Coronary Artery Calcium Score 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.

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 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 4136403: Impact of Coronary Artery Calcium Scores on Cardiovascular Risk and Preventive Therapies: A Systematic Review and Meta-Analysis

Introduction: Coronary artery calcium (CAC) serves as a key marker of atherosclerosis and is widely utilized in the noninvasive evaluation of coronary artery disease. We aim to compare cardiovascular risk outcomes and the likelihood of initiating or continuing pharmacological and lifestyle preventive therapies in asymptomatic and symptomatic patients with a CAC score greater than zero and those with a CAC score of zero with no established diagnosis of coronary artery disease. Methods: We performed systematic searches of PubMed, Scopus, Google Scholar, Cochrane Central, and ClinicalTrials.gov from inception to May 2024. Our search focused on randomized controlled trials and observational studies comparing outcomes between patients with a CAC score greater than zero and those with a CAC score of zero. Results: We included 53 observational studies, incorporating data from 210,672 asymptomatic and 32,477 symptomatic patients. Over a mean follow-up duration of 8.6 years, we observed that a CAC score greater than zero significantly correlated with an elevated risk of major adverse cardiovascular events (MACE) (OR: 5.58; 95% CI: 4.05–7.69; P < 0.00001). This association extended to all-cause mortality (OR: 3.90; 95% CI: 2.78–5.48; P < 0.00001), myocardial infarction (OR: 4.01; 95% CI: 3.45–4.65; P < 0.00001), and the need for revascularization (OR: 11.90; 95% CI: 6.82–20.78; P < 0.00001). Patients with a CAC score greater than zero were more likely to commence and continue aspirin therapy (OR: 2.45; 95% CI: 1.56–3.83; P < 0.0001 for initiation and OR: 1.71; 95% CI: 1.31–2.23; P < 0.0001 for continuation). Similar trends were noted for lipid-lowering medications (OR: 2.44; 95% CI: 1.57–3.79; P < 0.0001 for initiation and OR: 2.48; 95% CI: 1.53–4.01; P = 0.0002 for continuation), as well as the initiation of blood pressure medications (OR: 1.94; 95% CI: 1.61–2.33; P < 0.00001). Furthermore, a CAC score greater than zero was linked to increased adoption of lifestyle modifications, including enhanced physical activity (OR: 1.84; 95% CI: 1.41–2.41; P < 0.00001) and dietary changes (OR: 1.94; 95% CI: 1.52–2.49; P < 0.00001). Conclusion: Patients with elevated CAC scores are more likely to initiate and continue preventive pharmacological therapies and adopt beneficial lifestyle modifications. These findings underscore the importance of CAC scoring in guiding the management and prevention of cardiovascular disease in both asymptomatic and symptomatic populations.

Abstract 4137782: Fibrinogen-to-Albumin Ratio Does Not Correlate with Comprehensively Assessed Coronary Artery Disease Severity or High-Risk Plaque Features on Coronary Computed Tomographic Angiography

Background: Fibrinogen-to-albumin ratio (FAR) has been proposed as a readily available inflammatory biomarker associated with coronary artery disease (CAD). However, its association with CAD severity and prognosis has predominantly been assessed in patients with acute coronary syndromes (ACS). The Leiden score is a validated comprehensive measure of CAD incorporating stenosis proximity, severity, and plaque type that independently predicts cardiovascular events. Whether FAR is associated with Leiden score or high-risk plaque features on coronary computed tomographic angiography (CCTA) in stable outpatients is unknown. Methods: Adult outpatients undergoing clinically indicated CCTA were enrolled (5/2021-9/2023) in a prospective study assessing the relationship of plaque to immune markers and provided same-day pre-scan peripheral venous blood samples. CCTAs were post-processed and analyzed by the consensus of two expert readers blinded to clinical data using a 17-segment model to determine coronary artery calcium (CAC), Leiden score, and high-risk plaque features. Patients were grouped by FAR (quartiles), Leiden score (<5, 5-20, >20), and CAC score (0, >0-100, >100-300, >300-1000, >1000). Numerical variables were compared via Wilcoxon and Kruskal-Willis tests. Spearman correlation was calculated between FAR and Leiden score. Results: Of 284 patients, 53.8% were male, 86.7% were white, and 58.8% were on a statin (Table 1). Median FAR was 70.3 mg/g, 64.0% had a non-zero CAC score, and 25.0% had at least one segment with one high-risk plaque feature. Across quartiles of FAR, there was no difference in Leiden score (5.8 (IQR: 0.0-18.5), 12.4 (3.1-20.7), 8.0 (0.0-19.9), 6.8 (0.0-21.1), p=0.50) or probability of having at least one segment with at least one (29.6%, 23.9%, 23.9%, 22.5%, p=0.69) or two (18.3%, 14.1%, 12.7%, 15.5%, p=0.66) high-risk plaque features. There was no correlation between FAR and Leiden score (R=0.03, p=0.66). There was no difference in FAR when stratified by Leiden score (Table 1, p=0.53), CAC score (Table 2, p=0.50), or number of segments with at least one high-risk plaque feature (Table 3, p=0.18). Conclusion: In a prospective cohort of adult outpatients across a wide spectrum of CAD burden with high rates of baseline statin use, FAR was not associated with CAD or presence of high-risk plaque features on CCTA. Further evaluation of its role as an inflammatory biomarker in larger populations, particularly patients without ACS, is required.

Abstract 4122389: Accumulation of Epicardial Adipose Tissue as a Marker of Diastolic Dysfunction in Patients With Preserved Left Ventricular Ejection Fraction Undergoing Coronary Computed Tomography Angiograph

Background: Left ventricular diastolic dysfunction (LVDD) plays a major role in the pathophysiology of progression to heart failure with preserved left ventricular (LV) ejection fraction (EF). Although epicardial adipose tissue (EAT) is attracting attention for the underlying pathophysiology, whether increased EAT and coronary plaque burden are associated with LVDD is unclear in patients with chronic coronary artery disease (CAD) and preserved LVEF. Aims: To investigate the association between LVDD and EAT accumulation in chronic CAD patients with preserved LVEF. Methods: We included three hundred fourteen chronic CAD and preserved LVEF patients without history of heart failure (mean age: 66±13 years; 48% female). Thoracic tissue doppler echocardiography (TTDE) analysis included LVDD parameters, including left atrial volume index (LAVI), e’, E/e’ and tricuspid regurgitation (TR) velocity. LVDD was defined according to the American Society of Echocardiography guidelines. Coronary computed tomographic angiography (CCTA) analysis included EAT volume index (EAVi), coronary artery calcium score (CACS), and coronary plaque volume (%PV). Patients were divided into three groups according to EAVi: Group A as normal (<68.1 ml/m 2 , n=127), group B as low (68.1-89.4 ml/m 2 , n=95), and group C as high EATVi (>89.4 ml/m 2 , n=92). Multivariable logistic regression analysis was performed to investigate the association between the clinical parameters, TTDE and CCTA findings, and the presence of LVDD. Results: Compared with Group A, group C was older and more frequently suffered from renal dysfunction. Among the three groups, we observed significant differences in LV mass index, e’, E/e’, and CACS. The EAVi correlated with each LVDD diagnostic component, including e’, E/e’, left atrial volume index (all p<0.05), except for tricuspid regurgitation velocity. A multivariate model showed that age [odds ratio (OR), 1.13; 95% CI, 1.06-1.20; p<0.001] and EAVi (OR, 1.03; 95%CI, 1.01-1.04; p<0.05) were independently associated with LVDD, even after adjusting for LV mass index (OR, 1.1; p < 0.05). There was no independent association of CACS or %PV with LVDD (Table). Conclusion: This study demonstrates that accumulation of EAT and LV mass index but not plaque volume were independent predictors of LVDD in chronic CAD patients with preserved LVEF. Further study is needed to investigate whether EAT predicts the development to heart failure in this population.

Abstract 4136462: Provider understanding of Coronary Artery Calcium Scoring (CAC) testing in Atherosclerotic CArdiovascular Disease risk stratification and Racial Disparities Study (CAC-CARD) to reduce healthcare disparities

Background: Coronary Artery Calcium (CAC) scoring is critical in assessing Atherosclerotic Cardiovascular Disease (ASCVD) risk. Despite its utility, many primary care physicians lack confidence and familiarity with its application. Significant racial disparities in CAC scoring utilization have been observed, potentially affecting patient outcomes. Hypothesis: We hypothesized that a short targeted educational intervention would enhance physicians' confidence, knowledge, and utilization of CAC scoring and awareness of racial disparities. Methods: A pre- and post-intervention study (Image 1) was conducted among 39 physicians at the University of Louisville. The intervention included a 20-minute educational session on CAC scoring and racial disparities. A video summarizing the ACC2018 guidelines for prevention and cholesterol treatment was provided. A summary of key points for clinical practice was given. The ASCVD plus calculator app was provided. Data were collected using a structured questionnaire before and after the intervention. Viewing time and engagement were recorded. Descriptive and inferential statistics analyzed the data. Results: The average correct physician responses increased from a mean of 59.5% pre-intervention to 92.0% post-intervention. Post-intervention, the number of physicians who felt confident or very confident in CAC testing increased from 17.9% to 94.8%. Additionally, 33 out of 39 physicians (84.6%) reported likely to use CAC testing more frequently. Correct responses on racial disparities improved from 59% pre-intervention to 92.0% post-intervention. (Image 2). The average viewing time was 28 minutes. Time spent on the questionnaires was 14 min pre and 12 min post. Conclusion: Our targeted educational intervention significantly enhanced physicians' knowledge and confidence in CAC scoring for ASCVD risk assessment and raised awareness about racial disparities, promoting more equitable practices.

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 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 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 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 4117834: Utility of Abdominal Aortic Calcification Assessment for the Prediction of Major Adverse Cardiovascular Events in Liver Transplant Patients

Background: Cardiovascular disease is a leading cause of postoperative morbidity and mortality following liver transplantation (LT). Presence of abdominal aortic calcification (AAC) has been linked to cardiovascular events in the general population. We investigated whether AAC on pre-transplant computed tomography (CT) predicts major adverse cardiovascular events (MACE) post-LT. Methods: Consecutive LT patients between 2010-2018 from the Victorian Liver Transplant Unit (Australia) were included. Extent of AAC was quantified in a blinded fashion, with high AAC defined as a calcium score of ≥500. MACE was defined as any recorded episodes of acute coronary syndrome (ACS), ventricular arrhythmia, decompensated heart failure, or stroke. The primary outcome was post-LT MACE at 30 days and the secondary outcome was all-cause mortality at maximal follow-up. Results: Of 461 patients undergoing LT, 350 had suitable CTs for analysis, of which 90 (25.7%) had also undergone CT coronary angiography. High AAC was identified in 98 patients (28.0%). This finding demonstrated a moderate correlation with high coronary artery calcium score (CACS) ≥400 (r=0.52, p<0.001). Fifty-eight MACE occurred in 42 patients (12.0%) within 30-days. High AAC was associated with increased risk of 30-day MACE (OR=2.68 (95%CI 1.39-5.17), p=0.004), and long-term mortality (HR=2.52 (95%CI 1.29-4.92), p=0.007) at a median follow-up of 4.0 years. In addition, high AAC predicted an increased risk of ACS (OR 3.80 (95%CI 1.18-12.27), p=0.025), heart failure (OR 3.07 (95%CI 1.21-7.80), p=0.020) and atrial fibrillation (OR 2.04 (95%CI 1.02-4.07), p=0.048), with a trend to increased prevalence of ventricular arrhythmia (OR 2.67 (95%CI 0.84-8.50), p=0.10). Following multivariate analysis, high AAC remained a strong independent predictor of MACE (OR=3.49, 95%CI 1.21-10.06, p=0.021). Addition of AAC to the revised cardiac risk index (RCRI) improved model fit for predicting MACE (net reclassification improvement of 52.7% (p<0.001)). Conclusions: This study demonstrates for the first time that high AAC on routine abdominal CT scans is associated with a 3-fold increased risk of 30-day MACE post-LT, and improves cardiovascular risk prediction compared to traditional risk scores. Quantification of AAC may offer a simple method of improving cardiovascular risk assessment and implementation of preventative strategies in liver transplant patients, using pre-existing scans without additional cost or patient risk.

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 4120670: Pericoronary Adipose Tissue Inflammation as a Marker of Increased Coronary Plaque Burden in Patients With Chronic Coronary Artery Disease With Zero Calcium Score

Background: Dysfunctional or excess adiposity plays pivotal role in the development of coronary atherosclerosis. It remains unclear whether pericoroanry adipose tissue (PCAT) inflammation is associated with increased coronary plaque burden in its early stage of atherosclerosis, independent of traditional coronary risks or cardiovascular-kidney metabolic health. Purpose: To investigate the association of PCAT inflammation with coronary plaque burden in patients with newly suspected with chronic coronary artery disease (CAD) and zero calcium score who underwent coronary computed tomography angiography (CCTA). Methods: This retrospective CCTA study consists of 294 chronic CAD patients with zero calcium score (59 years, male 51 %). Chronic CAD was defined as stable condition with presence of increased non-calcified plaque burden on CCTA (Figure 1A-D). PCAT attenuation (PCATA) was assessed by fat attenuation index in the major three coronary arteries (right coronary artery, RCA; left anterior descending artery; LAD, and left circumflex coronary artery, LCX)(Figure 1C and D). Multivariable analysis using linear regression model was performed to determine independent predictors of increased %PV by adjusting for traditional coronary risks, metabolic risks, and chronic kidney disease (CKD). Hisayama Risk Score (HRS) was calculated to estimate 10-year cardiovascular risks. Results: Mean %plaque volume (PV) and PCATA-RCA was 44±4.0％ and -77±8.8 HU. %PV was correlated with age (p<0.05), systolic blood pressure (p<0.05), non-HDL cholesterol (p<0.05), Hisayama risk score (p<0.05, Figure 2), PCATA-RCA (p<0.001, Figure 3), PCATA-LAD (p<0.001), and LCX-PCATA (p<0.001). In a multivariable linear regression model adjusting for age, sex, hypertension, diabetes, dyslipidemia, and current smoking (model 1), PCATA-RCA was independently associated with %PV [beta, 0.17; 95% confidential interval (CI) 0.115-0.217, p < 0.001]. In a model adjusting for age, sex, metabolic syndrome, body mass index ≥23kg/mm 2 , and CKD (model 2), PCATA-RCA (beta, 0.18; 95% CI 0.128-0.232, p<0.001) and high-risk HRS (beta, 3.1; 95% CI 1.35−4.87, p<0.001) were independently associated with %PV. Similarly, independent associations of PCATA in LAD and LCX with %PV was observed. Conclusion: This study demonstrates that PCATA is a robust marker related to increased burden of coronary atherosclerosis even in the early stage of atherosclerosis as defined by zero coronary artery calcium score.

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

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

Abstract 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.

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.