Biopsychosocial Phenogroups in Individuals with Coronary Artery Disease and their Associated Cardiovascular Mortality Risks.

LEFT VENTRICULAR MASS PREDICTS CARDIAC REVERSE REMODELING IN PATIENTS TREATED WITH EMPAGLIFLOZIN: AN EXPLORATORY SUB-ANALYSIS OF THE EMPA-HEART CARDIOLINK-6 RANDOMIZED CONTROLLED TRIAL

Associations between plasma tryptophan and indole-3-propionic acid levels and mortality in patients with coronary artery disease

Cognitive impairment is a prevalent condition that substantially elevates mortality rates among the elderly. The impact of hypertension on mortality in older adults with cognitive impairment is a subject of contention. This study aims to examine the influence of hypertension on both all-cause and CVD-specific mortality in elderly individuals experiencing cognitive impairment within a prospective cohort. This study encompassed 2,925 participants (weighted 53,086,905) aged 60 years or older from National Health and Nutrition Examination Survey (NHANES) spanning 2011-2014. Incidence of all-cause and CVD-specific mortality was ascertained through linkage with National Death Index records until 31 December 2019. Survival was performed employing the Kaplan-Meier method. Hazard ratios (HRs) were calculated via Cox proportional hazards regression models. Over the follow-up period of up to 9.17 years [with a median (IQR) time to death of 6.58 years], equivalent to 18,731.56 (weighted 3.46 × 108) person-years, there were a total of 576 recorded deaths. Participants with CI exhibited a 1.96-fold higher risk of all-cause mortality (95% CI: 1.55-2.49; p < 0.01) and a 2.8-fold higher risk of CVD-specific mortality (95% CI: 1.83-4.29; p < 0.01) in comparison to participants without CI. Among participants with CI, concurrent hypertension comorbidity was linked to a 2.73-fold elevated risk of all-cause mortality (95% CI: 1.78-4.17; p < 0.01) and a 5.3-fold elevated risk of CVD-specific mortality (95% CI: 2.54-11.04; p < 0.01). Further stratified analyses revealed that the combined effects of hypertension and CI on all-cause and CVD-specific mortality were more pronounced in participants aged 60-69 years compared to those aged 70-80 years (p for interaction <0.01). The primary findings exhibited resilience across a series of sensitivity analyses. Participants with CI exhibited a markedly elevated risk of all-cause and CVD-specific mortality when coexisting with hypertension. Appropriate management of hypertension in patients with CI may be helpful in reducing the excess risk of death.

Background: Polycyclic aromatic hydrocarbons (PAHs) are widely detected chemicals in the U.S. population. Exposure to PAHs has been associated with adverse health outcomes including lung cancer and cardiovascular disease (CVD) though population-based studies examining mortality in relation to PAH exposure is sparse. We aimed to prospectively investigate the relationship of PAH biomarkers and all-cause, cancer-specific, and CVD-specific mortality in a representative sample of the U.S. population. Methods: The study population included 8,168 individuals ≥20 years old who participated in NHANES from 2001-2012. Urinary measures of eight hydroxylated PAH metabolites (OH-PAHs) from four parent compounds (naphthalene, pyrene, phenanthrene, fluorene) were assessed at baseline. Mortality status was ascertained by death certificates through data linkage with the NDI, followed-up until 2015. Survey-weighted Cox proportional hazards regression estimated adjusted hazards ratios (HRadj) and 95% confidence intervals (95%CI). We stratified by active smoking and environmental tobacco smoke (ETS) exposure, sex and race. Results: 912 deaths from all causes were observed over follow-up (mean=8.31 years). A log10 increase in ΣOH-PAHs was associated with a higher all-cause (HRadj: 1.39 [95%CI: 1.21, 1.61]), CVD-specific (HRadj: 1.48 [95%CI: 0.93, 2.34]), and cancer-specific mortality (HRadj: 1.12 [95%CI: 0.76, 1.66]). Stratified models suggest the risk of ΣOH-PAHs and all-cause mortality was higher for active smokers or those exposed to ETS (HRadj: 1.92 [95%CI: 1.39, 2.65]), compared to nonsmokers. In cancer-specific analyses, an increased risk was observed in women (HRadj: 1.49 [95%CI: 1.01, 2.20]), but not men. Compared to other races/ethnicities, risk of CVD-related mortality was highest for non-Hispanic black participants (HRadj: 1.97 [95%CI: 0.79, 4.91]). Discussion: Urinary ΣOH-PAHs was associated with higher all-cause, cancer-specific, and CVD-specific mortality among a representative sample of U.S. adults. This prospective examination of PAH biomarkers, representing exposure across multiple sources, suggests a role for PAHs in both overall mortality and diseases with the highest mortality rates.

Background: Metabolic syndrome (Mets) is documented to increase mortality in the general population. However, there are reports of lower mortality in end stage renal disease (ESRD) patients with obesity. We conducted a meta-analysis to determine the association of all-cause and cardiovascular disease (CVD) mortality, and residual renal function with Mets in ESRD subjects. Objectives: PubMed/MEDLINE, EMBASE, and CENTRAL from their inception to September 2014 were comprehensively searched for eligible studies assessing the effects of the metabolic syndrome in ESRD subjects. Inclusion criterion was ESRD participants who had hemodialysis (HD or peritoneal dialysis (PD). Renal transplant subjects were excluded. Two authors independently assessed article quality and extracted the data. The primary outcome was all-cause mortality and secondary outcomes were CVD death and residual renal function. Results: From 23 full-text articles, 7 studies involving 613 (all-cause mortality), 284 (CVD death) and 383 (residual renal function) participants were included in the meta-analysis that was based on the random effects model. Compared with the non-Mets, ESRD subjects with Mets had no significant difference in risk of all-cause mortality (pooled odds ratio= 1.65; 95% CI, 0.86, 3.17) (figure 1) or CVD death (pooled odds ratio= 1.67; 95% CI, 0.75, 3.69). There was also no difference in residual renal function between the two groups with pooled standard mean difference of -0.26 ml/min/1.73 m2 (95% CI: -0.62, 0.10). Conclusion: Metabolic syndrome is not associated with an increased risk of all-cause or CVD mortality in ESRD patients who underwent HD or PD.

To determine the impact of subclinical hypothyroidism (SCH) on the risk of cardiovascular disease (CVD) and all-cause mortality, a comprehensive meta-analysis was performed according to the age or coexisting CVD risk status of the participants. Studies regarding the association of SCH with all-cause mortality from PubMed and Embase databases were included. The pooled relative risk (RR) of CVD and all-cause mortality was calculated using the Mantel-Haenszel method. A subgroup analysis of participants with high CVD risk was conducted, including history of coronary, cerebral, or peripheral artery disease; dilated cardiomyopathy; heart failure; atrial fibrillation; venous thromboembolism; diabetes mellitus; or chronic kidney disease. In total, 35 eligible articles incorporating 555,530 participants were included. SCH was modestly associated with CVD and all-cause mortality (RR for CVD = 1.33 [confidence interval (CI) 1.14-1.54]; RR for all-cause mortality = 1.20 [CI 1.07-1.34]). However, the association was not observed in participants aged ≥65 years. Subgroup analysis showed that participants with SCH and high CVD risk showed a significantly higher risk of all-cause mortality (RR for CVD = 2.20 [CI 1.28-3.77]; RR for all-cause mortality = 1.66 [CI 1.41-1.94]), whereas those with SCH and low CVD risk did not. Additional subgroup analysis of six studies with a mean participant age of ≥65 years and high CVD risk showed a significant high risk of all-cause mortality in the SCH group (RR = 1.41 [CI 1.08-1.85]; I2 = 0%). SCH is associated with an increased CVD risk and all-cause mortality, particularly in participants with high CVD risk.

BackgroundCoronary artery disease (CAD) is a global problem with increasing incidence in Asia. Prior studies reported inter-ethnic differences in the prevalence of CAD rather than the severity of CAD. The angiographic “synergy between percutaneous coronary intervention (PCI) with taxus and cardiac surgery” (SYNTAX) score quantifies CAD severity and predicts outcomes. We studied CAD severity and all-cause mortality in four globally populous ethnic groups: Caucasians, Chinese, Indians and Malays.MethodsWe quantified SYNTAX scores of 1,000 multi-ethnic patients undergoing PCI in two tertiary hospitals in the Netherlands (Caucasians) and Singapore (Chinese, Indians and Malays). Within each ethnicity we studied 150 patients with stable CAD and 100 with ST-elevated myocardial infarction (STEMI). We made inter-ethnic comparisons of SYNTAX scores and all-cause mortality.ResultsDespite having a younger age (mean age Indians: 56.8 and Malays: 57.7 vs. Caucasians: 63.7 years), multivariable adjusted SYNTAX scores were significantly higher in Indians and Malays than Caucasians with stable CAD: 13.4 [11.9-14.9] and 13.4 [12.0-14.8] vs. 9.4 [8.1-10.8], p<0.001. Among STEMI patients, SYNTAX scores were highest in Chinese and Malays: 17.7 [15.9-19.5] and 18.8 [17.1-20.6] vs. 15.5 [13.5-17.4] and 12.7 [10.9-14.6] in Indians and Caucasians, p<0.001.Over a median follow-up of 709 days, 67 deaths (stable CAD: 37, STEMI: 30) occurred. Among STEMI patients, the SYNTAX score independently predicted all-cause mortality: HR 2.5 [1.7-3.8], p<0.001 for every 10-point increase. All-cause mortality was higher in Indian and Malay STEMI patients than Caucasians, independent of SYNTAX score (adjusted HR 7.2 [1.5-34.7], p=0.01 and 5.8 [1.2-27.2], p=0.02).ConclusionAmong stable CAD and STEMI patients requiring PCI, CAD is more severe in Indians and Malays than in Caucasians, despite having a younger age. Moreover, Indian and Malay STEMI patients had a greater adjusted risk of all-cause mortality than Caucasians, independent of SYNTAX score.

Hypertension (HTN) patients have higher risk of all-cause and cardiovascular disease (CVD)-specific mortality. Dietary patterns have been reported related to the risk of mortality, but their roles in HTN patients is unclear. To explore the relationships between different dietary patterns and all-cause/CVD-specific mortality and provide dietary guidance for HTN patients'prognosis improvement. Data of 27 618 HTN patients were extracted from the National Health and Nutrition Examination Survey(NHANES) database in this retrospective cohort study. The associations between Healthy Eating Index (HEI)-2015, Alternate Healthy Eating Index(AHEI)-2010, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean(MED) diet and all-cause and CVD-specific mortality were explored using univariate and multivariate Cox regression analyses with hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses of age, gender, body mass index, and comorbidity were also performed. The median follow-up time was 83 months. A total of 3462 patients died for all-cause and 1064 died due to CVD. After adjusting for covariates, we found that high adherence to AHEI-2010 (HR = 0.84 for all-cause; HR = 0.72 for CVD), and MED (HR = 0.84 for all-cause; HR = 0.77 for CVD) diet were associated with decreased risks of both all-cause and CVD-specific mortality. In patients who aged ≥65 years old, were normal/overweight, without complications, therelationships between different dietary patterns and risk of mortality were different. High scores of AHEI-2010 and MED may be associated with decreased risks of all-cause and CVD-specific mortality in patients with HTN.

Association of antiplatelet therapy with clinical outcomes in patients with peripheral artery disease

Background Patients with stable coronary artery disease (CAD) and atrial fibrillation (AF) are at elevated risk of adverse clinical outcomes, including stroke, myocardial infarction, and all-cause mortality. Blood pressure management plays a crucial role in this population; however, the impact of systolic blood pressure (SBP) on prognosis, particularly in patients with both AF and stable CAD, remains unclear. Previous studies have demonstrated an association between low SBP and a higher burden of comorbidities, which may influence clinical outcomes. The AFIRE (Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease; N Engl J Med 2019;381:1103–1113) trial established the efficacy and safety of rivaroxaban monotherapy compared to combination therapy (rivaroxaban plus a single antiplatelet) in patients with AF and stable CAD. However, whether SBP and comorbidity burden affect the choice of antithrombotic therapy in this population remains to be clarified. Purpose This post-hoc analysis of the AFIRE trial investigated the impact of SBP on clinical outcomes in patients with both AF and CAD and assessed the efficacy and safety of rivaroxaban monotherapy in different SBP subgroups. Methods A total of 2,135 patients were categorized by median baseline SBP: High SBP (&amp;gt;126 mmHg, n=1,042) and Low SBP (≤126 mmHg, n=1,093). The primary efficacy endpoint was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or all-cause mortality; the primary safety endpoint was major bleeding. Outcomes were compared between treatment strategies within each SBP group. Results Low SBP group (mean SBP: 116 mmHg) had a higher prevalence of renal failure, myocardial infarction, and heart failure than High SBP group (mean SBP: 136 mmHg). During a median follow-up of 24.1 months, the primary efficacy events occurred more frequently in Low SBP group (hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.13–1.98, p=0.004, Figure 1A). The incidence of major bleeding was comparable between groups (HR 1.30, 95% CI 0.89–2.07, p=0.14, Figure 1B). In Low SBP group, rivaroxaban monotherapy was associated with better efficacy (HR 0.66, 95% CI 0.41–0.86, p=0.006) and safety outcomes (HR 0.40, 95% CI 0.22–0.74, p=0.003, Figure 2A, B) compared with combination therapy. In contrast, in the High SBP group, efficacy and safety outcomes were similar between the two treatment strategies (efficacy: HR 0.91, 95% CI 0.58–1.40, p=0.67; safety: HR 0.99, 95% CI 0.52–1.89, p=0.99). Conclusion Patients with lower SBP and a high burden of comorbidities exhibited an increased risk of adverse clinical events. In this group, rivaroxaban monotherapy was associated with more favorable efficacy and safety outcomes compared to combination therapy. These findings highlight the potential influence of SBP and comorbidities in guiding antithrombotic strategies for patients with AF and stable CAD.

Background Although patients with severe aortic stenosis (AS) often also have significant concomitant coronary artery disease (CAD), the optimal timing of percutaneous coronary intervention (PCI) in relation to transcatheter aortic valve implantation (TAVI) remains uncertain. Purpose This meta-analysis evaluates the association of pre-TAVI PCI, concurrent PCI at the time of TAVI, and post-TAVI PCI on risk of all-cause mortality. Methods A literature search was conducted using the databases Pubmed, Embase, and Web of Science, looking for studies that evaluated the association of different timing of PCI with risk of the primary endpoint, all-cause mortality, in patients with CAD and severe AS undergoing TAVI. The search was not restricted by time or publication status. Results A total of 8 studies including 8,506 patients met the inclusion criteria. Patients were categorized into three groups: pre-TAVI PCI (n=2,323), concurrent PCI at TAVI (n=1,635), and staged post-TAVI PCI (n=4,548). The mean follow-up duration was 10.5 months, the mean age was 81 years, and 55% of the cohort were men. Compared to both pre-TAVI PCI and concurrent PCI strategies, post-TAVI PCI was associated with a significantly lower risk of all-cause mortality on follow-up in patients with CAD and severe AS (OR 2.11, 95% CI 1.41-3.17; p&amp;lt;0.01; OR 1.50, 95% CI 1.0-2.23; p=0.05). There was no significant difference in risk of all-cause mortality between pre-TAVI PCI and concurrent PCI at the time of TAVI (OR 0.95, 95% CI 0.77-1.19; p=0.68). Conclusion Based on the findings from this meta-analysis, deferring PCI until after TAVI may be associated with lower risk of mortality compared to performing PCI prior to or at the time of TAVI. However, additional high quality studies are needed to further establish these findings and to optimize the revascularization strategies for this patient population.Figure 1

Background/Introduction Lipid-lowering randomised clinical trials (RCTs) inform guideline recommendations on lipid-lowering therapy for the prevention of atherosclerotic cardiovascular disease (ASCVD). However, these trials were often conducted several decades ago and employed stringent eligibility criteria to ensure internal validity, which may not reflect the diversity of contemporary real-world patients. Whether ineligible patients with coronary artery disease (CAD), cerebrovascular disease (CeVD), and peripheral artery disease (PAD) have a different prognosis than eligible patients remains unknown. Purpose To evaluate the proportion of contemporary real-world patients meeting eligibility criteria for pivotal lipid-lowering trials and to compare clinical characteristics and long-term outcomes between trial-eligible and ineligible patients. Methods Lipid-lowering RCTs informing European and American guidelines for secondary ASCVD prevention were identified. Eligibility criteria from eight selected RCTs were applied to patients with CAD, CeVD, and PAD. These patients were enrolled in an ongoing prospective cohort of individuals aged 18–90 years with high cardiovascular risk, referred to a tertiary hospital between 2000 and 2023. Eligibility proportions were calculated for each trial, and differences in clinical characteristics and risks of recurrent cardiovascular events and all-cause mortality were analysed, accounting for competing risks. A sensitivity analysis was conducted in patients included from 2010 onwards. Results The study included 8,537 patients with established ASCVD, of whom 5,673 had CAD, 2,493 had CeVD, and 1,302 had PAD. The median follow-up was 8.8 years (interquartile range [IQR]: 4.2–13.9 years). Eligibility proportions for lipid-lowering RCTs ranged from 9–85% for CAD (Figure 1), 7–42% for CeVD, and 8–78% for PAD. Trial-eligible and ineligible patients exhibited differences in clinical characteristics in most trials, but they had largely comparable risks of recurrent cardiovascular events and all-cause mortality. Rate ratios for recurrent cardiovascular events ranged from 0.70 (95% confidence interval [CI]: 0.62–0.79) to 1.55 (95% CI: 1.37–1.75) for CAD (Figure 2), 0.68 (95% CI: 0.56–0.83) to 2.12 (95% CI: 1.60–2.81) for CeVD, and 0.83 (95% CI: 0.64–1.08) to 1.94 (95% CI: 1.40–2.70) for PAD. Conclusions Eligibility of contemporary real-world patients for lipid-lowering trials varied substantially between trials and ASCVD disease locations. Patients with CeVD were the least likely to be eligible compared with those with CAD and PAD. Despite differences in clinical characteristics, trial-eligible and ineligible patients had similar risks of recurrent cardiovascular events and all-cause mortality in most trials.

Negative emotional conditions contribute to the development of coronary artery disease (CAD). Depression and anxiety are prognostic factors in patients with CAD. The aim of our study was to investigate the association between emotional conditions and left ventricular (LV) systolic functions in CAD. 168 patients (102 men, 66 women, mean age 66.3 ± 9.9 years) with stable angina and multivessel disease (MVD) were included in the study. According to the LV ejection fraction (LVEF) in echocardiography, patients were divided into two groups, the preserved group (LVEF > 50%), and the impaired group (LVEF < 50%). The preserved group consisted of 94 patients and the impaired group consisted of 74 patients. Emotional status was evaluated using the Hamilton Depression (HAM-D), Hamilton Anxiety (HAM-A), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) scores. The prevalence of diabetes mellitus (DM) was significantly higher in the impaired group than in the preserved group (29.8% vs 56.8%, p < 0.01). The HAM-D, HAM-A, BAI and BDI scores were higher in the impaired group compared to the preserved group (HAM-D: 12.1 ± 3.3 vs 14.5 ± 2.3, p = 0.03; HAM-A: 12.7 ± 3.4 vs 14.3 ± 2.2, p = 0.01; BAI: 18.6 ± ± 6.4 vs 22.1 ± 6.6, p = 0.01 and BDI: 13.9 ± 2.5 vs 17.2 ± 2.0, p = 0.002, respectively). In multivariate analysis, BDI scores (odds ratio [OR]: 2.197, < 95% confidence interval [CI] 1.101-4.387; p = 0.026), HAM-A scores (OR: 1.912, < 95% Cl 1.092-2.974; p = 0.041) and DM (OR: 2.610, < 95% Cl 1.313-5.183; p = 0.006) were important risk factors for LV dysfunction in stable patients with MVD. This study demonstrated that emotional status and DM are factors associated with impaired LV systolic function in patients with stable CAD.

Association of Serum Magnesium and Calcium - Magnesium Ratio with Mortality in Patients with Coronary Artery Disease (P18-090-19)

Background Excess apolipoprotein B (apoB) levels provide important clinical information about the atherogenic particle burden not captured by traditional low-density lipoprotein cholesterol (LDL-C) levels alone. Despite its established association with the general population, the association between excess apoB and clinical outcomes in patients with coronary artery disease (CAD) remains under investigation. Objectives This study aimed to investigate the relationship between excess apoB levels and the risk of all-cause and cardiovascular mortality in patients diagnosed with CAD. Methods We conducted a pooled analysis of two cohorts: the Cardiorenal Improvement II (CIN-II) and the REal-world Data of CARdiometabolic ProtEcTion Study (RED-CARPET). This analysis included 68,616 patients with coronary artery disease (CAD) (mean age 63.1 ± 10.8 years; 72.2% male) who were undergoing statin therapy. We also incorporated data from the UK Biobank (UKB) as a validation cohort to enhance the generalizability of our findings. Cox proportional hazards regressions were used to evaluate the associations between excess apoB and the risk of cardiovascular and all-cause mortality. Excess apoB was calculated as the surplus of measured apoB over expected levels derived from LDL-C regressions in participants with triglycerides less than 1 mmol/L. Results Over a median follow-up of 5.2 years (interquartile range: 3.1-7.9 years), there were 10,835 (15.8%) death, with 5,090 (7.4%) attributable to cardiovascular causes. L-shape associations were observed between excess apoB and both cardiovascular and all-cause mortality. Compared to patients with excess apoB &amp;lt;11.5 mg/dL, those with excess apoB≥11.5 mg/dL had a 24% higher risk of cardiovascular mortality (adjusted hazard ratio [aHR]: 1.24; 95% confidence interval [CI]: 1.15–1.34; P &amp;lt; 0.001) and a 12% increase in all-cause mortality (aHR: 1.12; 95% CI: 1.06–1.18; P &amp;lt; 0.001). These associations remain significant across LDL-C spectrum for cardiovascular mortality and validated within the UK Biobank cohort. Conclusion Excess apoB, defined as the levels exceeding those predicted by LDL-C, is independently associated with an increased risk of cardiovascular mortality in CAD patients. This emphasizes the potential for excess apoB to provide prognostic information beyond traditional LDL-C measurements.