Coronary Artery Calcium Burden Research Articles

Integrating cardiovascular risk assessment into mobile low-dose CT lung screenings in rural Appalachia: A comprehensive analysis of the relationship between lung cancer risk, coronary artery calcium burden, and cardiovascular risk reduction strategies

ObjectiveMobile low-dose computed tomography (LDCT) lung screenings are part of an outreach program in rural Appalachia to detect early lung cancer. Coronary artery calcium (CAC) scoring on LDCT can identify calcium deposits in coronary arteries and can prompt consideration of risk modification for prevention of cardiovascular disease (CVD) events. It is not known if Lung CT Screening Reporting & Data System (Lung-RADS) scoring correlates with CAC scores. There is no clear guidance for patients undergoing LDCT screenings to receive follow-up regarding CAC or prevention of associated CVD risk. MethodsThis was a retrospective review of mobile LDCT LCS in adults with no known history of CVD. CT images were obtained at 100 kVp with a slice thickness of 3 mm. Agatston CAC scoring was performed retroactively. Lung-RADS scores were categorized as: Negative (1), Benign (2), Probably Benign (3), and Suspicious (4). CAC scoring was grouped as 0, 1–100, 101–399, and ≥400. Descriptive statistics and chi-square analyses were utilized. ResultsA total of 526 LDCT screenings were included. Over 54 % of patients had coronary calcification on LDCT LCS. 161 patients (30.6 %) had a CAC score of ≥100 and 75 patients (14.3 %) had a CAC score ≥400. Of patients with a CAC score ≥100, 7.5 % received referrals for follow-up after the LDCT screen and 9.3 % had additional cardiac testing. Of those with a CAC score ≥100 not already on a statin (45.3 %) and not already on aspirin (63.3 %), few were started within 3 months of LDCT for prevention (8.2 % and 5.9 % respectively). Among patients with a Lung-RADS score of 4, 17 % had a CAC score >400, whereas only 12 % with a Lung-RADS score of 1 fell into the same CAC category. Higher Lung-RADS scores correlated with fewer patients with CAC of 0. A significant correlation was observed between higher Lung-RADS scores and elevated CAC scores (p = 0.02). ConclusionIn patients with no CVD history, coronary artery calcification was frequently identified on mobile LDCT lung screenings in rural communities. Patients with higher probabilities of malignant lung nodules may also be at increased risk for significant coronary artery disease. Calcium scoring from LDCT screenings allowed for simultaneous assessment of lung cancer and CVD risk. Unfortunately, few referrals or CVD prevention medications were initiated. Awareness of CAC score utility, follow-up for identified coronary calcifications, and consideration of primary prevention medications when indicated, would be beneficial in patients undergoing LDCT lung screenings, especially in rural areas with limited healthcare access.

Laboratory parameters associated with elevated coronary artery calcium burden in patients with newly diagnosed type 2 diabetes mellitus

Laboratory parameters associated with elevated coronary artery calcium burden in patients with newly diagnosed type 2 diabetes mellitus

Abstract 6294: Subclinical atherosclerosis in newly diagnosed colorectal cancer patients

Abstract Introduction: Recent advances in early detection and treatment have improved survival rates for patients with colorectal cancer (CRC), and emerging data suggests patients may be at elevated risk of cardiovascular disease (CVD). However, there are no standard recommendations for assessing CVD risk in patients with CRC. Coronary artery calcium (CAC) is a measure of the quantity of coronary artery calcification using noninvasive scanning and has been shown to be predictive of CVD risk. This prospective cohort study utilizes CAC to evaluate the occurrence of subclinical atherosclerosis at the time of CRC diagnosis and the risk of major adverse cardiovascular events (MACE). Methods: The ColoCare Study is a prospective cohort study across six U.S. and European sites. Data from one of the ColoCare consortium sites in Los Angeles, California was analyzed. Adults with newly diagnosed stage I- IV colorectal cancer and available non-contrast CT scans were included. Electronic medical records were reviewed for assessment of baseline cardiovascular risk factors and adverse events. Subclinical atherosclerosis was defined as the presence of CAC (CAC>0). CAC was manually measured from routine oncologic diagnostic CT and PET-CT scans at the time of cancer diagnosis using the Agatston method. MACE was defined as hospitalization due to heart failure, cardiomyopathy, ischemic heart disease, or ischemic stroke after the diagnosis of CRC cancer. Multivariable-adjusted Cox regression was used to evaluate the association between CAC at diagnosis and the risk of MACE. Results: Among 109 individuals with CAC measured at the time of CRC diagnosis, 41 (37.6%) had subclinical atherosclerosis (CAC=1-399 [n=29], CAC>400 [n=12]). Individuals with CAC>0 were older (67.0 vs. 51.9 years, p<0.01), more likely to be former or current smokers (48.0 vs. 29.0 years, p=0.04), and to have hypertension (61% vs. 23%, p<0.01) compared to those without CAC (CAC=0). Among individuals with CAC (n=41), 51.2% had scores >100, and 29.2% had scores >400, indicating moderate and severe atherosclerosis respectively. Among patients with moderate or greater CAC burden (>100; statin therapy indicated), 28.6% were not on statin therapy. CAC>0 was associated with an increased incidence of MACE (13% vs. 53%, p<0.01). Discussion: Subclinical atherosclerosis was observed in nearly 40% of patients with CRC at diagnosis and MACE occurred in 38.2% of patients. Most patients were under-optimized for CVD risk, with nearly 30% of statin-eligible patients with at least moderate CAC burden not prescribed statin therapy. These findings highlight an opportunity for improved CVD risk mitigation in patients with CRC, including guidelines-based CVD risk factor modification. Citation Format: Julia A. Levy, Maimoona Nadri, Elham Kazemian, Katelyn M. Atkins, Jordan O. Gasho, Katrina D. Silos, Cody Ramin, Andriana P. Nikolova, Erin M. Siegel, Biljana Gigic, Adetunji T. Toriola, Jennifer Ose, Christopher I. Li, David Shibata, Cornelia M. Ulrich, Jane C. Figueiredo. Subclinical atherosclerosis in newly diagnosed colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6294.

Abstract P513: Coronary Artery Calcium Burden in Rural Alabama: Initial Findings From the Risk Underlying Rural Areas Longitudinal Cohort Study

Introduction: Individuals living in rural areas have a disproportionately high rate of cardiovascular disease (CVD) mortality. Coronary artery calcium (CAC) scanning may inform CVD risk stratification. However, the prevalence of CAC in rural areas is unknown. Research Question: What is the prevalence of CAC according to age, sex, and self-reported race (Black, White) in two rural counties in Alabama? Aims: To determine the prevalence of a CAC score >0, a CAC score ≥100, and premature CAC among rural persons without clinical CVD and the extent to which they differ by demographic group. Methods: We studied 789 participants between the age of 25 and 64 years in the Risk Underlying Rural Areas Longitudinal (RURAL) Cohort Study sample in Alabama who underwent CAC scoring on non-contrast cardiac computed tomography. Premature CAC was defined as CAC >0 for men <45 years old, and women <55 years old. Multivariable logistic regression (including age, sex, race) estimated adjusted odds ratios (aOR) for CAC >0 and CAC ≥100. Results: The median age was 51 years, 70% were women, and 80% were Black. Among the were 37% with CAC >0 the median CAC score was 64, while 14% had CAC ≥100 and 12% had premature CAC. Significant differences in all three CAC categories were consistently observed across age and sex, but not race ( Figure ). After adjusting for age and race, women had an approximate 70% lower odds of CAC >0 (aOR=0.29, 95% CI: 0.19-0.44) and CAC ≥100 (aOR=0.28, 95% CI: 0.18-0.43) compared to men. There were no significant differences in CAC >0 (aOR=0.70, 95% CI: 0.43-1.12) or CAC ≥100 (aOR=0.76, 95% CI: 0.46-1.25) for Black versus White persons independent of age and sex. Conclusion(s): In a Southern rural cohort of young and middle-aged persons, approximately one in three had prevalent CAC and one in eight had premature CAC. In contrast to previously published urban cohorts, rural Black adults had a similar CAC burden to their White counterparts. There is a need to explore the factors implicated in the high CAC burden within Southern rural communities.

Predictors of coronary artery calcium burden in asymptomatic patients with newly diagnosed type 2 diabetes mellitus.

Long-standing diabetes mellitus is often associated with cardiovascular complications. We aimed to evaluate the presence, extent and composition of subclinical atherosclerotic plaques in coronary arteries by Computed Tomography in patients with newly diagnosed type 2 diabetes mellitus (NDT2DM), and to identify the predictors. In this study 101 consecutive patients with NDT2DM were included. Patients were categorized into five groups based on their Coronary Artery Calcium Score (CACS) ranging from 0, 0-10, 11-100, 101-400 to >400. All parameters were compared across these groups. The average patient age was 54.4 ± 11.6years and 48 (47.5%) were females. Eight (7.9%) patients had CACS 0, 6.9% CACS 1-10, 42.6% CACS 11-100, 22.8% CACS 101-400 and 19.8% had CACS >400. Multiple regression analysis for the general data identified weight (p = .04) and systolic blood pressure (p = .033) as independent predictors for CACS. Asymptomatic patients with NDT2DM in more than 90% of cases may present with calcified atherosclerotic plaques and this may be predicted by: patient weight and the level of systolic arterial pressure. Our study emphasizes the need for comprehensive care and early prevention of cardiovascular complications in individuals with NDT2DM.

Age- and sex-based heterogeneity in coronary artery plaque presence and burden in familial hypercholesterolemia: A multi-national study

ObjectivesIndividuals with familial hypercholesterolemia (FH) are at an increased risk for coronary artery disease (CAD). While prior research has shown variability in coronary artery calcification (CAC) among those with FH, studies with small sample sizes and single-center recruitment have been limited in their ability to characterize CAC and plaque burden in subgroups based on age and sex. Understanding the spectrum of atherosclerosis may result in personalized risk assessment and tailored allocation of costly add-on, non-statin lipid-lowering therapies. We aimed to characterize the presence and burden of CAC and coronary plaque on computed tomography angiography (CTA) across age- and sex-stratified subgroups of individuals with FH who were without CAD at baseline. MethodsWe pooled 1,011 patients from six cohorts across Brazil, France, the Netherlands, Spain, and Australia. Our main measures of subclinical atherosclerosis included CAC ranges (i.e., 0, 1–100, 101–400, >400) and CTA-derived plaque burden (i.e., no plaque, non-obstructive CAD, obstructive CAD). ResultsNinety-five percent of individuals with FH (mean age: 48 years; 54% female; treated LDL-C: 154 mg/dL) had a molecular diagnosis and 899 (89%) were on statin therapy. Overall, 423 (42%) had CAC=0, 329 (33%) had CAC 1–100, 160 (16%) had CAC 101–400, and 99 (10%) had CAC >400. Compared to males, female patients were more likely to have CAC=0 (48% [n = 262] vs 35% [n = 161]) and no plaque on CTA (39% [n = 215] vs 26% [n = 120]). Among patients with CAC=0, 85 (20%) had non-obstructive CAD. Females also had a lower prevalence of obstructive CAD in CAC 1–100 (8% [n = 15] vs 18% [n = 26]), CAC 101–400 (32% [n = 22] vs 40% [n = 36]), and CAC >400 (52% [n = 16] vs 65% [n = 44]). Female patients aged 50–59 years were less likely to have obstructive CAD in CAC >400 (55% [n = 6] vs 70% [n = 19]). ConclusionIn this large, multi-national study, we found substantial age- and sex-based heterogeneity in CAC and plaque burden in a cohort of predominantly statin-treated individuals with FH, with evidence for a less pronounced increase in atherosclerosis among female patients. Future studies should examine the predictors of resilience to and long-term implications of the differential burden of subclinical coronary atherosclerosis in this higher risk population.

Abstract 18737: Coronary Artery Calcium for Allocation of Aspirin in Light of the 2022 USPSTF Guideline Recommendations: Results From the Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: The 2022 USPSTF guidelines issued a grade C recommendation for aspirin in patients aged 40-59 and recommended against its use in patients ≥ 60 years. We sought to assess if coronary artery calcium (CAC) would allow for personalized allocation of aspirin. Methods: Using MESA, aspirin naïve participants without high-risk bleeding features were identified. Participants were grouped by age into <60, ≥ 60 and stratified by CAC and ASCVD risk. The number needed to treat (NNT 5 ) and number needed to harm (NNH 5 ) was assessed by applying a 11% relative risk reduction in CVD and a 44% relative risk increase in major bleeding (2022 USPSTF meta-analysis) to the observed CVD and bleeding events from MESA Results: Of 6,814 participants, 4,506 met inclusion criteria. 2,235 were <60 years and 2,268 were ≥ 60 years. Figure-1 displays the interplay between baseline estimated ASCVD risk and CAC burden. In participants <60 years of age, both CAC and ASCVD risk >10% identified subgroups in whom the NNT was lower than the NNH: CAC 1-99 (NNT 5 -313, NNH 5 -517); CAC ≥100 (NNT 5 -152, NNH 5 -367); ASCVD risk >10% (NNT 5 -155, NNH 5 -554) Fig-1. In those ≥ 60 years CAC ≥100 identified subgroups with a lower NNT 5 -128 than NNH 5 -168, while ASCVD risk stratification did not. 6% of adults <60 years with <10% ASCVD risk and 30.3% of adults ≥ 60 years who had CAC ≥100, and who demonstrated benefit from the use of Aspirin, would not qualify for the use of aspirin using only ASCVD risk as per the 2022 USPSTF guideline recommendations. Conclusions: CAC identifies subgroups of patients <60 as well as those ≥ 60 years who would derive a net benefit from aspirin in primary prevention. A significant proportion of patients will be missed if only ASCVD risk scores are used for allocation of aspirin. CAC should be used to risk stratify individuals to personalize the allocation of aspirin

Abstract 13721: Coronary Artery Calcium for Risk Stratification Among Persons With Very-High High-Density Lipoprotein Cholesterol

Introduction: Persons with very-high high-density lipoprotein-cholesterol (HDL-C) may experience an increased mortality risk. However, the predictors of mortality among those with very-high HDL-C remain unknown. Hypothesis: Compared to traditional risk factors, coronary artery calcium (CAC) will more strongly stratify risk among individuals with very-high HDL-C. Aims: Among individuals with very-high HDL-C, to 1) calculate crude all-cause mortality rates across the burden of traditional risk factors and CAC, and 2) identify independent risk factors associated with all-cause mortality. Methods: There were 335 primary prevention patients from the CAC Consortium who had very-high HDL-C ( > 80 mg/dL in men, > 100 mg/dL in women) and available information on traditional CVD risk factors. Crude all-cause mortality rates were calculated per 1,000 person-years. Multivariable Cox proportional hazards regression assessed the association of traditional risk factors and CAC with mortality. Results: The mean age was 58.6 years old, 51.0% were women, 51.3% had prevalent CAC, and the median HDL-C was 100 mg/dL. There were 20 deaths (6.0%) over a median follow-up of 10.5 years, 7 (2.1%) of which were attributable to CVD. There was a stepwise higher crude mortality rate per 1,000 person-years across increasing CAC burden ( Central Illustration ). Independent of traditional risk factors, each 100 Agatston Unit increase in CAC score was associated with a 7% higher hazard of all-cause mortality (HR: 1.07, 95% CI: 1.01-1.12) and individuals with CAC > 1000 experienced a 5.75-fold higher hazard of mortality when compared to CAC=0 (HR: 5.75, 95% CI: 1.26-26.24). Beyond age, no traditional risk factor was associated with mortality in multivariable analyses. Conclusion: Measurement of CAC on non-contrast cardiac computed tomography may facilitate risk assessment among individuals with very-high HDL-C.

Long-term outcomes of lung cancer screening in males and females

BackgroundThis study explored female and male overall mortality and lung cancer (LC) survival in two LC screening (LCS) populations, focusing on the predictive value of coronary artery calcification (CAC) at baseline low-dose computed tomography (LDCT). MethodsThis retrospective study analysed data of 6495 heavy smokers enrolled in the MILD and BioMILD LCS trials between 2005 and 2016. The primary objective of the study was to assess sex differences in all-cause mortality and LC survival. CAC scores were automatically calculated on LDCT images by a validated artificial intelligence (AI) software. Sex differences in 12-year cause-specific mortality rates were stratified by age, pack-years and CAC score. ResultsThe study included 2368 females and 4127 males. The 12-year all-cause mortality rates were 4.1 % in females and 7.7 % in males (p < 0.0001), and median CAC score was 8.7 vs. 41 respectively (p < 0.0001). All-cause mortality increased with rising CAC scores (log-rank test, p < 0.0001) for both sexes. Although LC incidence was not different between the two sexes, females had lower rates of 12-year LC mortality (1.0 % vs. 1.9 %, p = 0.0052), and better LC survival from diagnosis (72.3 % vs. 51.7 %; p = 0.0005), with a similar proportion of stage I (58.1 % vs. 51.2 %, p = 0.2782). ConclusionsOur findings demonstrate that female LCS participants had lower rates of all-cause mortality at 12 years and better LC survival than their male counterparts, with similar LC incidence rates and stage at diagnosis. The lower CAC burden observed in women at all ages might contribute to explain their lower rates of all-cause mortality and better LC survival.

Association of Left Anterior Descending Coronary Artery Calcium Progression and Radiation Dose with Major Adverse Cardiac Events in Breast Cancer

Coronary artery calcium (CAC) is associated with increased risk of major adverse cardiac events (MACE). Accelerated CAC progression has been observed in patients with breast cancer after radiotherapy (RT) and there is a relationship between left anterior descending (LAD) coronary artery RT dose and the risk of coronary events. However, there is lack of consensus on LAD dose constraints for breast RT and limited data on the extent and impact of CAC progression. Our objective was to evaluate the association of LAD dose exposure and CAC progression with the risk of MACE in patients with breast cancer following RT. Retrospective analysis of 181 patients with breast cancer treated with RT between 2008 and 2019. CAC was manually measured on RT planning and follow-up CTs (with at least one-year interval) using the Agatston method. Coronary arteries were segmented using a deep learning-based automated algorithm and dosimetric parameters collected. MACE cumulative incidence was estimated, and Fine and Gray regressions performed, accounting for non-cardiac death as a competing risk. The median follow-up following RT was 70 months (interquartile range [IQR], 53-86). The median age was 63 years (IQR, 53-72), 43% had hypertension, 40% hyperlipidemia, 8% coronary heart disease (CHD). Most had pathologic stage I-II disease (76%). RT was targeted to breast/chest wall only in 60% and included regional nodes in 40% (internal mammary chain in 4%). The most common dose/fractionation was 48-50.4 Gy/25-28 fractions (67%) and 42.6-42.7 Gy/16 fractions (30%). At the time of RT, 68 (38%) had at least moderate CAC burden (CAC >100; statin-therapy indicated), but only 29 (43%) were on statin therapy. At a median interval of 44 months (IQR, 26-63), 55% (n = 84) had CAC progression, with a median increase of 52%/year (IQR, 18-193). The median time to MACE was 68 months (IQR, 53-85), with a 5-year cumulative incidence of 7.3% (15 MACE overall). Accounting for age and CHD, there was an increased risk of MACE with LAD CAC progression (subdistribution hazard ratio [SHR] 1.02/10 CAC points; 95% confidence interval [CI] 1.01 = 1.03; p = .007) and the volume of LAD receiving 15 Gy (LAD V15 Gy; SHR 1.03/%; 95% CI, 1.01-1.06; p = .004). There was no association between mean heart dose, chemotherapy, or Her2 therapy exposure and MACE (p>.05). LAD CAC progression and LAD V15 Gy dose exposure were associated with an increased risk of MACE following RT. Accelerated CAC progression was commonly observed, however most patients were under-optimized for cardiovascular (CV) risk, with less than half of statin-eligible patients with at least moderate CAC burden on statin therapy. Together, these data support more aggressive cardiac risk mitigation approaches, including guidelines-based CV risk factor modification and optimized sparing of LAD radiation dose.

SP10.10 Assessment of coronary artery calcification on pre-operative imaging to predict cardiovascular complications in colorectal cancer patients

Abstract Background All patients undergoing operative management of colorectal cancer have pre-operative Computer Tomography (CT) imaging of thorax to exclude metastatic disease. Incidental coronary artery calcification is rarely reported on CT. There are a variety of risk scores to predict cardiac complications in the peri-operative period. Current cardiac risk stratification tools do not incorporate radiological evidence of coronary artery calcification in their scoring systems. Methods A retrospective review of 100 patients with confirmed or suspected colorectal cancer. Demographic data was collected. A review of pre-operative CT thorax imaging was completed to ordinal score coronary artery calcification into none, mild, moderate and extensive. Peri-operative and post-operative cardiac and non-cardiac complications were documented. Results Seventy-nine percent of patients had evidence of coronary artery calcification on pre-operative CT thorax. 29 mild, 21 moderate, 29 extensive. Seven percent of patients had a cardiac complication and all of these had coronary artery calcification on CT pre-operatively. Twenty-six had non-cardiac complication and 22 of these had evidence of coronary artery calcification on pre-operative CT. Conclusions There is significant burden of coronary artery calcification in this patient population. This corresponds positively with peri- and post-operative cardiac and non-cardiac complications. Identification pre-operatively can help predict cardiac risk and therefore allow pre-operative cardiac optimisation.

Coronary Artery Calcium Scores in Older Adults With Diabetes and Their Association With Diabetes-Specific Risk Enhancers (from the Atherosclerosis Risk in Communities Study)

Coronary artery calcium (CAC) is a validated marker of atherosclerotic cardiovascular disease (ASCVD) risk; however, it is not routinely incorporated in ASCVD risk prediction in older adults with diabetes. We sought to assess the CAC distribution among this demographic and its association with "diabetes-specific risk enhancers," which are known to be associated with increased ASCVD risk. We used the ARIC (Atherosclerosis Risk in Communities) study data, including adults aged >75 years with diabetes, who had their CAC measured at ARIC visit 7 (2018 to 2019). The demographic characteristics of participants and their CAC distribution were analyzed using descriptive statistics. Multivariable-adjusted logistic regression models were used to estimate the association between diabetes-specific risk enhancers (duration of diabetes, albuminuria, chronic kidney disease, retinopathy, neuropathy, and ankle-brachial index) and elevated CAC, adjusting for age, gender, race, education level, dyslipidemia, hypertension, physical activity, smoking status, and family history of coronary heart disease. The mean age in our sample was 79.9 (SD 3.97) years, with 56.6% women and 62.1% White. The CAC scores were heterogenous, and the median CAC score was higher in participants with a greater number of diabetes risk enhancers, regardless of gender. In the multivariable-adjusted logistic regression models, participants with ≥2 diabetes-specific risk enhancers had greater odds of elevated CAC than those with <2 (odds ratio 2.31, 95% confidence interval 1.34 to 3.98). In conclusion, the distribution of CAC was heterogeneous among older adults with diabetes, with the CAC burden associated with the number of diabetes risk-enhancing factors present. These data may have implications for prognostication in older patients with diabetes and supports the possible incorporation of CAC in the assessment of cardiovascular disease risk in this population.

Coronary artery calcification as a predictor of adverse outcomes in patients hospitalized with COVID-19

BackgroundSubclinical coronary artery calcification (CAC) is a risk factor for adverse cardiovascular events, but studies investigating its association with outcomes in hospitalized patients with COVID-19 are limited. MethodsThis was a retrospective study of 457 patients without history of clinical coronary artery disease (CAD) who underwent chest CT imaging during COVID-19 hospitalization at MCW/Froedtert-affiliated hospitals from July 1, 2020 to July 1, 2021. Visually estimated CAC (yes/no) and CAC burden (none/mild/moderate/severe) were recorded from radiology reports. Unadjusted and adjusted regression models were used to assess associations between CAC and hospital length of stay (LOS), ICU admission, mechanical ventilation, and mortality. ResultsThe mean age was 63.1 ± 15.3 years. Presence of CAC was associated with mechanical ventilation (p = 0.01), ICU admission (p = 0.02), in-hospital or 30-day mortality (p < 0.01), and hospital LOS (p < 0.001). Compared to no CAC, hospital LOS was increased for mild (p = 0.01) and severe CAC (p = 0.02) after adjustment for covariates. Severe CAC was also associated with increased ICU admission (OR 3.97; p = 0.002) and mechanical ventilation (OR 3.08; p = 0.03) after adjustment. In unadjusted analysis, in-hospital or 30-day mortality increased with magnitude of CAC severity, with HR 2.43 (p = 0.003) for mild and HR 3.70 (p = 0.002) for severe CAC. However, associations with mortality were not significant after adjustment. ConclusionsCAC is associated with increased ICU admission, mechanical ventilation, hospital LOS, and in-hospital or 30-day mortality for patients hospitalized with COVID-19. Patients with severe CAC, and without clinical history of CAD, represent a high-risk population for morbidity and mortality.

Sleep Irregularity and Subclinical Markers of Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis.

Background Sleep irregularity has been linked to incident cardiovascular disease. Less is known about associations of sleep regularity with atherosclerosis. We examined cross-sectional associations of actigraphy-assessed sleep duration and sleep timing regularity with subclinical atherosclerosis in the community-based MESA (Multi-Ethnic Study of Atherosclerosis). Methods and Results MESA Sleep Ancillary Study participants (N=2032; mean age, 68.6±9.2 years; 37.9% White) completed 7-day wrist actigraphy. Participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intima-media thickness, and the ankle-brachial index. Sleep regularity was quantified by the 7-day with-in person SD of sleep duration and sleep onset timing. Relative risk regression models were used to calculate prevalence ratios and 95% CIs. Models are adjusted for demographics, cardiovascular disease risk factors, and other objectively assessed sleep characteristics including obstructive sleep apnea, sleep duration, and sleep fragmentation. After adjustment, compared with participants with more regular sleep durations (SD ≤60 minutes), participants with greater sleep duration irregularity (SD >120 minutes) were more likely to have high coronary artery calcium burden (>300; prevalence ratio, 1.33 [95% CI, 1.03-1.71]) and abnormal ankle-brachial index (<0.9; prevalence ratio, 1.75 [95% CI, 1.03-2.95]). Compared with participants with more regular sleep timing (SD ≤30 minutes), participants with irregular sleep timing (SD >90 minutes) were more likely to have high coronary artery calcium burden (prevalence ratio, 1.39 [95% CI, 1.07-1.82]). Associations persisted after adjustment for cardiovascular disease risk factors and average sleep duration, obstructive sleep apnea, and sleep fragmentation. Conclusions Sleep irregularity, particularly sleep duration irregularity, was associated with several measures of subclinical atherosclerosis. Sleep regularity may be a modifiable target for reducing atherosclerosis risk. Future investigation into cardiovascular risk reduction interventions targeting sleep irregularity may be warranted.

Transient left bundle branch block associated with very high coronary artery calcium: a case report.

Coronary artery calcium (CAC) is the measure of subclinical coronary artery atherosclerosis most strongly associated with atherosclerotic cardiovascular disease (ASCVD) risk. However, CAC is rarely reported in the inpatient setting to guide chest pain management. We present a case of very high CAC in a 64-year-old woman with hypertension, type 2 diabetes, and hyperlipidemia presenting with dyspnea. Initial electrocardiogram (ECG) demonstrated normal conduction with a heart rate of 76 beats/min, but new T-wave inversions in V1-V4 and a high-sensitivity troponin-I (hsTnI) value of 6 ng/L (normal < 6 ng/L). Repeat ECG in the emergency department showed normal sinus rhythm (heart rate of 80 beats/min); however, it subsequently demonstrated a left bundle branch block (LBBB) with a repeat hsTnI of 7 ng/L. Stress testing with pharmacologic single-photon emission computerized tomography did not show scintigraphic evidence of ischemia but noted extensive CAC and a concern for balanced ischemia. Subsequent coronary computed tomography angiography (CCTA) showed nonobstructive disease and a total Agatston CAC score of 1262. Invasive evaluation with left heart catheterization was deferred given the patient's unchanged symptoms and CCTA findings. Statin therapy was intensified and aspirin, metoprolol succinate, and antihypertension therapies were continued. Initiation of glucose-lowering therapy and lipoprotein(a) testing was strongly recommended on follow-up. Our case suggests that CAC ⩾ 1000 may be incidentally associated with transient LBBB during the workup of coronary artery disease. Here, we specifically show that functional testing that incorporates measurement of CAC burden can help to improve ASCVD-preventive pharmacotherapy initiation and intensification beyond the identification of obstructive disease alone.

Abstract 12093: Inter-Reader Reliability of Coronary Calcium Estimation From Non-Gated Chest Computed Tomography Scans Using a Semi-Quantitative Scoring Method

Introduction: Coronary artery calcium (CAC) is strongly associated with cardiovascular risk. CAC burden can be qualitatively estimated from non-gated chest computed tomography (CT) imaging and may be used to predict future cardiovascular outcomes. We evaluated whether resident physician trainees can reliably estimate CAC burden from existing non-gated chest CTs using a semi-quantitative scoring method. Methods: A group of 4 resident physicians without formal training in CT image interpretation underwent a training session to qualitatively estimate CAC burden from non-gated, contrast and non-contrast CT scans. CAC was estimated for each coronary artery as absent, mild (1-24% vessel length), moderate (25-49% vessel length) and severe (&gt;50% vessel length). All Chest CTs were reviewed by two physicians, each blinded to the interpretations of the other reviewer, to assess (a) the presence or absence of CAC, (b) the presence or absence of moderate-severe CAC, and (c) a semi-quantitative CAC index, at a per-patient level and by vessel. Inter-reader reliability (IRR) was assessed by percent agreement, Cohen's kappa coefficient, and the intraclass correlation coefficient (ICC). Results: Using a semi-quantitative scoring system to estimate an index of overall CAC burden, the ICC was 0.96 (CI 0.94-0.98). The percent agreement for the presence of any CAC was 74% (kappa 0.82) and 89% for moderate-to-severe CAC (kappa 0.85). The IRR stratified for each coronary vessel is shown in Table 1. CAC estimated from both contrast and non-contrast scans was associated with substantial agreement between readers ( Table 1 ). Conclusions: With a single training session, resident physicians can quickly and reliably estimate CAC burden from non-gated chest CT imaging. This may facilitate cardiovascular risk stratification in patients without dedicated cardiac testing. 1b

Abstract 15612: Association Between ECG-Derived Age With Coronary Artery Calcium

Introduction: We have previously shown that ECG-derived age (ECG-Age) predicts all-cause and cardiovascular (CV) mortality, reflecting physiologic age. We hypothesized that ECG-Age minus chronological age (Age-Gap) would be associated with coronary artery calcium (CAC) assessed by computer tomography. Methods: We developed a neural network model to predict ECG-Age using 12 lead ECGs from 399,750 training, 99,977 validation and 275,056 testing patients. We then applied the algorithm to 41,202 consecutive patients that from 1997-2020 underwent clinically indicated CAC and ECG within 1 year. Major modifiable CV risk factors were collected as part of preventive cardiology or general medical evaluations. Exclusion criteria were statin therapy, pacemakers, or history of coronary artery disease. Results: We included 41,202 subjects (68.5% males, 83.6% Caucasian), mean chronological age was 55.2±9.1 yrs and the ECG-Age was 56.01±9.3 yrs. The mean Age-Gap was -0.78±7 yrs, R 2 =0.78, p&lt;0.0001. Mean CAC score was 140.2±532.3, and 21,483 (52%) had CAC &gt;0. After adjustment for age and sex, those older by ECG (defined as having a positive Age-Gap) were more likely to have CAC&gt;0 (OR 1.35, 95% CI 1.34-2.37 for those with &gt;1 but &lt;2 SD of a positive Age-Gap; and OR 1.80, 95% CI 1.34-2.37 for those with ≥2 SD of a positive Age-Gap), while those younger by ECG were less likely to have any CAC (OR 0.70, 95% CI 0.57-0.87 for those with &gt;1 but &lt;2 SD of a negative Age-Gap; and OR 0.75, 95% CI 0.67-0.84 for those with ≥2 SD of a negative Age-Gap), respectively. This association remained significant after multivariate adjustment, Fig. A and increased with CAC burden, Fig. B , all P for trend &lt;0.01. Conclusions: The difference between physiologic AI-ECG age and chronologic age, something likely representing rate of biological aging, is associated with presence of CAC, further supporting the hypothesis that AI-ECG age can identify people more likely to have subclinical coronary atherosclerosis.

Abstract 11172: Heterogeneity in the Association Between the Presence of Coronary Artery Calcium and Cardiovascular Events: Multi-Ethnic Study of Atherosclerosis

Introduction: Coronary artery calcium (CAC) has been widely recognized as an important predictor of cardiovascular disease (CVD). Given the finite resources, it is important to identify individuals who would receive the most benefit from detecting positive CAC by screening. However, the evidence is limited as to whether the burden of positive CAC on CVD differs by multi-dimensional individual characteristics. We aimed to investigate the heterogeneity in the association between positive CAC and incident CVD. Methods: This longitudinal cohort study included adults aged ≥45 years free of cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis (MESA). After propensity score matching in a 1:1 ratio, we applied a machine-learning causal forest model to (i) evaluate the heterogeneity in the association between positive CAC and incident CVD and (ii) predict the increase in CVD risk at 10-year when CAC&gt;0 (vs. CAC=0) at the individual level. We then compared the estimated increase in CVD risk when CAC&gt;0 to the 10-year atherosclerotic CVD (ASCVD) risk calculated by the 2013 ACC/AHA pooled cohort equations. Results: Across 3,348 adults in our propensity score-matched analysis, our causal forest model showed heterogeneity in the association between CAC&gt;0 and incident CVD. We found a dose-response relationship of the estimated increase in CVD risk when CAC&gt;0 with higher calculated 10-year ASCVD risk ( Figure ). Even among 1,413 adults with low/borderline ASCVD risk, 689 (49.4%) showed ≥7.5% increase in CVD risk when CAC&gt;0; these individuals were more likely to be male, non-Hispanic Black or Hispanic, less educated, never smokers, and have unfavorable CVD risk factors than others. Conclusion: The increases in CVD risk when CAC&gt;0 were heterogeneous across individuals, and nearly half of people with low/borderline calculated ASCVD risk showed a large increase in CVD risk when CAC&gt;0, highlighting the need for CAC screening among such low-risk individuals.

Abstract 13215: Accuracy of Visual Qualitative Estimates of CAC Incidentally Found on Chest CT Compared With Formal CAC Scoring

Introduction: While coronary artery calcium (CAC) scoring improves CVD risk assessment, it remains underutilized and is often not covered by insurance. Coronary calcium can be detected on chest CT scans performed for other indications and may allow identification of higher-risk people without a dedicated CAC scan. However, qualitative CAC scoring on non-gated chest CT scans is not widely validated. Methods: Since 2016, radiologists at two large health systems in Dallas (an academic medical system and a large safety net hospital) have routinely documented the presence and severity of CAC (none, mild, moderate, large) on all chest CT scans. We identified all adults who underwent both dedicated CAC scanning and a separate chest CT scan within 6 months. We compared qualitative visual CAC by CT scan versus a CAC score from a dedicated, gated coronary CT scan. Results: From 2016-2021, 891 patients (mean age 60 ± 12y, 43% male, 61% White, 35% Black, 24% Hispanic) underwent both a CT scan and a CAC score. Of these, 424 had no CAC, 268 small, 137 moderate, and 62 large CAC on CT scan. Qualitative CAC estimate from non-gated CT scans were highly correlated with formal CAC scores (Kendalls tau-b=0.75, p&lt;0.0001, figure). To detect CAC (score &gt;0), qualitative assessment on CT had a sensitivity of 82%, specificity of 95%, positive predictive value (PPV) of 97%, and negative predictive value (NPV) of 77%. Only 6% with small, 1% with moderate, and 0% with large CAC on CT had a CAC score = 0. For detection of CAC ≥ 100, moderate to large CAC on CT had a sensitivity of 62%, specificity of 96%, PPV of 89%, and NPV of 84%. Discussion: At two different hospitals serving a diverse population, visual estimates of CAC on routine CT scans were strongly correlated with formal CAC scores from dedicated, gated CT scans. Incidental identification of CAC on routine CT scans should prompt more aggressive cardiovascular risk reduction, particularly when moderate to large CAC burden is seen.

Heterogeneity in the Association Between the Presence of Coronary Artery Calcium and Cardiovascular Events: A Machine-Learning Approach in the MESA Study.

Coronary artery calcium (CAC) has been widely recognized as an important predictor of cardiovascular disease (CVD). Given the finite resources, it is important to identify individuals who would receive the most benefit from detecting positive CAC by screening. However, the evidence is limited as to whether the burden of positive CAC on CVD differs by multidimensional individual characteristics. We sought to investigate the heterogeneity in the association between positive CAC and incident CVD. This cohort study included adults from MESA (Multi-Ethnic Study of Atherosclerosis) ages ≥45 years and free of cardiovascular disease. After propensity score matching in a 1:1 ratio, we applied a machine learning causal forest model to (1) evaluate the heterogeneity in the association between positive CAC and incident CVD, and (2) predict the increase in CVD risk at 10-years when CAC>0 (versus CAC=0) at the individual level. We then compared the estimated increase in CVD risk when CAC>0 to the absolute 10-year atherosclerotic CVD (ASCVD) risk calculated by the 2013 American College of Cardiology/American Heart Association pooled cohort equations. Across 3328 adults in our propensity score-matched analysis, our causal forest model showed the heterogeneity in the association between CAC>0 and incident CVD. We found a dose-response relationship of the estimated increase in CVD risk when CAC>0 with higher 10-year ASCVD risk. Almost all individuals (2293 of 2428 [94.4%]) with borderline risk of ASCVD or higher showed ≥2.5% increase in CVD risk when CAC>0. Even among 900 adults with low ASCVD risk, 689 (69.2%) showed ≥2.5% increase in CVD risk when CAC>0; these individuals were more likely to be male, Hispanic, and have unfavorable CVD risk factors than others. The expected increases in CVD risk when CAC>0 were heterogeneous across individuals. Moreover, nearly 70% of people with low ASCVD risk showed a large increase in CVD risk when CAC>0, highlighting the need for CAC screening among such low-risk individuals. Future studies are needed to assess whether targeting individuals for CAC measurements based on not only the absolute ASCVD risk but also the expected increase in CVD risk when CAC>0 improves cardiovascular outcomes.