Coronary Artery Calcium Research Articles

Coronary Computed Tomography Angiography in Heart Transplant Patients: Current Insights and Future Directions

Cardiac allograft vasculopathy (CAV) remains a significant challenge after heart transplantation, necessitating effective surveillance methods. This review centers around the role of coronary computed tomography angiography (CCTA) in CAV surveillance, given its unique capabilities to visualize and quantify CAV in comparison with other imaging modalities, including invasive coronary angiography and intravascular ultrasound. CCTA has shown good diagnostic performance for detecting and monitoring CAV, exemplified by a higher sensitivity and negative predictive value compared with invasive coronary angiography. Additionally, CCTA can provide valuable functional insights with fractional flow reserve integration. An additional, considerable benefit of CCTA is that it allows for the opportunity to assess other imaging markers of cardiometabolic and general health, including coronary artery calcium score, epicardial fat volume, liver fat, vertebral bone density, and lung density, which allows for a comprehensive assessment of the overall health of the patient.

Impact of tooth loss and patient characteristics on coronary artery calcium score classification and prediction.

This study, for the first time, explores the integration of data science and machine learning for the classification and prediction of coronary artery calcium (CAC) scores. It focuses on tooth loss and patient characteristics as key input features to enhance the accuracy of classifying CAC scores into tertiles and predicting their values. Advanced analytical techniques were employed to assess the effectiveness of tooth loss and patient characteristics in the classification and prediction of CAC scores. The study utilized data science and machine learning methodologies to analyze the relationships between these input features and CAC scores. The research evaluated the individual and combined contributions of patient characteristics and tooth loss on the accuracy of identifying individuals at higher risk of cardiovascular issues related to CAC. The findings indicated that patient characteristics were particularly effective for tertile classification of CAC scores, achieving a classification accuracy of 75%. Tooth loss alone provided more accurate predicted CAC scores with the smallest average mean squared error of regression and with a classification accuracy of 71%. The combination of patient characteristics and tooth loss demonstrated improved accuracy in identifying individuals at higher risk with the best sensitivity rate of 92% over patient characteristics (85%) and tooth loss (88%). The results highlight the significance of both oral health indicators and patient characteristics in predictive modeling and classification tasks for CAC scores. By integrating data science and machine learning techniques, the research provides a foundation for further exploration of the connections between oral health, patient characteristics, and cardiovascular outcomes, emphasizing their importance in advancing the accuracy of CAC score classification and prediction.

Factors associated with lipid lowering therapy in the multi-ethnic study of atherosclerosis.

Lipid-lowering therapy (LLT) plays a central role in managing atherosclerotic cardiovascular disease (ASCVD) risk, but its underuse is reported in over 40% of the qualified population in the United States. Studies on factors, particularly actionable factors associated with guideline-directed LLT are limited. This study evaluated participants from the Multi-Ethnic Study of Atherosclerosis (MESA) on their qualification for LLT at exam 5 (2010-2012) according to the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on cholesterol management. Participants were categorized as on-LLT or off-LLT at the following exam (2016-2018). Multi-variable relative risk (RR) models were used to analyze between LLT usage and factors prior to 2013, including age, gender, race/ethnicity, education level and medical insurance, income, smoking, body mass index (BMI), diabetes, hypertension, and presence of coronary artery calcium (CAC). Among the 2114 participants qualified for LLT at exam 5 with an average age of 70.7, 1,129 (53.4%) were on LLT while 985 (46.6%) were off LLT at exam 6. Black participants were less likely to be on LLT compared to the reference white participants (RR 0.80, 95% confidence interval CI 0.71-0.90). Higher BMI showed borderline significant association with LLT. Comorbidities of diabetes and hypertension were positively associated with LLT use (RR 1.39 and 1.23, 95% CI 1.27-1.52 and 1.10-1.36, respectively). CAC score > 0 as an indicator of subclinical ASCVD was strongly associated with LLT too, independent of other demographic or comorbidity factors (RR 1.38, 95% CI 1.21-1.56). This study identifies key factors influencing LLT use among MESA participants. Black participants were less likely to be on LLT, highlighting healthcare disparities. CAC presence was strongly associated with LLT use, suggesting that CAC measurement could be an actionable factor to improve adherence to LLT guidelines.

Polygenic Risk Scores and Extreme Coronary Artery Calcium Phenotypes (CAC=0 and CAC≥1000) in Adults ≥75 Years Old: The ARIC Study.

Coronary artery calcium (CAC) is heterogeneous in older age and is incompletely explained by traditional atherosclerotic cardiovascular disease risk factors. The extremes of subclinical atherosclerosis burden are strongly associated with either a low or high 10-year risk of incident atherosclerotic cardiovascular disease, respectively. However, the genetic underpinnings of differences in arterial aging remain unclear. We sought to determine the independent association of 2 polygenic scores for coronary heart disease (CHD) with CAC in adults ≥75 years of age. There were 1865 ARIC (Atherosclerosis Risk in Communities) participants who underwent genetic testing at visit 1 (1987-1989) and CAC scans at visit 7 (2018-2019). In the primary analysis, an externally derived multi-ancestry polygenic CHD risk score was calculated for both White and Black participants. Results were confirmed using a separate ARIC-derived polygenic CHD risk score, including ≥6 million variants computed for White participants. We used multivariable logistic regression models to assess the association of polygenic CHD risk with CAC, after adjusting for baseline, time-averaged lifestyle, traditional risk factors, and local ancestry principal components. In the primary analysis, the average age was 80.6 years old, 61.6% were women, and the median CAC score was 246 (189 participants with CAC=0, 364 participants with CAC≥1000). Compared with persons below the 20th percentile of polygenic CHD risk, persons with polygenic-CHD risk above the 80th percentile had 82% lower odds of having CAC=0 (odds ratio, 0.18 [95% CI, 0.09-0.37]) and had >4-fold higher odds of CAC≥1000 (odds ratio, 4.77 [95% CI, 2.88-7.88]). On a continuous scale, each SD increment increase in the polygenic risk score was associated with a 78% higher CAC score. Results were nearly identical using a second confirmatory polygenic CHD risk score in White participants. Polygenic CHD risk is robustly associated with a lower prevalence of CAC=0 and a higher prevalence of CAC≥1000 in adults ≥75 years of age, beyond lifestyle and traditional risk factors. These results suggest a heritable contribution to distinct healthy and unhealthy arterial aging phenotypes that persist throughout the life course.

Should coronary artery calcification be the mammogram of the heart? Precrime policing in atherosclerotic coronary artery disease

Should coronary artery calcification be the mammogram of the heart? Precrime policing in atherosclerotic coronary artery disease

Coronary artery calcium on lung cancer radiation planning CT aids cardiovascular risk assessment.

Patients with non-small cell lung cancer (NSCLC) undergoing thoracic radiation are at high cardiovascular risk. Semiquantitative assessment of coronary artery calcification (CAC) on baseline planning non-gated chest computed tomography (CT) scans may help further risk stratify patients. This study aimed to characterize the association between CAC and major adverse cardiovascular events (MACE; myocardial infarction or stroke) and assess the utility of semiquantitative assessment of CAC. Patients with NSCLC with non-contrast planning chest CT scans were evaluated for CAC. Planning scans were visually graded using the CAC-DRS method, stratifying patients into no, mild, moderate, and severe CAC groups. Demographics, comorbidities, and radiation treatment characteristics were gathered, and CAC groups were assessed for the incidence of MACE after initiation of radiation therapy. Out of 137 patients, 39 patients had no CAC, and 98 patients had any CAC (38 with mild CAC, 34 with moderate CAC, and 26 with severe CAC). There was 1 MACE event in the no CAC group and 11 in patients with any CAC. The presence of CAC was associated with increased MACE compared to no CAC (p = 0.034). Semiquantitative CAC analysis correlated with formal CAC scoring. There is a significantly lower incidence of MACE in patients with no CAC on planning CT compared to patients with higher burdens of CAC. CAC burden is an important risk factor for adverse cardiovascular events in patients with NSCLC undergoing thoracic radiation. Semiquantitative CAC scoring may be a useful proxy when formal CAC scoring is unavailable.

Abstract 4134911: Coronary Artery Calcium Predicts Cardiovascular Events in Individuals with Controlled Atherosclerotic Risk Factors: A Multi-Cohort Study

Background: There is residual risk of atherosclerotic cardiovascular disease (ASCVD) that remains despite adequate risk factor (RF) control. Coronary artery calcium (CAC) has demonstrated value in ASCVD risk stratification. We evaluated the value of CAC in identifying residual risk of ASCVD events among those with traditional RF control. Methods: Participants without clinical ASCVD were pooled from the Multi-Ethnic Study of Atherosclerosis, Heinz Nixdorf Recall Study, Framingham Heart Study, and Jackson Heart Study. RF control was classified as “guideline-concordant” and “optimal” (Figure 1). Participants were stratified by the number of controlled RFs at baseline and CAC score (CAC = 0, 1-99, ≥100). Cox proportional hazards models examined the association between CAC and incident ASCVD events. Results: The study included 14,780 individuals (mean age 58 years (SD: 11), 54% female, 59% White, 27% Black, 50% CAC = 0). Over a median follow-up of 14.6 years, there were 1,441 incident ASCVD events. The distribution of CAC and ASCVD event incidence is shown in Panel A; 10% of those with 3 optimal RFs and 19% of those with 3 guideline-concordant RFs controlled had CAC > 100. The rate of ASCVD events decreased with more RFs controlled and increased with higher CAC. Overall, optimal RF control was associated with lower ASCVD event rates compared to guideline-concordant control. At every level of RF control, CAC > 100 was associated with increased HRs for incident ASCVD (Panel B). Those with CAC ≥ 100 and controlled RFs experienced ASCVD rates numerically comparable to or exceeding those with uncontrolled RFs but CAC = 0 (Panel A). Adjusted HR (95% CI) for ASCVD events with CAC > 100 compared to CAC = 0 was 5.0 (2.0, 12.9) in optimal RF control and 3.7 (2.6, 5.4) in guideline-concordant RF control. Conclusion: There is significant heterogeneity in residual ASCVD risk among those with optimal or guideline-concordant traditional RF control and CAC can help identify this risk. Irrespective of RF control, a higher CAC burden was associated with increased ASCVD risk. Future studies could use CAC testing to identify those with higher residual ASCVD risk despite effective traditional RF control to target for novel therapies.

Abstract 4123501: Coronary Artery Calcium in Asymptomatic Arabs: Prevalence and Distribution

Background: Coronary artery calcification (CAC) is an established marker of subclinical atherosclerosis and predictor of cardiovascular events. Despite extensive research on CAC in various populations, data focusing on Arab populations, particularly asymptomatic individuals, is limited. Methods: We analyzed data from 2,739 asymptomatic self-referred Arabs included in the Kuwait Hospital Awareness Campaign for Early Detection of Atherosclerotic Coronary Artery Disease study. Traditional CVD risk factors were assessed, and ECG-gated cardiac CT imaging was used to measure using the Agatston method. Results: The mean±SD age of the sample was 48.4±9.8 and 41.8% were females. Kuwaitis comprised 61.6% of the sample, Egyptians 20.5%, and Levantines 16.4%. CAC was >0 in 32.3%, ≥100 in 11.5%, and ≥400 in 4% of the sample. CAC prevalence increased with age and was higher in Arab males with a 12 year earlier onset in males than females. The 50 th , 75 th , 90 th and 95 th percentiles of CAC for Arab females were, 0, 0, 39, and 167 and for males were 0, 25, 191, and 470, respectively. The presence of CAC was associated with traditional risk factors including diabetes, smoking, hypertension and LDL-C. Levantines and Kuwaitis had the highest prevalence of CAC and CVD risk factors; these groups were independently associated with higher CAC levels. In all age and sex subgroups except older males, the 75 th percentiles of CAC were below 100. Therefore, a larger number of subjects were identified as high risk using the 75 th age- and sex-specific CAC percentile than with CAC≥100 (19.3% vs 11.5%). Conclusion: This study provides comprehensive insights into subclinical atherosclerosis in asymptomatic Arabs, emphasizing the importance of early risk stratification for primary CVD prevention using CAC scoring. Our findings highlight that Arabs are not a homogeneous group with regards to prevalence of CVD risk factors and CAC. This study underscores the need to consider both absolute and age- and sex-specific CAC percentile values to inform primary prevention strategies in this predominantly young population.

Abstract 4138472: Bioactive Oxylipins Predict Coronary Artery Calcification Severity in Heart Failure with Preserved Ejection Fraction

Background: Inflammation is a common underlying cause in atherosclerosis and heart failure with preserved ejection fraction (HFpEF). Recent data have highlighted the critical role of circulating bioactive polyunsaturated fatty acid oxidized lipids, or oxylipins, in initiating and resolving inflammation. We sought to study the role of oxylipins in predicting coronary artery calcification (CAC) in HFpEF. Hypothesis: We hypothesize that oxylipins can predict and distinguish CAC severity in HFpEF patients. Methods: We collected venous blood samples during right heart catheterization from 71 HFpEF patients. We categorized patients by CT-based CAC severity: none (control; n=16), mild (<25% CAC, n=7), moderate (26-50% CAC, n=22), and severe (>50% CAC, n=26). We measured 143 oxylipins in all study participants using mass spectrometry. Along with unpaired T-tests, machine learning analysis was used to determine lipid permutation importance and evaluate predictive accuracy for CAC severity. Results: Demographic variables showed no significant differences between groups. Increased total cholesterol (p=0.031) and low HDL (p=0.011) were associated with CAC severity. Pro-inflammatory 12(S)-HHTrE (a degradation product of TxA2) levels were elevated in severe CAC vs control (p=0.031). The inactivated anti-inflammatory 5,6 DiHETrE levels were higher in moderate CAC vs control (p=0.032) and severe CAC vs control (p=0.021). Out of 143 oxylipins, the panel of LTB5, 11(R)-HEDE, 20-HETE, 5-HEPE, 11(12)-EpETrE, 14(15)-EpETE, 19,20-DiHDoPE, PD1, and 5-oxoETE were the most significant predictors of severe vs non-severe (none, mild, moderate) CAC, with 88.88% predictive accuracy. Conclusion: In HFpEF patients, CAC severity can be predicted by a novel panel of circulating, bioactive venous oxylipins.

Abstract 4137718: Coronary Artery Calcium for Risk Stratification of Heart Failure Mortality

Background: There is increasing interest in predicting heart failure (HF), a major cause of morbidity and mortality that exerts a significant financial burden. The role of coronary artery calcium (CAC), an accessible and inexpensive test, in predicting long-term HF mortality amongst asymptomatic adults remains unknown. Objectives: To determine if CAC burden is associated with HF-related mortality in the primary prevention population. Methods: The study included 66,636 primary prevention patients from the Coronary Artery Calcium Consortium. Multivariable competing risks regression was used to assess the association between CAC and HF-related mortality adjusting for demographics and traditional risk factors. Results: The mean age was 54.4 years, 67% male, 89% white, and 55% had CAC >0. A total of 260 HF-related mortality events were observed during a median follow up of 12.5 years, 75.3% of which occurred among those with a baseline CAC score >100. Compared with a CAC = 0, there was a stepwise higher risk (P < 0.005) of HF mortality for CAC 1-100 (subdistribution hazard ratio [SHR]: 2.27; 95% CI: 1.3-3.99), 100-400 (SHR: 3.68; 95% CI 2.1-6.43), and >400 (SHR: 7.05; 95% CI 4.05-12.29). This increasing risk of HF mortality across higher CAC scores persisted across age groups, sex, and in the intermediate and high-risk groups as calculated by the pooled cohort equation (PCE) and the PREVENT equation. Conclusions: Higher CAC is associated with increasing incidence of long-term HF-related mortality in the primary prevention population, particularly intermediate and high-risk patients. Early preventive approaches in patients with high CAC must focus on preventing heart failure and ASCVD with lifestyle changes and medications.

Abstract 4138473: Detailed Lipoprotein Profiling in Assessing Coronary Calcium Score Progression and Atherosclerotic Risk

Background: Coronary calcium scoring (CCS) evaluates atherosclerotic burden and cardiovascular risk, correlating with coronary artery disease (CAD) severity. Advances in Nuclear Magnetic Resonance ( 1 H-NMR) spectroscopy for lipoprotein fraction analysis highlight precise atherogenic lipid parameter estimation. Enhanced lipid testing, including sub-fractionation assays, improves risk assessment and identifies new biochemical markers for CAD burden. Hypothesis: Specific lipid fractions and subfractions are significantly associated with CCS progression, serving as biochemical markers of CAD progression. Aim: To evaluate the association between lipid fractions and subfractions with CCS progression, aiming to improve CAD risk stratification. Methods: This study used data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). CCS progression was any positive change in CCS values over 5 years. High-field 1 H-NMR spectroscopy assessed lipoprotein fractions and subfractions, including plasma concentration, particle size, cholesterol, and triglyceride content. Descriptive and inferential statistics compared baseline characteristics. Multivariable binary logistic regression models, both unadjusted and propensity score-adjusted, assessed associations between plasma levels of lipoprotein fractions and CCS progression. Statistical significance was set at p <0.05. Results/Data: In this study of 2,986 participants, 1,008 (33.8%) experienced CCS progression over 5 years. Significant associations were found between plasma lipoprotein fractions and CCS progression. Large, medium, and very small TRLP (89-37 and 29-24 nm) were linked to increased CCS risk, while small TRLP (36-30 nm) had an inverse association. Small cLDLP (20.4-19 nm) were directly associated with CCS progression, while medium and large cLDLP (23-20.5 nm) were inversely associated. Small cHDLP (7.4-8.0 nm) increased CCS risk, whereas medium to large cHDLP (8.1-13.0 nm) had an inverse association. Specific HDL subspecies (H7P to H3P, 12.0-8.7 nm) were inversely associated with CCS progression, while H2P and H1P (7.8-7.4 nm) increased CCS risk. TRLZ (30-100 nm) levels were positively associated with CCS progression, whereas LDLZ (19-22.5 nm) and HDLZ (7.1-13 nm) were inversely associated. Conclusion(s): Plasma levels of specific lipoprotein fractions and subfractions are associated with CCS progression, providing insights into the complexity of lipoprotein characteristics in CAD.

Abstract 4134977: Utility of Coronary Artery Calcium Scoring in Low-Risk Patients: the Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: Coronary artery calcium (CAC) scoring is a powerful tool for atherosclerotic cardiovascular disease (ASCVD) risk assessment. Guidelines recommend consideration of CAC scoring in intermediate risk patients, but it’s utility in low and borderline risk patients is less clear. Methods: We used data from 2,894 participants from MESA with low (<5%) or borderline (5-<7.5%) 10-year ASCVD risk defined by the pooled cohort equations (PCE). We evaluated the association between CAC score and coronary heart disease (CHD) and ASCVD risk using multivariable adjusted Cox proportional hazard models. We also evaluated if the addition of CAC to the pooled cohort equations (PCE) improved risk prediction using Harrell’s C-index and net reclassification improvement (NRI). Results/Data: Mean age was 54.1 ± 5.8 years with 66.9% women. Among low-risk individuals, the ASCVD event rate was 3.3% with CAC=0, and 7.8% with CAC>0, and 4.7% vs. 11.4% among borderline-risk individuals. Natural-log transformed CAC score was associated with increased ASCVD risk in low-risk (HR 1.35, 95% CI 1.22-1.50) and borderline-risk (HR 1.29, 95% CI 1.15-1.45) individuals. Similar results were seen for CHD with higher HRs ( Table 1 ). The addition of CAC to the PCE improved the C-index (SE) among low/borderline risk individuals from 0.620 (0.023) to 0.671 (0.024). Continuous NRI was also significant with the addition of CAC to the PCE in low/borderline risk (0.422, 95% CI 0.248-0.611). Greater improvement was seen for CHD ( Table 2 ). Conclusions: The presence of CAC in low and borderline risk individuals is associated with increased ASCVD and CHD risk. The addition of CAC scoring to the PCE improved risk prediction in low and borderline risk individuals, suggesting potential clinical utility in this population.

Abstract 4124606: Disparities in statin use following identification of Coronary Artery Calcium

Introduction: Coronary artery calcium (CAC) scoring is a useful tool for risk stratification in asymptomatic individuals, and guidelines recommend statin use in individuals with CAC. A growing body of research has aimed to identify and mitigate health disparities and their relation to CVD risk. Likewise, studies have highlighted social determinants of health (SDOH) that contribute to health disparities in CVD. We sought to extend this work by evaluating whether disparities exist with regards to statin use after identification of CAC within the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: The sample consisted of all MESA participants with baseline CAC >0, not already on statin therapy, and without prior CVD events (n=2665). The association between race/ethnicity, age, sex, primary language, and an aggregate SDOH score with statin prescription at short (exam 2, median 1.6 year) and long (exam 5, median 9.4 year) term follow-up was evaluated in logistic regression models with adjustment for traditional CVD risk factors. The SDOH score was created from 14 components which covered the 5 general domains described in the Healthy People 2030 initiative (Figure 1). Results: Rates of statin prescription after CAC identification by race/ethnicity, language, and SDOH score tertile are shown in Figure 2. At short-term follow up, those with a higher SDOH score (worse burden) (OR 0.39, 95% CI 0.16-0.91), Hispanic / Latino participants (OR 0.59, 95% CI 0.40-0.85) and Spanish speaking participants (OR 0.51, 95% CI 0.30-0.83) were less likely to report statin use following CAC identification. At long-term follow up, Black participants (OR 0.71, 95% CI 0.52-0.96), Chinese participants (OR 0.58, 95% CI 0.39-0.86) and Chinese speaking participants (OR 0.50, 95% CI 0.33-0.76) were also less likely to report statin use following CAC identification, and a trend was noted for SDOH score (OR 0.53, 95% CI 0.26-1.09). Conclusion: This study identifies disparities in statin use after identification of CAC by race/ethnicity, language and social determinants of health. Future studies should investigate underlying reasons for these disparities and potential interventions to reduce disparities in cardiovascular care.

Abstract 4136032: Digital Biomarkers Associated With Coronary Artery Calcium And Traditional Risk Factors Extracted From Facial Photos Through Multi-Label Deep Learning For Detecting Coronary Artery Disease

Background: Biomarkers like coronary artery calcium (CAC) and traditional risk factors are well-validated for coronary artery disease (CAD) assessment but not always available, and with limited workup efficiency and potential radiation risk. Facial features contain biological information related to atherosclerosis. Aims: We aim to extract CAC and traditional risk factor-associated digital biomarkers from facial images and evaluate their value in predicting CAD status compared with conventional clinical approaches. Methods: Suspected individuals referred for confirmatory CAD evaluation across nine centers were included. Participants in one center constituted the derivation set. External validation included one dataset of participants from a different time period in the derivation center and the other dataset from the other eight centers. We developed a multi-label deep-learning model to extract digital biomarkers from facial photos based on a multi-dimensional label of CAC score and eight traditional risk factors to comprehensively represent coronary atherosclerosis risk profile. The extracted digital biomarkers were evaluated for both effectiveness in reflecting components of the multi-dimensional label and clinical value in predicting obstructive CAD. Results: A total of 13248 facial photos from 3312 eligible participants (mean age, 58.5 years; 517 [25.9%] female) were included. In external validation, a set of digital biomarkers (FacialCAD) were extracted, effectively reflecting components of the multi-dimensional label, especially for CAC stratification (CAC>0, AUC 0.919 [0.885 – 0.949]; CAC≥100, AUC 0.906 [0.876 – 0.933]) and nearly perfect prediction for the age and sex. The performance of the FacialCAD in predicting obstructive CAD (AUC 0.721 [0.694–0.748]) significantly outperformed two guideline-recommended CAD models (0.721 vs. 0.653, P<0.001; 0.721 vs. 0.686, P=0.032), with further significant improvement when combined with these models (△AUC= +0.085, P<0.001; △AUC= +0.068, P<0.001). Conclusion: FacialCAD, a set of CAC and risk factors-associated novel digital biomarkers extracted from facial images, exhibited superior and incremental value to conventional clinical approaches in predicting CAD status.

Abstract 4138647: Opportunistic Screening for Cardiovascular Risk Using Chest X-Rays and Deep Learning: Associations with Coronary Artery Disease in the Project Baseline Health Study and Mass General Brigham Biobank

Introduction/Background: We previously demonstrated that an open-source deep learning model (CXR-CVD Risk) can predict 10-year major adverse cardiovascular events (myocardial infarction&stroke), based on a chest radiograph image (CXR). As deep learning models are black boxes, establishing the biological processes the model captures to predict risk may help build understanding and trust in the model. Research Questions/Hypothesis: To test associations between deep-learning derived CXR-CVD Risk and markers of cardiovascular disease including coronary artery calcium (CAC) and stenosis ≥50% on CT, systolic blood pressure (SBP), ankle brachial index (ABI), and prevalent myocardial infarction and stroke. Methods/Approach: We conducted external validation of CXR-CVD-Risk in two cohorts: 1) 2,097 volunteers in the Project Baseline Health Study (PBHS) and 2) 1,644 Mass General Brigham Biobank (MGBB) patients. The CXR-CVD-Risk model estimated 10-year cardiovascular event risk (probability between 0 and 1) from a CXR image. We calculated linear associations with SBP, ABI, and the logarithm of coronary artery calcium and odds ratios for prevalent hypertension, myocardial infarction, stroke, and, in the MGBB, coronary artery stenosis ≥50%. Analyses were adjusted for age, BMI, sex, smoking status, and enrolling site. Results/Data: CXR-CVD-Risk was associated with CAC in both populations (PBHS: 1.11-fold increase, 95% CI: [1.07-1.16]; MGBB: 1.03-fold increase [1.01-1.05] in CAC per 1% increase in CXR-CV-Risk). CXR-CVD-Risk was also associated with SBP (0.59 mmHg increase [0.24-0.93] in SBP per 1% increase in CXR-CV-Risk), history of hypertension, history of myocardial infarction, and stroke. There was an inverse association with ABI (0.010 decrease [0.005-0.014] in ABI) in the PBHS. In the MGBB, CXR-CVD-Risk was associated with coronary artery stenosis ≥50% (OR = 1.004 [1.002-1.007]). All estimates are after covariate adjustment. Conclusion: This deep learning CXR risk score was associated with coronary artery disease (calcium score and stenosis ≥50%), CVD risk factors, and prevalent CVD. Opportunistic screening using CXRs in the electronic record can identify patients at high risk of CVD who may benefit from prevention.

Abstract 4131815: The Prevalence of Normal Coronary Arteries as Determined by a Coronary Artery Calcium Score of Zero Amongst Subjects with Diabetes Mellitus

Background: The CDC reports that in 2021, 11.6% of the American population had diabetes mellitus (DM). Past literature has shown diabetes to be a significant risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). Research Question/Goal: Using data obtained through Computed Tomography Angiography (CTA), we aim to distinguish the risk factors associated with a coronary artery calcium (CAC) score of zero in subjects with DM and to identify the prevalence of non-calcified plaque in individuals with this score. Methods: We performed a retrospective study of patients with DM, who underwent CAC and CTA screenings from October 2004 to January 2024 at our center in Torrance, California to examine CTA outcomes in those with CAC Score of zero and greater than zero. Results: Among the cohort of 2,763 subjects with DM, the average age was 63.8±12.2 years, 62% male. Within this cohort, 465 (17%) subjects had a CAC Score of zero compared to 2,298 subjects with a CAC Score greater than zero with a median score of 428 (Interquartile range (IQR) 91-1267). DM subjects with CAC Score of zero were significantly younger (53.0±13.9 versus 66.0±10.6: p<0.001), were more likely to be female and had significantly lower rates of hypertension (57% versus 76%: p<0.001), and hyperlipidemia (63% versus 76%: p<0.001). In DM subjects with CAC Score of zero, 133 (29%) had a total plaque severity score of 1 or greater (median 1, IQR 1-2) while 332 (71%) had normal coronaries on CTA. Conclusions: A significant percentage of subjects with DM were determined to have a CAC score of zero. Subjects with normal coronary arteries were more likely to be younger, female, and/or absent of other chronic diseases such as hypertension and hyperlipidemia. Although age and sex are nonmodifiable risk factors of ASCVD, limiting the comorbid conditions associated with DM may be beneficial in preventing ASCVD in individuals with diabetes.

Abstract 4137687: Rotational atherectomy combined with cutting balloon before stent implantation for patients with severely calcified coronary lesions: A meta analysis

Background: Rotational atherectomy (RA) has been proven to treat coronary artery calcification (CAC) during percutaneous coronary intervention (PCI). Cutting balloons (CBs) are modified balloons (MB). Purpose: We aim to assess the safety and efficacy of RA followed by CB angioplasty (ROTACUT) before stent placement in CAC. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies, which were retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through January 2024. We used Stata version 17 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI). Results: We included eight studies with a total of 846 patients. There was no significant difference between ROTACUT and RA + bare balloons in major adverse cardiovascular events (MACE) (RR: 0.60 with 95% CI [0.31, 1.16], P= 0.13), the incidence of cardiac death (RR: 1.32 with 95% CI [0.42, 4.14], P= 0.64), the incidence of target vessel revascularization (TVR) (RR: 1.89 with 95% CI [0.40, 8.84], P= 0.42), the incidence of target lesion revascularization (TLR) (RR: 0.83 with 95% CI [0.39, 1.79], P= 0.64), procedural duration (MD: 0.78 with 95% CI [-4.68, 6.24], P = 0.78), incidence of stent thrombosis (RR: 0.81 with 95% CI [0.22, 2.95], P= 0.75), and the incidence of any procedure-related complications (RR: 0.86 with 95% CI [0.42, 1.75], P= 0.68). Conclusion: ROTACUT and RA + bare balloons demonstrated similar efficacy and safety profiles in terms of MACE, cardiac death, TVR, TLR, procedural duration, stent thrombosis, and all safety outcomes.

Abstract 4132875: Living Address Environmental Biotope Affects the Risk of Coronary Obstruction and Myocardial Ischemia Detected by Coronary Computed Tomography

Background: Several studies reported positive associations between air and noise pollution exposure and coronary artery calcification, but environmental effects on coronary obstruction and flow remain largely unknown. Hypothesis: Distance to road and airport, air pollution, and residential green space are linked to coronary artery obstruction and myocardial ischemia. Low CV-risk patients develop coronary obstruction due to environmental factors, while high-risk patients are more prone to develop myocardial ischemia. Methods: Consecutive patients screened by coronary CT angiography for stable chest pain between 01/01/2019 and 31/12/2020 were included in a registry. Distance to airport and major road, and exposure to PM2.5, NO 2 and normalized difference vegetation index (NDVI) were modelled at patients’ living address. Risk of obstructive coronary artery disease (OCAD, stenosis ≥50%) and abnormal fractional flow reserve (FFR CT <80%) was assessed using propensity score (PS)-adjusted logistic regression. Subgroup analysis was performed according to gender and Framingham CV-risk categories. Results: We enrolled 2620 patients, including 420 (16%) FFR CT analyses. OCAD was reported in 518 (20%) patients and abnormal FFR CT in 276 (11%). People with OCAD lived closer to the airport (10.841 [7.869-19.022] km vs. 12.297 [8.691-22.843] km, p<0.001). Distance to airport decreased OCAD risk (OR 0.983, 95%CI 0.974-0.992, per 1 km) in univariate analysis, with the association present in male, female, and low-risk patients. After PS-adjustment, a trend of association was present between airport distance and abnormal FFR CT risk (OR 0.986, 95%CI 0.969-1.003, per 1 km). Road distance tended to decrease OCAD risk in univariate and PS-adjusted analysis, in the general (OR 0.928, 95%CI 0.808-1.309; and OR 0.928, 95%CI 0.840-1.021, per 1 km) and high-risk population. NO 2 exposure tended to increase OCAD risk in univariate analysis (OR 1.012, 95%CI 0.997-1.027, per 1 µg/m 3 ), with the association only present in female patients, and disappearance after PS-adjustment. PM2.5 exposure showed no associations, while NDVI tended to increase OCAD risk in low-risk patients after PS-adjustment. Conclusion: Residential distance to airport is the major risk component compared to other urban exposome factors studied in this epidemiological observation. Green space tends to exert a cardioprotective effect in low-risk patients, whereas living close to major road worsens the risk in high-risk patients

Abstract 4141474: Impact of Serum 5-Hydroxytryptophan Levels on Coronary Artery Calcification Severity in Acute Coronary Syndrome Patients: Insights from the Microbiota-Gut-Brain Axis

Background: 5-Hydroxytryptophan (5-HTP) has shown positive clinical effects on various neuropsychiatric and metabolic disorders, particularly depression. While it is known to increase serotonin levels in the brain and gastrointestinal tract, its pharmacology remains largely unexplored. Additionally, 5-HTP influences the mouse gut microbiome, which is closely linked to depression through the "microbiota-gut-brain axis." However, the role of 5-HTP in vascular disease is not well understood. This study aimed to investigate the potential correlation between serum 5-HTP levels and the severity of coronary artery calcification (CAC) in patients with acute coronary syndrome (ACS). Methods and Results: This study included 183 ACS patients who underwent coronary angiography. The severity of coronary calcification was recorded, and serum 5-HTP levels were measured after the coronary event. The study period was from February 4, 2009, to August 9, 2020. The primary exposure variable was 5-HTP levels, and the primary outcome was the severity of coronary calcification assessed through fluoroscopy. Logistic regression was used to determine the association between 5-HTP levels and calcification severity, adjusting for age, gender, smoking status, chronic kidney disease, hyperlipidemia, and diabetes. Odds ratios (OR) and 95% confidence intervals (CI) measured the strength of associations, with statistical significance set at p < 0.05. High 5-HTP levels were significantly associated with more severe calcification (p = 0.04, OR = 3.3, 95% CI = 2.6 to 40686.5). For other factors, the OR for smokers was 0.97 (0.53 to 1.77); dyslipidemia 0.91 (0.5 to 1.63); hypertension 1.57 (0.87 to 2.82); male gender 1.35 (0.45 to 4.01); age 1.07 (1.03 to 1.10); diabetes 1.24 (0.67 to 2.31); chronic kidney disease 1.07 (0.33 to 3.50). After adjusting for conventional risk factors, the association between 5-HTP and calcification remained significant (p < 0.05). Conclusion: Higher 5-HTP levels are positively associated with greater severity of coronary artery calcification. This correlation persists even after adjusting for conventional risk factors.

Abstract 4136289: Aortic Valve Calcium as a Predictor of Chronic Kidney Disease in a Multi-Ethnic Cohort: The MESA Study

Background: Aortic valve calcium (AVC) is associated with an increased risk of cardiovascular disease, non-cardiovascular disease such as dementia, and all-cause mortality. Traditional atherosclerotic cardiovascular disease risk factors are associated with both AVC and chronic kidney disease (CKD), but whether there is an association between AVC and CKD is unknown. Objectives: To ascertain whether AVC quantified by cardiac CT scanning is independently associated with the long-term risk of incident CKD among individuals without a previous history of cardiovascular disease. Methods: We examined 6,346 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac CT scanning at Visit 1 (2000-02) and had an eGFR of ≥ 60 mL/min/1.73 m 2 . AVC was quantified using the Agatston method and categorized as 0, 1-99, and ≥100. Incident CKD was defined as an eGFR < 60 mL/min/1.73 m 2 accompanied with an at least 40% decline in eGFR from baseline, and/or a diagnosis of CKD and indicators of end stage renal disease extracted from hospital records using the International Classification of Disease (ICD) codes. We performed Kaplan-Meier survival curve analyses along with multivariable Cox proportional hazard regression models, adjusted for age, gender, race/ethnicity, highest level of education and traditional cardiovascular risk factors along with coronary artery calcium (CAC), lipoprotein (a) (Lp[a]), and the APOE-ε4 genotype to examine the association between AVC (categorical and log-transformed) and incident CKD. Results: Participants had a mean age 62.2±10.1 years, 53% were women, and AVC >0 was present in 795 (12%) participants. During a median follow-up time of 16.9 years, 982 (15%) participants developed incident CKD. AVC examined as a continuous variable was associated with a significantly increased risk of developing CKD (per log-unit [AVC+1] HR 1.06 [95% CI: 1.02-1.10]; p = 0.005). There was a stepwise increased risk for CKD with higher AVC levels ( Figure ). Similarly, in the multivariable adjusted Cox models, participants with AVC ≥100 had a higher risk of incident CKD, compared with the AVC=0 group (HR 1.48 [95% CI: 1.15-1.89]; p = 0.002). The observed associations remained after further adjusting for CAC score ( p = 0.024), Lp (a) ( p = 0.004), and the APOE-ε4 genotype ( p = 0.004). Conclusions: In a multi-ethnic cohort of participants free of CKD at baseline, AVC was independently associated with a higher risk of incident CKD.