Cox Proportional Hazards Regression Analysis Research Articles

White matter lesions as a prognostic marker of recurrence in cryptogenic stroke with high-risk patent foramen ovale

PurposeA high-risk patent foramen ovale (PFO) could be the cause of cryptogenic stroke, and an atrial septal aneurysm (ASA) increases the risk of stroke recurrence in cryptogenic stroke patients with a patent foramen ovale (PFO). Factors related to stroke recurrence according to PFO characteristics have not been fully evaluated. MethodsData from a multicenter, observational registry of ischemic stroke patients undergoing transesophageal echocardiography were used for this study. Patients were classified into three groups: high-risk PFO, PFO with large shunt (≥20 microbubbles) or ASA; right-to-left shunt (RLS), RLS including PFO with <20 microbubbles or without ASA, or pulmonary arteriovenous fistula; and negative RLS. Cox proportional hazards regression analysis was used to explore the factors related to stroke recurrence in these three groups. ResultsIn total, 586 patients (185 females; 65.5±13.2 years) were analyzed. In cryptogenic stroke (329 patients) with median follow-up of 4.2 (interquartile range, 1.0–6.1) years, 55 patients had stroke recurrence. The negative RLS, RLS, and high-risk PFO groups included 179, 90, and 60 patients, in which stroke recurrence occurred in 5.3%, 2.5%, and 4.6% per person-year, respectively. In patients with high-risk PFO, the National Institutes of Health stroke scale score (hazard ratio [HR] 1.257 [1.034-1.530]) and periventricular hyperintensity (HR 3.369 [1.103-10.294]) were predictors of stroke recurrence on multivariable Cox hazards analysis, but no factors were related to stroke recurrence in the RLS and negative RLS groups. ConclusionPeriventricular hyperintensity was shown to predict recurrent stroke in patients with a high-risk PFO.

The Significance of Comprehensive Metabolic Phenotypes in Cancer Risk: A Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.

The present study investigated the relationship between metabolic phenotypes and the risk of cancer in a Japanese population using the criteria of metabolic phenotypes based on an examination and those based on questionnaires. We used data from 25,357 subjects for examination-based analyses and those from 53,042 subjects for questionnaire-based analyses in the Japan Multi-Institutional Collaborative Cohort Study. Metabolic phenotypes were defined by classifying subjects according to their BMI (obesity: BMI ≥25 kg/m2; normal weight: BMI <25 kg/m2) and the number of metabolic abnormalities. Metabolic abnormalities were defined according to metabolic syndrome components of the Joint Interim Statement Criteria for examination-based analyses and self-reported histories of diabetes, dyslipidemia, and hypertension for questionnaire-based analyses. Cox proportional hazards regression analyses adjusted for potential confounders were performed for total and site-specific cancer incidence according to metabolic phenotypes. Metabolically unhealthy obesity (MUHO) was significantly associated with cancer incidence in both examination-based [HR (95% CI): 1.17 (1.01-1.36)] and questionnaire-based analyses [HR (95% CI): 1.15 (1.04-1.26)]. Regarding site-specific cancer in questionnaire-based analyses, metabolically healthy obesity and MUHO were associated with colorectum and liver cancers in all subjects and with breast cancer in female subjects. Subjects with a metabolically unhealthy normal weight had a higher risk of pancreatic cancer. Moreover, MUHO was associated with corpus uteri cancer in female subjects. This prospective cohort study suggests that metabolic phenotypes are important risk factors for total and some site-specific cancers in Japanese adults.

Haemorrhagic risk in elderly patients with atrial fibrillation that develop low platelet count during direct oral anticoagulant treatment: insights from the ATHERO-AF study

Abstract Background Bleeding risk in atrial fibrillation (AF) patients is complex and dynamic. Among others, thrombocytopenia has been suggested as a bleeding risk factors. No data on thrombocytopenia occurring during direct oral anticoagulants (DOACs) therapy are available. Purpose We investigated the incidence rate of thrombocytopenia and major bleeding (MB) in AF patients on DOACs. We also investigated whether the addition of incident thrombocytopenia to the HAS-BLED score might increase its predictive value compared to baseline HAS-BLED calculation. Methods 955 AF patients from the prospective ongoing ATHERO-AF study followed for a mean of 38.4±26.6 months. All patients were on DOACs. Thrombocytopenia was defined by a platelet count &amp;lt;150 x109/L registered during follow-up visits. MB events were defined according to ISTH definition and were recorded at each follow-up visit. Patients with thrombocytopenia at baseline were excluded. Multivariable Cox proportional hazards regression analysis was used to calculate the hazard ratio (HR) with 95% Confidence interval (95%CI) for each factor in relation to bleeding risk. Results Mean age was 77.3±9.0 years and 40.1% were women. During a follow-up, 139 patients developed thrombocytopenia with an incidence rate of 0.8% per year. We recorded no difference between thrombin and factor Xa inhibitors. During follow-up, 179 bleedings occurred, of which 80 were major. Patients experiencing bleedings were more likely to suffer from arterial hypertension, heart failure, anaemia and had higher CHA2DS2-VASc and HAS-BLED scores. At multivariable Cox proportional hazards regression analysis, factors associated with MB were incident thrombocytopenia (HR 1.995, 95%CI 1.211-3.288), antiplatelet use (HR 2.716 95%CI 1.269-5.816) and age (HR 1.033, 95%CI 1.003-1.064). The addition of incident thrombocytopenia to the HAS-BLED score increased the predictive value of baseline HAS-BLED in patients without thrombocytopenia for MB events (AUC from 0.54 to 0.61, p=0.016). Conclusion Incident thrombocytopenia is associated with an increased risk of MB. The addition of incident thrombocytopenia to the baseline HAS-BLED score increased its predictive value, suggesting that continuous bleeding risk evaluation of AF patients may provide additional prognostic information compared to the baseline only.

Estimated transmitral E- and A-wave overlapping predicted prognosis in patient with heart failure with preserved ejection

Abstract Background The impact of heart rate (HR) variability on clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF) is not fully understood. Variations in HR may affect transmitral blood flow and consequently left ventricular filling and left atrial pressure. Changes in HR can cause the transmitral E-wave and A-wave to merge at higher HRs, while their interval lengthens at slower HRs (Figure: left). A recent study (Izumida. ESC Heart Fail. 2020;7:3231) demonstrated that the degree of overlap or interval between E- and A-waves can be estimated using resting HR and the deceleration time of the E-wave (DcT) on Doppler echocardiography. Purpose This study aims to investigate the relationship between the estimated overlap length between E- and A-waves and prognosis in patients with HFpEF. Methods Echocardiography was performed before hospital discharge in 398 patients (80±9 years, 59.0% female) hospitalized for decompensated HFpEF who were registered in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) registry. The overlap length between E- and A waves was estimated using the formula [6.2 × HR (bpm) + 0.81 × DcT (ms) -589 (ms)] as previously described (a negative value means distance between two waves). Patients were divided into four groups based on quartiles of overlap length (Q1 to Q4, with Q4 representing the highest overlap length) and followed for a median duration of 759 days (interquartile range: 370, 1107 days) to observe all-cause mortality. Results The estimated overlap length in the study patients was -167±85 ms, and 105 deaths occurred during follow-up. The overlap length was selected as an independent predictor for all-cause mortality by Cox proportional hazards regression analysis (p=0.04), whereas HR or DcT was not. Kaplan-Meier curves indicated the difference in all-cause mortality among 4 groups (Figure: Right, p=0.02 by log-rank test), and the Q4 group (335 to -123ms) showed significantly higher mortality than the Q2 (-124 to -173 ms, p=0.03). Conclusion The overlap length of E and A predicted mortality in HFpEF patients, and the presence of overlap or shorter interval were associated with higher mortality. Optimal HR based on overlap length may be a new target for HFpEF therapy.Figure 1

Association of neutrophil-percentage-to-albumin ratio with mortality in cardiovascular disease patients complicating abnormal glucose metabolism

Abstract Background Cardiovascular disease (CVD) patients complicated with abnormal glucose metabolism are at especially higher risk of cardiovascular mortality. Therefore, it is critical to identify and manage CVD patients complicated with abnormal glucose metabolism at higher risk of mortality to improve the overall prognosis of such population. Evidence regarding neutrophil-percentage-to-albumin ratio (NPAR) and survival outcomes in CVD patients complicated with abnormal glucose metabolism remains scarce. Purpose To prospectively evaluate the association of NPAR with cardiovascular and all-cause mortality in CVD patients complicating abnormal glucose metabolism. Methods This study included 3,897 CVD patients with diabetes or pre-diabetes from the National Health and Nutrition Examination Survey (NHANES, 1999-2018). Mortality status was determined by access to NHANES public-use linked mortality files. Multivariate Cox proportional hazards regression analysis, threshold effect analysis, and stratified analysis were performed to examine the association of NPAR with cardiovascular and all-cause mortality. The prognostic value of NPAR was further assessed by time-dependent receiver operating characteristic (ROC) curve analysis. Results During a median follow-up period of 76 months, there were 703 cardiovascular deaths and 1,727 all-cause deaths. After adjusting for confounders, NPAR was positively nonlinear associated with cardiovascular and all-cause mortality. Furthermore, the thresholds of NPAR were identified for cardiovascular and all-cause mortality as 14.10 and 14.49, respectively. When the NPAR exceeded the thresholds, a 1-unit increase of NPAR was associated with a 16% and 18% greater hazard ratio (HR) for cardiovascular (HR = 1.16, 95% confidence interval (CI) = 1.08–1.23, P &amp;lt; 0.001) and all-cause mortality (HR = 1.18, 95% CI = 1.13–1.22, P &amp;lt; 0.001), respectively. The time-dependent ROC curve analysis showed that the NPAR had moderate prognostic value and outperformed the neutrophil-to-lymphocyte ratio for predicting short-term survival outcomes. Conclusions The NPAR is a superior predictor of survival outcomes in CVD patients complicated with abnormal glucose metabolism. The thresholds of 14.10 and 14.49 for cardiovascular and all-cause mortality, respectively.

Circulating secretoneurin concentrations predict 90-day mortality in patients with cardiogenic shock

Abstract Background Secretoneurin (SN) concentrations have been found to provide strong prognostic information in critically ill patients. Accordingly, in this study we hypothesized that SN would provide prognostic information in patients with cardiogenic shock. Objectives To evaluate the utility of SN concentrations to predict 90-day mortality in two multicenter, prospective clinical trials including patients with cardiogenic shock. Methods We measured SN concentrations with a CE-marked ELISA in patients with cardiogenic shock of all etiologies (Cohort #1, n=168) and in patients with post-myocardial infarction cardiogenic shock (Cohort #2, n=45). Inclusion criteria in both cohorts focused on systolic blood pressure &amp;lt;90 mmHg and evidence of tissue hypoperfusion, including increased lactate concentrations. We used Cohort #1 for primary analysis and Cohort #2 for validation. We assessed association between SN concentrations and mortality by Kaplan-Meier curves and by univariate and multivariable Cox proportional hazard regression analysis. Results Median age was 67 and 69 years (Cohort #1 and #2) and the patients were predominantly male (74% and 67%, respectively). Median SN concentration on study inclusion was 53 pmol/L in Cohort #1 and 50 pmol/L in Cohort #2, and SN concentrations decreased from study inclusion to 72 hours (p=0.03 for trend). 90-day mortality was 42% in Cohort #1 and patients with high SN concentrations had worse outcome (Figure A). Adjusting for variables that were associated with 90-day mortality in univariate analysis and not part of the inclusion selection, i.e., age, sex, comorbidities, blood pressure, estimated glomerular filtration rate, treatment, and N-terminal pro-B-type natriuretic peptide concentrations, SN concentrations on study inclusion were still associated with 90-day mortality: hazard ratio per 100 pmol/L increment 1.97 (1.29-3.01), p=0.002. 90-day mortality was 45% in Cohort #2 and SN concentrations were predictive of 90-day mortality also in Cohort #2 (Figure B). Conclusion SN concentrations provide incremental prognostic information to established risk indices in the early phase of cardiogenic shock.A. Cohort #1 with SN tertilesB. Cohort #2 divided by SN median

Housing items and amenities a non-traditional risk factors for all-cause and cardiovascular mortality

Abstract Background Higher satisfaction levels are associated with improved psychological well-being (PWB), such as housing amenities being a determinant of health. However, their potentially influencing effect on mortality risk at this moment is not enough. For this reason, searching for non-traditional risk factors that could reduce all-cause and cardiovascular disease (CVD) mortality risk is our primary objective of this study. Methods The cohort study was based on the framework of the international study Health, Alcohol and Psychosocial Factors in Eastern Europe (HAPIEE). Data from the Official Lithuanian Mortality Register were used to evaluate mortality from the baseline survey (2006- 2008) to 31 December 2022. The 20 housing items and amenities were used. The items were categorized into three groups: basic needs, socially oriented needs, and luxury. Results A total of 6472 participants aged 45-72 years were examined in the baseline survey. Cox proportional hazards regression analysis results show that increasing the number of housing items per 1 unit decreased the risk of all-cause mortality by 8% (Hazard ratio (HR)=0.92;95%CI 0.90-0.94) in males and by 7% (HR = 0.93;95%CI 0.91-0.96) in females. Increasing the number of housing items per 1 unit decreased the risk of mortality from CVD by 10% (HR = 0.90;95%CI 0.87-0.93) in males and by 9% (HR = 0.91;95% CI 0.87-0.95) in females (data adjusted by age, education, smoking, metabolic syndrome, PWB, CVD at baseline survey). Once more, the increased number of items from the luxury group (4-7 vs. 0-1) significantly decreased all-cause and CVD mortality risk (respectively in males HR = 0.74(95%CI 0.60-0.91) and HR = 0.71(95%CI 0.52-0.96); in females HR = 0.66(95%CI 0.48-0.91) and HR = 0.57(95%CI 0.33-0.96). Conclusions These data suggest that the increasing number of household items and amenities, as an essential aspect of people’s lives, may be used as non-traditional risk factors in assessing the risk of all-cause mortality and CVD. Key messages • Household items and amenities may be used as non-traditional risk factors in assessing the risk of all-cause mortality and CVD. • Increasing the number of housing items decreased the risk of all-cause and CVD mortality.

The prognostic and incremental value of T1 mapping for predicting adverse events in hypertrophic cardiomyopathy

Abstract Background In patients with hypertrophic cardiomyopathy (HCM), the prognostic value of native T1 and extracellular volume fraction (ECV) for adverse cardiovascular events has not been well defined. Methods Consecutive 663 participants with HCM who underwent cardiovascular magnetic resonance (CMR) were recruited. The follow-up endpoints included heart failure (HF)-related death and sudden cardiac death (SCD) or aborted SCD. Results During the median follow-up time of 44 months (interquartile range [IQR]: 23 to 66.0 months), 56 (8.4%) participants reached composite endpoints including 38 (5.7%) with SCD or aborted SCD, 16 (2.4%) with HF-related death and 2 (0.3%) with heart transplantation. On multivariable Cox proportional hazards regression analyses, native T1 including late gadolinium enhancement (LGE) from three short axes were significantly associated with cardiac death (basal native T1: hazard ratio [HR], 1.06 per 10 ms increase; 95% confidence interval [CI], 1.02 to 1.09; middle native T1: HR, 1.05 per 10 ms increase; 95% CI, 1.01 to 1.09; apical native T1: HR, 1.04 per 10 ms increase; 95% CI, 1.02 to 1.07; all P &amp;lt; 0.05) after adjustment for non-sustained ventricular tachycardia, history of syncope, the extent of LGE, left atrial size, and NYHA class. Conversely, only basal ECV was associated with cardiac death (basal ECV including LGE area: HR, 1.08 per 1% increase, 95%CI, 1.03 to 1.13, P = 0.001; basal ECV excluding LGE: HR, 1.1 per 1% increase; 95%CI, 1.04 to 1.16; P &amp;lt; 0.001) In addition, participants with increased mean native T1 (≥1349.4 ms) or basal ECV(≥ 29.4%) were more likely to suffer from cardiac death in the entire study cohort or the subgroup with low LGE extent (&amp;lt;15%) or low ESC risk score (&amp;lt;6%) (all P &amp;lt; 0.05). Furthermore, the addition of mean LV native T1 (≥1349.4 ms) or basal ECV (≥ 29.4%) to current risk factors in the guidelines could further improve prediction for the composite endpoint (C-index increased to 0.719 from 0.521 for the AHA/ACC risk model, P &amp;lt; 0.001; C index increased to 0.709 from 0.514 for the ESC risk model; P &amp;lt; 0.001). Conclusions In this study of patients with HCM, mean native T1 of three short axes and basal ECV were independently associated with cardiac death and added incremental value to conventional clinical predictors for patients with HCM.Figure 1.Demonstrative images.Figure 2 Incremental Value of T1 mapping

Association of R2-CHA2DS2-VASc score and clinical outcomes after bioprosthetic valve replacement: Subanalysis from BPV-AF registry

Abstract Background Although bioprosthetic valve (BPV) replacements are becoming more common, there are limited studies about prognostic prediction method for patients after BPV replacement. R2-CHA2DS2-VASc score is modified CHA2DS2-VASc score by adding reduced estimated glomerular filtration rate (eGFR &amp;lt; 60 mL/min/1.73m2). It is increasingly used for the prediction of cardiovascular (CV) events in patients with atrial fibrillation (AF), device implantation, and acute coronary syndrome. Purpose We aimed to evaluate the predictive value of R2-CHA2DS2-VASc score for future CV events in patients after BPV replacement. Methods BPV-AF, an observational, multicenter, prospective registry, enrolled AF patients that underwent BPV replacement. Patients were stratified into three risk groups according to their R2-CHA2DS2-VASc score as follows; low (scores, 0–1), moderate (scores, 2–4), and high (scores, 5–11). The primary outcome measure was a composite of stroke, systemic embolism, CV events including heart failure hospitalization, and cardiac death. Results A total of 766 patients were included in the analysis. The mean age was 80.3 years and 419 patients (54.7%) were female. Mean R2-CHA2DS2-VASc score was 4.1±1.5. Low, moderate, and high R2-CHA2DS2-VASc score groups consisted of 12 (1.6%), 178 (23.2%), and 576 (75.2%) patients, respectively. Median follow up period was 491 (interquartile range: 393-561) days. Kaplan-Meier analysis showed higher incidence of the composite CV events in high R2-CHA2DS2-VASc score group (Log rank test; p&amp;lt;0.01). Multivariate Cox proportional hazards regression analysis revealed that the R2CHA2DS2-VASc score as a continuous variable was an independent predictor of CV events (hazard ratio 1.33, 95% confidence interval 1.18 to 1.51, p&amp;lt;0.01). Conclusion The R2-CHA2DS2-VASc score is useful for CV risk stratification in AF patients after BPV replacement.Cumulative Incidence for Composite CV Ev

Neutrophil-to-lymphocyte ratio can predict the clinical prognosis of patients with primary adosteronism

Abstract Background Excess aldosterone-mediated inflammatory response is thought to be a factor in the high risk of cardiovascular events in patients with primary aldosteronism (PA). Leucocyte related inflammatory parameters, especially NLR, were significantly independent of aldosterone (PAC) in PA patients. However, the impact of NLR on the long-term prognosis of PA patients is unclear. Objective To explore the predictive value of neutrophil-to-lymphocyte ratio (NLR) on the long-term prognosis of patients with primary aldosteronism (PA). Methods The data for this study were derived from the Tianjin Health and Medical Big Data Super platform, comprising a retrospective cohort of patients discharged from 72 hospitals in our city from 2010 to 2023. According to the inclusion and exclusion criteria, 570 patients were ultimately included in the statistical analysis. Each patient had laboratory measurements, including blood cell counts, taken after admission and before interventional treatment. The primary endpoint was major cardiovascular events (MACEs), defined as cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke. Results During a mean follow-up period of 5 years, 125（21.9%）MACEs were recorded. ROC curve analysis displayed that the best cut-off value of NLR for predicting MACEs was 4.87. The MACEs of the high NLR group at 1 year, 3 years, and 5 years were higher than those of the low NLR group（25.0% vs 9.4%，40.3% vs17.1% 和 40.3% vs 19.3%；P＜0.05).Kaplan-Meier survival curve analysis showed that the survival rate of the low NLR group was higher than that of the high NLR group (P&amp;lt;0.001). The results of multivariate Cox proportional hazards regression analysis showed that NLR was an independent risk factor affecting the prognosis of PA patients, and the difference was statistically significant (P&amp;lt;0.05). Conclusions Elevated NLR is associated with adverse prognosis in patients with PA. NLR can serve as a simple and practical indicator to evaluate the long-term prognosis of PA patients. These findings warrant external validation, preferably in a prospective design.

The prognostic value of advanced lung cancer inflammation index in cancer survivors complicated with cardiovascular disease

Abstract Background The advanced lung cancer inflammation index (ALI) reflects systemic inflammatory and nutritional status, both of which are related to the prognosis of the disease. However, the prognostic value of ALI in cancer survivors with cardiovascular disease (CVD) remains unclear. Purpose This study was conducted to investigate the association of ALI with mortality in cancer survivors with CVD. Methods This study enrolled 955 cancer survivors with CVD from the National Health and Nutrition Examination Survey (NHANES, 1999-2018), and followed mortality status until December 31, 2019. Cox proportional hazards regression analysis and threshold effect analysis were applied to evaluate the relationship between ALI and all-cause, CVD-specific, and cancer-specific mortality. The prognostic value of ALI was further examined by time-dependent receiver operating characteristic (ROC) curve analysis. Results During a median follow-up period of 66.65 months, 490 all-cause deaths were observed, including 181 CVD-specific deaths and 121 cancer-specific deaths. After multivariate adjustment, ALI was inversely associated with all-cause, CVD-specific, and cancer-specific mortality in cancer survivors with CVD. Furthermore, L-shaped associations of ALI with mortality were discovered, with inflection points of 74.18 for all-cause and CVD-specific mortality and 55.50 for cancer-specific mortality. When the ALI was less than the inflection points, a 10-unit increase of ALI was associated with a 16%, 16%, and 25% decreased HR for all-cause, CVD-specific, and cancer-specific mortality, respectively. The time-dependent ROC curve analysis showed that the ALI had moderate predictive value for short- and long-term mortality. Conclusions The ALI is a significant prognostic indicator of mortality for cancer survivors with CVD. The findings allow for early prevention to improve the overall prognosis in such populations.

Risk and causes of hospital admission in patients with atrial fibrillation on treatment with oral anticoagulants

Abstract Background Atrial fibrillation (AF) is associated with an increased risk of hospitalisation, although the main reasons for hospital admission and the role of antiarrhythmic drugs are not clarified. Objective The aim of our study was to assess the incidence rate and the factors associated with all-cause, cardiovascular and AF-related causes of hospitalisation in patients suffering from AF. Methods This is a prospective single-centre ongoing study (ATHERO-AF cohort) which included 2782 patients affected by non-valvular AF on oral anticoagulants. The primary endpoints were all-cause, cardiovascular and AF-related hospitalisation. Cardiac hospitalizations were defined as (non-AF) arrhythmias, acute coronary syndromes, heart failure (HF), systemic embolism, hypertensive urgency, vascular/cardiac surgery. The AF-related hospitalisation was defined as a recurrence of AF in paroxysmal pattern or as a high-rate symptomatic AF episode in persistent/permanent patterns. Multivariable Cox proportional hazards regression analysis was used to calculate the hazard ratio (HR) with 95% Confidence interval (95%CI) for each factor in relation to risk of hospitalisation. Results Overall, 43.5% of patients were women with a mean age of 74.6±9.1year. Patients were followed for a mean of 31±26.8 months. We registered 1205 (12.1%/year) hospitalisations for any reason, 533 (5.7%/year) for cardiovascular causes and 180 (2.0%/year) were AF-related hospitalisations (Central illustration). Among the anti-arrhythmic drug use, we highlighted that flecainide and propafenone were associated with AF-related hospitalisations in paroxysmal and in persistent/permanent patterns (HR 1.861, 95%CI 1.116-3.101 and HR 1.947, 95%CI 1.069-3.548, respectively). Amiodarone (HR 3.012, 95%CI 1.835-4.943) and verapamil or diltiazem (HR 2.067, 95%CI 1.117-3.825) were associated with an increased risk of AF-related hospitalisations in persistent/permanent AF pattern. Furthermore, cancer was associated (HR 1.802, 95%CI 1.057-3.070) with increased risk of hospitalisation due to AF-related causes. Conversely, beta-blockers and digoxin were not associated with increased risk of hospital admission. Conclusions Hospitalisations of patients with AF are frequent for both cardiovascular and non-cardiovascular causes. Among the AF-related ones, the use of antiarrhythmic drugs emerged as associated with increased risk of hospitalisations, hypothesizing their poor effect in preventing AF episodes. For these reasons, we suggest carefully considering their use, reserving them for symptomatic patients with frequent AF recurrences.Central Illustration

Circulating secretoneurin concentrations predict cardiovascular death in ambulatory patients with heart failure

Abstract Background Secretoneurin (SN) is a novel biomarker, which predicts cardiovascular (CV)-related mortality in patients with acute dyspnea and sepsis. Higher SN concentrations have also been found associated with all-cause death in outpatients with heart failure (HF), but whether SN primarily reflects cardiovascular (CV)-related mortality in HF outpatients is not known. Objectives To evaluate the relation between SN concentrations and CV- &amp; non-CV death in ambulatory patients with HF. Methods We studied 184 consecutive patients who attended our HF clinic for routine follow up and had stored blood samples available for SN analysis. SN concentrations were measured with a CE-marked SN ELISA assay. We assessed the associations between SN concentrations and CV &amp; non-CV death. Mortality was ascertained using medical records, autopsy reports and death certificates, and CV deaths included sudden cardiac deaths or mortality due to myocardial infarction, HF or stroke. We assessed association with CV &amp; non-CV death by Kaplan-Meier curves and by Cox proportional hazard regression analysis. Results Median age was 76 years (range: 38-94 years) and two thirds were male. Sixty-three percent had HF with reduced ejection fraction, 22% had NYHA III/IV symptoms and median NT-proBNP was 1079 (interquartile range: 462-2347) ng/L. Median SN level was 60 (range: 21-134) pmol/L. In multivariable linear regression analysis, impaired renal function and lower body-mass index were significantly associated with increasing (log)SN concentration. During median follow up of 540 days, there were 18 CV deaths, including 15 HF deaths, and 7 non-CV deaths. A higher SN concentration was associated with higher risk of CV death, while we did not find statistically significant association between SN concentrations and non-CV deaths (Figure). Patients with SN concentration in the top tertile had 15-fold increased risk of CV death compared to patients with SN concentration in the lowest tertile. In multivariable Cox regression analysis that adjusted for age, NYHA functional class, frailty status, increasing SN concentrations were independently associated with CV death: hazard ratio per logSN (95% CI): 3.01 (1.02-8.90), p=0.04. Conclusion In ambulatory patients with HF, circulating SN concentrations were predictive of CV death. Higher SN concentrations in ambulatory HF patients seemed to be linked to impaired renal function and lower body-mass index. Figure: Kaplan Meier curves illustrating the relation between SN tertiles and (A) CV mortality (B) Non-CV mortality.

Integrated care using the ABC-stroke pathway improves cardiovascular outcomes and survival in patients with recent ischaemic stroke: a population-based cohort study

Abstract Background A recent European Society of Cardiology (ESC) Council on Stroke position paper proposed the ABC-stroke pathway, a holistic and integrated care approach to optimise the post-stroke management for patients with recent stroke, and associated heart disease. The ABC-stroke pathway is based on 3 pillars: "A" Appropriate Antithrombotic therapy; "B" Better functional and psychological status; and "C" Cardiovascular risk factors and Comorbidity optimisation (including lifestyle changes). There are limited data on the impact of adherence to the ABC-stroke pathway on post-stroke patient outcomes. Purpose We aimed to investigate the potential impact of ABC-stroke pathway adherence in the Clinical Data Analysis and Reporting System (CDARS) database in Hong Kong. Methods The analysis included patients with new-onset ischaemic stroke recorded in CDARS between 1st June 2006 and 31st May 2022. Multivariable Cox proportional hazards regression analyses were performed to evaluate the association between adherence to the ABC-stroke pathway and the primary outcome. The primary endpoint was a composite outcome of recurrent ischaemic stroke, transient ischaemic attack, haemorrhagic stroke, myocardial infarction, heart failure and all-cause death. Secondary outcomes were the individual components of the composite outcome, and cardiovascular death. Results Of the 9,669 included patients with ischaemic stroke (mean age 69.6 ± 13.4 years; 42.5% female), 58.1% were adherent to all 3 main ABC-stroke pillars. After 1 year of follow-up, adherence to the ABC-stroke pathway was associated with a lower risk of the primary composite endpoint (HR: 0.80; 95% CI: 0.72–0.88). Risk reductions increased progressively with a higher number of ABC-stroke criteria obtained (Figure 1). On multivariate analyses of the secondary outcomes, ABC-stroke pathway-adherent care was associated with a reduced risk of all-cause mortality (HR: 0.72; 95% CI: 0.62–0.85), cardiovascular death (SHR: 0.64; 95% CI: 0.45–0.90), haemorrhagic stroke (SHR: 0.50; 95% CI: 0.38–0.67) and heart failure (SHR: 0.771; 95% CI: 0.596-0.998) (Table 1). Conclusion In a large cohort of patients with ischaemic stroke, adherence to the ABC-stroke pathway was associated with a reduction of the risk of adverse outcomes.

The association between circulating B cell count and clinical outcomes in patients with heart failure

Abstract Background Despite advances in treatments, heart failure (HF) is still an growing health problem associated with a high mortality rate. In recent years, researchers have increasingly focused on the association between HF and the immune system. However, there have been only a few reports concerning the association between B cells and heart failure. The aim of the present study was to identify alterations in lymphocyte subset counts and examine whether lymphocyte subset counts are associated with clinical outcomes in patients with HF. Methods and Results We evaluated lymphocyte subset count, including CD3+ T cells, CD19+ B cells and CD56+ natural killer cells in consecutive 395 patients with HF. All patients were divided into three groups according to CD19+ B cell counts tertiles. First tertile group showed higher inflammation and higher prevalence of malnutrition compared to other groups. There were 79 all-cause deaths and 119 HF-related events during the median follow-up period of 374 days. We found that each lymphocyte subsets decreased with advancing New York Heart Association functional class. The receiver operating characteristics curve analysis demonstrated that the area under the curve of CD19+ B cell count for all-cause mortality was the greatest among lymphocyte subset counts. Kaplan-Meier analysis showed that patients with lowest tertile group had the highest rates of all-cause deaths and HF-related events than in other groups. Multivariate Cox proportional hazard regression analysis demonstrated that CD19+ B cell count was significantly associated with all-cause mortality and HF-related events after adjustment for confounding risk factors. Conclusion We for the first time demonstrated that the CD19+ B cell count was significantly associated with severity and clinical outcomes of HF.Kaplan-Meiyer curveforest plot

The relationship between retinal vascular parameters measured by artificial intelligence and the risk of new-onset cardiovascular disease in a Chinese community-based population

Abstract Background Studies on the association between retinal vascular diameter and tortuosity and the risk of new-onset cardiovascular disease (CVD) are controversial. The predictive value of retinal vascular parameters, measured through artificial intelligence (AI), for incident CVD risk in the community population, remains to be explored. Objectives Our study aims to investigate the association between retinal vascular parameters (diameter and tortuosity) measured through AI, and the risk of new-onset CVD in the Chinese community-based population. Methods We conducted a prospective cohort study on subjects from a Beijing community in China who were free of prevalent stroke or myocardial infarction and underwent retinal photography at baseline. By deep-learning algorithm, quantitative retinal vascular parameters were measured 0.5 to 1 disc diameter from the optic disc margin, including central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), arteriolar-to-venular ratio (AVR), curvature tortuosity arteriole (cTORTa), and curvature tortuosity venule (cTORTv). The primary endpoint was a new-onset major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, first non-fatal stroke, and first non-fatal acute myocardial infarction (AMI). The secondary endpoints included cardiovascular death, first stroke, and first AMI. Cox proportional-hazards regression analyses were performed. Results A total of 3,585 participants were included. The mean age was 56.49 ± 8.94 years, and 2,335 (65.1%) were female. Prevalence of prior hypertension and diabetes was 1594 (44.5%) and 676 (18.9%), respectively. During the follow-up (median, 7.53 years), there were 293 cases of new-onset MACE (8.2%), 44 cardiovascular deaths (1.2%), 226 strokes (6.3%), and 57 AMIs (1.6%). The Kaplan–Meier curves showed significant differences in cumulative hazards of new-onset MACE among tertiles of CRAE, CRVE, AVR, and cTORTa, but not for cTORTv (Figure 1). In Cox proportional-hazards models (Figure 2) adjusting for covariates, CRAE was negatively associated with the risk of new-onset MACE (per 10 μm increase, hazard ratio [HR]=0.95, 95% confidence interval [CI]: 0.92-0.99, P=0.009) and the risk of new-onset stroke (per 10 μm increase, HR=0.96, 95%CI: 0.92-1.00, P=0.04). Similarly, AVR was negatively associated with new-onset MACE risk (per 0.1 increase, HR=0.82, 95%CI: 0.72-0.94, P&amp;lt;0.001) and new-onset stroke risk (per 0.1 increase, HR=0.84, 95%CI: 0.73-0.98, P=0.022). No significant associations were observed between CAVE, cTORTa, and cTORTv with any of the primary or secondary endpoints. Conclusions CRAE and AVR, measured through AI, are associated with the risk of new-onset MACE in the Chinese population. These findings suggest the potential for AI-measured parameters in retinal vasculature to aid in stratifying CVD risk in the general population.

The associations of triglyceride glucose and its derived indexes with 10-year cardiovascular disease risk in a Chinese community-based population

Abstract Background The triglyceride-glucose (TyG) index has been regarded as a reliable surrogate marker of insulin resistance and an independent predictor of cardiovascular outcomes. However, the associations of the derived TyG indexes with incident CVD risk are controversial, and that the relevant data are sparse for the Chinese population studies. Objectives We aimed to investigate the association of TyG index and its derived indexes with incident CVD risk and to compare their predictive capacity in the Chinese community-based population. Methods We conducted a prospective cohort study on subjects from a Beijing community in China who were free of prevalent stroke or myocardial infarction at baseline. The primary endpoint was a new-onset major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, first non-fatal stroke, and first non-fatal acute myocardial infarction. Cox proportional-hazards regression analyses and time-dependent receiver operator characteristic curve analyses were performed. Results A total of 8,806 participants were included. The mean age was 56.51 ± 8.93 years, and 5,679 (64.5%) were female. The median value of TyG index, TyG-BMI, TyG-WC, and TyG-WHtR were 8.71 (8.34-9.12), 226.37 (201.02-252.87), 720.80 (653.52-791.03), and 4.47 (4.07-4.90), respectively. During a mean 9.7-year follow-up, a total of 877 (10%) cases of MACE were recorded. The Kaplan–Meier curves showed significant differences in cumulative hazards of new-onset MACE among tertiles of abovementioned indexes (Log rank P &amp;lt; 0.0001) (Figure 1). Multivariable Cox regression analyses revealed that TyG index, TyG-BMI, TyG-WC, and TyG-WHtR were positively associated with the hazards of MACE. Compared with tertile 1, the multivariable adjusted HRs (95% CIs) of incident CVD for tertile 3 were 1.26 (1.01-1.56), 1.57 (1.15-2.14), 1.54 (1.19-2.00), and 1.81 (1.40-2.33) for TyG, TyG-BMI, TyG-WC, and TyG-WHtR, respectively (Figure 2). There are no significant differences in the Harrell's C indexes among the various indexes compared to the TyG index (TyG index: 0.758 [0.743-0.774], TyG-BMI: 0.758 [0.743-0.773], TyG-WC: 0.758 [0.743-0.774], and TyG-WHtR: 0.760 [0.745-0.775]). Conclusions Higher TyG and its derived indexes are significantly associated with an increased risk of 10-year MACE. Our results suggest that TyG and its derived indexes may serve as a useful marker for stratifying CVD risk in the general population.

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.

Comparison of risk factors and mortality in veterans with HIV and those without HIV suffering first major acute cardiovascular events.

Previous studies have demonstrated that people with HIV have an increased atherosclerotic plaque vulnerability, making them more susceptible to severe cardiovascular complications. This study aimed to examine the clinical characteristics of people with HIV in comparison to people without HIV admitted to Veterans Health Administration (VHA) with their first major acute cardiovascular events (MACE) and compare their total mortality. We used national VHA data to extract data of those admitted to VHA hospitals with MACE defined as acute myocardial infarction (AMI), acute cerebrovascular accident (CVA) or cardiac arrest during the fiscal years 2003-2021. The hazard ratio (HR) of mortality for people with HIV versus people without HIV was estimated using Cox proportional hazard regression analysis. Out of 280 311 veterans, 2510 people with HIV and 277 801 people without HIV had their first MACE during the study period. People with HIV were younger, more likely to be African American, had a lower prevalence of diabetes mellitus and hypertension, similar total cholesterol levels and a lower mean 10-year cardiovascular risk score (25.4 in people with HIV vs. 28.7 in people without HIV). Among MACE components, people with HIV had a higher proportion of CVA (27% vs. 21.3%, p < 0.001) and cardiac arrest (13.0% vs. 8.4%, p < 0.001) but a lower incidence of AMI (62.4% vs. 72.5%, p < 0.001) than people without HIV. Additionally, people with HIV had a higher risk of total mortality (adjusted HR: 2.05, 95% confidence interval: 1.90-2.22) compared with people without HIV. People with HIV experience MACE at younger ages despite lower cardiovascular risks and similar baseline cholesterol and blood pressure levels. People with HIV had higher mortality and a higher risk of having ventricular fibrillation arrest and stroke as their first MACE.

5-Fluorouracil combined with CalliSphere drug-eluting beads or conventional transarterial chemoembolization for unresectable hepatocellular carcinoma: a propensity score weighting analysis

This study aimed to assess the effectiveness and safety of 5-Fluorouracil (5-Fu) combined with conventional transarterial chemoembolization (cTACE) compared to 5-Fu combined with drug-eluting bead transarterial chemoembolization (DEB-TACE) using CalliSpheres for the treatment of unresectable hepatocellular carcinoma (HCC) using propensity score weighting methods. This retrospective analysis included 131 patients with HCC treated with 5-Fu combined with cTACE (5-Fu-cTACE group, n = 65) or DEB-TACE (5-Fu-DEB-TACE group, n = 66) at the Affiliated Hospital of North Sichuan Medical College from January 2019 to December 2022. Based on the baseline data and laboratory indicators, propensity score weighting was used to reduce confounding bias. Modified response evaluation criteria in solid tumors (mRECIST) were used to evaluate clinical efficacy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the disease control rate (DCR), objective response rate (ORR) and adverse events (AEs). PFS was assessed using Kaplan‒Meier analysis and Cox proportional hazards models. The ORRs at 1 month (M1) after treatment in the 5-Fu-DEB-TACE group and 5-Fu-cTACE group were 90.9% and 76.9%, respectively (P = 0.029), while at this time, the DCRs were 93.9% in the 5-Fu-DEB-TACE group and 90.8% in the 5-Fu-cTACE group (P = 0.494). At 3 months (M3) after treatment, the 5-Fu-DEB-TACE group had a higher ORR (84.8% vs. 56.9%, P < 0.001) and DCR (84.8% vs. 72.3%, P = 0.08). The ORR at 6 months (M6) was also higher in the 5-Fu-DEB-TACE group than in the 5-Fu-cTACE group (72.7% vs. 50.8%, P = 0.01). The median PFS after treatment with 5-Fu-DEB-TACE was longer than that after treatment with 5-Fu-cTACE (11 months vs. 6 months) (P = 0.004). Cox proportional hazards regression analysis indicated that 5-Fu-DEB-TACE (HR = 0.590, P = 0.044), Model for End-Stage Liver Disease (MELD) intermediate risk (HR = 2.470, P = 0.010), BCLC stage B (HR = 2.303, P = 0.036), BCLC stage C (HR = 3.354, P = 0.002) and ascitic fluid (HR = 2.004, P = 0.046) were independent predictors of PFS. No treatment-related deaths occurred in this study. The 5-Fu-DEB-TACE group had a greater incidence of abdominal pain (72.7% vs. 47.7%, P = 0.003). However, the incidence of postoperative elevated transaminase levels was higher in the 5-Fu-cTACE group (83.1% vs. 66.6%, P = 0.031). Subgroups analysis showed patients receiving 5-Fu-DEB-TACE have better PFS compared to those receiving 5-Fu-cTACE in the BCLC stage A group (P = 0.0093), BCLC stage B group (P = 0.0096), multifocal group (P = 0.0056), Child-Pugh stage A group (P<0.001), non- extrahepatic metastasis group (P = 0.022), non-vascular invasion group (P = 0.0093), and the group with a largest tumor diameter ≥ 5 cm (P = 0.0048). At M1, M3, and M6, patients with preserved liver function and in some cases of low tumor burden had higher Objective Response Rate (ORR) and Disease Control Rate (DCR) (P < 0.05). Compared with 5-Fu-cTACE, 5-Fu-DEB-TACE has superior therapeutic efficacy, prolongs PFS, and reduces hepatotoxicity. However, it is associated with an increased incidence of postoperative abdominal pain.