no-significant or discordant LV dilatation, those with concordant LV dilatation were more likely to be men, had a lower prevalence of systemic arterial hypertension and were more symptomatic. Concerning the echocardiographic characteristics, patients with concordant LV dilatation showed more severe AR, worse LV systolic function and larger left atrial volumes compared to the other two LV dilatation groups. During a median follow-up of 89 (IQR,54-132) months, 168 (16%) patients died and 484 (45%) underwent aortic valve surgery (AVS). Patients with concordant LV dilatation had worse 10-year survival (72%) compared to the groups (Figure 2), but benefited more from AVS based on a landmark analysis (p=0.001). In multivariable analysis, a significant association with the risk of all-cause mortality was observed for the presence of discordant (HR 1.645, 95%CI 1.077-2.513;p=0.021) or concordant LV dilatation (HR 2.695, 95% CI 1.710 to 4.249;p<0.001) after adjusting for the variables significant in the univariate analysis such as, age, male gender, NYHA class III-IV, AVS as a time-dependent covariate and LV ejection fraction (LVEF) ≤55%. Moreover, the addition of LV dilatation groups to a basal model including the above mentioned clinical and echocardiographic variables led to a significant increase in the predictivity of the model (Chi-square difference=21.1,p<0.001). Conclusion In patients with significant AR, LV dilatation detected by linear and/or volumetric measures was independently associated with increased mortality. Combining both methods for assessment of LV remodeling may improve risk stratification of these patients.

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

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 role of anticoagulation in atrial high-rate episodes: a meta-analysis

Abstract Background The role of anticoagulation in patients with atrial high-rate episodes (AHRE), who have no prior history of atrial fibrillation or atrial flutter, is being extensively studied. Purpose Given the increased thrombo-embolic risk in patients who have atrial high-rate episodes, our aim was to evaluate whether anticoagulation leads to enhanced clinical outcomes compared to no anticoagulation (1). Methods We searched PubMed, EMBASE, and the Cochrane Library, through February 2024, for studies evaluating outcomes in patients with atrial high-rate episodes managed with oral anticoagulation (OAC) compared to those not managed with oral anticoagulation. Outcomes assessed were ischemic stroke, thromboembolic events, major bleeding, and all-cause mortality. A fixed-effects model was used to calculate pooled risk risk ratios (RR) and their 95% confidence intervals (CI). Results A total of 4 studies comprising 6788 patients were included. Anticoagulation was associated with a significant reduction in the risks of ischemic stroke (RR 0.66; 95% CI 0.49 - 0.90; P = 0.0084) and thromboembolic events (RR 0.70; 95% CI 0.55 - 0.89; P = 0.0037). Compared to atrial high-rate episodes not managed with anticoagulation, there was a significantly increased risk of major bleeding with anticoagulation (RR 1.57; 95% CI 1.23 - 2.00; P = 0.0002), while the risk of all-cause mortality was similar (RR 1.07; 95% CI 0.95 - 1.21; P = 0.2437). Conclusion Our study suggests that anticoagulation in patients with atrial high-rate episodes decreases the risks of ischemic stroke and thromboembolic events, while increasing the risk of major bleeding, compared patients not managed with anticoagulation. Our study does not show a mortality benefit with the use of anticoagulation in patients with atrial high-rate episodes. Further studies are needed to confirm the safety and efficacy of anticoagulation in atrial high-rate episodes.Forest Plots of Outcomes Assessed

Depression and its impact on stroke risk and mortality in post-percutaneous coronary intervention patients: a nationwide retrospective cohort study

Abstract Background/Introduction Cardiovascular disease (CVD) remains a leading cause of global mortality, with percutaneous coronary intervention (PCI) being a common therapeutic procedure for managing CVD. While depression is recognized as a risk factor for adverse cardiovascular outcomes post-PCI, its association with stroke risk in this patient group has been less explored. Purpose This study aims to evaluate the association between pre-existing depression and the incidence of stroke, alongside other cardiovascular outcomes and mortality, in patients undergoing PCI. Methods Utilizing the Korean National Health Insurance Service database, a population-based retrospective cohort study was conducted, encompassing individuals who underwent PCI between 2010 and 2017, with a follow-up until 2019. Depression was identified through ICD-10 codes prior to PCI. The primary outcome was acute stroke incidence, with all-cause mortality and revascularization as secondary outcomes. Adjustments were made for sociodemographic, lifestyle factors, and comorbidities. Results Among 164,198 individuals, those with pre-existing depression (17.4% of the cohort) exhibited a 27% increased risk of acute stroke (aHR 1.27, 95% CI 1.20-1.35) and a 25% higher risk of all-cause mortality (aHR 1.25, 95% CI 1.21-1.29) compared to those without. The association was stronger in individuals under 65 years and varied by sex, with males showing a higher risk of mortality. Conclusion(s) Pre-existing depression in patients undergoing PCI is associated with a significantly increased risk of stroke and all-cause mortality, particularly in younger patients. These findings highlight the importance of depression management as part of comprehensive care in post-PCI patients, suggesting potential benefits in reducing stroke risk and improving survival outcomes. Further research is warranted to explore the mechanisms and intervention strategies that could mitigate these risks.Study FlowchartRisk of stroke and all-cause death

Impact of right ventricular - pulmonary arterial coupling on mortality after transcatheter aortic valve implantation in patients with aortic stenosis

Abstract Background Aortic stenosis (AS) leads to left ventricle (LV) pressure overload. In more advanced stages of the disease, this pressure, which is transmitted through the pulmonary vasculature, may result in right ventricle (RV) remodeling and eventual dilatation and disfunction. RV failure is associated with impair prognosis, even after relief of the obstruction. The interplay of pulmonary arterial (PA) pressure and RV function can be assess using RV-PA coupling index; in a compensate state RV function is coupled with pulmonary pressure, and this function has a proper response to an increase in pulmonary afterload; in contrast, when RV function uncouples with pulmonary pressure it means that RV function can no longer sustain PA afterload, leading to a decompensate state. RV-PA uncoupling has already been associated with poor prognosis in other heart conditions, such as heart failure or pulmonary hypertension; however, there is still not much evidence on how RV-PA uncoupling prior transcatheter aortic valve implantation (TAVI) impacts on mortality. Purpose Assess the impact of RV-PA uncoupling on all-cause mortality after TAVI in patients with aortic stenosis. Methods In a prospective TAVI registry, patients were included if they had an adequate echocardiographic evaluation prior TAVI. All-cause mortality after the procedure was analyzed in two subgroups, according to their RV-PA coupling status. RV-PA was assess using tricuspid annular plane systolic excursion (TAPSE) and pulmonary arterial systolic pressure (PASP). The cut-off value was 0.39, consistent with other studies. Hazard ratios (HR) are calculated by univariate and multivariate Cox proportional hazard model. Multivariate adjustment included baseline characteristics – including age, gender, hypertension, diabetes, dyslipidemia, atrial fibrillation, and serum albumin –, and Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) and European System for Cardiac Operative Risk Evaluation (EUROSCORE) II. Results A total of 1190 patients underwent TAVI from January 2011 to December 2023; 315 patients were eligible, with mean age 82,24 years (± 8,0), 52% being women, and a mean EUROSCORE II score of 4.0 (± 9,3). The RV-PA cut-off value of 0.39 stratified patients into groups of RV-PA coupling (n = 194/63,6 %) or uncoupling (n = 121/38,4 %). During follow-up time (35,94 months ±25,6), patients with unpaired coupling had a 64% more risk of all-cause mortality in univariate analysis and, after adjusting for the parameters above, a 58% increased risk in multivariate analysis. Table. Conclusions Patients with significant aortic stenosis who had an impair RV-PA coupling prior TAVI had a significant increased risk of all-cause mortality. This suggests the need to incorporate this parameter to our right-side hemodynamics evaluation prior the procedure. Broader experience to determine its application and cut-off value are still needed.

Increased cancer incidence in patients with pre-existing heart failure: results from a French Nationwide Cohort study

Abstract Background It is unclear whether patients with a history of heart failure (HF) have an increased risk of developing cancer. Purpose To assess the incidence of cancer (all types) in patients with pre-existing HF compared with patients without known HF at a nationwide level. Secondary objectives include analysis by cancer site and impact on all-cause mortality. Methods We used the French National Administrative Health Data System (SNDS), a comprehensive database containing all health care information (outpatient and hospital) for 99% of the French population, to identify adult patients with a first diagnosis of HF (ICD-10 diagnosis code I50) between 2010 and 2019 and without a personal history of cancer before HF diagnosis. HF patients were matched for sex and age to HF-free and cancer-free individuals (3:1 ratio), randomly identified in the SNDS. Incident cancers were identified by corresponding ICD 10th codes. Results We found 330,867 adult patients with a first diagnosis of HF between 2010 and 2019, and 992,601 matched controls (54.7% women, mean age 77.7±13.5 years in both groups). There was an increased risk of a first cancer in HF patients as compared to controls: 28,151 (8.5%) in HF patients over a mean follow-up of 4.3±2.8 years vs. 77,325(7.8%) in controls over a mean follow-up of 4.9±2.8 years (unadjusted HR: 1.12 [1.11-1.13], P<0.001). The higher risk of new cancer in HF patients remained after adjustment for major comorbidities (i.e., ischemic heart disease, diabetes, arterial hypertension, renal dysfunction, morbid obesity), age, sex, year of diagnosis, region of residence, tobacco use and alcohol consumption (adjusted HR=1.06, [1.04-1.07]; P<0.0001). Overall, the estimated attributable risk of new cancer after HF was 16.53% (9.88-16.76%). This increased risk was observed for most solid malignancies (especially colorectal and lung cancer), and for multiple myeloma. We finally observed that the risk of all-cause mortality after cancer diagnosis was significantly higher in patients with pre-existing HF compared to controls (adjusted HR: 1.36 [1.33-1.39], P<0.001). Conclusions People with a history of HF have a higher risk of developing cancer than the general population. These findings suggest that cancer screening strategies should be encouraged in patients with HF.