Higher Risk Of Cardiovascular Death Research Articles

Association of weight change with cardiovascular events and all-cause mortality in obese participants with cardiovascular disease: a prospective cohort study

BackgroundStudies have examined the association between weight change and risk of cardiovascular (CV) outcomes in the general population. However, very few literature reported the association among obese people with established...

Impact of polypharmacy on patients undergoing revascularisation for peripheral arterial disease.

Background: To evaluate the impact of polypharmacy, defined as the concurrent use of five or more medications, on the clinical outcomes of patients undergoing revascularisation for symptomatic peripheral arterial disease (PAD). Patients and methods: This is a retrospective analysis of consecutive PAD patients treated by surgical, endovascular or hybrid therapy in a tertiary center between January 2017 and December 2017. The composite of amputation and/or death (amputation-free survival; AFS) was the primary endpoint. Mortality, major limb amputation, risk for Major Cardio-Cerobro-vascular Events (MACCE) and re-intervention during follow-up were additionally analyzed. Results: A total of 560 patients (369 male, 66%) were included. Mean age was 72.43 ± 38.67, while the main indication for treatment was lifestyle limiting claudication (330 patients, 59%). Most patients (434, 78%) were treated with endovascular means, and the commonest anatomical site of intervention was the femoropopliteal arterial segment (449 patients, 80%). A total of 409 (73%) met the criteria for polypharmacy. Cox regression analysis showed that polypharmacy was an independent predictor of death (exp: 4.72, p=0.008), MACCE (exp: 2.82, p=0.001), re-intervention (exp 1.51, p=0.0016) and of the composite outcome of AFS (exp: 3.46, p=0.021) but not of major amputation (exp: 1.26, p=0.686). Propensity-score matching analysis showed that even when controlling for comorbidity and procedural characteristics, polypharmacy is associated with a higher risk of cardiovascular death (p<0.001), MACCE (p<0.001), and re-intervention (p=0.001). Conclusions: In this study, polypharmacy was associated with unfavourable clinical outcomes for patients undergoing revascularisation for symptomatic PAD, without influencing the risk for major limb amputation.

Combined Effect of Air Pollution and Genetic Risk on Incident Cardiovascular Diseases.

Whether genetic susceptibility to cardiovascular diseases (CVDs) enhances the vulnerability to adverse cardiovascular outcomes by air pollution is unknown. We assessed the combined effect of air pollution and genetic predispositions on CVD risk. From the UK Biobank cohort, we selected genetically unrelated White British participants without CVD. Levels of ambient particulate matter with a diameter of <2.5 μm (PM2.5) and <10 μm were estimated using land use regression models. An individual's genetic predisposition to CVDs was determined by polygenic risk scores for coronary artery disease, myocardial infarction, stroke, ischemic stroke, heart failure, and atrial fibrillation. We stratified mortality and CVD risk by PM2.5 exposure across high and low genetic risk groups. A total of 249 082 participants (aged 56.9±8.0 years, 46.8% men) were followed for a median of 10.8 years. The combined effect of PM2.5 exposure and the genetic predisposition of CVD demonstrated the highest risk of cardiovascular death in the high genetic risk group with the greatest PM2.5 exposure (adjusted hazard ratios ranging from 1.73 to 2.12 across the polygenic risk score of each CVD). The combination of higher exposure to ambient PM2.5 and high genetic risk was associated with higher incidence of all CVDs, although no significant interactions were observed between genetic risk and PM2.5 exposure on cardiovascular death or CVD events. A combination of greater PM2.5 exposure and higher genetic predisposition to particular CVDs was modestly associated with elevated risks of cardiovascular death and CVDs. Not only alleviating PM2.5 exposure in the general population but also implementing individualized preventive approach for those at high genetic risk might be beneficial.

Asociación en J entre la apolipoproteína B y resultados CV en pacientes con síndrome coronario crónico tratados con estatinas

Introduction and objectivesThe association between apolipoprotein B (apoB) and residual cardiovascular (CV) risk in patients with chronic coronary syndrome (CCS) remains unclear. We aimed to investigate the association between apoB levels and CV outcomes in statin-treated CCS patients. MethodsWe enrolled 8641 statin-treated CCS patients at Fuwai Hospital. The patients were divided into 5 groups based on to apoB quintiles (Q1 to Q5). The primary endpoint was 3-year CV events, including CV death, nonfatal myocardial infarction, and nonfatal stroke. ResultsDuring a median follow-up of 3.17 years, there were 232 (2.7%) CV events. After multivariable adjustment, a restricted cubic spline illustrated a J-shaped relationship between apoB levels and 3-year CV events, with the risk remaining flat until apoB levels exceeded 0.73g/L, after which the risk increased (nonlinear P <.05). Kaplan-Meier curves showed the lowest CV event rate in the Q3 group (0.68-0.78g/L). Compared with the Q3 group, multivariable Cox regression models revealed that both low (Q1, ≤0.57g/L) and high (Q5, >0.93g/L) apoB levels were associated with an increased risk of major adverse cardiac events (all P <.05). Notably, patients with low apoB levels (Q1) had the highest risk of CV death (HR, 2.44; 95%CI, 1.17-5.08). ConclusionsOur analysis indicates that both low and high levels of apoB are associated with elevated CV risk, with the risk being particularly pronounced at higher levels (> 0.73g/L).

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 &amp;lt; 0.01), cardiovascular death (HR 1.35 [1.20-1.50] p &amp;lt; 0.0001), all-cause mortality (HR 1.08 [1.01-1.16] p &amp;lt; 0.05) and CHB (HR 1.35 [1.16-1.56] p &amp;lt; 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 &amp;lt; 0.0001), all-cause mortality (HR 1.20 [1.12-1.29] p &amp;lt; 0.0001) and CHB (HR 1.15 [1.01-1.32] p &amp;lt; 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

Pathogenic cardiomyopathy gene variants inform prognosis in atrial fibrillation: results from exome sequencing in over 17,000 patients in TIMI trials

Abstract Background Rare genetic variants in cardiomyopathy genes are associated with risk of atrial fibrillation (AF), even in the absence of overt ventricular dysfunction. Data on clinical outcomes for rare genetic variant carriers among patients with AF remain sparse. Purpose We aimed to study the prognostic implication of rare pathogenic/likely pathogenic (PLP) variants for dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) in patients with AF from large, well-phenotyped randomized clinical trials. Methods and results Rare variants were called using exome sequencing data in 5 large clinical trials from the TIMI study group (ENGAGE-AF, FOURIER, SAVOR, PEGASUS, DECLARE). PLP variants for cardiomyopathy were identified using phenotype- and gene-specific curation of protein-truncating variants and high-confidence variant classifications from the ClinVar database. In 17,190 patients with a history of AF, we identified 421 (2.4%) PLP variant carriers (age 67±10, 35% women) and 16,769 (97.6%) pts without PLP variants (age 70±9, 36% women). Among these individuals, we identified 265 DCM carriers (1.5%), 106 (0.6%) HCM carriers and 54 (0.3%) ARVC carriers. In this cohort, 9,275 (54%) had a history of heart failure (HF) and 2,991 (17.4%) prior ischemic stroke. Over 2.5 years median follow-up, 1,365 pts (7.9%) were hospitalized for HF, 599 (3.5%) had an ischemic stroke, and 1147 (6.7%) died of cardiovascular causes. In logistic regression analyses adjusting for age, sex, trial, and principal components of ancestry, PLP variants were significantly associated with a history of HF (OR 1.66, p&amp;lt;0.0001), most notably for DCM variants (OR 1.97, 1.48-2.62, p&amp;lt;0.0001). PLP variants were independently associated with incident HF admissions (adj HR 1.75, 1.39-2.29, p&amp;lt;0.0001), most notably for HCM (adj HR 2.59, 1.68-3.99, p&amp;lt;0.0001) and ARVC variants (adj HR 2.50, 1.34-4.66, p=0.004). The increased risk of HF admissions remained consistent in patients with (adj HR 1.49, 1.11-2.00, p=0.009) and those without (adj HR 1.88, 1.00-3.54, p=0.049) a history of HF. PLP variants were also associated with higher risk of cardiovascular death (adj HR 1.46, 1.06-2.02, p=0.02), most notably for DCM variants (adj HR 1.77, 1.21-2.58, p=0.003). In contrast, PLP variants were not associated with history of ischemic stroke at baseline (adj OR 0.99, p=0.96) nor with incident ischemic stroke (adj HR 0.95, p=0.84). Conclusion In patients with AF, rare cardiomyopathy gene variants are associated with increased risks of HF and of cardiovascular death, but not stroke. These results, collected from large well-phenotyped randomized clinical trials, demonstrate an important prognostic implication for rare genetic variants for CMP in pts with AF.

Prognostic impact of myocarditis as aetiology compared with dilated cardiomyopathy and ischaemic heart disease in heart failure

Abstract Background A subgroup of myocarditis can lead to heart failure. However, whether prognosis of myocarditis-induced heart failure differs from other heart failure remains largely unknown. Aim This study aimed to investigate the prognostic impact of myocarditis induced heart failure compared with heart failure with dilated cardiomyopathy and ischaemic heart disease as causes respectively in the overall population and a propensity score-matched cohort, based on patient-level data from the Swedish Heart Failure Registry (SwedeHF). Methods Patients with heart failure (HF) were enrolled from the SwedeHF (2003-2020) linked with the National Patient Register, and the Swedish Cause of Death Register. Endpoints were all-cause mortality, cardiovascular death, and hospital re-admissions, followed up from the index date until censoring or event. Results Of 54416 patients identified through the SwedeHF with HF, 418 hade myocarditis as aetiology (MC-HF), 6,871 with dilated cardiomyopathy (DCM-HF) and 47127 with ischemic heart diseases (IHD-HF). In general patients with MC-HF have shorter disease duration and less comorbidities compared with DCM-HF and IHD-HF, but older than DCM-HF and younger than IHD-HF. Compared with DCM-HF, MC-HF are associated with 29% higher risk for all cause mortality [(1.29 (1.07 - 1.55), p=0.0079] and 40% higher risk for cardiovascular death [ 1.40 (1.09 - 1.80), p=0.0088], and 19 % higher risk for heart failure rehospitalization [1.19 (1.03 - 1.37), p=0.018] and even higher risk by censoring within one-year . However, compared with IHD-HF, patients with MC-HF have similar risk for all cause mortality [0.95 (0.80 - 1.13), p=0.54], cardiovascular death [0.95 (0.75 - 1.20), p=0.65], and heart failure rehospitalization [0.93 (0.81 - 1.06), p=0.29]. Similar results were obtained from a propensity 1:2 matched cohort. No significant interactions were found regardless of age (&amp;lt; and &amp;lt; 70 years) , sex, LVEF (≥50%, 40-49%, 30-39% and &amp;lt; 30%) for all cause mortality comparing MC-HF vs DCM-HF, and MC-HF vs IHD-HF. Conclusion Patients with myocarditis-induced heart failure have worse outcome than heart failure due to dilated cardiomyopathy, with even higher risk during one year. This finding highlights the importance of early and more effective customized management of patients with myocarditis in particular those with high risk to develope heart failure.

Undetected heart failure in tertiary care: prevalence, predictors and outcomes

Abstract Background Undetected heart failure (HF) seems to be unexpectedly common in primary care. We hypothesized that undetected HF may also be common in tertiary care, even in care pathways including cardiologists. Methods We assessed prevalence, predictors, and outcome of undetected HF in a large prospective cohort study enrolling patients referred for myocardial perfusion single photon emission tomography (MPI-SPECT) with central adjudication of HF according to guidelines. Findings were validated in two independent prospective cohorts (outpatient cardiac rehabilitation program, major noncardiac surgery). Prevalence of undetected HF, ratio of undetected HF to known HF and number needed to screen (NNS) were the primary endpoints. Results Among 3623 patients, median age 68 years, 31% women. 100 patients (3%) had known HF and 928 patients (25.6%) were adjudicated to have undetected HF, resulting in a ratio of undetected to known HF of 9.3-to-1 and a NNS of 2.8. Older age, atrial fibrillation, and previous pacemaker implantation were strong independent predictors of undetected HF. Patients with undetected HF were at significantly higher risk of cardiovascular death or HF hospitalization (adjusted HR 1.47 [95%CI, 1.17-1.85] versus no HF). These findings were confirmed in both validation cohorts: among 970 and 1563 patients the prevalence of undetected HF was 21.5% and 19%, ratio of undetected HF to known HF 0.7-to-1 and 2.8-to-1, NNS 2.2 and 3.7, respectively. Conclusion The prevalence of undetected HF is high also in tertiary care, even higher with older age, atrial fibrillation, and previous pacemaker implantation, and associated with increased risk of cardiovascular death or HF hospitalization.Prevalence of undetected HFKaplan-Meier cumulative incidence curves

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.

Left Atrial Appendage Thrombus as a Marker of Disease Severity in 500 Patients with Atrial Fibrillation on Oral Anticoagulation: A 13-Year Follow-Up Study.

Background/Objective: Whether left atrial appendage thrombus (LAAT) in patients with atrial fibrillation (AF) on chronic anticoagulation significantly increases cardiovascular risk is unknown. This study aimed to assess LAAT prevalence and its predictive role in cardiovascular events among consecutive anticoagulated patients with AF admitted for electrical cardioversion. Methods: This prospective study included 500 patients. The primary outcome was LAAT on transesophageal echocardiography. Patients were followed up for a median of 1927.5 (interquartile range 1004-2643) days to assess cardiovascular events. Results: LAAT was detected in 65 (13%) patients. No significant differences in stroke, transient ischemic attack, systemic thromboembolic events, or myocardial infarction prevalence were observed between patients with AF with and without LAAT. Hospitalization for heart failure (HF) was more frequent in patients with LAAT than in those without LAAT; however, the effect of LAAT on HF hospitalization was not statistically significant. Patients with LAAT had a significantly higher risk of cardiovascular death than those without LAAT. LAAT and greater left atrial (LA) diameter were associated with higher rates of cardiovascular death. The independent HF hospitalization predictors were greater LA diameter, lower left ventricular ejection fraction (LVEF), and estimated glomerular filtration rate (eGFR). Conclusions: Patients with AF who received anticoagulation therapy showed a high prevalence of LAAT. LAAT and greater LA diameter were associated with significantly higher rates of cardiovascular death. LAAT, greater LA diameter, lower LVEF, and lower eGFR were associated with poor prognosis in anticoagulated patients with AF and were predictors of disease severity.

J-shaped association between apolipoprotein B and CV outcomes in statin-treated patients with chronic coronary syndrome

Introduction and objectivesThe association between apolipoprotein B (apoB) and residual cardiovascular (CV) risk in patients with chronic coronary syndrome (CCS) remains unclear. We aimed to investigate the association between apoB levels and CV outcomes in statin-treated CCS patients. MethodsWe enrolled 8641 statin-treated CCS patients at Fuwai Hospital. The patients were divided into 5 groups based on to apoB quintiles (Q1 to Q5). The primary endpoint was 3-year CV events, including CV death, nonfatal myocardial infarction, and nonfatal stroke. ResultsDuring a median follow-up of 3.17 years, there were 232 (2.7%) CV events. After multivariable adjustment, a restricted cubic spline illustrated a J-shaped relationship between apoB levels and 3-year CV events, with the risk remaining flat until apoB levels exceeded 0.73g/L, after which the risk increased (nonlinear P <.05). Kaplan-Meier curves showed the lowest CV event rate in the Q3 group (0.68-0.78g/L). Compared with the Q3 group, multivariable Cox regression models revealed that both low (Q1, ≤0.57g/L) and high (Q5, >0.93g/L) apoB levels were associated with an increased risk of major adverse cardiac events (all P <.05). Notably, patients with low apoB levels (Q1) had the highest risk of CV death (HR, 2.44; 95%CI, 1.17-5.08). ConclusionsOur analysis indicates that both low and high levels of apoB are associated with elevated CV risk, with the risk being particularly pronounced at higher levels (> 0.73g/L).

Proprotein convertase subtilisin/kexin type 9 as a drug target for abdominal aortic aneurysm.

There are no current drug therapies to limit abdominal aortic aneurysm (AAA) growth. This review summarizes evidence suggesting that inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) may be a drug target to limit AAA growth. Mendelian randomization studies suggest that raised LDL and non-HDL-cholesterol are causal in AAA formation. PCSK9 was reported to be upregulated in human AAA samples compared to aortic samples from organ donors. PCSK9 gain of function viral vectors promoted aortic expansion in C57BL/6 mice infused with angiotensin II. The effect of altering PCSK9 expression in the aortic perfusion elastase model was reported to be inconsistent. Mutations in the gene encoding PCSK9, which increase serum cholesterol, were associated with increased risk of human AAA. Patients with AAA also have a high risk of cardiovascular death, myocardial infarction and stroke. Recent research suggests that PCSK9 inhibition would substantially reduce the risk of these events. Past research suggests that drugs that inhibit PCSK9 have potential as a novel therapy for AAA to both limit aneurysm growth and reduce risk of cardiovascular events. A large multinational randomized controlled trial is needed to test if PCSK9 inhibition limits AAA growth and cardiovascular events.

The relationship between low levels of albuminuria and mortality among adults without major cardiovascular risk factors.

The aim of this study is to determine whether elevated levels of albuminuria within the low range [urinary albumin-to-creatinine ratio (UACR) <30 mg/g] are linked to cardiovascular death in adults lacking major cardiovascular risk factors. The association between UACR and cardiovascular mortality was investigated among 12 835 participants in the 1999-2014 National Health and Nutrition Examination Survey using Cox proportional hazard models and confounder-adjusted survival curves. We excluded participants with baseline cardiovascular disease, hypertension, diabetes, pre-diabetes, an estimated glomerular filtration rate <60 mL/min/1.73 m2, currently pregnant, and those who received dialysis last year. Over a median follow-up of 12.3 years, 110 and 621 participants experienced cardiovascular and all-cause mortality. In multivariable-adjusted models, each doubling of UACR was associated with a 36% higher risk of cardiovascular death [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.02-1.82] and a 24% higher risk of all-cause mortality (HR 1.24, 95% CI 1.10-1.39). The 15-year adjusted cumulative incidences of cardiovascular mortality were 0.91, 0.99, and 2.1% for UACR levels of <4.18, 4.18 to <6.91, and ≥6.91 mg/g, respectively. The 15-year adjusted cumulative incidences of all-cause mortality were 5.1, 6.1, and 7.4% for UACR levels of <4.18, 4.18 to <6.91, and ≥6.91 mg/g, respectively. Adults with elevated levels of albuminuria within the low range (UACR <30 mg/g) and no major cardiovascular risk factors had elevated risks of cardiovascular and all-cause mortality. The risk increased linearly with higher albuminuria levels. This emphasizes a risk gradient across all albuminuria levels, even within the supposedly normal range, adding to the existing evidence.

Unsupervised Cluster Analysis in Patients with Cardiorenal Syndromes: Identifying Vascular Aspects.

Background/Objectives: Cardiorenal syndrome (CRS) is a disorder of the heart and kidneys, with one type of organ dysfunction affecting the other. The pathophysiology is complex, and its actual description has been questioned. We used clustering analysis to identify clinically relevant phenogroups among patients with CRS. Methods: Data for patients admitted from 1 January 2012 to 31 December 2012 were collected from the French national medico-administrative database. Patients with a diagnosis of heart failure and chronic kidney disease and at least 5 years of follow-up were included. Results: In total, 13,665 patients were included and four clusters were identified. Cluster 1 could be described as the vascular-diabetes cluster. It comprised 1930 patients (14.1%), among which 60% had diabetes, 94% had coronary artery disease (CAD), and 80% had peripheral artery disease (PAD). Cluster 2 could be described as the vascular cluster. It comprised 2487 patients (18.2%), among which 33% had diabetes, 85% had CAD, and 78% had PAD. Cluster 3 could be described as the metabolic cluster. It comprised 2163 patients (15.8%), among which 87% had diabetes, 67% dyslipidemia, and 62% obesity. Cluster 4 comprised 7085 patients (51.8%) and could be described as the low-vascular cluster. The vascular cluster was the only one associated with a higher risk of cardiovascular death (HR: 1.48 [1.32-1.66]). The metabolic cluster was associated with a higher risk of kidney replacement therapy (HR: 1.33 [1.17-1.51]). Conclusions: Our study supports a new classification of CRS based on the vascular aspect of pathophysiology differentiating microvascular or macrovascular lesions. These results could have an impact on patients' medical treatment.

#2509 Longitudinal haemoglobin levels and mortality in an elderly population with advanced chronic kidney disease: insights from the EQUAL Study

Abstract Background and Aims The relationship between haemoglobin (Hb) levels and clinical outcomes in chronic kidney disease (CKD) is more intricate than previously understood, as both low and high values can have detrimental effects. Although the association between Hb and patient outcomes is widely reported, few studies have focused on older patients with advanced CKD or have explored this relationship both before and after kidney replacement therapy (KRT) initiation. The primary objective of this study is to describe the relationship between Hb levels and mortality in older patients with advanced CKD in the continuum from pre-KRT phase to subsequent KRT initiation, and to evaluate any effect modification by KRT initiation. Method We used data from the European QUALity Study on treatment in advanced CKD (EQUAL) cohort which includes patients aged ≥65 years and eGFR ≤20 ml/min per 1.73 m2 from six European countries. The association between Hb and all-cause and cause-specific mortality (cardiovascular [CV] and non-cardiovascular [non-CV] mortality) was explored in three separate CKD populations: pre-KRT, KRT and transition-CKD (transition phase surrounding the start of KRT) population. Multivariable adjusted time-dependent Cox regression models and natural cubic splines were used to investigate the association between longitudinal Hb levels (as categorical and continuous variable) and mortality risk in the pre-KRT and KRT population. The area under the Hb trajectory (AUC Hb) before KRT initiation was calculated to evaluate the relationship between the cumulative exposure of Hb before KRT initiation and all-cause mortality after KRT initiation in the transition-CKD population. We evaluated effect modification by pre-specified variables on the relationship between Hb and mortality. Results Overall, 1716 CKD patients were included in the study. During a median follow up of 3.0 years (IQR 2.6), 614 patients died, resulting in a 5-year survival probability of 51% (95% CI 48, 55). Low Hb levels were consistently associated with increased mortality risk in all study populations (Figure). A U-shaped association between both the lowest and highest levels of Hb and mortality risk was observed (Figure). A similar association was observed for non-CV mortality, with lower Hb values associated with an increased mortality risk (Figure). Conversely, a trend towards higher risk of cardiovascular death was observed as Hb levels increase, especially in the whole population and pre-KRT population (Figure), albeit not statistically significant. Low cumulative exposure of Hb in the transition-CKD population was associated with increased mortality risk after transitioning to KRT (p = 0.047). In subgroup analysis diabetic patients were more susceptible to low Hb levels (p-value for interaction = 0.003) while patients on ESA therapy (p-value for interaction = 0.005) or initiating KRT (p-value for interaction = 0.024) showed increased mortality risk for high Hb levels. Conclusion The relationship between Hb levels and mortality in advanced CKD patients is complex. Low Hb levels consistently indicate an increased risk of mortality, while high Hb levels also appear to have a negative effect, increasing mortality risk, particularly in patients receiving ESA therapy and after KRT initiation. Our work emphasizes how different stages of advanced kidney disease (i.e., before and after initiating KRT), as well as comorbidities such as diabetes or medications such as ESA therapy can significantly influence the relationship between Hb and mortality.

Effect of orthostatic hypotension on long-term prognosis of elderly patients with stable coronary artery disease: a retrospective cohort study.

The long-term prognosis of patients with stable coronary artery disease (CAD) combined with orthostatic hypotension (OH) has rarely been reported. This research was designed to examine whether OH increases the risk of all-cause mortality and cardiovascular death among patients with stable CAD. We retrospectively analyzed retired military personnel over 65 years of age who were hospitalized at the General Hospital of Southern Theater Command of the Chinese People's Liberation Army between March and July 2010. A total of 924 patients with stable CAD were included, among whom 263 had OH. The risk of all-cause mortality and cardiovascular death in OH and non-OH groups were analyzed with the Cox proportional hazards models, and restricted cubic spline plots were utilized for subgroup analyses. Furthermore, competing risk models were applied for sensitivity analyses. The median age of the patients was 82.00 (80.00-85.00) years. Over 159 months of follow-up, the loss to follow-up rate was 2.27%, and all-cause mortality was observed in 574 (63.57%) patients, including 184 with OH. Moreover, cardiovascular death occurred in 127 patients (13.73%), with 58 cases associated with OH. Although the relationship between OH and all-cause mortality was non-significant [body mass index (BMI) < 25 group, adjusted hazard ratio (HR) = 1.10 with a 95% confidence interval (CI): 0.82-1.40; BMI ≥ 25 group, adjusted HR = 1.30, 95% CI: 0.98-1.70], it was independently related to a growing risk of cardiovascular death (adjusted HR = 1.80, 95% CI: 1.20-2.60). This finding was further validated by using a competing risk model (subdistribution HR = 1.74, 95% CI: 1.22-2.49). Moreover, age, low-density lipoprotein cholesterol, and frequency of hospital admissions were identified as risk factors of cardiovascular death among patients with OH (P < 0.05). Our study, based on retired military personnel with stable CAD, found that OH led to a significantly higher risk of cardiovascular death, but it was not noticeably associated with all-cause mortality on long-term prognosis.

Outcomes with T-wave discordance of left bundle branch block and preserved or mildly reduced ejection fraction.

Left bundle branch block (LBBB) is associated with an increased risk of adverse outcomes for patients with heart failure. The prognosis of LBBB in patients with a preserved ejection fraction (EF) remains controversial. This study investigated the predictive value of T-wave discordance for the prognosis of patients with LBBB and preserved or mildly reduced EF. We enrolled 707 patients with complete LBBB and left ventricular (LV) EF≥40% observed using electrocardiograms (ECGs) and echocardiograms between January 2010 and December 2018. Their serial ECGs were reviewed during the follow-up period. The T-wave pattern was classified as discordant LBBB (dLBBB) or concordant LBBB (cLBBB) according to the 12-lead ECG T-wave morphology. The primary outcome was the composite of cardiovascular death or hospitalization for heart failure during a median follow-up period of 3.1years. A multivariable Cox regression analysis was used to evaluate the independent predictors of the primary outcome. Patients with dLBBB had more comorbidities, a higher heart rate, a longer QRS and QTc duration, a larger LV end-systolic volume and left atrial dimension, a lower LVEF, and a higher mitral E/A ratio and E/e', compared with those with cLBBB. Older age [hazard ratio (HR)=1.023, 95% confidence interval (CI)=1.001-1.046, P=0.023], history of heart failure (HR=2.440, 95% CI=1.524-3.905, P=0.001), chronic kidney disease (HR=1.917, 95% CI=1.182-3.110, P=0.008), larger LV end-systolic volume (HR=1.046, 95% CI=1.017-1.075, P=0.002), lower LVEF (HR=0.916, 95% CI=0.885-0.948, P=0.001), and presence of dLBBB (HR=1.63, 95% CI=1.011-2.628, P=0.032) were independent predictors of the primary outcome in patients with LBBB and LVEF≥40%. The discordant or concordant T-wave morphology of LBBB could transform from one subtype to the other in up to 23% of the study population during the follow-up period, and individuals with persistent or transformed dLBBB faced an increased risk of cardiovascular death or non-fatal heart failure hospitalization. In patients with LBBB and EF≥40%, dLBBB serves as an independent predictor of a higher risk of cardiovascular death or non-fatal heart failure hospitalization.

Sacubitril/Valsartan-Related Hypotension in Patients With Heart Failure and Preserved or Mildly Reduced Ejection Fraction

BackgroundHypotension is a potential adverse effect of sacubitril/valsartan, but there are limited data regarding the predictors and implications of treatment-related hypotension in heart failure (HF) with mildly reduced and preserved ejection fraction. ObjectivesWe investigated predictors of treatment-associated hypotension, clinical outcomes after hypotension, and the relationship between left ventricular ejection fraction (LVEF) and incidence of hypotension in the PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction) trial. MethodsPARAGON-HF randomized patients with chronic HF (≥45%) to sacubitril/valsartan or valsartan. Following randomization, hypotension was defined as investigator-reported hypotension with a systolic blood pressure <100 mm Hg. Predictors of hypotension were assessed using multivariable Cox models. Associations between hypotension and clinical outcomes were evaluated in time-updated Cox models. The relationship among treatment, LVEF, and incident rates of hypotension and clinical outcomes was estimated using Poisson regression models. ResultsOf 4,796 patients in PARAGON-HF, 637 (13%) experienced hypotension, more frequently in the sacubitril/valsartan arm (P < 0.001). Following documented hypotension, patients had higher risk of cardiovascular death and total HF hospitalizations (adjusted RR: 1.63; 95% CI: 1.27-2.09; P < 0.001) and all-cause death (adjusted HR: 1.62; 95% CI: 1.28-2.05; P < 0.001). LVEF modified the association between sacubitril/valsartan and risk of hypotension (Pinteraction = 0.019) such that patients with LVEF ≥60% experienced substantially higher treatment-related risks of hypotension. ConclusionsIn PARAGON-HF, a higher LVEF was associated with an increased risk of hypotension in patients treated with sacubitril/valsartan compared with valsartan. Because these subjects are also less likely to derive clinical benefit from sacubitril/valsartan, our data reinforce that the benefit/risk ratio favors the use of sacubitril/valsartan in patients with LVEF below normal, but not at higher LVEF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711)

Right Ventricular Dysfunction in Patients With Concomitant Tricuspid Regurgitation Undergoing Transcatheter Aortic Valve Implantation.

This study investigated the impact and predictive factors of concomitant significant tricuspid regurgitation (TR) and evaluated the roles of right ventricle (RV) function and the etiology of TR in the clinical outcomes of patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). We assessed grading of TR severity, TR etiology, and RV function in pre- and post-TAVI transthoracic echocardiograms for 678 patients at Keio University School of Medicine. TR etiology was divided into 3 groups: primary TR, ventricular functional TR (FTR), and atrial FTR. The primary outcomes were all-cause and cardiovascular death. At baseline, moderate or greater TR was found in 55 (8%) patients and, after adjustment for comorbidities, was associated with increased all-cause death (hazard ratio [HR] 2.11; 95% confidence interval [CI] 1.19-3.77; P=0.011) and cardiovascular death (HR 2.29; 95% CI 1.06-4.99; P=0.036). RV dysfunction (RVD) also remained an independent predictor of cardiovascular death (HR 2.06; 95% CI 1.03-4.14; P=0.042). Among the TR etiology groups, patients with ventricular FTR had the lowest survival rate (P<0.001). Patients with persistent RVD after TAVI had a higher risk of cardiovascular death than those with a normal or recovered RV function (P<0.001). The etiology of TR and RV function play an important role in predicting outcomes in concomitant TR patients undergoing TAVI.

Evaluation of the Prognostic Role of Neutrophil-Lymphocyte Ratio, C-Reactive Protein-Albumin Ratio, and Platelet-Lymphocyte Ratio in Patients with the Co-Presentation of Coronary Artery Disease and COVID-19.

The purpose of this study was to investigate the role of neutrophil-lymphocyte ratio (NLR), C-reactive protein-albumin ratio (CAR), and platelet-lymphocyte ratio (PLR) in the prognosis of patients with coronary artery disease (CAD) complicated with coronavirus disease 2019 (COVID-19). This study included 265 patients. A receiver operating characteristic (ROC) curve analysis was performed to preliminarily evaluate the predictive ability of NLR, CAR, and PLR for all-cause death. The primary outcome was all-cause death during hospitalization, while the secondary outcomes were cardiovascular death and respiratory failure death. The Cox proportional hazard model with adjusted covariates was used to analyze the cumulative risk of outcomes. We also conducted subgroup analyses based on the acute and chronic characteristics of CAD. Propensity score matching (PSM) was used to further evaluate the robustness of the primary outcome. The ROC curve analysis results showed that the area under curve (AUC) values were 0.686 (95% CI 0.592-0.781, P<0.001) for NLR, 0.749 (95% CI 0.667-0.832, P<0.001) for CAR, and 0.571 (95% CI 0.455-0.687, P=0.232) for PLR. The Cox proportional hazard model showed that trends in NLR and PLR did not affect the risk of all-cause death (P=0.096 and P=0.544 for trend, respectively), but a higher CAR level corresponded to a higher risk of all-cause death (P<0.001 for trend). Similarly, The trends of NLR and PLR did not affect the risk of cardiovascular death and respiratory failure death, while a higher CAR level corresponded to a higher risk of cardiovascular death and respiratory failure death. The results of subgroup analyses and PSM were consistent with the total cohort. In patients with CAD complicated with COVID-19, a higher CAR level corresponded to a higher risk of all-cause death, cardiovascular death, and respiratory failure death, while trends in NLR and PLR did not.