Presence Of Coronary Artery Calcification Research Articles

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.

Coronary Artery Calcification on Low-Dose Lung Cancer Screening CT in South Korea: Visual and Artificial Intelligence-Based Assessment and Association With Cardiovascular Events.

Background: Coronary artery calcification (CAC) on lung cancer screening low-dose chest CT (LDCT) is a cardiovascular risk marker. South Korea was the first Asian country to initiate a national LDCT lung cancer screening program, although CAC-related outcomes are poorly explored. Objective: To evaluate CAC prevalence and severity using visual analysis and artificial intelligence (AI) methods and to characterize CAC's association with major adverse cardiovascular events (MACEs) in patients undergoing LDCT in Korea's national lung cancer screening program. Methods: This retrospective study included 1002 patients (mean age, 62.4±5.4 years; 994 men, 8 women) who underwent LDCT at two Korean medical centers between April 2017 and May 2023 as part of Korea's national lung cancer screening program. Two radiologists independently assessed CAC presence and severity using visual analysis, consulting a third radiologist to resolve differences. Two AI software applications were also used to assess CAC presence and severity. MACE occurrences were identified by EMR review. Results: Interreader agreement for CAC presence and severity, expressed as kappa, were 0.793 and 0.671, respectively. CAC prevalence was 53.4% by consensus visual assessment, 56.6% by AI software I, and 60.1% by AI software II. CAC severity was mild, moderate, and severe by consensus visual analysis in 28.0%, 10.3% and 15.1%; by AI software I in 39.9%, 14.0%, and 6.2%; and by AI software II in 34.9%, 14.3%, and 7.3%. MACE occurred in 36 of 625 (5.6%) patients with follow-up after LDCT (median, 1108 days). MACE incidence in patients with no, mild, moderate, and severe CAC, for consensus visual analysis was 1.1%, 5.0%, 2.9%, and 8.6% (p<.001); for AI software I was 1.3%, 3.0%, 7.9%, and 11.3% (p<.001); and for AI software II was 1.2%, 5.0%, 7.7%, and 9.6% (p<.001) Conclusion: For Korea's national lung cancer screening program, MACE occurrence increased significantly with increasing CAC severity, whether assessed by visual analysis or AI software. The study is limited by the large sex imbalance for Korea's national lung cancer screening program. Clinical Impact: The findings provide reference data for healthcare practitioners engaged in developing and overseeing national lung cancer screening programs, highlighting the importance of routine CAC evaluation.

Impact of optimal cholesterol levels on subclinical atherosclerosis in the absence of risk factors in young adults

Background and aimsTo assess the association of blood lipids with the prevalence, incidence, and progression of subclinical atherosclerosis among young individuals without dyslipidemia and other traditional cardiovascular risk factors (CVRFs). MethodsA total of 1270 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study aged 32–46 years who were free of cardiovascular disease, diabetes, hypertension, current smoking, and dyslipidemia (total cholesterol [TC] ≥ 240 mg/dL, triglycerides [TG] ≥ 150 mg/dL, low-density lipoprotein cholesterol [LDL-C] ≥ 160 mg/dL, high-density lipoprotein cholesterol [HDL-C] < 40 mg/dL, or taking lipid-lowering medications) were included. A subgroup with optimal lipids within the low-CVRF group was defined with TC < 200 mg/dL, LDL-C < 100 mg/dL, non-HDL-C < 130 mg/dL, and women with HDL-C ≥ 50 mg/dL. ResultsA 1-SD higher TC (25.9 mg/dL), LDL-C (24.7 mg/dL), and non-HDL-C (26.6 mg/dL) were associated with a greater risk of presence (hazard ratios: 1.30–1.36), incidence (1.30–1.32), and progression (1.31–1.35) of coronary artery calcium (CAC) and a 42–44% greater odds of composite mean carotid intima-media thickness (CIMT) ≥ 75th percentile [780 μm] (p < 0.05). Repeating the analyses in a subset of participants with a CAC score of zero did not alter the association of TC, LDL-C, and non-HDL-C with CIMT. In the subgroup with optimal lipids, these lipid indices remained associated with an increased risk of presence and incidence of CAC and greater CIMT measures. ConclusionsAmong adults aged 32–46 years, in the absence of traditional CVRFs, elevated cholesterol levels, even within what is considered optimal, are associated with atherosclerosis and arteriopathy.

Contemporary approach to heavily calcified lesions: tools of the trade, challenges, and pitfalls

Coronary artery calcifications (CAC) affect more than 90% of men and more than 67% of women older than 70; the spread is mainly due to the high occurrence of major cardiovascular risk factors. The presence of CAC can be detected by several noninvasive and invasive methods like computed tomography (CT), coronary angiography (CA), Intravascular Ultrasound (IVUS), and Optical Coherence Tomography (OCT), with each system providing different information that can be used in the treatment strategy of CAC. Several devices can modify calcium during PCI: high-pressure non-compliant balloons, cutting/scoring balloons, atheroablative technologies, and intravascular Lithotripsy (IVL). Each technique has advantages and disadvantages that every interventional cardiologist should know to perform an optimal PCI and to achieve the best result and clinical outcome. This is a narrative review that aims to illustrate the contemporary management of CAC, focusing on the available techniques to assess calcifications and their novel advancements and explaining the existing tools to treat CAC with a focus on their significant challenges and pitfalls.

Small Dense Low-Density Lipoprotein Cholesterol and Coronary Artery Calcification in the Multi-Ethnic Study of Atherosclerosis.

Elevated small dense-LDL-cholesterol (sd-LDL-C) increases atherosclerotic cardiovascular disease (CVD) risk. Although coronary artery calcium (CAC) is widely used for predicting CVD events, few studies have examined the relationship between sd-LDL-C and CAC. This study included 4672 individuals with directly-measured baseline sd-LDL-C and CAC from the Multi-Ethnic Study of Atherosclerosis (mean [SD] age: 61.9 [10.4] years; 52.5% women; 47.3% with baseline CAC [mean score >0]). We used multivariable general linear models and restricted cubic splines with goodness of fit testing to evaluate the association of sd-LDL-C with the presence of CAC. Odds ratios (OR [95% CI]) were adjusted for demographics and cardiovascular risk factors, including estimated total LDL-C. Higher quartiles of sd-LDL-C were associated with presence of CAC, even after accounting for total LDL-C. Compared to the lowest quartile of sd-LDL-C, participants in Quartiles 2, 3 and 4 had higher odds for the presence of baseline CAC (Quartile 2 OR: 1.24 [1.00, 1.53]; Quartile 3 OR: 1.51 [1.19, 1.93]; and Quartile 4 OR 1.59 [1.17, 2.16]). Splines suggested a quadratic curvilinear relationship of continuous sd-LDL-C with CAC after adjustment for demographics and CVD risk factors (quadratic vs. first-order sd-LDL-C terms likelihood ratio test: p=0.015), but not after accounting for total LDL-C (quadratic vs. first-order terms: p=0.156). In a large, multi-ethnic sample without known CVD, higher sd-LDL-C was associated with the presence of CAC, above and beyond total LDL-C. Whether selective direct measurement of sd-LDL-C is indicated to refine cardiovascular risk assessment in primary prevention warrants further investigation.

Plasma proteomics for prediction of subclinical coronary artery calcifications in primary prevention

Recent developments in high-throughput proteomic technologies enable the discovery of novel biomarkers of coronary atherosclerosis. The aims of this study were to test if plasma protein subsets could detect coronary artery calcifications (CAC) in asymptomatic individuals and if they add predictive value beyond traditional risk factors. Using proximity extension assays, 1,342 plasma proteins were measured in 1,827 individuals from the Impaired Glucose Tolerance and Microbiota (IGTM) study and 883 individuals from the Swedish Cardiopulmonary BioImage Study (SCAPIS) aged 50-64 years without history of ischaemic heart disease and with CAC assessed by computed tomography. After data-driven feature selection, extreme gradient boosting machine learning models were trained on the IGTM cohort to predict the presence of CAC using combinations of proteins and traditional risk factors. The trained models were validated in SCAPIS. The best plasma protein subset (44 proteins) predicted CAC with an area under the curve (AUC) of 0.691 in the validation cohort. However, this was not better than prediction by traditional risk factors alone (AUC = 0.710, P = .17). Adding proteins to traditional risk factors did not improve the predictions (AUC = 0.705, P = .6). Most of these 44 proteins were highly correlated with traditional risk factors. A plasma protein subset that could predict the presence of subclinical CAC was identified but it did not outperform nor improve a model based on traditional risk factors. Thus, support for this targeted proteomics platform to predict subclinical CAC beyond traditional risk factors was not found.

Artificial Intelligence in Coronary Artery Calcium Scoring Detection and Quantification.

Coronary artery calcium (CAC) is a marker of coronary atherosclerosis, and the presence and severity of CAC have been shown to be powerful predictors of future cardiovascular events. Due to its value in risk discrimination and reclassification beyond traditional risk factors, CAC has been supported by recent guidelines, particularly for the purposes of informing shared decision-making regarding the use of preventive therapies. In addition to dedicated ECG-gated CAC scans, the presence and severity of CAC can also be accurately estimated on non-contrast chest computed tomography scans performed for other clinical indications. However, the presence of such "incidental" CAC is rarely reported. Advances in artificial intelligence have now enabled automatic CAC scoring for both cardiac and non-cardiac CT scans. Various AI approaches, from rule-based models to machine learning algorithms and deep learning, have been applied to automate CAC scoring. Convolutional neural networks, a deep learning technique, have had the most successful approach, with high agreement with manual scoring demonstrated in multiple studies. Such automated CAC measurements may enable wider and more accurate detection of CAC from non-gated CT studies, thus improving the efficiency of healthcare systems to identify and treat previously undiagnosed coronary artery disease.

Association between bone mineral density and coronary plaque burden in patients with coronary artery disease: a cross-sectional study using quantitative computed tomography.

To evaluate the association between osteoporosis and coronary calcification and coronary plaque burden in patients with atherosclerosis and coronary artery disease (CAD). This study included 290 men and 177 postmenopausal women with angiography-confirmed atherosclerosis or CAD who underwent chest multidetector row computed tomography covering L1-L2 between September 2020 and October 2021. Quantitative computed tomography was used to measure the lumbar vertebra's bone mineral density (BMD). The coronary artery calcium score (CACS) and total coronary plaque burden were quantified using the Agatston and modified Gensini scores, respectively. Associations between BMD and CACS and modified Gensini scores were assessed using multivariate regression analysis. Lasso regression was used in model selection. In men, BMD was inversely associated with CACS [ β  = -0.24; 95% confidence interval (CI), -0.35 to -0.13; P  < 0.001) and coronary artery calcification (CAC) presence [odds ratio (OR) = 0.71; 95% CI, 0.52-0.96; P  = 0.03) in the unadjusted model. After adjusting for age, modified Gensini score, prior percutaneous coronary intervention and hypertension, BMD was inversely associated with CACS ( β  = -0.11; 95% CI, -0.22 to -0.01; P  = 0.04). In postmenopausal women, BMD was inversely associated with CACS ( β  = -0.24; 95% CI, -0.39 to 0.10; P  < 0.001) and CAC presence (OR = 0.66; 95% CI, 0.47-0.92; P  = 0.01) in the unadjusted model but no other models ( P  > 0.05). In both sexes, BMD did not correlate with the modified Gensini score or CAD prevalence (all P  > 0.05). In patients with coronary atherosclerosis and CAD, BMD of the lumbar vertebra correlated inversely with CACS in men but not postmenopausal women. Additionally, BMD did not correlate with the modified Gensini score in both sexes.

Coronary artery calcium and the risk of a cardiovascular events and mortality in younger adults: a meta-analysis.

ACC/AHA 2019 prevention guidelines recommend utilizing coronary artery calcium (CAC) to stratify cardiovascular risk in selected cases. However, data regarding CAC and risk in younger adults is less robust due to the lower prevalence of CAC and lower incidence of events. The objective of this meta-analysis is to determine the ability of CAC to predict the risk of cardiovascular events and mortality in adults less than 50. PubMed and Cochrane CENTRAL databases were electronically searched through May 2022 for studies with a primary prevention cohort under age 55 who underwent CAC scoring. Six observational studies with a total of 45,919 individuals with an average age of 43.1 and mean follow-up of 12.1 years were included. The presence of CAC was associated with an increased risk of adverse events (pooled hazard ratio (HR) = 1.80, 95% confidence interval (CI) 1.26-2.56, P = 0.012, I2 = 65.5). Compared to a CAC of 0, a CAC of 1-100 did carry an increased risk of cardiovascular events (pooled HR = 1.85, 95% CI 1.08-3.16, p = 0.0248, I2 = 50.3), but not mortality (pooled HR = 1.20, 95% CI 0.85-1.69, p = 0.2917), while a CAC > 100 did carry an increased risk of cardiovascular events (pooled HR = 6.57, 95% CI 3.23-13.36, p < 0.0001, I2 = 72.6) and mortality (pooled HR = 2.91, 95% CI 2.23-3.80, p < 0.0001) . In a meta-analysis of younger adults undergoing CAC scoring, a CAC of 1-100 was associated with a higher likelihood of cardiovascular events, while a CAC>100 was associated with a higher likelihood of cardiovascular events and mortality.

Using Artificial Intelligence to Semi-Quantitate Coronary Calcium as an ‘Incidentaloma’ on Non-Gated, Non-Contrast CT Scans, A Single-Center Descriptive Study in West Michigan.

INTRODUCTION Non-gated, non-contrast computed tomography (CT) scans are commonly ordered for a variety of non-cardiac indications, but do not routinely comment on the presence of coronary artery calcium (CAC)/atherosclerotic cardiovascular disease (ASCVD) which is known to correlate with increased cardiovascular risk. Artificial intelligence (AI) algorithms can help detect and quantify CAC/ASCVD which can lead to early treatment and improved outcomes. METHODS Using an FDA-approved algorithm (NANOX AI) to measure coronary artery calcium (CAC) on non-gated, non-contrast CT chest, 536 serial scans were evaluated in this single-center retrospective study. Scans were categorized by Agatston scores as normal-mild (&lt;100), moderate (100-399), or severe (≥400). AI results were validated by cardiologist’s overread. Patient charts were retrospectively analyzed for clinical characteristics. RESULTS Of the 527 patients included in this analysis, a total of 258 (48.96%) had moderate-severe disease; of these, 164 patients (63.57%, p&lt; 0.001) had no previous diagnosis of CAD. Of those with moderate-severe disease 135 of 258 (52.33% p=0.006) were not on aspirin and 96 (37.21% p=0.093) were not on statin therapy. Cardiologist interpretation demonstrated 88.76% agreement with AI classification. DISCUSSION/CONCLUSION Machine learning utilized in CT scans obtained for non-cardiac indications can detect and semi-quantitate CAC accurately. Artificial intelligence algorithms can accurately be applied to non-gated, non-contrast CT scans to identify CAC/ASCVD allowing for early medical intervention and improved clinical outcomes.

Reporting of coronary artery calcification on chest CT studies in patients with interstitial lung disease

To evaluate the prevalence of coronary artery calcification (CAC) on non-contrast computed tomography (CT) of the thorax in patients with interstitial lung disease (ILD), assess consistency of CAC reporting and assess incidence of subsequent cardiac events. Patients with known interstitial lung disease who underwent a CT thorax over a 2-year period were retrospectively reviewed. Presence of CAC was assessed using a visual scale for CAC reporting and graded as mild, moderate, or severe by two cardiothoracic radiologists. CT reports were reviewed to determine if presence of CAC had been described. Electronic medical records were reviewed for any subsequent cardiothoracic events from the date of the CT thorax to present. 254 patients were included in the analysis (54.7% men; mean age 59.9 yo). 43.7% had CAC on their CT thorax; however, in 87.3% of those, reports did not comment on its presence. 8 patients had cardiac events; 7 of them had CAC on CT although only in 1 case this was reported. Global CAC and LAD CAC Patients with cardiac events had a significantly higher global CAC (p=0.016) and LAD CAC (p=0.048) when compared to patients without. We demonstrated a high prevalence of CAC in ILD patients and its significant association with adverse cardiac events. Unfortunately, CAC on CT thorax is still largely unreported. As per recent BSCI/BSCCT and BSTI guidelines, reporting of CAC should become part of routine practice, as may prompt prevention and impact on patients outcome.

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.

Coronary artery calcification is associated with smaller increases in femoral neck bone mineral density with anti-resorptive therapy

Abstract Introduction Patients with osteoporosis are at high cardiovascular risk, partly due to vascular calcification, such as in the coronary vessels. It is uncertain if the presence of coronary artery calcification (CAC) effects bone mineral density (BMD) response to anti-resorptive treatment – first line therapy for osteoporosis. We therefore assessed changes in BMD following initiation of anti-resorptive treatment for osteoporosis in patients with and without evidence of CAC. Methods Individuals dispensed at least one prescription for an anti-resorptive medication (bisphosphonates or denosumab) at Monash Health between 2009-2022 were identified. Unique record numbers for these individuals were then cross-matched against the cardiac CT imaging service at Monash Heart (HREC#73603). CAC was detected using a 320-slice CT coronary angiogram (CTCA). We included only those patients having a baseline BMD measurement within two years of CTCA. The annualised percentage change in femoral neck BMD was calculated and adjusted for age, sex, height, weight, and number of years on anti-resorptive treatment. Results 106 individuals were identified of which 85 (women=70 [85%], median age=73 years [interquartile range 64-79 years]) had a follow-up BMD measurement including 19 with, and 66 without, evidence of CAC. Those with CAC were older (76 years versus 64 years, p&amp;lt;0.001). There were 70 bisphosphonate users and 15 denosumab users. Individuals with evidence of CAC experienced, on average, a 1.2% lower increase [(0.345% (0.343 to 0.348) versus -0.881% (-0.883 to -0.879), mean difference -1.226% (-1.493 to -0.959; p&amp;lt;0.05)] in annualised femoral neck BMD with anti-resorptive therapy after adjusting for important clinical risk factors. Interpretation These preliminary data suggests that CTCA-determined CAC may negatively impact femoral neck BMD increases with anti-resorptive therapy. This is perhaps consistent with existing and evolving hypotheses of dysregulatory processes driving ectopic calcium deposition, which we surmise would partially counter the effects of anti-resorptive therapy and potentially manifest as CAC. Thus, of particular interest will be the comparison of cardiovascular outcomes of patients with known CAC with and without anti-resorptive therapy, with the hypothesis that anti-resorptive therapy may potentially have cardioprotective effects in context of CAC. Analysis of the full cohort is underway.Table 1

Abstract 12041: Coronary Artery Calcium and All-Cause Mortality in the Multicenter Aids Cohort Study: MACS

Introduction: People living with HIV (PLWH) have more subclinical cardiovascular disease than people without HIV (PWOH), but few studies have evaluated risk for mortality based on coronary artery calcium (CAC) among this population. Purpose: This study aimed to determine the association between CAC and all-cause mortality among male PLWH and PWOH and to identify a potential interaction with HIV serostatus. Methods: The study population was derived from the MACS, a US prospective observational cohort study including male PLWH and PWOH. Participants underwent cardiac non-contrast computed tomography from July 2004 to November 2013. Men with atrial fibrillation, coronary heart disease, or coronary revascularization were excluded. Cox proportional hazards model was used to calculate adjusted hazard ratios [aHR] for all-cause mortality among men with vs. without baseline CAC (Agatston score&gt;0) and per standard deviation (SD) increment in continuous Agatston score [log (CAC+1)], controlling for demographic and cardiac risk factors. CAC differences by HIV serostatus were evaluated using multiplicative CACхHIV interaction terms. Results: Among 1344 males (mean age 50 years, CAC prevalence 46%, 823 (61%) PLWH), we observed 110 deaths (13%) among PLWH and 41 deaths (8%) among PWOH during the follow-up period (median: 13.4 years). Among PLWH, 62% had an undetectable plasma HIV viral load, the median CD4 cell nadir was 284 cells/μL, and 17% had a history of clinical AIDS. The age-adjusted mortality rate was 13.5 (95% CI: 11.0-16.5) among PLWH and 7.8 (5.4-10.9) among PWOH per 1000 person-years. CAC presence was associated with all-cause mortality among all participants (aHR=1.47, 95% CI: 1.02-2.11, p=0.04), and among PLWH (aHR=1.61, 1.04-2.47, p=0.03). In PWOH, we found no significant association (aHR=1.27, 0.63-2.59, p=0.50), although the interaction was not significant (p= 0.49). Higher log (CAC+1) was also associated with all-cause mortality among all participants (aHR=1.37 per SD, 1.15-1.63, p&lt;0.001) and among strata (PLWH, aHR=1.40, 1.13-1.73, p=0.002; and PWOH aHR=1.38, 1.00-1.91, p=0.049). Conclusion: CAC predicts all-cause mortality in a large cohort of PLWH and PWOH, with no significant difference in this association by HIV serostatus.

Abstract 13805: Associations of Subclavian Artery Calcification With Future Cardiovascular Events and Death: The Multi-Ethnic Study of Atherosclerosis

Introduction: Atherosclerosis affects the upper limbs and may be a marker of diffuse atherosclerosis and increased risk for cardiovascular events. Hypothesis: Subclavian artery calcification (SAC) and thoracic aorta calcification (TAC) obtained by chest CT provide additional information about future CV events and death beyond coronary artery calcification (CAC) and CV risk factors. Methods: Chest CT scans of MESA participants (N = 2519) at exam 5 (2016-18) were interrogated for the presence and extent of SAC, TAC, and CAC. Proportional hazards regression was conducted for associations with incident total CVD events (n = 209), adjusted for age, race/ethnicity, and sex, then SAC, TAC, and CAC adjusted for demographics and each other, and finally adding adjustment for CV risk factors. Results: The mean age of the sample was 68.3±9.2 years; 48% were male, 27% Black, 13% Chinese, 22% Hispanic, 38% White. The prevalence of any calcification was 62% for SAC, while being 60 and 69% for TAC and CAC, respectively. Among those with any calcification, N and median Agatston score were SAC: 1704, 76; TAC: 1655, 152; CAC 1896, 135. CAC predicted future events in all models (Table). After adjustment for demographics, the ln(Agatston score +1) in each calcified vascular bed predicted future CVD. Mean±SD of the predictors were ln(SAC+1): 2.4±2.4, ln(TAC+1) 2.7±2.9 and ln(CAC+1) 3.1±2.6. SAC, but not TAC, was still predictive after mutual adjustment. SAC was marginally predictive (HR: 1.08, p = 0.06) when CV risk factors were also included in the model. Conclusions: Calcification was common in all 3 vascular beds, but there is no evidence that predictions using SAC and TAC are independent of CAC. We speculate that although the tendency to calcify is similar across vascular beds, CAC is most relevant for incident CVD.

Identification of novel biomarkers for the prediction of subclinical coronary artery atherosclerosis in patients with rheumatoid arthritis: an exploratory analysis

BackgroundCardiovascular (CV) risk estimation calculators for the general population underperform in patients with rheumatoid arthritis (RA). The purpose of this study was to identify relevant protein biomarkers that could be added to traditional CV risk calculators to improve the capacity of coronary artery calcification (CAC) prediction in individuals with RA. In a second step, we quantify the improvement of this prediction of CAC when these circulating biomarkers are added to standard risk scores.MethodsA panel of 141 serum and plasma proteins, which represent a broad base of both CV and RA biology, were evaluated and prioritized as candidate biomarkers. Of these, 39 proteins were selected and measured by commercial ELISA or quantitative mass spectroscopy in 561 individuals with RA in whom a measure of CAC and frozen sera were available. The patients were randomly split 50:50 into a training/validation cohort. Discrimination (using area under the receiver operator characteristic curves) and re-classification (through net reclassification improvement and integrated discrimination improvement calculation) analyses were performed first in the training cohort and replicated in the validation cohort, to estimate the increase in prediction accuracy for CAC using the ACA/AHA (American College of Cardiology and the American Heart Association) score with, compared to without, addition of these circulating biomarkers.ResultsThe model containing ACC/AHA score plus cytokines (osteopontin, cartilage glycoprotein-39, cystatin C, and chemokine (C–C motif) ligand 18) and plus quantitative mass spectroscopy biomarkers (serpin D1, paraoxonase, and clusterin) had a statistically significant positive net reclassifications index and integrated discrimination improvement for the prediction of CAC, using ACC/AHA score without any biomarkers as the reference category. These results were confirmed in the validation cohort.ConclusionIn this exploratory analysis, the addition of several circulating CV and RA biomarkers to a standard CV risk calculator yielded significant improvements in discrimination and reclassification for the presence of CAC in individuals with RA.

Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials.

This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD =  - 0.06, 95% CI =  - 0.19; 0.06 and SMD = 0.26, 95% CI =  - 0.66; 1.19), but significantly different (p-value = 0.04). Meta-regression and subgroup analyses did not show any significant differences in pooled estimates across covariates. The effect of statins on CAC differs across study designs. OSs demonstrate associations between statin use and higher CAC scores and presence while being prone to confounding by indication. Effects from RCTs do not reach statistical significance and vary depending on the quantification method, hampering drawing conclusions. Further investigations are required to address the limitations inherent in each approach.

Low-density lipoprotein subclasses over the menopausal transition and risk of coronary calcification and carotid atherosclerosis: the SWAN Heart and HDL ancillary studies.

Perimenopausal women experience a steep increase in low-density lipoprotein cholesterol (LDL-C) that is related to a higher risk of carotid plaque later in life. Low-density lipoprotein subclasses have been linked to cardiovascular diseases beyond LDL-C, promising a better risk stratification. We aim to characterize changes in LDL subclasses and assess their associations with presence of coronary artery calcium (CAC score ≥10) and carotid intima-media thickness (cIMT) over the menopausal transition (MT) and by menopause stage. Nuclear magnetic resonance spectroscopy LDL subclasses were measured for a maximum of five time points. Coronary artery calcification and cIMT were measured for a maximum of two time points. LOESS (locally weighted regression with scatter smoothing) plots, linear mixed-effects models, and generalized estimating equations were used for analyses. The study included 471 women (baseline: age, 50.2 ± 2.7 years; 79.0% premenopausal/early perimenopausal), of whom 221 had data on CAC or cIMT. Low-density lipoprotein subclasses increased over the MT, whereas intermediate density-lipoprotein particles declined. In adjusted models, higher total LDL particles (LDL-P) and apolipoprotein B were associated with greater CAC prevalence and greater cIMT. Although none of the associations were modified by menopause stage, higher LDL-C, apolipoprotein B, and total LDL-P were associated with greater cIMT during the perimenopause or postmenopause stages, whereas higher LDL-C and small LDL-P were associated with greater CAC prevalence, mainly during perimenopause. During the MT, women experience significant increases in LDL subclasses found to be related to greater cIMT levels and CAC prevalence. Whether these changes could better predict future risk of hard cardiovascular disease events beyond LDL-C remains a research question to address.

Impaired metabolism predicts coronary artery calcification in women with systemic lupus erythematosus

Patients with systemic lupus erythematosus (SLE) exhibit a high risk for cardiovascular diseases (CVD) which is not fully explained by the classical Framingham risk factors. SLE is characterized by major metabolic alterations which can contribute to the elevated prevalence of CVD. A comprehensive analysis of the circulating metabolome and lipidome was conducted in a large cohort of 211 women with SLE who underwent a multi-detector computed tomography scan for quantification of coronary artery calcium (CAC), a robust predictor of coronary heart disease (CHD). Beyond traditional risk factors, including age and hypertension, disease activity and duration were independent risk factors for developing CAC in women with SLE. The presence of coronary calcium was associated with major alterations of circulating lipidome dominated by an elevated abundance of ceramides with very long chain fatty acids. Alterations in multiple metabolic pathways, including purine, arginine and proline metabolism, and microbiota-derived metabolites, were also associated with CAC in women with SLE. Logistic regression with bootstrapping of lipidomic and metabolomic variables were used to develop prognostic scores. Strikingly, combining metabolic and lipidomic variables with clinical and biological parameters markedly improved the prediction (area under the curve: 0.887, p<0.001) of the presence of coronary calcium in women with SLE. The present study uncovers the contribution of disturbed metabolism to the presence of coronary artery calcium and the associated risk of CHD in SLE. Identification of novel lipid and metabolite biomarkers may help stratifying patients for reducing CVD morbidity and mortality in SLE. INSERM and Sorbonne Université.

Is coronary artery calcium an independent risk factor for white matter hyperintensity?

BackgroundCardiovascular diseases have been considered the primary cause of disability and death worldwide. Coronary artery calcium (CAC) is an important indicator of the severity of coronary atherosclerosis. This study is aimed to investigate the relationship between CAC and white matter hyperintensity (WMH) in the context of diagnostic utility.MethodsA retrospective analysis was conducted on 342 patients with a diagnosis of WMH on magnetic resonance images (MRI) who also underwent chest computed tomography (CT) scans. WMH volumes were automatically measured using a lesion prediction algorithm. Subjects were divided into four groups based on the CAC score obtained from chest CT scans. A multilevel mixed-effects linear regression model considering conventional vascular risk factors assessed the association between total WMH volume and CAC score.ResultsOverall, participants with coronary artery calcium (CAC score > 0) had larger WMH volumes than those without calcium (CAC score = 0), and WMH volumes were statistically different between the four CAC score groups, with increasing CAC scores, the volume of WMH significantly increased. In the linear regression model 1 of the high CAC score group, for every 1% increase in CAC score, the WMH volume increases by 2.96%. After including other covariates in model 2 and model 3, the β coefficient in the high CAC group remains higher than in the low and medium CAC score groups.ConclusionIn elderly adults, the presence and severity of CAC is related to an increase in WMH volume. Our findings suggest an association between two different vascular bed diseases in addition to traditional vascular risk factors, possibly indicating a comorbid mechanism.