Introduction and Objective: Excess cortisol can contribute to type 2 diabetes (T2D) and cardiometabolic diseases, especially when they are difficult to control despite standard of care treatment. The CATALYST study (NCT05772169) found that 24% of 1057 US individuals with difficult-to-control T2D had endogenous hypercortisolism (HC), and the prevalence was 37% in those taking ≥3 antihypertensives. The MOMENTUM study (NCT06829537) found that 27% of individuals with resistant hypertension (rHTN) had HC. We assessed HC prevalence and differences in characteristics in MOMENTUM participants with rHTN and hemoglobin A1c (HbA1c) ≥7.5%. Methods: We screened adults ≥18 years with rHTN (systolic blood pressure [SBP] ≥130 mmHg on ≥3 antihypertensive classes [including a diuretic] or on ≥4 classes regardless of SBP) with a 1-mg overnight dexamethasone suppression test (DST; HC=post-DST cortisol >1.8 μg/dL with dexamethasone ≥140 ng/dL). Key exclusion criteria were conditions that could interfere with the DST or lead to an incorrect rHTN diagnosis. Clinical characteristics were summarized using descriptive statistics. Results: Of participants, 17% (181/1086) had rHTN and HbA1c ≥7.5%. HC prevalence differed across HbA1c groups (P<0.05; X2 test) and was highest in the HbA1c ≥7.5% group (33%). In this group, individuals with HC vs without HC, respectively, were older (aged ≥65 years, 56% vs 44%), and had more use of insulin (58% vs 49%), metformin (56% vs 50%), SGLT2 inhibitors (37% vs 32%), GLP-1 RAs (including tirzepatide; 41% vs 34%), and lipid-modifying agents (76% vs 72%) and less use of sulfonylureas (14% vs 21%). Atrial fibrillation was more frequent (15% vs 5%), but coronary artery disease was similar (14% vs 15%). Conclusion: About one-third of MOMENTUM participants with rHTN and HbA1c ≥7.5% had HC, consistent with CATALYST results. HC was associated with a higher burden of T2D medications and atrial fibrillation vs no HC. These findings support the need for HC screening in rHTN and T2D. Disclosure G. Umpierrez: Research Support; Current; Abbott, Dexcom, Inc., Bayer AG. Advisory Panel; Ended; Sanofi-Aventis U.S., Dexcom, Inc. Other - Education grant; Current; Lilly Diabetes, Abbott Diabetes. Advisory Panel; Current; Glycare, Glucotrack. Research Support; Current; Corcept Therapeutics. V. Aroda: Research Support; Current; Amgen Inc. Research Support; Ended; Applied Therapeutics. Research Support; Current; AstraZeneca. Other - Biomea; institutional consultant and research support; Current; Biomea. Research Support; Current; Boehringer Ingelheim International GmbH, Corcept Therapeutics, Eli Lilly and Company, Fractyl Health, Inc., Novo Nordisk, Pfizer Inc. Consultant; Current; Recordati S.p.A. Research Support; Current; Rhythm Pharmaceuticals, Inc. Consultant; Ended; Servier Laboratories, Mediflix, Inc., Roche Pharmaceuticals, Sanofi. Other - spouse is an employee; Current; Flagship Pioneering. Other - spouse was an employee; Ended; AditumBio, Johnson & Johnson. M. Budoff: Speaker's Bureau; Current; Amgen Inc. Research Support; Current; Lilly. Speaker's Bureau; Current; Novo Nordisk A/S, Lilly. R.S. Busch: Research Support; Current; Eli Lilly and Company, Novo Nordisk, Corcept Therapeutics. Speaker's Bureau; Current; Corcept Therapeutics, Bayer AG, Madrigal Pharmaceuticals, Inc., Ascendis Pharma A/S. Research Support; Current; AstraZeneca. D. Cheung: Research Support; Current; Lilly, Corcept Therapeutics. R.A. DeFronzo: Advisory Panel; Ended; AstraZeneca. Research Support; Current; AstraZeneca. Advisory Panel; Current; Novo Nordisk. Research Support; Current; Eli Lilly and Company. Advisory Panel; Current; Corcept Therapeutics. Speaker's Bureau; Current; Corcept Therapeutics. Consultant; Current; Alnylam Pharmaceuticals, Inc. Advisory Panel; Current; Regeneron Pharmaceuticals Inc., Aardvark. B. Eilerman: Speaker's Bureau; Current; Corcept Therapeutics, Lilly, Novo Nordisk, Abbott, Dexcom, Inc. Advisory Panel; Current; Recordati S.p.A. V. Fonseca: Consultant; Current; Abbott Diabetes. Stock/Shareholder; Current; BRAVO4HEALTH, LLC. Consultant; Ended; Bayer AG. Consultant; Current; Eli Lilly and Company, Corcept Therapeutics, Regeneron Pharmaceuticals Inc., Boehringer Ingelheim International GmbH. Stock/Shareholder; Current; Vertex Pharmaceuticals Incorporated. S. Gupta: None. Y. Handelsman: Consultant; Current; Amgen Inc. Advisory Panel; Current; AstraZeneca. Research Support; Current; AstraZeneca. Advisory Panel; Ended; Bayer AG. Advisory Panel; Current; Corcept Therapeutics. Research Support; Current; Corcept Therapeutics. Advisory Panel; Ended; Boehringer Ingelheim International GmbH. Research Support; Current; Ionis Pharmaceuticals. Advisory Panel; Current; Merck Sharp & Dohme Corp. Research Support; Current; Merck Sharp & Dohme Corp. M. Kipnes: None. J.Y. Park: None. A. Philis-Tsimikas: Research Support; Current; Dexcom, Inc., Lilly, Novo Nordisk. Advisory Panel; Current; Novo Nordisk, Gan & Lee Pharmaceuticals. Research Support; Current; Sanofi-Aventis U.S. L. Sloan: Speaker's Bureau; Current; Abbott, AstraZeneca. Advisory Panel; Current; Corcept Therapeutics. Speaker's Bureau; Current; Corcept Therapeutics, Boehringer Ingelheim International GmbH, Bayer AG, Eli Lilly and Company, Lilly. Advisory Panel; Current; Idorsia Pharmaceuticals Ltd. Speaker's Bureau; Current; Madrigal Pharmaceuticals, Inc. Advisory Panel; Current; Novo Nordisk. Advisory Panel; Ended; Xeris Pharmaceuticals, Inc. Speaker's Bureau; Ended; Xeris Pharmaceuticals, Inc. Y. Tian: Employee; Current; Corcept Therapeutics. Employee; Ended; Gilead Sciences, Inc. T.K. Schlafly: Employee; Current; Corcept Therapeutics. Stock/Shareholder; Current; Corcept Therapeutics. D.F. Einhorn: Employee; Current; Corcept Therapeutics. J.B. Buse: Consultant; Current; Aardvark Therapeutics, Altimmune, Alveus Therapeutics, Amgen Inc., Antag Therapeutics, Aqua Medical, AstraZeneca, Boehringer Ingelheim International GmbH. Other - Consultant and clinical trial support; Current; Corcept Therapeutics. Consultant; Ended; Dexcom, Inc. Consultant; Current; Eli Lilly and Company. Consultant; Ended; embecta. Consultant; Current; General Medicines Inc. Other - Consultant and clinical trial support; Current; GentiBio. Consultant; Ended; Insulet Corporation. Consultant; Current; Kayothera. Other - Consultant and stock options; Current; Metsera. Other - Expert witness; Ended; Medtronic. Other - Consultant and investigator; Current; Novo Nordisk. Consultant; Current; Recordati S.p.A, Sparrow Pharmaceuticals. Consultant; Ended; Tandem Diabetes Care, Inc. Consultant; Current; Vertex Pharmaceuticals Incorporated, vTv Therapeutics, Zealand Pharma A/S. Funding This study is funded by Corcept Therapeutics Incorporated

Background Hypertension is a leading modifiable risk factor for cardiovascular disease and premature death among adults. Up to 18% of individuals with hypertension have resistant hypertension (rHTN), which substantially increases the risk of adverse clinical outcomes. Endogenous hypercortisolism can result in rHTN through multiple mechanisms. Objectives MOMENTUM (NCT06829537) is the first large, observational, multicenter study examining the prevalence of endogenous hypercortisolism among adults with rHTN in the United States. Methods Target enrollment is approximately 1,000 participants. To be eligible, adults aged ≥18 years must have rHTN, defined using the American Heart Association criteria (systolic blood pressure ≥130 mm Hg despite ≥3 antihypertensive medications of different classes at maximally tolerated doses, including a diuretic, or ≥4 medications from different classes regardless of systolic blood pressure). Endogenous hypercortisolism is defined as cortisol level >1.8 μg/dL on the 1-mg overnight dexamethasone suppression test with adequate dexamethasone (≥140 ng/dL). The primary endpoint is endogenous hypercortisolism prevalence. Conclusions MOMENTUM will provide new insight into endogenous hypercortisolism in patients with resistant hypertension.

AIMS:Premature advanced subclinical coronary atherosclerosis among young adults is an under-recognized and unique disease phenotype that has not been well characterized. METHODS AND RESULTS:We used data from 44 047 participants with no prior CVD history (59.8% male) from the Coronary Artery Calcium (CAC) Consortium. We defined advanced disease as CAC ≥ 90th percentile for age, sex, and race and compared the risk factor profile of persons with advanced disease to those without CAC and those with CAC < 90th percentile. Using multivariable-adjusted Cox proportional hazard and competing risks regression, we assessed the association of premature advanced disease with all-cause, cardiovascular, and coronary heart disease (CHD) mortality. Of 44 047 participants, 18 561 (42.2%) had CAC. Among those with CAC, 6680 (36.0%) had CAC ≥ 90th percentile. Notably, 76.4% of those with CAC ≥ 90th percentile had multivessel CAC compared with 40.6% of those with CAC < 90th percentile. After a mean follow-up of 12.5 ± 3.6 years, the incidence per 1000 person-years of all-cause (2.93 vs. 1.85 vs. 1.11), cardiovascular (1.11 vs. 0.39 vs. 0.21), and CHD mortality (0.65 vs. 0.19 vs. 0.08) was highest in the advanced disease group compared with CAC < 90th percentile and the no CAC group. Persons with CAC ≥ 90th percentile had a higher multivariable-adjusted risk of all-cause [HR: 2.17 (1.83-2.57)], cardiovascular [sub-distribution hazard ratios (SHR): 3.89 (2.78-5.44)], and CHD mortality [SHR: 5.45 (3.38-8.78)], compared with those without CAC. In the subgroup analysis, there was no difference in mortality between men and women with advanced CAC. CONCLUSION:Premature advanced atherosclerosis is a distinct clinical phenotype that strongly predicts all-cause and cause-specific mortality. Among persons with CAC at young age, those with scores ≥90th percentile have the highest risk of early death and should be identified in future guidelines as a focus for aggressive clinical prevention.

Introduction Coronary artery calcium (CAC) scoring is a commonly used tool for cardiovascular disease (CVD) risk assessment and is reported using the Agatston score. However, there has been increasing interest in measures of CAC beyond the Agatston score, including measures capturing the overall distribution of vessel calcification. We assessed the association between 30-year traditional risk factor exposure and the presence of a more diffuse pattern of CAC in older adults aged 75 and older. Methods We studied participants in the Atherosclerosis Risk in Communities (ARIC) study who underwent CAC scoring and were free of prior CVD. Time-weighted average exposure to traditional cardiovascular risk factors (over 30 years) was calculated. The CAC diffusivity index was calculated for each participant as 1 - (CAC in most affected vessel/total CAC). to capture distribution of calcification, and associations between traditional risk factors and more diffuse CAC patterns were studied. Results In 2,201 participants (mean age 80, 61.8% women), time-averaged exposure to systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), ever smoking, male sex, and limited education were independently associated with more diffuse CAC (p<0.05). Conclusion Longitudinal exposure to traditional CVD risk factors including higher SBP, higher LDL-C, lower HDL-C, and smoking was associated with a more diffuse pattern of CAC in a population of adults aged 75 and older.

Background It is unknown whether subclinical emphysema-like changes, quantified at chest CT, are associated with loss of bone mineral density (BMD) in individuals without clinical chronic obstructive pulmonary disease (COPD). Purpose To identify early imaging markers of lung and bone health using deep learning-based imaging analysis in a large multiethnic cohort. Materials and Methods Chest CT scans obtained using the SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) protocol during examination 5 and 6 of the prospective Multi-Ethnic Study of Atherosclerosis (MESA) were secondarily analyzed (April 2010-March 2018). Percentage emphysema was quantified at examination, and thoracic vertebral BMD was assessed at both examinations using a validated deep learning-based segmentation model. Participants with clinical COPD as determined on the basis of spirometry or self-reports were excluded. Linear mixed-effects models were constructed and adjusted for demographic characteristics and covariates, including smoking status, physical activity, and scanner type, and the interaction effect of sex was analyzed. Results The cross-sectional analysis included 2312 participants (median age, 67 years [IQR, 61-75 years]; 1285 female participants), and the longitudinal study included 1109 participants (median age, 65 years [IQR, 60-72 years]; 614 female participants) with available follow-up CT data. A greater percentage of emphysema-like changes was associated with lower BMD (β = -1.14 mg/cm3 [95% CI: -1.76, -0.53]) cross-sectionally and with greater annual BMD loss (β = -0.07 mg/cm3 per year [95% CI: -0.13, -0.01]) longitudinally. Interaction effects were identified for sex (P < .001) and race or ethnicity (P = .049). In stratified models, the associations were significant for men (β = -0.38 mg/cm3 per year [95% CI: -0.48, -0.28]) and Black/African American participants (β = -0.24 mg/cm3 per year [95% CI: -0.39, -0.09]). The Johnson-Neyman method revealed more than 2.7% emphysema as a threshold for a decrease in BMD among men, which corresponded to 39% of the male participants. The results remained robust after adjustment for pulmonary function and chronic respiratory symptoms. Conclusion In individuals without COPD, a greater percentage of emphysema-like changes was independently associated with faster vertebral bone loss, particularly in men, suggesting that subclinical emphysema may be a novel imaging marker of systemic skeletal decline. Clinical trial registration no. NCT0000548 © RSNA, 2026 Supplemental material is available for this article. See also the editorial by Fukuda in this issue.

Introduction and Objective: American Diabetes Association (ADA) guidelines recommend early assessment of lipid levels in patients with diabetes mellitus (DM) and, in those at increased cardiovascular (CV) risk, initiation of lipid-lowering therapy (LLT) to reduce the risk of a first CV event and improve long-term outcomes. We examined lipid management patterns in patients with high-risk DM at risk for their first major atherosclerotic CV event in 11 databases from North America, Europe, and Asia-Pacific. Methods: Patients aged ≥ 50 years with coronary artery disease (CAD), atherosclerotic cerebrovascular disease (CeVD), or peripheral artery disease (PAD) or high-risk DM (defined as DM with microvascular complications or chronic insulin use) and elevated lipids and additional CV risk factors but no history of myocardial infarction or stroke were selected from de-identified claims or electronic medical records (2017-2022). The earliest date when all criteria were met was defined as the index. This analysis summarizes LLT use, LLT intensification, and low-density lipoprotein cholesterol (LDL-C) goal achievement based on local guidelines for the high-risk DM subgroup. Results: Out of 354,643 patients with high-risk DM (51% female), 14% also had CAD, atherosclerotic CeVD, or PAD. Fewer than half of the patients were on LLT at index (46%), and statin monotherapy was the predominant regimen (87%). For patients not on LLT at index, about 1 in 4 (26%) initiated LLT within 1 year post-index; for those who had ongoing LLT, 7% intensified their LLT within 1 year post-index. Around 42% of patients underwent LDL-C testing within 1 year of follow-up (n = 149,495), and 22% met their local guideline-recommended LDL-C goal. Conclusion: These findings show that globally, patients with high-risk DM are frequently untreated or undertreated, not having optimal lipid monitoring, and only a minority achieve ADA-recommended lipid management targets to lower the risk of major ischemic events. Disclosure Q. Chan: Employee; Current; Amgen Inc. S. Sakhuja: Employee; Current; Amgen Inc. M. Budoff: Speaker's Bureau; Current; Amgen Inc. Research Support; Current; Lilly. Speaker's Bureau; Current; Novo Nordisk A/S, Lilly. J. Cegla: Consultant; Current; Novartis Pharmaceuticals Corporation, Eli Lilly and Company, Amryt Pharma Plc, Amgen Inc., Daiichi Sankyo, Chiesi USA, Inc. J.H. Cornel: Advisory Panel; Current; Amgen Inc., Janssen Research & Development, LLC, Novo Nordisk, Sanofi. E. Hagstrom: Research Support; Ended; Pfizer Inc. Consultant; Current; Amgen Inc. Research Support; Current; Amgen Inc. Advisory Panel; Ended; Amarin Corporation. Research Support; Current; Novo Nordisk. Advisory Panel; Ended; Novo Nordisk. Speaker's Bureau; Ended; Sanofi. Other - National lead coin trial; Current; AstraZeneca. Advisory Panel; Ended; Bayer AG. G. Paiva da Silva Lima: Employee; Current; Amgen Inc. Stock/Shareholder; Current; Amgen Inc. M. Sibartie: Employee; Current; Amgen Inc. Stock/Shareholder; Current; Amgen Inc. I.C. Wong: Research Support; Current; Amgen Inc.

AIMS:Aortic valve calcium (AVC) is strongly associated with the risk for severe aortic stenosis (AS). The prevalence of AVC increases with age, but the impact of age on the progression of AVC and its association with moderate-severe AS is unknown. METHODS AND RESULTS:Our study included 6810 participants (52.9% women) without overt cardiovascular disease between ages 45 and 84 from the Multi-Ethnic Study of Atherosclerosis. AVC was measured using non-contrast cardiac CT at Visit 1. Progression was calculated as the change in AVC divided by years between CT scans (2-10 years). Incident moderate-severe AS was adjudicated using medical chart review and echocardiogram data from Visit 6 (median follow-up of 16 years). The association between AVC and moderate-severe AS was assessed using multivariable adjusted Cox proportional hazards ratios. There were 5899 participants with AVC = 0 and 911 with AVC >0. There were 3834 participants age <65 years and 2979 age ≥65 years. The median AVC was 34.1 AU (IQR 13-1113) for participants <65 vs. 69.0 AU (IQR 23-2453) for participants ≥65. Participants <65 and ≥65 years had no significant difference in median annualized AVC progression within the baseline AVC categories of 1-99 (10 vs. 12 AU/year, P = 0.303) and AVC ≥100 (50 vs. 47 AU/year, P = 0.846). AVC >0 was associated with a similar significantly higher risk of incident moderate-severe AS for both younger (HR 13.37; 95% CI 5.67-31.52) and older participants (HR 10.59, 95% CI 6.77-16.56). CONCLUSION:AVC progression was significantly associated with baseline AVC burden and was similar for younger vs. older persons after accounting for baseline AVC. The presence of AVC was significantly associated with a higher long-term risk for moderate-severe AS among both younger and older participants.

BACKGROUND South Asian populations have a high risk of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcification (CAC) can guide clinical decision making in patients with intermediate ASCVD risk. Thoracic aortic calcification (TAC) can be measured from the same computed tomography scan, though it is unknown whether TAC may help reclassify ASCVD risk. METHODS We conducted a cross-sectional analysis of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. Ten-year ASCVD risk was calculated using the American Heart Association Predicting Risk of cardiovascular disease Events equation (PREVENT), categorized as <5%, 5 to <10% or ≥10%. TAC and CAC scores were categorized as 0, 1-99, and ≥100. We determined associations of traditional risk factors with TAC and CAC and used cubic spline functions to examine non-linear associations between PREVENT and TAC and CAC, overall and stratified by gender. RESULTS Of 960 participants, 59.4% had any CAC, 53.8% had any TAC, and 42.4% had both CAC and TAC. Any TAC and any CAC were each more likely with older age, among men, and in those with hypertension, diabetes, higher LDL-cholesterol, and statin use. Higher PREVENT-ASCVD risk was associated with higher TAC in women and higher CAC in men. Among women, TAC was significantly higher than CAC in PREVENT scores ≥7%. CONCLUSION In South Asian US adults, higher PREVENT-ASCVD risk is associated with higher CAC and TAC. TAC burden is higher than CAC among women with PREVENT scores 5 to <10%. Further studies should explore if high TAC is predictive of clinical events.

BACKGROUND:People with HIV are at elevated risk for atherosclerotic cardiovascular disease despite viral suppression, suggesting contributions from nontraditional mechanisms. Coronary vascular inflammation may play a role, but its relationship to plaque progression remains incompletely defined. The perivascular fat attenuation index (FAI) score, derived from coronary computed tomography angiography, is associated with vascular inflammation. We evaluated whether coronary inflammation is associated with the incidence and progression of coronary plaque and whether these relationships differ by HIV status. METHODS:A total of 504 men (n=292 with HIV; n=212 without HIV) from the Multicenter AIDS Cohort Study underwent coronary computed tomography angiography over a median of 4.5 years (3.8-4.9). FAI measurements were performed on baseline scans. Changes in noncalcified, calcified, and total plaque volumes were categorized into tertiles of progression. Associations were estimated using multinomial logistic regression adjusted for interscan time and cardiovascular risk factors. Modified Poisson regression estimated incident plaque. RESULTS:Higher FAI scores in the left anterior descending (LAD) and left circumflex were associated with greater odds of belonging to the highest tertile of noncalcified (LAD odds ratio [OR], 1.83 [1.27-2.64]; left circumflex OR, 2.55 [1.66-3.91]); calcified (LAD OR, 2.62 [1.64-4.18]; left circumflex OR, 3.92 [2.36-6.51]); and total plaque progression (LAD OR, 1.81 [1.25-2.62]; left circumflex OR, 2.65 [1.71-4.10]) among men with HIV (MWH), per SD increase in FAI score after adjusting for cardiovascular risk factors, and remained significant after adjustment for baseline plaque. Higher LAD FAI score was associated with incident calcified plaque in men with HIV (RR, 1.21 [1.01-1.46]). Associations for noncalcified and calcified plaque progression were stronger in men with HIV than in men without HIV. CONCLUSIONS:Coronary inflammation, assessed by FAI, is independently associated with incident and progressive coronary plaque in men with HIV. These findings support a role for vascular inflammation in accelerated atherosclerosis in people with HIV and highlight FAI as a potential biomarker for risk stratification.

Background: Cardiovascular-Kidney-Metabolic (CKM) syndrome, a cluster of conditions, including cardiovascular disease, chronic kidney disease, and type 2 diabetes, is classified by the American Heart Association (AHA) into five stages of severity (0-4). Since 2023, CKM has been widely recognized as a major health concern in the United States (U.S.); however, evidence of social determinants of health (SDOH) influencing its trajectory under current medical care remains limited. Objective: This study investigated 5- and 10-year patterns of CKM trajectories and their association with SDOH among U.S. adults. Methods: Data were pooled from two U.S. cohort studies: the Multi-Ethnic Study of Atherosclerosis and the Coronary Artery Risk Development in Young Adults. CKM stages were defined according to AHA criteria, and their trajectories were classified as regressed, stable, and progressed, based on 5-year (2000-2005) and 10-year (2000-2010) stage changes, which were assessed as a binary outcome (progressed vs. regressed/stable). SDOH were evaluated across four major domains: economic stability, education, community and social context, and health care. Multivariable logistic regression was applied to examine associations between SDOH and CKM trajectories. Results: A total of 6543 adults with CKM were included (mean age 53.3 years (SEM 0.16); 54.1% female; 46.3% White), and most had stable CKM status (Y5: 67.1%; Y10: 55.6%). Over a 5-year follow-up, being unmarried was associated with higher odds of progression after adjusting for demographic and lifestyle factors (OR 1.15, 95% CI 1.01-1.31). Over 10 years of follow-up, being unemployed (OR 1.38, 95% CI 1.03-1.84) and unmarried (OR 1.14, 95% CI 1.00-1.29) were associated with higher odds of progression. Individuals with ≥ 3 adverse SDOH factors were more likely to experience progression over 5- (OR 1.11, 95% CI 1.02-1.20) and 10-year follow-up (OR 1.09, 95% CI 1.01-1.17) consistently. Conclusion: This study demonstrates that individuals with adverse SDOH profiles are more likely to experience CKM progression over 5- and 10-year follow-up. These findings highlight the need for tailored strategies for CKM syndrome management that specifically address the impact of unfavorable SDOH.

Background Coronary angiography (CA) and percutaneous coronary intervention (PCI) are widely used for diagnosing and treating coronary artery disease (CAD) but may cause bleeding-related in-hospital complications, especially with femoral access. This study evaluated the incidence and predictors of access-site bleeding events and related outcomes in central Iran. Methods In this retrospective cohort, 1,369 patients underwent CA and PCI at Afshar Hospital, Yazd, between 2020 and 2022. Demographic, clinical, and procedural data were collected. Bleeding events were classified using the Bleeding Academic Research Consortium (BARC) criteria, and high bleeding risk was defined according to the Academic Research Consortium for High Bleeding Risk (ARC-HBR). Logistic regression identified independent predictors. Results Bleeding-related in-hospital complications occurred in 143 patients (10.4%), most commonly inguinal hematoma (8.4%), major bleeding (1.6%), and mortality (0.6%). BARC Type 2 bleeding was most frequent (8.4%), followed by Type 3a (1.6%) and 3b (0.3%). Based on ARC-HBR, 13.5% of patients met at least one major or two minor high bleeding risk criteria. Multivariate analysis showed that elevated international normalized ratio (INR) (OR=2.15; 95% CI: 1.22–3.72; P=0.006) and anticoagulant use (OR=1.8; 95% CI: 1.14–2.85; P=0.011) were significantly associated with complications. Conclusion Bleeding-related complications, particularly hematoma, major bleeding, and procedure-related mortality, occurred in over 10% of patients undergoing CA and PCI. Anticoagulant therapy and elevated INR were key predictors, highlighting the importance of individualized risk assessment and bleeding risk stratification using tools like BARC and ARC-HBR.

Background South Asians (SA) face disproportionately high rates of premature coronary artery disease (CAD), often underestimated by traditional risk calculators. We aim to characterize CT angiography (CTA)-derived plaque composition, plaque burden, and association with risk factors among SA in the DILWALE registry. Methods Clinically indicated coronary CTAs from 341 patients in the Baylor Scott and White DILWALE registry were analyzed using Artificial intelligence enabled quantitative coronary plaque analysis (AIQCPA) to characterize age- and sex-specific plaque burden. Results Of 341 patients, 63% (n=215) exhibited any plaque by AIQCPA. Non-calcified plaque (NCP) was the predominant plaque subtype across all age groups, but calcified plaque volumes increased with age. The median PAV was 3.5% (IQR 0-18.5%). Age, male sex, and statin use were significant predictors of the presence of any plaque, while age and male sex predicted the presence of low attenuation plaque ≥ 10 mm3. Conclusion This study represents one of the largest CTA based cohorts evaluating plaque characteristics in SA in the United States. Our findings highlight the value of AIQCPA CTA in revealing subclinical plaque, particularly non-calcified plaque in SA. Future studies should identify optimal imaging strategies for SA along with outcome-based validation of plaque characteristics.

BACKGROUND:Aortic valve calcification (AVC) is the primary process leading to aortic stenosis. We examined whether polygenic risk scores (PRS) are associated with AVC beyond traditional atherosclerotic cardiovascular disease risk factors. METHODS:We included 6812 participants in MESA (Multi-Ethnic Study of Atherosclerosis) with computed tomography-measured AVC at Visit 1. Using previously published PRS we calculated weighted PRS, standardized within each ancestry group. The cross-sectional association per 1 SD higher PRS with AVC >0 was examined using multivariable logistic regression modeling with Bonferroni correction. The mean age was 62 years old, 53% were female, and 913 (13.4%) had AVC >0 at baseline. RESULTS:The PRS for coronary artery disease (hazard ratio [HR], 1.16 [95% CI, 1.07-1.26]), systolic blood pressure (HR, 1.1 [95% CI, 1.020-1.2]), low-density lipoprotein cholesterol (HR, 1.16 [95% CI, 1.06-1.25]), and lipoprotein(a) (HR, 1.11 [95% CI, 1.02-1.20]) were significantly associated with AVC, whereas the other PRS including coronary artery calcium (HR, 1.02 [95% CI, 0.94-1.10]) and C-reactive protein (HR, 0.97 [95% CI, 0.89-1.05]) were not. In sex-stratified analyses, the PRS for coronary artery disease, low-density lipoprotein cholesterol, and lipoprotein(a) were significantly associated with AVC >0 for both sexes (P<0.05), whereas the systolic blood pressure PRS was borderline significant for women (HR, 1.10 [95% CI, 0.97-1.25]) and significant for men (HR, 1.11 [95% CI 1.00-1.24]). CONCLUSIONS:Our results confirm the role of atherogenic lipids in the pathogenesis of AVC and suggest that systolic blood pressure and the genetic risk factors for CAD are also important risk factors. The lack of association for the coronary artery calcium PRS with AVC >0 strongly suggests significant differences exist in the calcification pathways for AVC and coronary artery calcium.

BACKGROUND:Markers of renal function have been added to the Predicting Risk of Cardiovascular Disease Events and Systematic Coronary Risk Evaluation cardiovascular risk calculators to enhance risk prediction. Here we examine the role of estimated glomerular filtration (eGFR) and urine albumin creatinine ratio (UACR)-and related dichotomous cut points (eGFR <60 mL/minute per 1.73 m2 and albuminuria ≥30 mg albumin/gram creatinine)-for prediction of coronary heart disease, cardiovascular disease (CVD) outcomes (CVD mortality, heart failure, stroke, total CVD), and total mortality, using the MESA (Multi-Ethnic Study of Athersclerosis) calculator, which includes coronary artery calcium scores as a predictor in addition to traditional CVD risk factors. METHODS:The study included 6707 participants without clinical CVD with coronary artery calcium scoring. Cox proportional hazards models, adjusted for covariates including coronary artery calcium, were used to gauge the association of UACR, eGFR, albuminuria, and eGFR<60 with outcomes and change in disease prediction by area under the curve compared with models not including renal variables. Prespecified subgroups-age, sex, race or ethnicity, diabetes-were examined. RESULTS:UACR and albuminuria were significantly associated with most study outcomes; eGFR and eGFR<60 were less consistently related. Albuminuria significantly increased disease prediction for heart failure and for total mortality (P<0.001) but not for other outcomes. When prespecified subgroups were examined, UACR and albuminuria significantly improved prediction for many outcomes in participants >65 years of age, and for all outcomes in participants with diabetes. CONCLUSIONS:When coronary artery calcium is known, albuminuria improves heart failure prediction. Albuminuria and UACR each improve total mortality prediction as well. UACR and albuminuria improve prediction for all outcomes in people with diabetes.

Introduction: Smoking is a major risk factor for atherosclerosis, but its impact is heterogeneous across different vascular beds (e.g., stronger association with peripheral artery disease than coronary disease). However, whether the association of cigarette smoking with vascular calcification is (dis)similar across vascular beds is uncertain. Methods: In 1,961 ARIC participants without a history of coronary heart disease at visit 7 (2018-19), we quantified the associations of pack-years of smoking and years since cessation with coronary artery calcium (CAC) and extra-coronary calcification (ECC) using multivariable logistic regression models. High CAC and ECC (aortic valve, aortic valve ring, mitral valve, ascending aorta, and descending aorta calcification) were defined as Agatston score >75th percentile and were analyzed separately as dependent variables. Results: Pack-years of smoking demonstrated an independent and robust dose-response relationship with CAC, ascending and descending aorta calcification, and aortic valve ring calcification (Table). The association was particularly evident for descending aorta calcification (e.g., adjusted odds ratio [aOR] 3.57 [95%CI 2.46-5.19] for ≥40 pack-years). The results were similar for the duration since smoking cessation, with the most prolonged risk seen for the descending aorta (i.e., even ≥30 years of smoking cessation had OR of 1.34 [1.03-1.47]). Aortic valve and mitral valve calcification demonstrated modest associations with smoking. Conclusions: Cigarette smoking showed a robust association with coronary and extra-coronary calcification, and its association was particularly strong with descending aorta calcification. Our findings further emphasize the harm of smoking on broad ranges of vascular beds and simultaneously highlight unique pathophysiologic mechanisms across different vascular beds and cardiac valves.