Long-term Cardiovascular Mortality Research Articles

High long-term mortality in ischaemic heart disease accentuated among ethnic minorities in Eastern Europe: findings from a prospective all-comers percutaneous coronary intervention registry in Romania

BackgroundLong-term outcomes in cardiovascular diseases are historically under-reported in Eastern Europe. Our aim was to report long-term survival and to identify survival predictors in a prospective Romanian percutaneous coronary intervention...

Abstract 4123814: Long-term Incidence of Cardiovascular Events and Mortality in Patients with and without Weight Regain After Bariatric Surgery in the Swedish Obese Subjects Study

Background: Obesity shortens life expectancy, while bariatric surgery causes large weight loss and increases median life expectancy by approximately 3 years. However, weight regain after bariatric surgery is common, and its impact on health remains uncertain. In this study, we examined whether weight regain following bariatric surgery is associated with long-term cardiovascular outcomes and mortality. Methods: We analyzed patients undergoing bariatric surgery in the prospective Swedish Obese Subjects study, aged 37-60 with a BMI≥34 (men) or ≥38 (women), recruited 1987-2001. Patients who regained ≥20% of their 1-year weight loss after 4 years (regain group; n=715) were compared to those who regained less (maintenance group; n=631). Information on cardiovascular disease as well as overall and cardiovascular mortality was obtained from the Swedish Population and Address Register, the Swedish Cause of Death Register, and the Swedish National Patient Register. Median follow-up was 27 years. Results: Average weight change from year 1 to year 4 was +12.8 kg and -0.2 kg in the regain and maintenance groups, respectively. The incidence of major adverse cardiovascular events (myocardial infarction, stroke and heart failure) was similar between the groups, with 185 events in the regain group and 137 in the maintenance group. This corresponds to 11.6 events per 1000 person-years (95% CI: 10.1-13.5) for the regain group, and 10.0 events per 1000 person-years (95% CI: 8.3-12.4) for the maintenance group. The adjusted HR was 1.16 (95% CI: 0.92-1.46), p=0.213. During follow-up, there were 216 deaths in the regain group and 184 in the maintenance group, resulting in nearly identical overall mortality rates of 12.4 per 1000 person-years for both groups (95% CI for regain: 10.9-14.2, maintenance: 10.9-14.3). The number of deaths from cardiovascular disease was 77 in the regain group and 57 in the maintenance group, corresponding to similar incidence rates of 4.4 per 1000 person-years (95% CI: 3.5-5.5) and 3.8 per 1000 person-years (95% CI: 3.0-5.0), respectively (p=0.550). Conclusions: The incidence of major adverse cardiovascular events, as well as total and cardiovascular mortality, was similar between the weight regain and maintenance groups. This suggests that the beneficial association between bariatric surgery and reduced cardiovascular events persists despite weight regain.

Association Between Atrial Fibrillation and Long-term Mortality in Acute MI Patients.

AF is a common complication of an acute MI (AMI) and goes along with adverse events. Nevertheless, the therapeutical guidelines and pharmacological possibilities have improved over the past years. Therefore, this contemporary study aimed to clarify the effect of AF on long-term mortality in patients with incident AMI. This study included 2,313 patients aged 25-84 years with initial AMI that occurred from 2009 until 2017, documented within the population-based Augsburg Myocardial Infarction Registry. Patients were monitored from hospital admission, with a median follow-up duration of 4.5 years (interquartile range 4.4 years). Survival analysis and multivariable Cox regression analysis were conducted to explore the relationship between AF and long-term all-cause and cardiovascular disease mortality. Altogether, 156 individuals had AF on their admission ECG, while the remaining 2,157 presented with sinus rhythm (SR). Patients with AF were significantly older, more frequently had arterial hypertension, non-ST-segment elevation MI, worse kidney function, smaller AMIs, and were more often former and non-smokers. An increased long-term all-cause mortality was observed among the AF group. (AF patients 39.1%, SR group 16.7%), Upon multivariable adjustment, a HR of 1.40 (95% CI [1.05-1.87]; p=0.023) was calculated when comparing the AF with SR patients. An independently increased risk of long-term mortality for patients with AF compared with patients with SR in case of incident AMI was identified. Therefore, AF should be considered as a serious risk factor in AMI patients, and must be treated aggressively to reduce mortality risk.

Long-term cardiovascular outcomes of immune checkpoint inhibitor-related myocarditis: A large single-centre analysis.

Immune checkpoint inhibitors (ICI) are the cornerstone of modern oncology; however, side effects such as ICI-related myocarditis (irM) can be fatal. Recently, Bonaca proposed criteria for irM; however, it is unknown if they correlate well with cardiovascular (CV) ICI-related adverse events. Additionally, whether incident irM portends worse long-term CV outcomes remains unclear. We aimed to determine the incidence of long-term CV comorbidities and CV mortality among irM patients. The ICI-related adverse event (irAE) registry was queried to identify irM patients by using Bonaca criteria. Random controls were selected after excluding patients with other concomitant irAEs. Patients' demographics, comorbidities and myocarditis presenting features were gathered. Outcomes included 2-year freedom from CV comorbidities (composite of atrial fibrillation, stroke, myocardial infarction and heart failure) and freedom from CV death. IrM was treated as a time-varying covariate. Seventy-six patients developed irM at a median of 167days (mean age 69, 63.2% male, 47% lung cancer). Majority of patients had new wall motion abnormalities or EKG changes on presentation. Mean LVEF was 43%, median peak TnT was 0.81, and median NTproBNP was 2057 at irM onset. Two-year freedom from CV comorbidities (67% vs 86.8%, P<0.001) and death (93.4% vs 99.3%, P=0.003) was lower among irM patients. Incident irM was an independent predictor of CV death (HR 8.28, P=0.048), but not CV comorbidities (HR 2.21, P=0.080). This is the largest case-control study on irM highlighting worse long-term CV outcomes. Future studies are needed to establish appropriate therapeutic strategies and efficient screening strategies for irM survivors.

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 &amp;lt;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

Statin use before acute coronary syndrome and coronary risk factors, clinical presentation, interventions, and outcomes: ACC-NCDR-CathPCI Registry in India

Abstract Background Statins are used for coronary artery disease (CAD) primary and secondary prevention. Limited studies on the association of statin use before acute coronary syndrome (ACS) with clinical presentation and outcomes are available. Purpose We compared statin-user and statin-naïve ACS patients for clinical and angiographic findings and in-hospital and 3-year outcomes following percutaneous coronary intervention (PCI). Methods Successive patients with ACS who underwent PCI from Sep’17 to Dec’23 were enrolled in the ACC-NCDR-CathPCI registry in India. Details of risk factors, clinical presentation, coronary angiography, interventions and in-hospital were recorded. Follow-up data in a sub-cohort recruited from Apr’19 to Mar’22 were obtained for incident major cardiovascular events (MCE) (cardiovascular deaths, recurrent ACS, PCI and bypass surgery). Results 8296 ACS patients were enrolled; prior statin use was in 3149 (38%) and statin naïve were 5147 (62%). Statin-user vs statin-naïve patients were older (61.6+10 vs 59.7+11y), with more hypertension (60.1 vs 48.6%), diabetes (35.8 vs 31.8%), pre-existing CAD (PCI 20.9 vs 9.1%; CABG 5.0 vs 2.3%) and lower mean total, LDL, and NHDL cholesterol (p&amp;lt;0.001). Statin users had less ST-elevation myocardial infarction (STEMI) (28.4% vs 45.2%), more non-STEMI (65.2 vs 50.8%), better LVEF (46.3+10 vs 44.5+10%), &amp;gt;2 coronary stents (35.5 vs 29.5%), lower mechanical circulatory support (2.2 vs 3.9%) and lower median hospitalization (66.1 vs 68.5h) (p&amp;lt;0.001). In statin-users incidence of in-hospital CAD deaths was 29 (0.92%) vs 78 (1.52%) (odds ratio, OR 0.61, 95% confidence intervals 0.39-0.93) and all-cause deaths 33 (1.05) vs 91(1.77%) (OR 0.59, 95%CI 0.39-0.88) (p&amp;lt;0.01). ORs attenuated following multivariate adjustments for risk factors, clinical presentation and interventions. In the follow up cohort (n=3813, high-intensity statins 99.6%), among baseline statin-users incident MCE was 98 (6.9%) vs 214 (8.9%) (hazard ratio, HR 0.76, 95%CI 0.59-0.97) and CVD deaths were in 46 (3.2%) vs 113 (4.7%) (HR 0.68, 95%CI 0.48-0.96) with attenuation following adjustment for baseline clinical variables and interventions. Conclusions Acute coronary syndrome patients taking pre-admission statins have significantly lower in-hospital and long-term cardiovascular and all-cause mortality following PCI.

Multi-modal artificial intelligence-based prediction for cardiovascular mortality after transcatheter aortic valve implantation: a time-to-event survival prediction

Abstract Background Predicting long-term outcomes following Transcatheter Aortic Valve Implantation (TAVI) presents a significant challenge. Objective We aimed to predict post-TAVI long-term cardiovascular mortality using multimodal data and employing time-to-event artificial intelligence (AI) algorithms. Methods This study enrolled 3,973 consecutive patients from the prospective TAVI registry (between August 2007 and June 2023). Multimodal information was collected and extracted as numerical data for each patient, encompassing clinical history, medication, laboratory, procedural characteristics, ECG, angiography, echocardiography (TTE and TEE), and CT. Clinical outcomes were adjudicated by an independent clinical event committee. From the multimodal information, 147 features were extracted at baseline before the TAVI procedure. The datasets were divided into a training/validation set (80%) and a hold-out test set (20%) for model development and evaluation, respectively. Cox-LASSO feature selection was employed to identify the most relevant features, followed by the implementation of Random Survival Forest (RSF), Gradient Boosting Survival Analysis (GBSA), and Survival Support Vector Machine (SSVM) to predict the timing and occurrence of cardiac death events in patients. Feature selection, model parameters, and hyperparameters selection were performed using 10-fold cross-validation on the training set. Model performance was evaluated using different metrics, such as the concordance index (c-index) and cumulative Area Under the Curve (C-AUC) on a 20% untouched test set. Results In the patient cohort, 28.4% experienced cardiovascular death. Features were selected from various modalities, including 22 from clinical history, two from medication, eight from laboratory tests, one from ECG, eight from CT scans, and five from echocardiography and angiography. In the univariate Cox-PH model, all features exhibited a C-index ranging from 0.50 to 0.57. In the test set, the conventional Multivariate Cox-PH model achieves a c-index of 0.59 (C-AUC: 0.56). RSF, GBSA, and SSVM achieve a C-index of 0.70 (C-AUC: 0.69), 0.66 (C-AUC: 0.64), and 0.69 (C-AUC: 0.68), respectively, in the holdout test set. Conclusion Integrating multimodal information, encompassing imaging, signal, laboratory data, and clinical history, with AI algorithms has markedly enhanced the prediction of long-term cardiac outcomes following the TAVI procedure. The initially developed model can predict the probability of cardiac death up to 10 years. Furthermore, the RFS model significantly outperformed the conventional Cox model in predicting time-to-event outcomes.

Interpretable machine learning model for predicting long-term cardiovascular mortality risk in chronic kidney disease patients using SHAP explainers

Abstract Background Patients with chronic kidney disease (CKD) exhibited a pronounced burden of cardiac mortality. However, early prediction of cardiovascular mortality risk in CKD patients remains an unmet medical need. Purpose This study aimed to evaluate the performance of machine learning (ML) algorithms and identify the most influential factors in predicting long-term cardiac mortality among CKD patients. Methods Six ML models were developed, with the most effective one chosen for predicting and categorising patients into high-risk and low-risk groups based on the maximal Youden’s index. Differences in survival rates were assessed using the log-rank test on Kaplan-Meier curves. Cox regression analysis was employed to investigate the relationship between ML-predicted risk scores and mortality. Furthermore, the SHapley Additive exPlanations (SHAP) method was implemented to provide personalised explanations for model decisions. Results The auto-encoder (AE) model achieved the highest AUC of 0.94, with a sensitivity of 80.95% and specificity of 96.34%. Compared to individuals in low-risk group, those in high-risk group exhibited a significantly elevated risk of cardiovascular mortality (adjusted hazard ratio [HR]: 48.24; P &amp;lt;0.001). According to the SHAP model, age, C-reactive protein, blood urea nitrogen and hypertension were identified as the four most influential factors in the AE model. Conclusions Our study successfully developed an AE machine learning model for predicting 10-year cardiovascular mortality among CKD patients. The combination of ML model and SHAP aids doctors in understanding key features in the model, improving their insight into decision-making related to disease severity assessment, thus facilitating early preventive strategies in clinical practice.

Plasma Protein Biomarkers and Long-Term Cardiovascular Mortality Risk in Patients With Chronic Coronary Heart Disease.

Protein biomarkers that reflect different pathophysiological pathways have been associated with the risk of adverse cardiovascular events. However, it is uncertain whether these associations are sustained with increasing years after the biomarkers are measured. In this cohort study, 7745 patients with coronary heart disease who participated in the LIPID (Long-Term Intervention With Pravastatin in Ischemic Disease) trial, BNP (B-type natriuretic peptide), troponin I, cystatin-C, C-reactive protein, d-dimer and midregional proadrenomedullin were measured at baseline and after 1 year. Discrimination of plasma biomarker concentrations for cardiovascular death were evaluated in landmark analyses from 1 year for the next 5 years of the randomized trial, and for 10 additional years after trial completion. All 6 biomarkers were associated with risk of cardiovascular death (n=1903) both during and after the clinical trial (each P<0.001). C-statistics for BNP were 0.706 and 0.704; cystatin-C, 0.686 and 0.693; troponin I, 0.686 and 0.689; C-reactive protein, 0.655 and 0.684; d-dimer, 0.670 and 0.679, and midregional adrenomedullin, 0.686 and 0.688, respectively. In multivariable models, adding all 6 biomarkers to models with clinical risk factors increased the C-statistic for cardiovascular death from 0.709 to 0.775 during the clinical trial, and from 0.713 to 0.751 during 10-year follow-up after the randomized trial (P<0.001 for both). In patients with chronic coronary heart disease, biomarkers that reflect different pathophysiological pathways are associated with the risk of cardiovascular death for at least the next 15 years.

Association between estimated pulse wave velocity and the risk of mortality in patients with subarachnoid hemorrhage: a retrospective cohort study based on the MIMIC database

BackgroundThe estimated pulse wave velocity (ePWV) is a recently developed, simple and useful tool to measure arterial stiffness and to predict long-term cardiovascular mortality. However, the association of ePWV with mortality risk in patients with subarachnoid hemorrhage (SAH) is unclear. Herein, this study aims to assess the potential prediction value of ePWV on short- and long-term mortality of SAH patients.MethodsData of adult patients with no traumatic SAH were extracted from the Medical Information Mart for Intensive Care (MIMIC) III and IV database in this retrospective cohort study. Weighted univariate and multivariable Cox regression analyses were used to explore the associations of ePWV levels with 30-day mortality and 1-year mortality in SAH patients. The evaluation indexes were hazard ratios (HRs) and 95% confidence intervals (CIs). In addition, subgroup analyses of age, the sequential organ failure assessment (SOFA) score, surgery, atrial fibrillation (AF), renal failure (RF), hepatic diseases, chronic obstructive pulmonary disease (COPD), sepsis, hypertension, and diabetes mellitus (DM) were also performed.ResultsAmong 1,481 eligible patients, 339 died within 30 days and 435 died within 1 year. After adjusting for covariates, ePWV ≥ 12.10 was associated with higher risk of both 30-day mortality (HR = 1.77, 95%CI: 1.17–2.67) and 1-year mortality (HR = 1.97, 95%CI: 1.36–2.85), compared to ePWV < 10.12. The receiver operator characteristic (ROC) curves showed that compared to single SOFA score, ePWV combined with SOFA score had a relative superior predictive performance on both 30-day mortality and 1-year mortality, with the area under the curves (AUCs) of 0.740 vs. 0.664 and 0.754 vs. 0.658. This positive relationship between ePWV and mortality risk was also found in age ≥ 65 years old, SOFA score < 2, non-surgery, non-hepatic diseases, non-COPD, non-hypertension, non-DM, and sepsis subgroups.ConclusionBaseline ePWV level may have potential prediction value on short- and long-term mortality in SAH patients. However, the application of ePWV in SAH prognosis needs further clarification.

Strain rate during isovolumic relaxation as a prognostic biomarker for long-term cardiovascular morbidity and mortality: an exploratory study on a general population.

Left ventricular (LV) strain rate (SR) during early relaxation correlates with LV filling pressures and has been assessed as a prognostic biomarker in several cardiac diseases. Conversely, even though LV SR during isovolumic relaxation (SRIVR)is more strongly related to invasive measurements of LV diastolic function, to date, studies on the role of SRIVR in the long-term prognosis assessment are lacking. Thus, the goal of this study was to assess the potential additive prognostic value of SRIVR on top of conventional cardiovascular risk factors in a general population. 657 subjects (mean age 51.6y; 47.6% males) were included in this study and, besides clinical and standard echocardiographic assessment, tissue Doppler imaging (TDI)-based SR was measured during IVR (SRIVR), early diastole (SRe), and atrial contraction (SRa) in the mid-segment of the inferior, inferolateral, lateral, and septal wall of the LV. During the follow-up period (median 12.1years), the total number of major adverse cardiac events was 85 (13.4%). Overall, after adjustment for known cardiovascular risk factors and important echocardiographic indices in a multivariable-adjusted Cox regression model, SRIVR of the inferolateral wall (SRIVRinflat) remained an independent predictor of fatal and nonfatal cardiac events (HR: 1.49, p = 0.016), along with GLS (HR: 1.35, p = 0.027), age (HR: 1.09, p < 0.001), and male sex (HR: 2.06, p = 0.037). None of SRIVR measured in the other myocardial walls were associated with cardiac outcome. SRIVRinflat predicted adverse outcome in the general population, on top of conventional cardiovascular factors. However, its incremental value as a prognosticator remained limited.

Cardiac Effects of Renin-Angiotensin System Inhibitors in Nonproteinuric CKD.

In contrast to proteinuric chronic kidney disease (CKD), the relative cardioprotective benefits of antihypertensive medications in nonproteinuric CKD are unknown. We examined long-term cardiovascular outcomes and mortality in patients with nonproteinuric CKD treated with renin-angiotensin system inhibitors (RASIs) versus other antihypertensive medications. Among participants of the CRIC study (Chronic Renal Insufficiency Cohort) without proteinuria, we used intention-to-treat analyses with inverse probability of treatment weighting and Cox proportional hazards modeling to determine the association of RASIs versus other antihypertensive medications with a composite cardiovascular outcome (myocardial infarction, stroke, heart failure hospitalization, and death) and mortality. Secondary analyses included per-protocol analyses accounting for continuous adherence and time-updated analyses accounting for the proportion of time using RASIs during follow-up. A total of 2806 participants met the inclusion criteria. In the intention-to-treat analyses, RASIs versus other antihypertensive medications were not associated with an appreciable difference in cardiovascular events (adjusted hazard ratio [aHR], 0.94 [95% CI, 0.80-1.11]) or mortality (aHR, 1.06 [95% CI, 0.88-1.28]). In the per-protocol analyses, RASIs were associated with a lower risk of adverse cardiovascular events (aHR, 0.78 [95% CI, 0.63-0.97]) and mortality (aHR, 0.64 [95% CI, 0.48-0.85]). Similarly, in the time-updated analyses, a higher proportion of RASI use over time was associated with a lower mortality risk (aHR, 0.33 [95% CI, 0.14-0.86]). Among individuals with nonproteinuric CKD, after accounting for time-updated use, RASIs are associated with fewer cardiovascular events and a lower mortality risk compared with other antihypertensive medications. Patients with nonproteinuric CKD may benefit from prioritizing RASIs for hypertension management.

Circadian heart rate fluctuations predict cardiovascular and all-cause mortality in type 2 and type 1 diabetes: a 21-year retrospective longitudinal study.

Circadian heart rate (HR) fluctuations are associated with cardiovascular health. We examined their relationship with microvascular disease and long-term survival in patients with diabetes. In this secondary analysis from the CHAMP1ON cohort of 497 adults with metabolic disease, 349 participants who had type 1 or type 2 diabetes, baseline 24h ambulatory blood pressure and HR monitoring (ABPM), and survival data over a 21-year observational follow-up were included. Clinical features, microvascular complications, and mortality rates were examined in participants with low circadian HR fluctuations (24h-HR SD below the median of 30.4) and blunted nocturnal HR dip (<10%). Low 24h-HR SD and blunted nocturnal HR dip were associated with an adverse cardiometabolic risk profile and 12-23% higher prevalence of cardiac autonomic neuropathy and nephropathy. After 6,251 person-years follow-up (21.0 [14.0-21.0] years), a total of 136 (39%) deaths occurred, of which 100 (68%) of cardiovascular cause. The low 24h-HR SD group had a higher risk for both cardiovascular (adjusted hazard ratio [aHR] 2.00, 95%CI 1.30-3.08, p=0.002) and all-cause mortality (aHR 1.61, 95%CI 1.13-2.29, p=0.009), compared with high 24h-HR SD. Similarly, patients with blunted nocturnal HR dip had a higher risk for cardiovascular (aHR 1.63, 95%CI 1.08-2.46, p=0.019) and all-cause mortality (aHR 1.69, 95%CI 1.20-2.38, p=0.003), compared with those with preserved nocturnal HR dip. Impaired circadian HR fluctuations are associated with microvascular disease and long-term cardiovascular and all-cause mortality in diabetes. ABPM-derived HR measures may provide a widely available and inexpensive risk stratification tool in this high-risk population.

The neutrophil-lymphocyte ratio predicts all-cause and cardiovascular mortality among United States adults with COPD: results from NHANES 1999-2018.

Neutrophil-to-lymphocyte ratio (NLR) is considered a biomarker of systemic inflammation and immune activation. However, its relationship with the risk of mortality in patients with chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to investigate the association between NLR and the risk of all-cause and cardiovascular mortality in patients with COPD. Data were collected from the National Health and Nutrition Examination Survey (NHANES) from January 1999 to December 2018. The calculation method of NLR involves dividing the neutrophil count by the lymphocyte count in the total blood cell count. The optimal NLR threshold associated with survival outcomes was determined using the maximally selected rank statistics method (MSRSM). The relationship between NLR and the risk of all-cause mortality and cardiovascular mortality in COPD was investigated using a weighted multivariable Cox regression model. Additionally, restricted cubic spline (RCS) was employed to discuss the potential relationship between NLR patients in different groups and the risk of mortality. In this study, 716 adults with COPD were included using the maximally selected rank statistics method, among whom 208 had higher NLR (≥2.56) and 508 had lower NLR (<2.56). During a median follow-up of 111.5 months, 162 COPD patients died from all causes, and 49 patients died from cardiovascular diseases. After adjusting for demographic, socioeconomic status, and lifestyle factors, the risk of all-cause mortality (HR = 2.07, 95%CI: 1.46-2.94) and cardiovascular mortality (HR = 3.03, 95%CI: 1.63-5.65) in patients with higher NLR was increased by 2-3 times compared to those with lower NLR. Kaplan-Meier analysis revealed significantly lower survival rates in patients with higher NLR for all-cause mortality and cardiovascular mortality (p < 0.05). Restricted cubic spline analysis showed a linear correlation between NLR and the risk of all-cause mortality and cardiovascular mortality. NLR has a high value in independently predicting long-term all-cause and cardiovascular mortality risks in community-dwelling COPD patients. Therefore, NLR can serve as a cost-effective and widely available indicator for assessing the prognosis of COPD patients.

Epigenetic age acceleration and mortality risk prediction in U.S. adults.

Epigenetic clocks have emerged as novel measures of biological age and potential predictors of mortality. We aimed to test whether epigenetic age acceleration (EAA) estimated using different epigenetic clocks predict long-term overall, cardiovascular or cancer mortality. We analyzed data from 2,105 participants to the 1999-2002 National Health and Nutrition Examination Survey aged ≥50 years old who were followed for mortality through 2019. EAAs was calculated from the residuals of Horvath, Hannum, SkinBlood, Pheno, Zhang, Lin, Weidner, Vidal-Bralo and Grim epigenetic clocks regressed on chronological age. Using cox proportional hazards regression, we estimated the hazard ratio (HR) and 95% confidence interval (CI) for the association of EAA (per 5-year) and the DunedinPoAm pace of aging (per 10% increase) with overall, cardiovascular and cancer mortality, adjusting for covariates and white blood cell composition. During a median follow-up of 17.5 years, 998 deaths occurred, including 272 from cardiovascular disease and 209 from cancer. Overall mortality was most significantly predicted by Grim EAA (P < 0.0001; HR: 1.50, 95% CI: 1.32-1.71) followed by Hannum (P = 0.001; HR: 1.16, 95% CI: 1.07-1.27), Pheno (P = 0.001; HR: 1.13, 95% CI: 1.05-1.21), Horvath (P = 0.007; HR: 1.13, 95% CI: 1.04-1.22) and Vidal-Bralo (P = 0.008; HR: 1.13, 95% CI: 1.03-1.23) EAAs. Grim EAA predicted cardiovascular mortality (P < 0.0001; HR: 1.55, 95% CI: 1.29-1.86), whereas Hannum (P = 0.006; HR: 1.24, 95% CI: 1.07-1.44), Horvath (P = 0.02; HR: 1.18, 95% CI: 1.02-1.35) and Grim (P = 0.049; HR: 1.37, 95% CI: 1.00-1.87) EAAs predicted cancer mortality. DunedinPoAm pace of aging was associated with overall (P = 0.003; HR: 1.23, 95% CI: 1.08-1.38) and cardiovascular (P = 0.04; HR: 1.25, 95% CI: 1.01-1.55) mortality. In a U.S. representative sample, Horvath, Hannum, Pheno, Vidal-Bralo and Grim EAA all predicted overall mortality but only Grim EAA predicted cardiovascular mortality and Horvath, Hannum or Grim EAA predicted cancer mortality. Pace of aging predicted overall and cardiovascular mortality.

Life's Essential 8 and the Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis.

The benefits of achieving optimal cardiovascular health (CVH) through Life's Simple 7 (LS7) are well-documented across diverse populations. In this study, we assess the updated metrics, Life's Essential 8 (LE8), and their association with long-term cardiovascular disease (CVD) outcomes and mortality. We conducted a comprehensive systematic review, searching PubMed, Google Scholar, Cochrane Library, and ScienceDirect from January 2022 until June 2024, focusing on studies that specifically assessed the impact of LE8 on CVH. The statistical analysis used RevMan 5.4 and applied a random effects model to synthesize hazard ratios (HRs) for primary and secondary outcomes. This study is registered in PROSPERO (CRD42024558493). Our final analysis comprised 34 observational studies, encompassing 1,786,664 participants aged 18-80, with an average follow-up of approximately 11.6 years. Pooled analysis revealed a statistically significant decrease in the risk of CVD among individuals with higher LE8 scores compared to those with lower scores, with an HR of 0.47 (95% CI: 0.39 to 0.56, p < 0.00001). Higher LE8 scores were also associated with significant reductions in both all-cause mortality (HR: 0.54, 95% CI: 0.43 to 0.69, p < 0.00001) and CVD-related mortality (HR: 0.37, 95% CI: 0.26 to 0.52, p < 0.00001. Moreover, individuals with high LE8 scores have a 56% lower risk of coronary heart disease and a 48% lower risk of stroke. LE8 has a strong inverse association with CVD risk and mortality, with higher LE8 scores corresponding to significantly lower risk levels.

Insulin-based or non-insulin-based insulin resistance indicators and risk of long-term cardiovascular and all-cause mortality in the general population: A 25-year cohort study

ObjectiveAlthough insulin resistance (IR) has been recognized to be a causal component in various diseases, current information on the relationship between IR and long-term mortality in the general population is limited and conclusions varied among different IR indicators and different populations. We aimed to assess associations between different measurements of IR with long-term all-cause mortality and cardiovascular mortality risk for the general population. Research design and methodsWe included 13,909 individuals from the Third National Health and Nutrition Examination Survey. Mortality was identified via National Death Index information until December 31, 2019. IR was measured using fasting insulin, homeostasis model assessment of IR (HOMA-IR), homeostasis model assessment of β-cell function, quantitative insulin sensitivity check index (QUICKI), insulin-to-glucose ratio (IGR), triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), and hypertriglyceridemic-waist phenotype. ResultsDuring median 25-year follow-up, 5,306 all-cause mortality events occurred. After multivariate adjustment, variables significantly associated with elevated all-cause mortality risk were (hazard ratio [95 % confidence interval]): higher insulin (1.07 [1.02;1.13]); HOMA-IR (1.08 [1.03;1.13]); IGR (1.05 [1.00;1.11]); TyG (1.07 [1.00;1.14]); TyG-BMI (1.24 [1.02;1.51]); lower QUICKI (0.91 [0.86–0.96]). After stratification by diabetes status, higher insulin, HOMA-IR, TyG-BMI and lower QUICKI were significantly associated with increased risk of all-cause mortality in both diabetes and non-diabetes populations (all P for interaction > 0.05). Higher TyG (adjusted HR 1.17 [1.09;1.26], P for interaction = 0.018) and hypertriglyceridemic-waist phenotype (adjusted HR 1.26 [1.08;1.46], P for interaction = 0.047) were significantly associated with increased risk of all-cause mortality in patients with diabetes, however, these associations could not be seen in people without diabetes. Similar results were observed between the above-mentioned IR indicators and cardiovascular death. ConclusionsFasting insulin, HOMA-IR, TyG-BMI, and QUICKI may indicate mortality risk in diabetes and non-diabetes populations, with TyG and the hypertriglyceridemic-waist phenotype showing particular relevance for individuals with diabetes. Further studies are needed to validate these findings and determine their broader applicability.

Long-term cardiovascular outcomes and mortality with enzyme replacement therapy in patients with mucopolysaccharidosis type II.

Mucopolysaccharidosis type II (MPS II) is a rare multisystemic lysosomal disorder in which cardiac issues can lead to serious dysfunction and an increased risk of fatal cardiac failure. However, studies on major adverse cardiac event (MACE) outcomes in MPS II are lacking. This study evaluated the cardiovascular outcomes and impact of enzyme replacement therapy (ERT) in patients with MPS II in South Korea. In this national cohort study, utilizing data from the National Health Insurance Database, we evaluated 127 patients with MPS II over a 14-year period to investigate the effects of ERT on MACE and all-cause mortality. We tracked MACE incidence, defined by hospitalizations for cardiovascular events, from diagnosis and adjusted the hazard ratios for MACE using Cox modeling. Over an average follow-up period of 7.3 years, we identified 16 cases of MACE among patients (17.35 per 1000 person-years; 95% confidence interval, 10.74-26.83). Patients receiving ERT exhibited a significantly lower incidence of MACE than untreated patients, with cumulative incidences showing a marked difference of 8.3 years. Notably, initiating ERT at earlier stages post-diagnosis was associated with improved outcomes, underscoring the importance of timely treatment. The key risk factors for MACE included specific arrhythmias, a history of invasive procedures, and depression. Early ERT significantly reduced MACE risk and increased survival in patients with MPS II. This underscores the importance of prompt treatment initiation and comprehensive care to address key risk factors and advocates for an expanded therapeutic strategy to enhance MPS II outcomes.

The Outcomes of Surgical Pulmonary Embolectomy for Pulmonary Embolism: A Meta-Analysis.

Objectives: The purpose of this study is to assess the efficacy, short- and long-term cardiovascular and non-cardiovascular mortalities and postoperative morbidities of surgical pulmonary embolectomy (SPE) for patients with massive or submassive pulmonary embolism. Methods: A comprehensive literature review was performed to identify articles reporting SPE for pulmonary embolism. The outcomes included in-hospital and long-term mortality in addition to postoperative morbidities. The random effect inverse variance method was used. Cumulative meta-analysis, leave-one-out sensitivity analysis, subgroup analysis and meta-regression were performed. Results: Among the 1949 searched studies in our systematic literature search, 78 studies met our inclusion criteria, including 6859 cases. The mean age ranged from 42 to 65 years. The percentage of males ranged from 25.6% to 86.7%. The median rate of preoperative cardiac arrest was 27.6%. The percentage of contraindications to preoperative systemic thrombolysis was 30.4%. The preoperative systemic thrombolysis use was 11.5%. The in-hospital mortality was estimated to be 21.96% (95% CI: 19.21-24.98); in-hospital mortality from direct cardiovascular causes was estimated to be 16.05% (95% CI: 12.95-19.73). With a weighted median follow-up of 3.05 years, the late cardiovascular and non-cardiovascular mortality incidence rates were 0.39 and 0.90 per person-year, respectively. The incidence of pulmonary bleeding, gastrointestinal bleeding, surgical site bleeding, non-surgical site bleeding and wound complications was 0.62%, 4.70%, 4.84%, 5.80% and 7.2%, respectively. Cumulative meta-analysis showed a decline in hospital mortality for SPE from 42.86% in 1965 to 20.56% in 2024. Meta-regression revealed that the publication year and male sex were associated with lower in-hospital mortality, while preoperative cardiac arrest, the need for inotropes or vasopressors and preoperative mechanical ventilation were associated with higher in-hospital mortality. Conclusions: This study demonstrates acceptable perioperative mortality rates and late cardiovascular and non-cardiovascular mortality in patients who undergo SPE for massive or submassive pulmonary embolism.

Impact of COVID-19 and Non-COVID-19 Hospitalized Pneumonia on Longer-Term Cardiovascular Mortality in People With Type 2 Diabetes: ANationwide Prospective Cohort Study From Scotland.

In this study we examine whether hospitalized coronavirus disease 2019 (COVID-19) pneumonia increases long-term cardiovascular mortality more than other hospitalized pneumonias in people with type 2 diabetes and aim to quantify the relative cardiovascular disease (CVD) mortality risks associated with COVID-19 versus non-COVID-19 pneumonia. With use of the SCI-Diabetes register, two cohorts were identified: individuals with type 2 diabetes in 2016 and at the 2020 pandemic onset. Hospital and death records were linked for determination of pneumonia exposure and CVD deaths. Poisson regression estimated rate ratios (RRs) for CVD death associated with both pneumonia types, with adjustment for confounders. Median follow-up durations were 1,461 days (2016 cohort) and 700 days (2020 cohort). The adjusted RR for CVD death following non-COVID-19 pneumonia was 5.51 (95% CI 5.31-5.71) prepandemic and 7.3 (6.86-7.76) during the pandemic. For COVID-19 pneumonia, the RR was 9.13 (8.55-9.75). Beyond 30 days post pneumonia, the RRs converged, to 4.24 (3.90-4.60) for non-COVID-19 and 3.35 (3.00-3.74) for COVID-19 pneumonia, consistent even with exclusion of prior CVD cases. Hospitalized pneumonia, irrespective of causal agent, marks an increased risk for CVD death immediately and over the long-term. COVID-19 pneumonia poses a higher CVD death risk than other pneumonias in the short-term, but this distinction diminishes over time. These insights underscore the need for including pneumonia in CVD risk assessments, with particular attention to the acute impact of COVID-19 pneumonia.