Coronary Artery Disease Outcomes Research Articles

Coronary atherosclerosis in athletes: emerging concepts and preventive strategies.

There should be no assumption that an athlete is immune to coronary artery disease (CAD), even when traditional cardiovascular (CV) risk factors appear well-managed. Excelling in certain aspects of health does not equate to total CV protection. Recent data from cardiac imaging studies have raised the possibility that long-term, high-volume, high-intensity endurance exercise is associated with coronary atherosclerosis. Whilst the risk of CV events has not been shown to rise with athletic activity, the potential for CAD should not be overlooked as it is the leading cause of sudden cardiac death in athletes >35 years of age (i.e. 'Masters athletes'). Evaluating both traditional and non-traditional risk factors for CAD is the most important part of pre-participation evaluation in Masters athletes. When managing athletes at risk of CAD it is important to adopt a shared decision-making approach regarding lifestyle adaptation and lipid-lowering treatments. In the great majority of athletes, after excluding the presence of symptoms and inducible ischaemia, this advice should include encouragement to continue exercising as available data indicate that higher levels of fitness are associated with a markedly attenuated incidence of coronary events regardless of the severity of coronary disease. Future research is needed to establish the relationship between clinically relevant CAD outcomes and coronary artery calcification in Masters Athletes, the role of sex, as well as exploration of the mechanisms underpinning these unexpected CV adaptations.

Clinical Outcomes and Long-Term Prognosis in Patients Undergoing Angioplasty

Objective: To investigate the influence of lifestyle factors, including smoking, physical activity, and dietary habits, on the severity of coronary artery disease (CAD) in patients without comorbidities and to identifying the prevalence of unhealthy lifestyle habits and exploring their relationship with CAD severity. Methodology: This was a prospective observational cohort study conducted at Hayatabad Medical Complex, Peshawar, from January to June 2022. A total of 200 patients with CAD and no comorbidities were included. Data on lifestyle factors were collected through standardized questionnaires and clinical records. Statistical analyses, including chi-square tests, were applied to assess associations between lifestyle factors and CAD severity. Results: The results indicated that 45% of patients were smokers, 40% were physically inactive, and 53% had unhealthy dietary habits. Despite the prevalence of these risk factors, no statistically significant association was found between smoking status and CAD severity (p > 0.05). However, the cumulative effect of unhealthy lifestyle factors was evident, with higher CAD severity noted in patients exhibiting multiple risk factors. Conclusion: The study highlights the significant impact of lifestyle factors on CAD outcomes, reinforcing the need for public health interventions targeting smoking cessation, physical activity, and dietary improvements. Effective lifestyle modifications can potentially reduce the progression of CAD in the local population.

The association of Serum Klotho with the prevalence of cardiovascular disease and prognosis in general population: results from the National Health and Nutrition Examination Survey 2007-2016.

Previous studies have extensively investigated traditional predictors of cardiovascular disease (CVD) development, progression, and prognosis. However, the influence of novel indicators such as Klotho, on CVD prevalence and prognosis in the general population remains unclear. This was an observational study that utilized cross-sectional and longitudinal methods to examine the general population in the National Health and Nutrition Examination Survey (NHANES) 2007-2016. The participants were divided into four groups according to the Klotho quartiles. Primary outcome was CVD [coronary artery disease (CAD), congestive heart failure, and stroke], secondary outcomes were all-cause mortality and cardiovascular mortality. Survey-weighted binary logistic regression analysis was used to analyze the association between Klotho and the prevalence of primary outcome, and the restricted cubic spline (RCS) curve was used to further analyze the nonlinear relationship. Subgroup analyses were conducted to investigate the association between Klotho values and CVD prevalence using survey-weighted binary logistic regression. The incidence of the secondary outcomes among four groups was assessed through Kaplan-Meier survival analysis. Additionally, the relationship between Klotho values and secondary endpoints was explored using survey-weighted Cox proportional hazards regression across various patient subpopulations. A total of 12,146 participants (56.8 ± 10.7 years, 48.5% male) were included in our study. The total incidence of CVD was 9.9% (n = 1201), of which 4.7% (n = 574) were CAD, 3.7% (n = 454) were congestive heart failure, and 4.1% (n = 497) were stroke. Binary logistics regression analysis showed that higher Klotho quartiles were associated with the decreased prevalence of CVD [Quartile 4 vs. Quartile 1: odds ratio (OR) (95% CI): 0.77 (0.64-0.93), P = 0.006] and congestive heart failure [Quartile 4 vs. Quartile 1: 0.75 (0.56-0.99), P = 0.048], However, no significant associations were found between Klotho levels and the outcomes of CAD or stroke. RCS curve illustrated a high Klotho value was negatively correlated with the prevalence of CVD (nonlinear P = 0.838), congestive heart failure (nonlinear P = 0.110) and stroke (nonlinear P = 0.972). No significant interactions were observed in any subgroups regarding the associations between Klotho and prevalence of CVD. After a median follow-up period of 93 months (range: from 1 to 160 months), there were 1228 cases (10.1%) of all-cause mortality in the general population, including 296 cases (2.4%) of cardiovascular mortality. The Kaplan-Meier curves indicated that lower Klotho levels were associated with a significant increase in all-cause mortality across the general population, CVD population, and non-CVD population. As Klotho levels decreased, there was also a notable rise in cardiovascular mortality in both the general population and the CVD population. In the overall population, Cox regression analyses demonstrated that higher Klotho values were associated with a decreased risk of both all-cause and cardiovascular mortality. And no significant interaction was observed in the CVD subgroup regarding the association between Klotho and mortality. High Klotho level was associated with low prevalence of CVD and low risk of mortality in general population.

Modeling the Impact of Extracellular Vesicle Cargoes in the Diagnosis of Coronary Artery Disease.

Objectives: We aimed to assess the relationship among circulating extracellular vesicles (EVs), hypoxia-related proteins, and the conventional risk factors of life-threatening coronary artery disease (CAD) to find more precise novel biomarkers. Methods: Patients were categorized based on coronary CT angiography. Patients with a Segment Involvement Score > 5 were identified as CAD patients. Individuals with a Segment Involvement Score < 5 were considered control subjects. The characterization of EVs and analysis of the plasma concentration of growth differentiation factor-15 were performed using multicolor or bead-based flow cytometry. The plasma protein levels of glycogen phosphorylase, muscle form, clusterin, and carboxypeptidase N subunit 1 were determined using an enzyme-linked immunosorbent assay. Multiple logistic regression was used to determine the association of the biomarkers with the CAD outcome after accounting for established risk factors. The analysis was built in three steps: first, we included the basic clinical and laboratory variables (Model 1), then we integrated the plasma protein values (Model 2), and finally, we complemented it with the circulating EV pattern (Model 3). To assess the discrimination value of the models, an area under (AUC) the receiver operating curve was calculated and compared across the three models. Results: The area under the curve (AUC) values were 0.68, 0.77, and 0.84 in Models 1, 2, and 3, respectively. The variables with the greatest impact on the AUC values were hemoglobin (0.2 (0.16-0.26)) in Model 1, carboxypeptidase N subunit 1 (0.12 (0.09-0.14)) in Model 2, and circulating CD41+/CD61+ EVs (0.31 (0.15-0.5)) in Model 3. A correlation analysis showed a significant impact of circulating CD41+/CD61+ platelet-derived EVs (p = 0.03, r = -0.4176) in Model 3. Conclusions: Based on our results, the circulating EV profile can be used as a supportive biomarker, along with the conventional laboratory markers of CAD, and it enables a more sensitive, non-invasive diagnostic analysis of CAD.

Causal association between visceral fat and coronary artery disease: a large-scale mendelian randomization analysis

Abstract Background While increased body mass index (BMI) is an established risk factor, the residual risk associated with visceral fat, remains a concern. We aimed to perform a Mendelian randomization to explore the causal relationship between visceral fat and the risk of coronary artery disease (CAD), aiming to address gaps left by observational studies that may be influenced by confounding factors and reverse causation. Methods Leveraging large-scale genome-wide association study (GWAS) databases, we identified single-nucleotide polymorphisms (SNPs) associated with visceral fat. These genetic instruments were analyzed to infer causal relationships with CAD outcomes, drawing data from the CARDIoGRAMplusC4D consortium for CAD, and additional databases for related cardiovascular conditions. We performed a Two-sample Mendelian Randomization (MR) to test the genetic association between the visceral obesity and Coronary Artery Disease (CAD). Results The analysis encompassed data from a combined cohort exceeding 500,000 participants, revealing a significant causal relationship between increased levels of visceral fat and the risk of CAD. The observed odds ratio (OR) for CAD per standard deviation (SD) increase in visceral fat was [OR, 1.48 ] ([95% CI, 1.33-1.64]; P&amp;lt;0.001), indicating a robust association which remains independent from BMI on mediation analysis. Notably, the study's methodology ensured minimal risk of pleiotropy, reinforcing the validity of the findings. Conclusions This Mendelian randomization study provides compelling evidence of a genetic causal link between visceral fat and coronary artery disease. The findings suggest that beyond BMI, visceral fat represents a significant, independent risk factor for CAD, underscoring the importance of considering comprehensive lipid management in cardiovascular risk reduction strategies. Further research is warranted to explore potential mechanisms and therapeutic targets associated with visceral fat in the context of cardiovascular disease.

Laterality of Radiation Therapy in Breast Cancer is Not Associated With Increased Risk of Coronary Artery Disease in the Contemporary Era

BackgroundExternal beam radiation therapy (EBRT) is a critical component of breast cancer (BC) therapy. Given the improvement in technology in the contemporary era, we hypothesize there is no difference the development of or worsening of existing coronary artery disease (CAD) in patients with BC receiving left vs right sided radiation. MethodsFor the meta-analysis portion of our study, we searched PubMed, Web of Science, and Scopus and included studies from January 1999 to September 2022. CAD was identified using a homogenous metric across multiple studies included. We computed the risk ratio (RR) for included studies using a random effects model. For the institutional cohort portion of our study, we selected high cardiovascular risk patients diagnosed with BC between 2010-2022 if they met our inclusion criteria. We performed a Cox proportional hazards model with stepwise adjustment. ResultsA pooled random effects model with 9 studies showed that patients with left-sided BC receiving EBRT had a 10% increased risk of CAD when compared to patients with right-sided BC receiving EBRT (RR: 1.10, 95% CI: 1.02 - 1.18, p = 0.01). However, subgroup analysis of 6 studies that included patients diagnosed after 1980 did not show a significant difference in CAD based on BC laterality (RR: 1.07, 95% CI: 0.95 – 1.20, p = 0.27). For the institutional cohort portion of the study, we found that patients with left-sided BC who received EBRT did not have a significantly higher risk for CAD when compared to their right-sided counterparts (HR = 0.73, 95% CI: 0.34 - 1.54, p = 0.402). ConclusionOur study suggests a historical trend of increased CAD in BC patients receiving left-sided EBRT. Data from patients diagnosed after 2010 in our institutional cohort did not show a significant difference, emphasizing that modern EBRT regimens are safe, and laterality of BC does not affect CAD outcomes in the short term after a breast cancer diagnosis.

Lipoprotein(a) as a cardiovascular risk factor among patients with and without diabetes Mellitus: the Mass General Brigham Lp(a) Registry

BackgroundDiabetes mellitus (DM) and Lp(a) are well-established predictors of coronary artery disease (CAD) outcomes. However, their combined association remains poorly understood.ObjectiveTo investigate the relationship between elevated Lp(a) and DM with CAD outcomes.MethodsRetrospective analysis of the MGB Lp(a) Registry involving patients ≥ 18 years who underwent Lp(a) measurements between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasms, and prior atherosclerotic cardiovascular disease (ASCVD). The primary outcome was a combination of cardiovascular death or myocardial infarction (MI). Elevated Lp(a) was defined as > 90th percentile (≥ 216 nmol/L).ResultsAmong 6,238 patients who met the eligibility criteria, the median age was 54, 45% were women, and 12% had DM. Patients with DM were older, more frequently male, and had a higher prevalence of additional cardiovascular risk factors. Over a median follow-up of 12.9 years, patients with either DM or elevated Lp(a) experienced higher rates of the primary outcome. Notably, those with elevated Lp(a) had a higher incidence of the primary outcome regardless of their DM status. The annual event rates were as follows: No-DM and Lp(a) < 90th% − 0.6%; No-DM and Lp(a) > 90th% − 1.3%; DM and Lp(a) < 90th% − 1.9%; DM and Lp(a) > 90th% − 4.7% (p < 0.001). After adjusting for confounders, elevated Lp(a) remained independently associated with the primary outcome among both patients with DM (HR = 2.66 [95%CI: 1.55–4.58], p < 0.001) and those without DM (HR = 2.01 [95%CI: 1.48–2.74], p < 0.001).ConclusionsElevated Lp(a) constitutes an independent and incremental risk factor for CAD outcomes in patients with and without DM.

The Impact of Coronary Artery Disease on Outcomes in Patients Hospitalized With Pre-eclampsia.

Introduction Pre-eclampsia leads to long-lasting cardiovascular effects in women in the postpartum period, but prevalence and in-hospital adverse events of coronary artery disease (CAD) in women with pre-eclampsia are poorly understood. The prevalence, outcomes, and mortality risks identified in this study allow for possible routes of clinical intervention of CAD in women with pre-eclampsia. The purpose of this study was to determine the prevalence and outcomes of CAD in women diagnosed with pre-eclampsia compared to those with pre-eclampsia with no history of CAD. Predictors of mortality in pre-eclampsia were also analyzed. Methods Data were obtained from the National Inpatient Sample from January 2016 to December 2019. We used the multivariate logistic regression to assess the independent association of CAD with outcomes in patients admitted with pre-eclampsia. We also used the multivariate logistic regression to analyze predictors of mortality in patients hospitalized with pre-eclampsia. Results Women with pre-eclampsia admitted between January 2016 and December 2019 were included in our analysis. A total of 256,010 patients were diagnosed with pre-eclampsia. Of these patients, 174 (0.1%) patients had CAD. Multivariate analysis demonstrated that CAD in patients with pre-eclampsia was independently associated with angioplasty (adjusted odds ratio [aOR] 62.28; 95% CI 20.459-189.591; p=0.001), permanent pacemaker (aOR 35.129; 95% CI 13.821-89.287; p=0.001), left heart catheterization (aOR 29.416; 95% CI 7.236-119.557; p=0.001), non-ST-elevation myocardial infarction (NSTEMI) (aOR 25.832; 95% CI 7.653-87.189; p=0.001), and congestive heart failure (CHF) (aOR 13.948; 95% CI 7.648-25.438; p=0.001). We also used the multivariate logistic regression model to assess predictors of mortality in patients admitted with pre-eclampsia. These included age at admission (aOR 1.064; 95% CI 1.009-1.121; p=0.021), Asian/Pacific-Islander race (aOR 4.893; 95% CI 1.884-12.711; p=0.001), and comorbidities such as CHF (aOR 19.405; 95% CI 6.408-58.768; p=0.001), eclampsia (aOR 17.253; 95% CI 5.323-55.924; p=0.001), syndrome of HELLP (hemolysis, elevated liver enzymes, low platelets) (aOR 6.204; 95% CI 2.849-13.510; p=0.001), coagulopathy (aOR 6.524; 95% CI 1.997-21.308; p=0.002), and liver disease (aOR 5.217; 95% CI 1.156-23.554; p=0.032). Conclusion In a large cohort of patients admitted with pre-eclampsia, we found the prevalence of CAD to be 0.1%. CAD was associated with several clinical outcomes, including NSTEMI. Predictors of mortality in patients with pre-eclampsia included demographic variables such as age and Asian race, as well as comorbidities such as CHF and coagulopathy.

Cardiovascular morbidity and mortality following hypertensive disorders of pregnancy

ObjectivesTo determine whether hypertensive disorders of pregnancy (HDP) are associated with maternal coronary artery disease (CAD) and other cardiovascular (CV) diseases within 10–20 years following delivery. Study designRetrospective cohort including all women who delivered ≥ 1 pregnancy ≥ 20 weeks’ gestation within a single health system from 1998 to 2008. We excluded those with CV risk factors preceding first delivery or with no follow-up after delivery. The exposure of interest was any HDP, determined by ICD coding. Main outcome measuresThe primary outcome was a composite of ICD codes for CAD, peripheral vascular disease, and CV events (myocardial infarction, stroke, and death). Multivariable Cox proportional hazards estimated the association between exposure and outcomes. A nested cohort of women who underwent cardiac catheterization had a primary outcome of angiographic CAD, and multivariable logistic regression estimated the association between HDP and CAD. ResultsOf 33,959 women included, 2,385 women had HDP. HDP was associated with the composite outcome (adjusted HR 1.50, 95 % CI 1.11, 2.03). There was a significant difference in event-free survival between groups (p = 0.003) with a median follow-up of 17.3 years. 592 women (1.7 %) underwent cardiac catheterization: 20 of 90 women with HDP had CAD (22.2 %) on angiography vs 49 of 502 without HDP (9.8 %, p < 0.001). HDP was associated with angiographic CAD (adjusted OR 2.08, 95 % CI 1.05, 4.11). ConclusionsWomen with HDP had twice the incidence of CAD on angiography compared to parous women without HDP. Obstetric history may inform the decision to perform cardiac catheterization in relatively young women.

Computed tomographic angiography measures of coronary plaque in clinical trials: opportunities and considerations to accelerate drug translation.

Atherosclerotic coronary artery disease (CAD) is the causal pathological process driving most major adverse cardiovascular events (MACE) worldwide. The complex development of atherosclerosis manifests as intimal plaque which occurs in the presence or absence of traditional risk factors. There are numerous effective medications for modifying CAD but new pharmacologic therapies require increasingly large and expensive cardiovascular outcome trials to assess their potential impact on MACE and to obtain regulatory approval. For many disease areas, nearly a half of drugs are approved by the U.S. Food & Drug Administration based on beneficial effects on surrogate endpoints. For cardiovascular disease, only low-density lipoprotein cholesterol and blood pressure are approved as surrogates for cardiovascular disease. Valid surrogates of CAD are urgently needed to facilitate robust evaluation of novel, beneficial treatments and inspire investment. Fortunately, advances in non-invasive imaging offer new opportunity for accelerating CAD drug development. Coronary computed tomography angiography (CCTA) is the most advanced candidate, with the ability to measure accurately and reproducibly characterize the underlying causal disease itself. Indeed, favourable changes in plaque burden have been shown to be associated with improved outcomes, and CCTA may have a unique role as an effective surrogate endpoint for therapies that are designed to improve CAD outcomes. CCTA also has the potential to de-risk clinical endpoint-based trials both financially and by enrichment of participants at higher likelihood of MACE. Furthermore, total non-calcified, and high-risk plaque volume, and their change over time, provide a causally linked measure of coronary artery disease which is inextricably linked to MACE, and represents a robust surrogate imaging biomarker with potential to be endorsed by regulatory authorities. Global consensus on specific imaging endpoints and protocols for optimal clinical trial design is essential as we work towards a rigorous, sustainable and staged pathway for new CAD therapies.

Sex differences in the impact of body mass index on outcomes of coronary artery disease in Koreans.

Obesity is often considered a risk factor for cardiovascular disease, but recent studies have shown conflicting results regarding the effect of BMI on the prognosis of coronary artery disease (CAD). This study aimed to evaluate the relationship between BMI and clinical outcomes of CAD according to sex in a Korean population. A total of 3476 patients with a significant CAD who underwent percutaneous coronary intervention (PCI) were enrolled. Patients were classified as follows according to BMI using the Asia-Pacific cutoff points: underweight (<18.5 kg/m 2 ), normal weight (18.5-22.9 kg/m 2 ), overweight (23.0-24.9 kg/m 2 ) and obese (≥25 kg/m 2 ) patients. Underweight and normal weight patients were further categorized into the lower BMI group, whereas overweight and obese patients were categorized into the higher BMI group. The primary endpoint was all-cause mortality. Among women, the higher BMI group showed poor clinical features in the prevalence of hypertension and chest pain presentation, and among men, the higher BMI group had a significantly lower rate of chronic renal failure. At the end of the follow-up period (median 53.5 months), the all-cause mortality rate was lower in the higher BMI group in men, and cardiovascular death and stroke rates were significantly lower in the higher BMI group in women. In Korean CAD patients treated with PCI, inverse correlations were observed between the clinical outcomes and BMI, but there were differences between men and women.

Correlation of neutrophil to lymphocyte ratio to severity of coronary artery disease and in-hospital clinical outcomes in patients with acute coronary syndrome: A prospective observational study

Objective: To explore correlation of neutrophil-to-lymphocyte ratio (NLR) to severity of coronary artery disease (CAD) and in-hospital clinical outcomes in patients with acute coronary syndrome (ACS). Methods: In this prospective and observational study, we recruited 500 patients with ACS. For all the eligible patients, demographic details were collected, and laboratory parameters were evaluated. The CAD severity was evaluated in terms of the number of involved vessels. The NLR was calculated based on neutrophils and lymphocytes and the correlation of various risk factors and severity and outcome of CAD was performed. Results: 77.2% of Patients was male, and 52% of the patients aged between 55-70 years. Based on the type of ACS, 396 out of 500 patients had ST-elevation myocardial infarction. An ascending trend in the white blood cell levels and NLR value was noted as the severity of the ACS increased and the highest white blood cell levels and NLR was noted among class IV patients. The mean NLR value among the non-survivors were higher compared to the survivors (9.52±5.72 vs. 4.76±2.36; P&lt;0.01). Receiver operating curve showed that the cut-off NLR value was 5.76 with a sensitivity of 75.0% and a specificity of 77.3%. Conclusions: The NLR can be used as an independent prognostic marker in ACS. An elevated NLR value serves as a reliable predictor for short-term complications, notably in-hospital mortality.

Associations between low serum levels of ANRIL and some common gene SNPs in Iranian patients with premature coronary artery disease

Coronary artery disease (CAD) is the major cause of mortality in the world. Premature development of CAD can be attributed to women under 55 and men under 45. Many genetic factors play a part in premature CAD. Among them, ANRIL, a long noncoding RNA is located at the 9p21 risk locus, and its expression seems to be correlated with CAD. In the current study, premature CAD and control blood samples, with and without Type 2 Diabetes (T2D), were genotyped for six SNPs at the 9p21 locus. Additionally, ANRIL serum expression was assessed in both groups using real-time PCR. It was performed using different primers targeting exons 1, 5–6, and 19. The χ2 test for association, along with t-tests and ANOVA, was employed for statistical analysis. In this study, we did not find any significant correlation between premature coronary artery disease and rs10757274, rs2383206, rs2383207, rs496892, rs10757278 and rs10738605. However, a lower ANRIL expression was correlated with each SNP risk genotype. Despite the correlation between lower ANRIL expression and CAD, Type 2 diabetes was associated with higher ANRIL expression. Altogether, the correlation between ANRIL expression and the genotypes of the studied SNPs indicated that genetic variants, even those in intronic regions, affect long noncoding RNA expression levels. In conclusion, we recommend combining genetic variants with expression analysis when developing screening strategies for families with premature CAD. To prevent the devastating outcomes of CAD in young adults, it is crucial to discover noninvasive genetic-based screening tests.

Analysis of ANRIL Isoforms and Key Genes in Patients with Severe Coronary Artery Disease.

ANRIL (Antisense Noncoding RNA in the INK4 Locus), also named CDKN2B-AS1, is a long non-coding RNA with outstanding functions that regulates genes involved in atherosclerosis development. ANRIL genotypes and the expression of linear and circular isoforms have been associated with coronary artery disease (CAD). The CDKN2A and the CDKN2B genes at the CDKN2A/B locus encode the Cyclin-Dependent Kinase inhibitor protein (CDKI) p16INK4a and the p53 regulatory protein p14ARF, which are involved in cell cycle regulation, aging, senescence, and apoptosis. Abnormal ANRIL expression regulates vascular endothelial growth factor (VEGF) gene expression, and upregulated Vascular Endothelial Growth Factor (VEGF) promotes angiogenesis by activating the NF-κB signaling pathway. Here, we explored associations between determinations of the linear, circular, and linear-to-circular ANRIL gene expression ratio, CDKN2A, VEGF and its receptor kinase insert domain-containing receptor (KDR) and cardiovascular risk factors and all-cause mortality in high-risk coronary patients before they undergo coronary artery bypass grafting surgery (CABG). We found that the expression of ANRIL isoforms may help in the prediction of CAD outcomes. Linear isoforms were correlated with a worse cardiovascular risk profile while the expression of circular isoforms of ANRIL correlated with a decrease in oxidative stress. However, the determination of the linear versus circular ratio of ANRIL did not report additional information to that determined by the evaluation of individual isoforms. Although the expressions of the VEFG and KDR genes correlated with a decrease in oxidative stress, in binary logistic regression analysis it was observed that only the expression of linear isoforms of ANRIL and VEGF significantly contributed to the prediction of the number of surgical revascularizations.

Abstract 16844: Identifying Splenic Radiomics Features Associated With Risk of Coronary Artery Disease

Introduction: Inflammation is a validated mechanism for residual coronary artery disease (CAD) risk via clinical trials and analysis of germline and somatic genetic variation in blood cells. While the spleen plays an important role in regulating inflammation, the role it plays in CAD is unclear. Hypothesis: We aim to test the hypothesis that radiographic splenic biomarkers may offer novel insights for CAD. Methods: We used deep learning to segment spleens from the abdominal MRIs of 38,474 patients in the UK Biobank. CAD was defined as history of coronary artery bypass grafting, myocardial infarction (MI), coronary artery angioplasty, or billing codes (OPCS-4: K40, K41, K45, K49, K50.2, K75). We extracted image features using the pyradiomics package. To identify image features associated with CAD, we used L1-regularized logistic regression models with the splenic features and clinical features used in the Pooled Cohort Equations (PCE) for outcomes of CAD and cardiovascular disease (CVD) events (defined as a composite of CAD, MI, and stroke outcomes). We computed the area under the receiver operating characteristic (AUROC) on a held-out 30% of the patient population and determined 95% confidence intervals using 1,000 Monte-Carlo resampled bootstraps. Results: Study participants had mean (SD) age 55.1 (7.5) years, 19,921 (51.8%) were women, 1,412 (3.7%) had CAD, and 2,473 (6.4%) had CVD events. The model to predict CAD using the splenic and PCE features had an AUROC of 0.84 (95% CI, 0.84-0.85), and 3 out of 10 significant covariates were splenic features. 1-SD increases in sphericity, minor axis length, and entropy in neighboring voxel gray levels were associated with 5.4% (95% CI, 5.1-5.7) higher, 13.3% (95% CI, 13.0-13.6) lower, and 10.5% (95% CI, 10.2-10.8) higher odds of CAD after adjustment. Results were consistent in the model to predict CVD events, and decreased minor axis length and increased texture variation were associated with increased risk. Model performance was lower for older age groups, who had higher incidences of CAD. Conclusions: This study leverages deep-learning methods across a population based cohort to highlight splenic features correlated with CAD and offers new opportunities to understand the role of the hematopoietic system in CAD.

Abstract 16466: Sex-Specific Risks of Air Pollution on Coronary Artery Disease and Adverse Events: Insights From the PROMISE Trial

Introduction: Sex-specific differences in coronary artery disease (CAD) have significant implications, yet the potential sex-specific impact of air pollution on CAD and adverse outcomes remains unexplored. Hypothesis: The association between air pollution and CT-derived CAD phenotype or cardiovascular (CV) events varies by sex. Methods: We assessed annual average exposure to particulate matter (PM 2.5 &amp; PM 10 ) and ozone by home zip codes in the CT arm of the PROMISE trial. Pollutant exposure was related to CAD measures on CT (any plaque, obstructive CAD (stenosis ≥50%), high-risk plaque (HRP)) and composite endpoint (death, myocardial infarction, unstable angina), adjusting for age, obesity, ASCVD risk, and Socioeconomic Determinants of Health, using sex-stratified regression analyses. Results: We analyzed 2,252 (52%) women and 2,091 (48%) men (62±8 vs. 59±8 years, p&lt;0.001) with intermediate ASCVD risk (12% vs. 17%, p&lt;0.001). Women were less frequently exposed to PM 2.5 ≥9.5 μm/m 3 (45.1% vs. 48.8%, p=0.011) but more frequently to ozone &gt;45 ppb (40.5% vs. 36.8%, p=0.011) compared to men. Exposure to PM 2.5 ≥9.5 μm/m 3 related to 42% higher odds of obstructive CAD (aOR 1.42, 95%CI: 1.02-1.97, p=0.040) in women but not in men. High PM 10 and ozone exposures did not relate to stenosis or HRP in either sex (p&gt;0.14) (Figure 1a) . Exposure to ozone &gt;45 ppb was related to a higher hazard of events in men (aHR 2.20, 95%CI: 1.36-3.55, p=0.001) but not in women (aHR 1.05, 95%CI: 0.58-1.90, p=0.88). Exposure to high PM 2.5 and PM 10 levels was not associated with events in sex-stratified analysis (Figure 1b) . Conclusions: Sex significantly influences pollutant impact on CAD. High PM 2.5 exposure increases obstructive CAD risk exclusively in women, while high ozone exposure raises CV event risk in men. Findings stress the need for sex-specific strategies in combating pollution's cardiovascular effects.

The Relationship Between C-reactive Protein Albumin Ratio and Long-Term Mortality in Patients With Acute Coronary Syndrome.

Background Coronary artery disease (CAD) is one of the leading causes of death worldwide. CRP/albumin ratio is a sensitive indicator of inflammatory status. It has been shown that this parameter may be associated with poor short-term outcomes in CAD. In this study, we investigated the relationship between long-term mortality and the CRP/albumin ratio in patients with acute coronary syndromes (ACS). Material and methods This study was conducted on patients who applied to our hospital between January 2015 and December 2019 and were diagnosed with ACS. A total of 1689 patients were included in the study. Patients were divided into two groups according to mortality status, and long-term mortality predictors were investigated. Results The average follow-up period was 38.9±10.3 months. The mean age of the entire study group was 56.6±12.2 years, and 1440 (80.5%) of the patients were male. Comorbid diseases and blood parameters were significant between the two groups. In the regression analysis, creatine, hemoglobin, white blood cell count (WBC), neutrophil-lymphocyte ratio (NLR), and CRP albumin ratio (CAR) were found to be independent predictors. In the ROC analysis, it was observed that CAR had the best predictive value. Discussion An increased CAR level is an independent predictor of long-term mortality in ACS patients. It can be used in both short-term and long-term risk stratification for ACS patients.

Assessing the association between genetic and phenotypic features of dilated cardiomyopathy and outcome in patients with coronary artery disease.

To examine the relevance of genetic and cardiovascular magnetic resonance (CMR) features of dilated cardiomyopathy (DCM) in individuals with coronary artery disease (CAD). This study includes two cohorts. First, individuals with CAD recruited into the UK Biobank (UKB) were evaluated. Second, patients with CAD referred to a tertiary centre for evaluation with late gadolinium enhancement (LGE)-CMR were recruited (London cohort); patients underwent genetic sequencing as part of the research protocol and long-term follow-up. From 31 154 individuals with CAD recruited to UKB, rare pathogenic variants in DCM genes were associated with increased risk of death or major adverse cardiac events (hazard ratio 1.57, 95% confidence interval [CI] 1.22-2.01, p < 0.001). Of 1619 individuals with CAD included from the UKB CMR substudy, participants with a rare variant in a DCM-associated gene had lower left ventricular ejection fraction (LVEF) compared to genotype negative individuals (mean 47 ± 10% vs. 57 ± 8%, p < 0.001). Of 453 patients in the London cohort, 63 (14%) had non-infarct pattern LGE (NI-LGE) on CMR. Patients with NI-LGE had lower LVEF (mean 38 ± 18% vs. 48 ± 16%, p < 0.001) compared to patients without NI-LGE, with no significant difference in the burden of rare protein altering variants in DCM-associated genes between groups (9.5% vs. 6.7%, odds ratio 1.5, 95% CI 0.4-4.3, p = 0.4). NI-LGE was not independently associated with adverse clinical outcomes. Rare pathogenic variants in DCM-associated genes impact left ventricular remodelling and outcomes in stable CAD. NI-LGE is associated with adverse remodelling but is not an independent predictor of outcome and had no rare genetic basis in our study.

Education level and the use of coronary computed tomography, functional testing, coronary angiography, revascularization, and outcomes-a 10-year Danish, nationwide, registry-based follow-up study.

Coronary computed tomography angiography (CCTA) can guide downstream preventive treatment and improve patient prognosis, but its use in relation to education level remains unexplored. This nationwide register-based cohort study assessed all residents in Denmark between 2008 and 2018 without coronary artery disease (CAD) and 50-80 years of age (n=1 469 724). Residents were divided according to four levels of education: low, lower-mid, higher-mid, and high. Outcomes were CCTA, functional testing, invasive coronary angiography (ICA), revascularization, and major adverse cardiovascular and cerebrovascular events (MACCE). Individuals with the lowest education level underwent CCTA (absolute risk [AR] 3.95% individuals aged≥50-59, AR 3.62% individuals aged≥60-69, and AR 2.19% individuals aged≥70-80) less often than individuals of lower-mid (AR 4.16%, AR 3.90%, and AR 2.41%), higher-mid (AR 4.38%, AR 4.30%, and AR 2.45%) and highest education level (AR 3.98%, AR 4.37%, and AR 2.30%). Similar differences were observed for functional testing. Conversely, use of ICA, and risks of revascularization and MACCE were more common among individuals of lowest education level. Among patients examined with CCTA (n=50234), patients of lowest education level less often underwent functional testing and more likely initiated preventive medication, underwent ICA, revascularization, and experienced MACCE. Despite tax-financed healthcare in Denmark, individuals of lowest education level were less likely to undergo CCTA and functional testing than persons of higher education level. Invasive coronary angiography utilization, revascularization, and MACCE risks were higher for individuals of lowest education level. Among CCTA-examined patients, patients of lowest education level were more likely to initiate preventive medication and had the highest risks of revascularization and MACCE when compared to higher education level groups. These findings suggest that the preventive potential of CCTA is underutilized in individuals of lower education level, a proxy for socioeconomic status. Socioeconomic differences in CAD assessment, care, and outcomes are likely even larger without tax-financed healthcare.

Age-Specific Cardiovascular Risk Factors for Major Adverse Cardiac Events in Patients Undergoing Myocardial Perfusion Imaging.

The prevalence of traditional cardiovascular risk factors shows different age-specific patterns. It is not known whether the prognostic impact of risk factors is similarly age-specific. We evaluated the profiles of cardiovascular risk factors and their prognostic impact on coronary artery disease (CAD) in relation to age. We included 3667 patients with suspected or known CAD undergoing stress myocardial perfusion imaging (MPI). We evaluated the risk for major adverse cardiac events (MACE) within three years from the index MPI in patients belonging to three groups according to age tertile distribution: <59, 59-68, and >68 years. Gender, body mass index, diabetes, hypertension, dyslipidemia, family history of CAD, smoking, angina, dyspnea, previous CAD, and MPI outcome were assessed as risk factors by a multivariable Cox's regression. The three-year risk of MACE increased progressively with age and was 9%, 13%, and 18% for each group, respectively (p < 0.0001). Dyspnea and abnormal MPI outcome were significant risk factors for all age groups. Diabetes and smoking were significant from the age of 59 onwards, while hypertension resulted significant for patients older than 68 years. The number of risk factors was significantly associated with the occurrence of MACE increase with age. It is noteworthy that a personal history of CAD was not useful for risk stratification, while MPI results were.