Risk Of Cardiovascular Mortality Research Articles

Association of dietary niacin intake with all-cause and cardiovascular mortality: National Health and Nutrition Examination Survey (NHANES) 2003-2018.

The long-term health impacts of niacin are still debated, and the association between dietary niacin and mortality risk in populations hasn't been extensively explored. This study included 26,746 US adults aged 20 years or older from the National Health and Nutrition Examination Survey 2003-2018, with a median follow-up of 9.17 years. During this period, there were 3,551 all-cause deaths, including 1,096 cardiovascular deaths. Cox models were used to compare hazard ratios (HRs) for mortality among participants grouped into different dietary niacin intake quartiles. Participants with the highest dietary niacin intake had a lower risk of all-cause mortality (HR 0.74, 95%CI 0.63-0.86) compared to those in the lowest intake quartile. For cardiovascular mortality, the HR was 0.73 (95%CI 0.57-0.95) in the highest niacin intake quartile. A dose-response relationship was revealed between dietary niacin intake and mortality by restricted cubic spline. Subgroup analysis showed a significant interaction between dietary niacin intake and diabetes concerning all-cause mortality (P = 0.046). In this population-based cohort study, higher dietary niacin intake correlates with lower risk of all-cause and cardiovascular mortality among US adults. The influence of niacin intake on all-cause mortality appears to be more significant in non-diabetic individuals compared to those with diabetes.

Use of bisphosphonates in chronic kidney disease is associated with cardiovascular death.

Chronic kidney disease (CKD) is associated with increased cardiovascular risk, which may be mediated by vascular calcification. Based on evidence that bisphosphonates inhibit vascular calcification, we hypothesized use of bisphosphonates in CKD would be associated with lower incident cardiovascular disease (CVD), CVD-related mortality, and all-cause mortality. This was a longitudinal observational study including 2,593 Framingham Offspring participants. We used propensity score-adjusted Cox regression models to determine the association between bisphosphonate use and outcomes: time to incident CVD, time to CVD-related mortality, and time to all-cause mortality. The data were stratified by presence or absence of CKD, defined as estimated glomerular filtration rate <60 mL/min/1.73m2. The propensity score included age, sex, hypertension, smoking status, diabetes, total cholesterol, high-density lipoprotein, and self-reported history of fracture. In unadjusted and propensity score-adjusted analyses, those with CKD using bisphosphonates had a trend toward increased incident CVD risk (adjusted hazard ratio (HR) 1.66 (95% CI, 93-2.97)) compared to those with CKD not using bisphosphonates. Those with CKD using bisphosphonates also had increased risk of cardiovascular mortality in the propensity score-adjusted model (adjusted HR 2.20 (95% CI, 1.12-4.32)). There was no significant association between bisphosphonate use and all-cause mortality in participants with CKD. Among individuals without CKD, bisphosphonate use was significantly associated with an increase in all-cause mortality in the propensity-score adjusted analysis (adjusted HR 1.59 (95% CI, 1.27-1.98)). However, there was no significant association between bisphosphonate use and incident CVD events (adjusted HR 0.85 95% CI, 0.63-1.16) or CVD-related death (adjusted HR 0.70 (95% CI 0.36-1.37) in those without CKD. Contrary to our hypothesis, bisphosphonate use was associated with a trend toward increased incident CVD and a two-fold higher risk of CVD mortality in CKD.

Effectiveness and safety of mineralocorticoid receptor antagonists in heart failure patients with and without diabetes: a systematic review and meta-analysis.

Mineralocorticoid receptor antagonists (MRAs) have been shown to improve outcomes in various populations of heart failure (HF) patients. However, the impact of concomitant diseases, such as diabetes mellitus (DM), on these outcomes remains unclear. This meta-analysis aimed to evaluate the efficacy and safety of MRAs in heart failure patients with and without diabetes mellitus. A systematic search was conducted on PubMed, Scopus, and Google Scholar databases up to April 30, 2024. Data analysis was performed using a random-effects model to account for variability across studies, and statistical analysis was carried out using Review Manager 5.4. Efficacy and safety parameters were evaluated in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. The meta-analysis included a total of 21,832 subjects from ten studies. The pooled results demonstrated that MRAs, compared to placebo, significantly reduced all-cause mortality in HF patients with and without DM (RR: 0.85; 95%CI 0.75-0.96; p = 0.009). A similar effect was observed in HF patients without DM (RR: 0.83; 95%CI 0.71-0.97; p = 0.02), while no significant effect was detected in the DM subgroup (RR: 0.87; 95%CI 0.69-1.11; p = 0.27). Both treatments had comparable effects on cardiovascular mortality in HF patients with and without DM (RR: 0.88; 95%CI 0.82-0.94; p = 0.0002), in HF patients with DM (RR: 0.90; 95%CI 0.81-1.01; p = 0.08), and in the non-DM subgroup (RR: 0.86; 95%CI 0.79-0.94; p = 0.0009). MRAs significantly reduced the risk of cardiovascular mortality in HF patients with and without DM (RR: 0.82; 95%CI 0.72-0.94; p = 0.005) and in HF patients with DM (RR: 0.79; 95%CI 0.63-0.98; p = 0.03), but no significant effect was observed in the non-DM subgroup (RR: 0.85; 95%CI 0.69-1.05; p = 0.13). Furthermore, compared to placebo, MRAs were associated with an increased risk of hyperkalemia (> 5.5 mEq/L) in HF patients with and without DM (RR: 1.63; 95%CI 1.18-2.24; p = 0.003), particularly in HF patients with DM (RR: 1.44; 95%CI 0.97-2.13; p = 0.07) and in the non-DM subgroup (RR: 1.87; 95%CI 1.34-2.61; p = 0.0002). MRAs are effective in reducing all-cause mortality, cardiovascular death, and cardiovascular mortality in heart failure patients. However, the use of MRAs is associated with an increased risk of hyperkalemia, necessitating careful monitoring, particularly in patients with diabetes mellitus.

Impact of serum carotenoids on cardiovascular mortality risk in middle-aged and elderly adults with metabolic syndrome

BackgroundMetabolic syndrome (MetS), characterized by abdominal adiposity, hypertension, hyperglycemia, and dyslipidemia, is associated with dysregulated immune function, elevated oxidative stress, and chronic low-grade inflammation. Aging exacerbates insulin resistance and the prevalence of MetS. Dietary antioxidants, such as carotenoids, may play a role in preventing cardiovascular disease (CVD) mortality, but evidence remains mixed, particularly among middle-aged and elderly individuals with MetS.MethodsWe analyzed data from 6,601 participants aged 40 years and above with MetS from the National Health and Nutrition Examination Survey (NHANES) III (1988–1994) and NHANES 2001–2006 cycles. Serum concentrations of α-carotene, β-carotene, lycopene, β-cryptoxanthin, and combined lutein/zeaxanthin were quantified. Participants were followed for a median of 16.8 years. Cox proportional-hazards models were used to assess the association between serum carotenoid concentrations and CVD mortality risk, with adjustment for potential confounders.ResultsDuring the follow-up period, 1,237 CVD deaths were identified. Analysis revealed an inverse dose–response relationship between serum lycopene levels and cardiovascular mortality risk. Compared to the lowest quartile, the multivariable-adjusted hazard ratios (95% confidence intervals) for ascending quartiles of serum lycopene were 0.84 (0.71, 1.00), 0.87 (0.74, 1.03), and 0.77 (0.61, 0.97), with a significant trend (p = 0.039). No significant associations were observed for other carotenoids.ConclusionIn this prospective cohort study of 40-year-old and older individuals with MetS, we observed an inverse association between serum lycopene levels and CVD mortality risk.

Elevated neutrophil percentage-to-albumin ratio predicts increased all-cause and cardiovascular mortality among individuals with diabetes.

Evidence regarding the neutrophil percentage-to-albumin ratio (NPAR) and mortality risk in diabetes patients is scarce. This study aimed at investigating the prognostic value of NPAR for mortality in patients with diabetes. This retrospective analysis was conducted on 6,962 diabetic patients from the NHANES database. Restricted cubic spline (RCS) was used to visualize the association of the NPAR with mortality risk. Weighted multivariable Cox regression models and subgroup analyses were adopted to assess the association of the NPAR with all-cause and cardiovascular mortality. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to evaluate the accuracy of the NPAR in predicting survival outcomes. Mediation analysis explored the indirect impact of NPAR on mortality mediated through eGFR. During a median follow-up of 6.7 years, there were 1,804 deaths were recorded, including 602 cardiovascular deaths. The RCS regression showed that NPAR has a J-shaped association with all-cause mortality, and a positive linear association with CVD mortality. Each one-unit increase in NPAR was linked with a 14% and 12% increased risk of all-cause and cardiovascular mortality, respectively. The association was consistent in subgroup analyses based on age, sex, race, BMI, hypertension, CKD, and history of CVD. The time-dependent ROC curve showed the area under the curve of were 0.809 for all-cause mortality, and 0.780 for CVD mortality. In mediation analyses, eGFR partially mediated these relationships. An elevated NPAR is independently associated with increased all-cause and cardiovascular mortality in diabetes patients.

Abstract 4124875: Association between Elevated Lipoprotein(a) and Cardiovascular Events and Mortality in a Nationally Representative Sample of US Medicare, Medicaid, and Commercial Enrollees with ASCVD

Background: Elevated lipoprotein(a) [Lp(a)] is an independent and causal risk driver for atherosclerotic cardiovascular disease (ASCVD). Few patients with ASCVD receive Lp(a) screening and real-world data assessing the association between elevated Lp(a) and risk of cardiovascular (CV) events and mortality is limited. Objectives: To examine the association of elevated Lp(a) and risk of CV events and death in an ASCVD population using large US health claims databases. Methods: Patients with ASCVD were pooled from US Medicare, commercial, and Medicaid health plans from 2017 to 2022. Lp(a) levels were linked at the patient level from HealthVerity Lab Data and categorized as: &lt;30 mg/dL (&lt;75 nmol/L), ≥30-&lt;50 mg/dL ( &gt; 75-&lt;125 nmol/L), ≥50-&lt;70 mg/dL ( &gt; 125-&lt;175 nmol/L), ≥70-&lt;90 mg/dL (≥175-&lt;225 nmol/L) and ≥90 mg/dL (≥225 nmol/L). Patients were followed from the 1 st ASCVD diagnosis (index) to insurance plan disenrollment, death, or end of study. Cox regression, adjusted for age, sex, race, insurance, comorbidities, LDL-C, and other risk factors, measured the association between Lp(a) levels and risk of CV events and death. Results: Of 28.8 million ASCVD patients, 180,240 (0.6%) had Lp(a) levels: mean(±SD) age 68.6±1 years, 50.1% male, 5.9% Black, 2.8% Hispanic, 2.1% Asian, 72.8% Medicare, 21.8% commercial, and 5.4% Medicaid. Mean follow-up was 3.7 years; 23.3% and 15.7% had Lp(a) ≥50mg/dL [≥125 nmol/L] and ≥70 mg/dL (≥175 nmol/L), respectively. Black patients had highest median Lp(a) (50 mg/dL/111 nmol/L), followed by Asian (13.5 mg/dL/35.5 nmol/L), White (13 mg/dL/32 nmol/L), and Hispanic (11.5 mg/dL/29 nmol/L) patients. Lp(a) levels of ≥30-&lt;50 mg/dL, ≥50-&lt;70 mg/dL, ≥70-&lt;90 mg/dL, and ≥90 mg/dL were associated with 7%, 10%, 16%, and 26% greater risks of CV events vs. &lt;30 mg/dL (p-values &lt;0.0001; cumulative incidence reported in Figure 1). All-cause mortality risk was also greater for those with Lp(a) ≥90 mg/dL vs. &lt;30 mg/dL: hazard ratio (HR)=1.11, p=0.003. Similar trends persisted for patients with LDL-C ≤70 mg/dL. Conclusion: In this national-scale real-world cohort of patients with ASCVD, Lp(a) testing is infrequent and elevated Lp(a) levels were significantly associated with a greater risk of CV events and mortality.

Abstract 4132498: Hemodynamic and Clinical Outcomes with Balloon-Expandable Valves Versus Self-Expanding Valves in Patients with Small Aortic Annulus Undergoing Transcatheter Aortic Valve Implantation: A Meta-Analysis of Randomized Controlled Trials and Propensity Score Matched Studies

Background: Transcatheter aortic valve implantation (TAVI) is thought to be more effective than surgery for patients with small aortic annulus (SAA), however, the comparative efficacy of different transcatheter heart valves (THVs) remains uncertain. The objective of this meta-analysis was to compare the effects of balloon-expandable valves (BEVs) and self-expanding valves (SEVs) on hemodynamic parameters and clinical outcomes in patients with SAA who underwent TAVI. Methods: A thorough literature search was performed across PubMed/MEDLINE, Embase, and the Cochrane Library from their inception until May 2024 to identify eligible randomized controlled trials (RCTs) and propensity-score matched (PSM) studies. Clinical outcomes were evaluated using a random-effects model to pool risk ratios (RRs) with 95% confidence intervals (CIs). Results: The analysis included 8 studies; 2 RCTs and 6 PSM studies, with a total of 2,180 patients with SAA. BEVs were associated with a smaller indexed effective orifice area (MD: -0.18, 95% CI: -0.31 to -0.05) and a higher transvalvular mean pressure gradient (MD: 5.23, 95% CI 3.44 to 7.02) than SEVs. The risk for prosthesis-patient mismatch (PPM) (RR= 1.82, 95% CI: 1.27 to 2.60) and severe PPM (RR= 2.77, 95% CI: 1.93 to 3.98) was significantly higher for patients receiving BEVs than those receiving SEVs. However, no significant difference was observed between BEVs and SEVs regarding the risk of paravalvular leak (RR= 0.98, 95% CI: 0.57 to 1.69) and the permanent pacemaker implantation (RR= 0.78, 95% CI: 0.50 to 1.23). Although patients receiving BEVs showed a slightly lower risk of major bleeding events (RR= 0.69, 95% CI: 0.49 to 0.99), BEVs were associated with a significantly increased risk of 1-year cardiovascular mortality (RR= 1.61, 95% CI: 1.05 to 2.47) compared to those receiving SEVs. However, no significant differences were observed between BEVs and SEVs regarding 30-day all-cause mortality (RR= 1.19, 95% CI: 0.57 to 2.49), 1-year all-cause mortality (RR= 1.17, 95% CI: 0.89 to 1.53), stroke rates (RR= 0.83, 95% CI: 0.52 to 1.31) and any vascular complication (RR= 1.13, 95% CI: 0.72 to 1.75). Conclusion: In patients with SAA, SEVs showed reduced risks of PPM and severe PPM compared to BEVs, along with a larger indexed effective orifice area. Moreover, SEVs were associated with a lower risk of 1-year cardiovascular mortality.

Total, dietary, and supplemental calcium intake and risk of all-cause, cardiovascular, and cancer mortality among U.S. adults: a prospective cohort study from the National Health and Nutrition Examination Survey.

The study aimed to investigate the association of total, dietary, or supplemental calcium intake with all-cause, cardiovascular, and cancer mortality in American adults. This prospective cohort study used the National Health and Nutrition Examination Survey from 2005 to 2018. Participants were categorized into tertiles based on calcium intake. Risks of all-cause, cancer, or cardiovascular mortality and the dose-response relationship were estimated using weighted Cox proportional hazard regression and restricted cubic splines, with adjustments for demographic characteristics, comorbidities, laboratory parameters, and dietary data. In total, 6172 participants were included (median age: 61 years), and 869 had died (CVD:217, cancer:224) during a median follow-up of 81 months. After adjusting for confounders, higher total calcium(≥ 1660mg/d) [HR, 95%CI: 0.867 (0.865-0.869)], dietary calcium(≥ 1075mg/d) [HR, 95%CI: 0.711 (0.709-0.713)], and supplemental calcium (≥ 600mg/d) [HR, 95%CI: 0.786 (0.784-0.787)] intake groups were associated with lower all-cause mortality risk compared to the lowest intake group. Similar beneficial associations were found for cardiovascular, cancer mortality, and across subgroups of various ages, genders, races and body mass indexes. In the dose-response analysis, a 'J-shaped' nonlinear relationship was observed between calcium intake and the risk of all-cause, cardiovascular, and cancer mortality. Higher levels of total, dietary, or supplemental calcium were associated with lower all-cause, cardiovascular, or cancer mortality. However, a nonlinear association between calcium intake and mortality suggested that excessive calcium intake beyond a certain threshold may increase mortality risk.

Abstract 4132159: Dietary Intake of Niacin and Risk of Cardiovascular Mortality in The Golestan Cohort Study

Introduction: Recent studies have linked niacin metabolism with vascular inflammation and cardiovascular disease (CVD); however, the association is still inconclusive regarding dietary intake, and the findings may not be generalizable to various populations. In this longitudinal study within a Middle Eastern population, we aimed to assess the relationship between dietary intake of B vitamins, including niacin, and the risk of CVD mortality. Methods: Our study utilized data from the Golestan Cohort Study, which has tracked 50,045 participants aged 40-75 years since 2004. We excluded subjects who reported extreme total energy intake or had a positive history of cancer, CVD, or diabetes at baseline. Vitamin B intake estimations including thiamin, riboflavin, niacin, pyridoxamine, folate, and cobalamin intake were derived from the baseline food frequency questionnaire, noting that supplement use was uncommon in this cohort. To adjust for calorie intakes, we employed the nutrient density method. Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for cardiovascular mortality, using the lowest quintile of intake as the reference group for vitamins and adjusting for potential confounders. Results: We analyzed 42,456 subjects with a mean age of 51.5 ± 8.7 years at baseline. During 579,339 person-years of follow-up (median: 14.1 years), 3,065 CVD deaths were recorded. The median dietary intake of niacin was 25.3 mg/d (Recommended Dietary Allowance = 14-16 mg/d). We observed significant associations between niacin intake (HR Q5 vs. Q1 = 1.13, 95% CI = 1.01-1.26, P trend &lt;0.05) and CVD mortality. When niacin was modeled as a continuous linear variable, it was associated with a greater risk of CVD mortality (HR = 1.05, 95% CI = 1.01-1.09) per 2 mg/1000Kcal/d increase. None of the other B vitamin intakes evaluated were associated with CVD mortality in this population. Conclusion: These findings suggest that among B vitamins, only dietary niacin intake was positively associated with CVD mortality. Further confirmation in larger studies is needed.

Abstract 4148070: Clonal Hematopoeisis of Indeterminate Potential and Risk of Autopsy-defined Sudden Cardiac Death

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) has been associated with an increased risk of coronary artery disease (CAD) and cardiovascular (CV) mortality. Whether CHIP may affect myocardium beyond promoting CAD, or its potential association with sudden cardiac death (SCD), the most feared manifestation of CV disease, is unknown. Research Questions/Hypothesis: We hypothesize that CHIP-mutant macrophages infiltrate the myocardium and are associated with autopsy-defined arrhythmic death. Goals/Aims: (1) determine rate of CHIP at time of death in an unselected, countywide study of all incident sudden deaths; (2) evaluate whether CHIP-mutant macrophages infiltrate into myocardium; and (3) evaluate potential association of CHIP with autopsy-confirmed arrhythmic causes among countywide sudden deaths Methods/Approach: We used autopsy to adjudicate arrhythmic from non-arrhythmic (PE, stroke, overdose, tamponade) causes in 1,148 sudden deaths and 141 trauma control deaths in San Francisco County from 2011-23. DNA was extracted from frozen blood samples collected at time of death from 399 consented cases. Sequencing of 22 CHIP-associated genes was performed to ~2000x mean target coverage. All pathogenic/likely pathogenic CHIP variants at &gt;2% variant allele frequency (VAF) were considered CHIP+. DNA was then isolated from left ventricular (LV) tissue sampled at autopsy in all CHIP+ blood cases and sequenced as above. Results: Of 399 consented cases, 70 blood samples (17.5%) were CHIP+ (range 2%-39.6%; mean age 70.6 years vs. 58.1 years for CHIP-). The most frequent mutant genes were DNMT3A, TET2, and ASXL1. Proportion of arrhythmic causes among sudden deaths was similar for CHIP+ vs. CHIP- cases (36 of 70 [52%] vs. 171 of 329 [51%]). Sequencing of available LV tissue from 61 CHIP+ blood cases revealed 67% (n=41) harbored the same CHIP mutation identified in blood at &gt;0.2% VAF (range 0.2%-4.3%). Proportion of arrhythmic causes among sudden deaths was significantly higher in cases where both blood and LV were CHIP+ (24 of 41 [58.5%] vs. 5 of 19 [26.3%] CHIP+ blood/CHIP- LV, p=0.02). Conclusions: Prevalence of CHIP positivity at sudden death is similar to published studies and correlated with age. CHIP+ status in myocardial tissue but not peripheral blood was associated with arrhythmic causes of sudden death, suggesting a direct tissue effect of CHIP-mutant macrophages.

Abstract 4129965: Efficacy of Sodium Glucose Cotransporter 2 Inhibitors In Patients With Acute Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in patients with or without type 2 diabetes and heart failure (HF). However, studies have shown conflicting evidence regarding their efficacy in patients following acute myocardial infarction (MI). We conducted a systematic review and meta-analysis to synthesize the available evidence regarding the effectiveness of SGLT2 inhibitors in MI. Methods: A systematic literature search was conducted using PubMed/MEDLINE, the Cochrane Library, and Embase databases to identify randomized controlled trials (RCTs) that compared clinical outcomes of SGLT2 inhibitors with placebo following MI. We conducted the statistical analysis using RevMan, version 5.4, and pooled risk ratios (RRs) along the corresponding 95% confidence interval (CI) for all outcomes. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. Results: Five RCTs reporting data for 11,211 patients were included in our study. Our pooled analysis showed that SGLT2 inhibitors significantly reduced the risk of hospitalizations for heart failure (HHF) (RR = 0.76, 95% CI: 0.61-0.88, p = 0.001; high certainty). In terms of absolute effects, this translated to 12 fewer HHF per 1,000 patients who received SGLT2 inhibitors compared with the placebo (absolute risk difference 12 (95% CI 17 to 5) fewer per 1000 patients) in patients with MI. However, the risk of all-cause mortality (RR = 1.05, 95% CI: 0.78-1.41, p = 0.76; high certainty), cardiovascular (CV) mortality (RR = 1.04, 95% CI = 0.84-1.29, p = 0.73; high certainty), and all-cause hospitalizations (RR = 1.06, 95% CI: 0.96-1.17, p = 0.25; high certainty) remained comparable across the two groups. Conclusion: SGLT2 inhibitors reduce HHF without affecting all-cause mortality, CV mortality, and all-cause hospitalizations. However, further evidence is required to reach a definitive conclusion.

Abstract 4140134: Impact of Cancer on Outcomes in Patients with Acute Myocardial Infarction; a Systematic Review and Meta-analysis.

Background: Cardiovascular diseases are the second leading cause of death among cancer patients, after cancer-related mortality. It has not been well established if a patient's malignancy status increases their risk of cardiovascular events following a myocardial infarction (MI). Hypothesis: This study aims to assess the impact of cancer on cardiovascular outcomes following an acute myocardial infarction. Methods: We systematically searched electronic databases such as Pubmed, Embase and Cochrane Library from inception until March 2024 using the appropriate Mesh terms, “ cancer,” “myocardial infarction,” and “cardiovascular mortality”, “in-hospital mortality”. Pooled relative risk and their corresponding confidence interval were calculated using the random effect model. A p-value of &lt;0.05 was considered statistically significant. Results: A meta-analysis was conducted with seven articles, with 32856 cancer patients and 520421 noncancer patients with MI. Pooled analysis showed that patients with cancer had to have a significantly higher risk of recurrent MI in (RR 1.49, 95% CI:1.03-1.96), major bleeding (RR 1.96, 95% CI: 1.28-2.64), cerebral infarction (RR 1.29, 95% CI: 1.21-1.38), the in-hospital mortality rate (RR 1.62, 95% CI: 1.04-2.20), cardiovascular mortality (RR 1.57, 95% CI: 1.00-2.13), and hospitalization due to heart failure (RR 1.51, 95% CI 1.46, 1.56) when compared with noncancer patients. Conclusion: This study shows that cancer is strongly associated with an increased risk of recurrent MI, major bleeding, cerebral infarction, hospital mortality, cardiovascular mortality, and hospitalisation due to heart failure in patients with acute MI. Proper monitoring of cardiac function and lab markers can be effective in reducing morbidity and mortality.

The Neutrophil-to-Lymphocyte Ratio Predicts Cardiovascular Outcomes in Patients With Diabetes: A Systematic Review and Meta-Analysis.

The neutrophil-to-lymphocyte ratio (NLR) has been found as a potential biomarker for acute inflammation and the prognosis of different diseases. Here, we provided a meta-analysis of studies evaluating the association of NLR with cardiovascular outcomes among patients with diabetes. We searched PubMed, Scopus, and Web of Science databases from inception to April 06, 2024, to include papers based on eligible criteria. The outcomes of interest were all-cause mortality, cardiovascular mortality, major adverse cardiovascular events, myocardial infarction, and stroke. The pooled risk ratio (RR) and corresponding 95% confidence intervals (CI) were reported. Meta-analysis was performed using StataMP 14.0. A total of 15 studies involving 407,512 participants were included. Meta-analysis revealed that both categorical and continuous NLRs are linked to increased risk of all-cause mortality (RR = 1.68; 95% CI, 1.49-1.88; P < 0.001 and RR = 1.03; 95% CI, 1.03-1.03; P < 0.001, respectively) and cardiovascular mortality (RR = 2.04; 95% CI, 1.58-2.63; P < 0.001 and RR = 1.25; 95% CI, 1.19-1.32; P < 0.001, respectively) in patients with diabetes. However, NLR was not associated with the risk of major adverse cardiovascular events, myocardial infarction, and stroke in patients with diabetes. Subgroup analysis revealed sample size as the main source of the heterogeneity found between studies. The findings suggest NLR as a prognostic marker for mortality outcomes in patients with diabetes, providing clinicians with a noninvasive and readily available indicator for risk assessment and patient management.

Abstract 4134572: Assessing Sex Differences in the Relationship Between Social Isolation and Incident Atherosclerotic Cardiovascular Disease and Death Using Data from the U.S. Health and Retirement Study

Background: Inadequate social connection has been associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) and mortality. There are insufficient and conflicting data on whether sex differences play a role in this relationship. Therefore, we sought to further examine the relationship between sex, social isolation, and these subsequent events. Methods: We analyzed Health and Retirement Study (HRS) and RAND data collected biennially from 8,987 individuals enrolled from 2004-2020 who completed at least 1 Leave Behind Questionnaire (LBQ). Social isolation was determined from LBQ data using a previously validated 6-item scale where scores of 3 or greater indicated social isolation. Development of ASCVD was classified as new self-reported myocardial infarction or stroke at any follow-up assessment. Mortality was determined with RAND longitudinal data, which was available for all individuals. We examined the incidence of ASCVD in socially isolated and not socially isolated individuals using a cumulative incidence function accounting for the competing risk of death. Results: Mean age at baseline LBQ survey was 55.7 years and 43% of the sample were male. In the sample, 23% identified as Black, 63% identified as White, and 13% identified as Other. Social isolation was present in 1,653 (18%) individuals at their baseline survey. ASCVD developed in 484 (5%) participants, and 593 (7%) participants died over the study’s follow-up period. Cumulative incidence analysis showed no significant difference in ASCVD incidence between socially isolated and non-socially isolated groups for either sex (male p-value: 0.15; female: 0.09) (Figure). However, the incidence of death was significantly increased for both socially isolated sexes (male p-value: &lt;0.001; female: &lt;0.001). Conclusion: While socially isolated participants were not at significantly increased risk of incident ASCVD, they were at significantly increased risk of mortality, irrespective of sex. This highlights the need for continued public health initiatives that foster social connection to enhance the well-being of the general population. The study is limited by reliance on self-report for ASCVD, which may underestimate disease incidence.

Income-Related Disparities in Mortality Among Young Adults With Type 2 Diabetes.

Previous studies have indicated an inverse association between income and mortality. However, differences in health outcomes according to the income level of young adults with type 2 diabetes (T2D) compared with older adults with T2D have not been elucidated. To estimate the overall and cause-specific mortality risks among patients with T2D according to income and age. This retrospective nationwide cohort study in South Korea included adults aged 20 to 79 years who were diagnosed with T2D between January 1, 2008, and December 31, 2013, and followed up until December 31, 2019, and age- and sex-matched controls without diabetes. Data were analyzed between January 1, 2023, and August 27, 2024. Risks of all-cause, cardiovascular, and cancer mortality were estimated according to participants' income, which was categorized into 3 levels (low, middle, and high) based on the health insurance premium. Logistic regression analyses and Cox proportional hazard regression analyses were performed according to age groups (20-39, 40-59, and 60-79 years). A total of 1 240 780 adults (604 975 patients with T2D and 635 805 age- and sex-matched controls without diabetes) were included in the analyses. Their mean (SD) age was 56.9 (11.8) years, and 626 176 (50.5%) were men. Overall, the risk of mortality increased with lower income among patients with T2D, as well as in comparison with controls without diabetes. There was an inverse association between income and mortality risk in younger individuals (adjusted hazard ratios of all-cause mortality in the low income vs high income subgroups with T2D were 2.88 [95% CI, 2.25-3.69] in those aged 20 to 39 years, 1.90 [95% CI, 1.81-2.00] in those aged 40 to 59 years, and 1.26 [95% CI, 1.23-1.29] in those aged 60 to 79 years; P < .001 for comparing risk ratios between age groups). The pattern of income-related disparities in younger individuals was observed in cardiovascular mortality but less in cancer mortality. In this cohort study of 1 240 780 individuals aged 20 to 79 years, the risk of mortality with low income was most prominent among individuals with T2D aged 20 to 39 years. These findings highlight the need for socioeconomic support to reduce income-related health disparities in younger individuals.

Abstract 4124226: Long-term exposure to air pollutants and incidence of cardiovascular disease events and mortality in The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air)

Introduction: Exposure to ambient air pollution may increase the risk of cardiovascular disease events and mortality, but prior publications have primarily included administrative cohorts with outcomes that have not been individually reviewed and with air pollution estimates created without cohort-specific exposure monitoring. Multi-Ethnic Study of Atherosclerosis (MESA) is a multi-site cohort study designed specifically to prospectively collect and adjudicate cardiovascular disease (CVD) events. MESA Air recruited additional participants into sub-cohorts for enhanced air pollution variation and sample size. Research Question: The aim of this analysis was to characterize the relationship between long-term exposure to nitrogen dioxide (NO 2 ) and fine particulate matter (PM 2.5 ) and all-cause mortality and CVD events. Methods: Air pollution exposure was assessed using address history with a purpose-built exposure model incorporating cohort-specific monitoring including measurement and validation at participant homes. We used Cox models to assess the risk of rolling 2-year average exposures on all cause-mortality and on a composite CVD endpoint (definite angina, probable angina with revascularization, myocardial infarction, atherosclerosis or other CVD death, resuscitated cardiac arrest, and stroke). Models were stratified for baseline hazard by age, sub-cohort, and recruitment year and were additionally adjusted for age, sex, race/ethnicity, field center, smoking/second-hand smoke, pack-years, physical activity, education, income, neighborhood socioeconomic status, and statin use. Results: MESA Air participants were aged 44-87 years at enrollment between 2000 and 2007; follow-up averaged 14 years. 6,915 participants had follow-up for events, NO 2 exposure, and covariate information. We observed 1,442 deaths and 985 CVD events. The interquartile range over all 2-year averages was 10.5-23.1 ppb for NO 2 and 10.1-14.9 µ/m 3 for PM 2.5 . The adjusted hazard ratio (aHR) for a 10 ppb increment in NO 2 was 1.38 (95% CI: 1.17, 1.64) for all-cause mortality and 1.16 (95% CI: 0.95, 1.42) for incident CVD events. The aHR for a 5 µg/m 3 increment in PM 2.5 was 1.20 (95% CI: 0.99, 1.46) for all-cause mortality and 1.15 (95% CI: 0.95, 1.39) for incident CVD events Conclusions: These results add to growing literature demonstrating an association between air pollution exposure, mortality, and CVD in a cohort with well-characterized clinical endpoints and cohort-specific exposure assessment.

Abstract 4134637: Impact of Glucagon-Like Peptide-1 Agonists on Cardiovascular Outcomes in Chronic Kidney Disease Stage 5: A Propensity Score-Matched Analysis

Background: Patients with chronic kidney disease stage 5 (CKD-5) face heightened risks of cardiovascular (CV) complications and mortality. Glucagon-like peptide-1 agonists (GLP-1a), primarily used in type 2 diabetes, are being investigated for potential CV benefits in this population. This study aims to evaluate the impact of GLP-1a treatment on CV outcomes and survival among CKD-5 patients. Methods: This retrospective cohort study utilized data of adult patients diagnosed with CKD-5 between January 2014 and August 2023 from the TriNetX global research network. A propensity score matching analysis of those treated with GLP-1a for at least six months versus those never exposed to GLP-1a therapy was conducted. Results: Our analysis showed significantly reduced odds for the composite primary outcome of acute myocardial infarction (AMI), stroke, and mortality (OR = 0.66, 95% CI: 0.57-0.78, p&lt;0.001), and other CV outcomes such as cardiac arrest, hypertensive crisis, and hypertensive urgency, among the GLP-1a cohort compared with the non-GLP-1a cohort. Kaplan-Meier survival analysis revealed a significantly higher five-year incidence-free probability for the composite primary outcome (63.5% vs. 50.5%, p&lt;0.001) and for other CV outcomes such as hypertensive events, AMI, cardiac arrest, and hemorrhagic stroke for the GLP-1a cohort. Conclusion: The study suggests that GLP-1a therapy in CKD 5 patients may confer certain CV benefits. Further investigations are warranted to elucidate the underlying mechanisms and confirm the therapeutic efficacy of GLP-1a in this patient population.

Abstract 4140192: Time Trends in Outcomes of Trans-Catheter Aortic Valve Replacement with Balloon-expanding Versus Self-expanding Valves: A Meta-analysis of Randomized Controlled Trials

Background: The research on the outcomes of transcatheter aortic valve replacement with balloon-expandable valves (BEV) and self-expanding valves (SEV) are limited. Hypothesis: This study aims to compare the clinical and hemodynamic outcomes of BEV and SEV at short-term (30 days), mid-term (1 year), and long-term (&gt;1 year) endpoints. Methods: PubMed, Embase, Scopus, and Cochrane Library databases were searched up to April 25, 2024, for randomized controlled trials (RCTs). Random-effect model (DerSimonian–Laird method) was used to pool the risk ratios (RR), mean differences (MD) and 95% confidence interval (CI) for binary and continuous outcomes, respectively. Results: A total of 11 RCTs comprising 4,325 patients (2,295 BEV, 2,030 SEV) were included. At short-term, the risk of cardiovascular (RR: 0.56, 95% CI: 0.36-0.87) and all-cause mortality (RR: 0.54, 95% CI: 0.35-0.81) were lower in the BEV group. However, no differences were noted between the two treatment modalities in longer follow-ups despite the lower risk of moderate to severe paravalvular leak (PVL) among BEV patients. The risk of stroke was comparable between two groups across all three follow-up endpoints, albeit a limited number of studies suggesting the BEV group showed a greater risk of clinical valve thrombosis in mid-term and long-term assessments. The need for permanent pacemaker implantation was lower in BEV arm in short-term (RR: 0.56, 95% CI: 0.37-0.87) and mid-term (RR: 0.78, 95% CI: 0.64-0.94). Yet, this difference was not observed in long-term follow-ups. Conversely, the SEV group had a larger effective orifice area with lower mean transvalvular pressure gradient from short-term (MD: 0.17, 95% CI: 0.07-0.26 and MD: 3.71, 95% CI: 2.64-4.78, respectively) to long-term (MD: 0.25, 95% CI: 0.17-0.32 and MD: 3.73, 95% CI: 3.19-4.27, respectively) periods. Conclusions: BEV is associated with reduced risk of clinical outcomes at short-term; however, most differences diminish in longer evaluations, except for moderate to severe PVL. Conversely, SEV is linked to better hemodynamic outcomes and a lower risk of clinical valve thrombosis across all follow-up durations.

Abstract 4135861: Lipoprotein(a) and Its Impact on Left Ventricular Remodeling Over a Decade: The Multi-Ethnic Study of Atherosclerosis

Background: Lipoprotein (a) (Lp[a]) is associated with an increased risk of cardiovascular disease and mortality, as well as heart failure and myocardial fibrosis. However, the link between Lp(a) and cardiac remodeling as a pathway to adverse cardiac outcomes remains unknown. Objectives: This study investigated the relationship between Lp(a) levels and longitudinal changes in the left ventricular (LV) remodeling over a decade among individuals without a previous history of cardiovascular disease. Methods: 2,366 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac MRI at Visit 1 (2000-02) and Visit 5 (2010-12) and had available Lp(a) at baseline were examined. Lp(a) was analyzed as a continuous and a categorical variable based on quartiles (Q1[&lt;7.6 mg/dL], Q2[7.6-16.7 mg/dL], Q3[16.8-38.8 mg/dL], Q4[&gt;38.8 mg/dL]). Multivariable linear regression analysis was used to examine the association of Lp(a) with changes in cardiac MRI measures of LV remodeling ( Table ). Results: Participants had a mean age 60±9 years and 53% were women. Over 10-year follow-up, LV indexed volumes decreased, while LV indexed mass and mass to volume ratio increased across all the Lp(a) quartiles. However, LV ejection fraction only decreased in the third and fourth Lp(a) quartiles. Lp(a) examined as a continuous variable was associated with an increase in LV end-systolic indexed volume (per log-unit Lp[a]; β 0.32 mL/m 2 ; P = 0.01), LV indexed mass (per log-unit Lp[a]; β 0.38 g/m 2 ; P = 0.02), and a decrease in LV ejection fraction (per log-unit Lp[a]; β -0.29 %; P = 0.02) over 10 years after adjusting for sociodemographic and traditional cardiovascular risk factors ( Table ). Similarly, the fourth Lp(a) quartile was associated with an increase in LV end-systolic indexed volume (β 1.07 mL/m 2 ; P = 0.01), LV indexed mass (β 1.17 g/m 2 ; P = 0.02) and a decrease in LV ejection fraction (β -1.01 %; P = 0.01) compared to the first Lp(a) quartile after controlling for risk factors. The observed associations remained significant after further adjusting for aortic valve calcium score at Visit 1 ( Table - Model 3), and baseline coronary artery calcium score and interim myocardial infarction ( Table - Model 4). Conclusions: In a multi-ethnic cohort of participants free of cardiovascular disease at baseline, higher Lp(a) levels were independently associated with an increase in LV end-systolic volume and LV mass as well as a decrease in LV ejection fraction over the span of a decade.

Abstract 4138306: Impact of Early Menopause and Hormonal Replacement Therapy on Aortic Stenosis Progressio

Background: Early menopause is associated with an increased risk of cardiovascular disease and mortality in women. The present study aimed to examine the impact of early menopause and hormonal replacement therapy (HRT) on the progression of aortic stenosis (AS). Methods: Thirty-three postmenopausal women (mean age 65 ± 10 years) with mild or moderate AS prospectively recruited in the PROGRESSA study (NCT01679431) were included in this sub-analysis. All patients underwent multidetector computed tomography and Doppler-echocardiography at least twice during follow-up to assess both anatomic and hemodynamic AS severity, based on aortic valve calcification (AVC), mean pressure gradient (MG), and aortic valve area indexed to body surface area (AVA). Annualized changes in AVC, MG and AVAi were calculated between baseline and the last follow-up. Results: Over a median follow-up of 2 [1-4] years, early menopausal women had a faster progression rate of AVC, MG, and AVAi compared to other women: (100[58-130] vs. 23[2-71] AU/year, p=0.03); (2.37[0.82-3.61] vs. 0.31[0.01-1.78] mmHg/year, p=0.04); and (-0.12[-0.23-0.002] vs. -0.004[-0.07-0.08] cm 2 /m 2 /year, p=0.08) respectively. In multivariate analysis adjusted for age, AS severity at baseline, and comorbidities, early menopause remained significantly associated with faster AVC progression (p=0.003). Moreover, after comprehensive adjustment, women who received HRT (45%) had a slower progression rate of AVC (20[10-42] AU/year vs. 62[2-100], adjusted p=0.04). Conclusion: Early menopause is associated with faster progression of AS, both anatomically and hemodynamically. However, the use of HRT is associated with slower progression of AS. Integrating female-specific risk factors, particularly menopausal history and hormonal therapy status, into the clinical management of AS could enhance patient care.