Higher Coronary Artery Calcium Research Articles

Association between physical activity and coronary artery calcification estimated by computed tomography: A systematic review

BackgroundThe relationship between physical activity and coronary artery calcification (CAC) was evaluated in different studies during the last years, although the results were conflicting. ObjectiveThe main objective of the present systematic review was to assess the association between different levels of physical activity and CAC score estimated by computed tomography (CT). MethodsThis systematic review was performed according to PRISMA guidelines. A literature search was performed to detect studies that evaluated the association between physical activity and CAC score. The levels of physical activity evaluated were those reported by the original publications. The CAC score was estimated by CT and was reported in Agatston units. ResultsTwenty six studies including 89,405 subjects were considered eligible for this research. The studies developed in the general population showed different results regarding the association between physical activity and CAC score: no association (7 studies), a positive association (4 studies), an inverse relationship (6 studies), a U-shaped relationship (2 studies), or different results depending on the subgroup evaluated (2 studies). In the largest studies, a positive association was observed. When we analyzed the studies that evaluated athletes, four studies showed a positive association between exercise intensity and CAC. ConclusionThis systematic review showed disparate results regarding the association between physical activity and CAC score. The largest studies and most studies developed in athletes suggest that intense physical activity could be associated with high CAC score, although this hypothesis should be confirmed in future research.

Abstract 13889: Effect of Eicosapentaenoic and Docosahexaenoic Acid Supplementation on Noncalcified Coronary Plaque and Coronary Artery Calcium Score in Subjects With Coronary Artery Disease According to Hypertension Status

Introduction: Higher amounts of noncalcified plaque and higher coronary artery calcium (CAC) scores are associated with increased cardiovascular events and mortality. The effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on noncalcified coronary plaque and more advanced calcified plaque as measured by the CAC score according to hypertensive (HTN) status is unknown. Methods: A total of 242 subjects with coronary artery disease (CAD) on statin were randomized to 3.36 g of EPA+DHA or none (control) for 30 months. Coronary plaque composition and CAC scores were measured with computed tomographic coronary angiography at baseline and 30-month follow-up. Results: Mean (SD) age was 63.1 years (7.7); mean (SD) LDL-C: 77.8 mg/dL (27.3) and median [IQR] triglyceride (TG): 117.5 mg/dL [81.3,166.8]. Despite a significantly higher CAC score at baseline in HTN subjects, both HTN and normotensive (NTN) subjects had similar CAC progression over 30 months with no difference between EPA+DHA and control groups (Figure B). NTN subjects on EPA+DHA had a 20.7% reduction in TG level and 36.6% lower neutrophil count, a marker of inflammation, and lack of progression of noncalcified plaque compared to control who had progression (median % change: -7.6 vs 13.2 mm 3 /mm, P=0.008) (Figure A). In contrast, HTN subjects on EPA+DHA and control had progression of noncalcified coronary plaque with no significant difference between the two groups (Figure A) Conclusions: EPA+DHA prevented progression of noncalcified plaque in NTN subjects but not HTN subjects with no effect on more advanced plaque which has calcified in the setting of low LDL-C and TG levels. The benefit of EPA+DHA in CAD patients on statin therapy appears limited to noncalcified coronary plaque in NTN subjects. Whether this benefit is related to more favorable effects on inflammation based on blood pressure status should be examined further.

Coronary artery calcium score and its association with stroke: A systematic review and meta-analysis.

The relationship between coronary artery calcium (CAC) score and incident stroke is controversial. We conducted a systematic review of the literature evaluating CAC score and incident stroke. A search of MEDLINE and EMBASE was performed, and data were extracted from relevant studies. Statistical pooling with random-effects meta-analysis was undertaken to evaluate the risk of incident stroke with any CAC vs. no CAC, 1-100 CAC vs. no CAC, and >100 CAC vs. no CAC. Data from nine different cohort studies from the United States and Europe with a total of 61,096 patients were included in this review. The mean age of patients in the studies ranged from 44 to 69 years, and follow-up duration ranged from a median of 5.5 years to 12.3 years. The crude stroke event varied from 1.6% to 9.5%. Meta-analysis of risk of incident stroke with any vs. no CAC (RR 1.70 95% CI 0.87-3.31, I2 = 95%) and for CAC 1-100 vs. no CAC (RR 1.54 95% CI 0.75-3.17, I2 = 93%) was not statistically significant. For CAC >100, the risk of incident stroke was significantly higher compared with no CAC (RR 2.61 95% CI 1.51-4.52, I2 = 89%). When one study which included only young adults was excluded, there was significant increase in risk of incident stroke with all categories of CAC. There is an association between high CAC score and incident stroke, but more studies are needed to determine how patients with incidental CAC should be managed from the perspective of stroke prevention.

Prognostic value of FFRCT in patients with stable chest pain – a 3-year follow-up of the ADVANCE-DK registry

Abstract Introduction The short-term safety of using coronary CT angiography (CTA) derived fractional flow reserve (FFRCT) to guide downstream testing after CTA is well documented. Whether the prognostic information provided by FFRCT can be extended to sustained follow-up and to patients with a high degree of coronary artery calcification (CAC) is unknown. Purpose To evaluate the association between FFRCT and clinical outcomes in new onset stable symptomatic patients with coronary stenosis up to 3 years after CTA index testing. Methods Multicenter 3-year follow-up study of 900 patients from the Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care (ADVANCE) registry at three Danish sites, the “ADVANCE-DK Registry”. All patients had at least one ≥30% coronary stenosis by CTA and underwent subsequent core laboratory FFRCT analysis by HeartFlow. The criterium for an abnormal FFRCT test result was an FFRCT value ≤0.80 (2 cm distal to stenosis). High CAC was defined as a CAC score ≥400. The primary endpoint (PE) was a composite of all-cause death and spontaneous myocardial infarction (MI). The secondary endpoint (SE) was a composite of cardiovascular (CV) death and spontaneous MI. Events were adjudicated by an independent clinical committee. Results Patient characteristics are given in Table 1. Coronary stenosis ≥50% was present in 750 (83%) patients. In total 36 patients suffered a PE (all-cause death, n=24; MI, n=12) and 22 an SE (CV death, n=10; MI, n=12). An abnormal vs a normal FFRCT test result was associated with an increased risk of the PE and of the SE both overall and in patients with high CAC; PE (all), 6.6% vs 2.1%, relative risk (RR): 3.1; 95% CI: 1.6–6.3, p<0.001, SE (all), 5.0% vs 0.6%, RR: 8.7; 95% CI: non assessable, p<0.001, PE (high CAC), 9.0% vs 2.2%, RR: 4.1; 85% CI: 1.4–11.8, p=0.001, and SE (high CAC), 6.6% vs 0.5%, RR: 12.0; 95% CI: non assessable, p=0.01, respectively, Figure 1. The observed increased risk in patients with an abnormal vs a normal FFRCT test result persisted after adjustment for degree of stenosis by CCTA (< / ≥50%) and amount of CAC (< / ≥400): PE, adjusted RR: 2.5; 95% CI: 1.2–5.2, p=0.02, and SE, adjusted RR: 8.0; 95% CI: 2.1–30.2, p=0.002. Conclusion Patients with stable chest pain, stenosis by CTA and a normal FFRCT test result have a low risk of adverse outcomes during 3 years of follow-up. An abnormal FFRCT identifies patients at increased risk of death or spontaneous MI. These associations are consistent in patients with high levels of CAC. Funding Acknowledgement Type of funding sources: None.

Associations of segment-specific pulse wave velocity with vascular calcification: the Atherosclerosis Risk in Communities (ARIC) Study

Abstract Background Pulse wave velocity (PWV) is a non-invasive measure of arterial stiffness and a predictor of cardiovascular disease (CVD). Vascular calcification, especially coronary artery calcium (CAC) measured by computed tomography (CT), is one of the strongest predictors of CVD but requires radiation for measurement. PWV may be helpful to identify persons with vascular calcification who may benefit from formal assessment of vascular calcification with CT. However, the associations between PWV and vascular calcification across different vascular beds have not been fully investigated. Purpose The aims of this study were to quantify the association between PWV and calcification at different segments and to explore whether PWV can identify individuals with vascular calcification beyond traditional risk factors. Methods Among 1486 ARIC Study participants (mean age 79.3 [SD 4.2] years), we measured PWV by OMRON VP1000plus at the following segments: heart-carotid (hcPWV), heart-femoral (hfPWV), carotid-femoral (cfPWV), heart-ankle (haPWV), brachial-ankle (baPWV) and femoral-ankle (faPWV). Participants were stratified into four groups based on quartiles of each PWV measure. Dependent (i.e., outcome) variables were high calcium score (≥75th percentile of Agatston score by CT) of the following vascular beds (including valves): coronary arteries, aortic valve ring, aortic valve, mitral valve, ascending aorta, and descending aorta. We ran multivariable logistic regression models and assessed c-statistics as a measure of prediction discrimination. Results Only cfPWV was significantly positively associated with high CAC (adjusted odds ratio [OR] for the highest vs. lowest quartile: 1.73 [95% CI: 1.17–2.55]) (green dot in figure). The associations were overall most evident for descending aorta calcification, with significantly positive results for hfPWV (gold dot in figure), cfPWV (green dot), haPWV (emerald dot), and baPWV (blue dot). For example, adjusted OR for the highest vs. lowest quartile of cfPWV was 4.08 (2.70–6.24). hfPWV and cfPWV were significantly associated with mitral valve calcification as well. In contrast, faPWV (purple dots) was inversely associated with calcification of aortic valve ring, ascending aorta, and descending aorta. For descending aorta calcification, even the second highest quartile of the following measures demonstrated significant adjusted OR: hfPWV (3.21 [2.11–4.95]), cfPWV (2.11 [1.40–3.20]), and baPWV (1.75 [1.14–2.69]). Simultaneously adding cfPWV and hfPWV improved c-statistic for CAC (Δc-statistic 0.011 [0.0007–0.022]) and descending aorta calcification (0.035 [0.017–0.053]). Conclusions The associations of PWV with vascular calcification varied substantially across segments, with descending aorta calcification most closely linked to PWV measures and cfPWV most robustly associated with calcification of multiple vascular beds. cfPWV and hfPWV, together, improved discrimination of high CAC beyond traditional risk factors. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The National Heart, Lung, and Blood Institute, National Institutes of Health

Potential impact of replacing SCORE with SCORE-2 on risk classification and statin eligibility – a coronary calcium score correlation study

Abstract Background Recently, the European Society of Cardiology issued new algorithms to estimate the 10-year risk of atherosclerotic cardiovascular disease (ASCVD), along with new age-specific thresholds to classify individuals as low-to-moderate, high, or very-high risk. The aim of this study was to compare the latest SCORE-2 model with the older SCORE (Systematic COronary Risk Evaluation) in their ability to identify individuals with high coronary artery calcium score (CACS), and assess the relationship between potential eligibility for statin therapy and CACS. Methods Individuals 40–69 years old without diabetes or known ASCVD were identified in a single center registry of patients undergoing CACS and coronary CT angiography for suspected coronary artery disease. SCORE and SCORE-2 were calculated and used with each patient's untreated LDL-C values to assess eligibility for statin therapy. High CACS was defined as an Agatston score ≥100. Results A total of 389 pts (46% men, mean age 58±8 years) were included, of which 15% (n=60) were active smokers. The mean systolic blood pressure and untreated LDL-C values were 136±17 mmHg and 155±65 mg/dL, respectively. The proportion of patients classified as low-to-moderate risk, high risk, and very high risk was 93%, 6% and 1% using the SCORE algorithm, and 42%, 44%, and 14% using SCORE-2, respectively. Overall, 218 patients (56%) would have their risk category revised upwards, while no patients would be downgraded. The median CACS was 5 (IQR 0–71 AU), with 166 patients (43%) having CACS = 0, and 81 (21%) presenting CACS values ≥100. SCORE and SCORE-2 showed similar discriminative power to identify patients with CACS ≥100 (C-statistic 0.77, 95% CI 0.71–0.82, vs. 0.75, 95% CI 0.69–0.80, P=0.109 for comparison]. The up-reclassification of risk conveyed by SCORE-2 affected patients across all categories of CACS (Fig. 1). The proportion of patients in whom statin therapy would generally be indicated was higher with the SCORE-2 criteria vs. the SCORE algorithm (61% vs. 29%, respectively, p<0.001). The broadening of potential indication for statin therapy spanned all categories of CACS, including patients with CACS = 0 (Fig. 2). Conclusion Even though the discriminative power of SCORE-2 is similar to the older SCORE, the introduction of age-specific thresholds results in the up-reclassification of risk in roughly half of the patients. The application of SCORE-2 will broaden statin eligibility overall, not only in patients with high atherosclerotic burden, but also in those with CACS = 0. These findings support the use of risk modifiers in selected patients to improve the effectiveness of statin therapy. Funding Acknowledgement Type of funding sources: None.

Correlations Between Coronary Artery Disease, Coronary Artery Calcium Score, and Lipoprotein(a) Level in Korea.

BackgroundLipoprotein(a) (Lp(a)) levels are associated with coronary artery disease (CAD) and aortic valve calcification. This study aimed to determine the correlation between Lp(a) levels and coronary artery calcium (CAC) scores in patients who underwent coronary computed tomography angiography (CCTA).MethodsThis was a single-center observational study. The patients had not been previously diagnosed with CAD and underwent CCTA and Lp(a) measurement in a three-month timeframe. Coronary angiography and further management were performed according to the physician’s decision. Of the 252 patients, 81 and 171 patients underwent coronary revascularization and received medical treatment only, respectively. To examine the relationship between Lp(a) and CAC score and between Lp(a) and CAD, we divided the patients by Lp(a) level (50 mg/dL) and CAC score (400).ResultsNo relationship was observed between Lp(a) and CAD or other risk factors for CAD. There were no differences in the ratio of patients who underwent coronary revascularization or in the CAC score according to an Lp(a) level of 50 mg/dL. There was no difference in Lp(a) level at a CAC score of 400. The proportion of patients who underwent coronary revascularization was high in the high CAC score group (50.6% vs 23.7%, p = 0.000). No association was observed between Lp(a) level and CAC score in the Spearman correlation (0.000, p < 0.998).ConclusionCorrelations between Lp(a) level and CAC score and between Lp(a) and CAD were not observed in this Korean cohort study. However, a high CAC score was correlated with coronary revascularization.

Strenuous Endurance Exercise and the Heart: Physiological versus Pathological Adaptations.

Although the benefits of regular physical activity on cardiovascular health are well established, the effects of strenuous endurance exercise (SEE) have been a matter of debate since ancient times. In this article, we aim to provide a balanced overview of what is known about SEE and the heart-from epidemiological evidence to recent cardiac imaging findings. Lifelong SEE is overall cardioprotective, with endurance master athletes showing in fact a youthful heart. Yet, some lines of research remain open, such as the need to elucidate the time-course and potential relevance of transient declines in heart function (or increases in biomarkers of cardiac injury) with SEE. The underlying mechanisms and clinical relevance of SEE-associated atrial fibrillation, myocardial fibrosis, or high coronary artery calcium scores also remain to be elucidated. © 2022 American Physiological Society. Compr Physiol 12:1-19, 2022.

Association between Coronary Artery Plaque Progression and Liver Fibrosis Biomarkers in Population with Low Calcium Scores.

Background: The severity of nonalcoholic fatty liver disease (NAFLD) has been found to be associated with atherosclerosis burden. However, whether liver fibrosis scores can be used to predict atherosclerosis progression, especially for patients with low calcium scores, remains undetermined. Methods: A total of 165 subjects who underwent repeated coronary computed tomography angiography (CCTA) and had low calcium scores (<100) were enrolled. The segment stenosis score (SSS) from the CCTA was measured, and the association between SSS progression and biochemical parameters was analyzed in addition to liver fibrosis scores, including nonalcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 index (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI), and Forns score. Results: When compared with those without plaque at baseline (SSS = 0), subjects with plaque had higher blood pressure, higher coronary artery calcium (CAC) scores, and higher liver fibrosis scores, including Forns score, Fib-4, and NFS. During the medium follow-up interval of 24.7 months, 60 (39.4%) patients displayed SSS progression, while the remaining 105 (63.6%) patients showed no CAD progression. In a multivariate analysis, being male having a high diastolic blood pressure (DBP), and having a high NFS liver fibrosis score were independently associated with the odds ratio for SSS progression. Conclusions: Higher baseline blood pressure and liver fibrosis markers are associated with the presence of coronary artery disease (CAD) plaques in subjects in early CAD stages. For disease progression, the male gender, DBP, and NFS appear to be independently associated with coronary atherosclerosis plaque progression in subjects with low calcium scores.

Long-term exposure to air pollution, coronary artery calcification, and carotid artery plaques in the population-based Swedish SCAPIS Gothenburg cohort

Long-term exposure to air pollution is associated with cardiovascular events. A main suggested mechanism is that air pollution accelerates the progression of atherosclerosis, yet current evidence is inconsistent regarding the association between air pollution and coronary artery and carotid artery atherosclerosis, which are well-established causes of myocardial infarction and stroke. We studied associations between low levels of long-term air pollution, coronary artery calcium (CAC) score, and the prevalence and area of carotid artery plaques, in a middle-aged population-based cohort.The Swedish CArdioPulmonary bioImage Study (SCAPIS) Gothenburg cohort was recruited during 2013–2017 and thoroughly examined for cardiovascular risk factors, including computed tomography of the heart and ultrasonography of the carotid arteries. In 5070 participants (age 50–64 years), yearly residential exposures to air pollution (PM2.5, PM10, PMcoarse, NOx, and exhaust-specific PM2.5 1990–2015) were estimated using high-resolution dispersion models. We used Poisson regression to examine associations between long-term (26 years’ mean) exposure to air pollutants and CAC score, and prevalence of carotid artery plaques, adjusted for potential confounders. Among participants with carotid artery plaques, we also examined the association with plaque area using linear regression.Mean exposure to PM2.5 was low by international standards (8.5 μg/m3). There were no consistent associations between long-term total PM2.5 exposure and CAC score or presence of carotid artery plaques, but an association between total PM2.5 and larger plaque area in participants with carotid plaques. Associations with traffic-related air pollutants were consistently positive for both a high CAC score and bilateral carotid artery plaques. These associations were independent of road traffic noise. We found stronger associations among men and participants with cardiovascular risk factors. The results lend some support to atherosclerosis as a main modifiable pathway between low levels of traffic-related ambient air pollution and cardiovascular disease, especially in vulnerable individuals.

Pre-screening to guide coronary artery calcium scoring for early identification of high-risk individuals in the general population.

To evaluate the ability of Systematic COronary Risk Estimation 2 (SCORE2) and other pre-screening methods to identify individuals with high coronary artery calcium score (CACS) in the general population. Computed tomography-based CACS quantification was performed in 6530 individuals aged 45 years or older from the general population. Various pre-screening methods to guide referral for CACS were evaluated. Miss rates for high CACS (CACS ≥300 and ≥100) were evaluated for various pre-screening methods: moderate (≥5%) and high (≥10%) SCORE2 risk, any traditional coronary artery disease (CAD) risk factor, any Risk Or Benefit IN Screening for CArdiovascular Disease (ROBINSCA) risk factor, and moderately (>3 mg/24 h) increased urine albumin excretion (UAE). Out of 6530 participants, 643 (9.8%) had CACS ≥300 and 1236 (18.9%) had CACS ≥100. For CACS ≥300 and CACS ≥100, miss rate was 32 and 41% for pre-screening by moderate (≥5%) SCORE2 risk and 81 and 87% for high (≥10%) SCORE2 risk, respectively. For CACS ≥300 and CACS ≥100, miss rate was 8 and 11% for pre-screening by at least one CAD risk factor, 24 and 25% for at least one ROBINSCA risk factor, and 67 and 67% for moderately increased UAE, respectively. Many individuals with high CACS in the general population are left unidentified when only performing CACS in case of at least moderate (≥5%) SCORE2, which closely resembles current clinical practice. Less stringent pre-screening by presence of at least one CAD risk factor to guide CACS identifies more individuals with high CACS and could improve CAD prevention.

468 Potential Impact Of Replacing Score With Score-2 On Risk Classification And Statin Eligibility - A Coronary Calcium Score Correlation Study

Introduction: Recently, the European Society of Cardiology issued new algorithms to estimate the 10-year risk of atherosclerotic cardiovascular disease (ASCVD), along with age-specific thresholds to classify individuals as low-to-moderate, high, or very-high risk. The aim of this study was to compare SCORE-2 with SCORE (Systematic COronary Risk Evaluation) in their ability to identify individuals with high coronary artery calcium score (CACS), and assess the relationship between eligibility for statin therapy and CACS.

Polygenic risk score for hypercholesterolemia in a Brazilian familial hypercholesterolemia cohort

Background and aimsFamilial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of LDL-C leading to premature cardiovascular disease (CAD). Only about 40% of individuals with a clinical diagnosis of FH have a causative genetic variant identified, and a proportion of genetically negative cases may have a polygenic cause rather than a still unidentified monogenic cause. This work aims to evaluate and validate the role of a polygenic risk score (PRS) associated with hypercholesterolemia in a Brazilian FH cohort and its clinical implications. MethodsWe analyzed a previously derived PRS of 12 and 6 SNPs (Single Nucleotide Polymorphism) in 684 FH individuals (491 mutation-negative [FH/M−], 193 mutation-positive [FH/M+]) and in 1605 controls. Coronary artery calcium (CAC) score was also evaluated. ResultsThe PRS was independently associated with LDL-C in control individuals (p < 0.001). Within this group, in individuals in the highest quartile of the 12 SNPs PRS, the odds ratio for CAC score >100 was 1.7 (95% CI: 1.01–2.88, p = 0.04) after adjustment for age and sex. Subjects in the FH/M− group had the highest mean score in both 12 and 6 SNPs PRS (38.25 and 27.82, respectively) when compared to the other two groups (p = 2.2 × 10-16). Both scores were also higher in the FH/M+ group (36.48 and 26.26, respectively) when compared to the control group (p < 0.001 for the two scores) but inferior to the FH/M− group. Within FH individuals, the presence of a higher PRS score was not associated with LDL-C levels or with CAD risk. ConclusionA higher PRS is associated with significantly higher levels of LDL-C and it is independently associated with higher CAC in the Brazilian general population. A polygenic cause can explain a fraction of FH/M− individuals but does not appear to be a modulator of the clinical phenotype among FH individuals, regardless of mutation status.

Serum anti-malondialdehyde-acetaldehyde IgA antibody concentration improves prediction of coronary atherosclerosis beyond traditional risk factors in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) have increased atherosclerosis; oxidative stress may be a contributor. Oxidative stress produces immunogenic malondialdehyde-acetaldehyde (MAA) protein adducts and anti-MAA antibodies are detectable in human serum. We hypothesized that anti-MAA antibody concentrations are associated with coronary atherosclerosis in RA patients. Serum concentrations of anti-MAA antibodies (IgA, IgG, and IgM) were measured in 166 RA patients using ELISA cross-sectionally. Relationship between anti-MAA antibody concentrations and cardiovascular and metabolic measures and predictive accuracy of anti-MAA antibodies for presence of coronary artery calcium (CAC) and high CAC (≥ 300 Agatston units or ≥ 75th percentile) were assessed. Only serum IgA anti-MAA antibody concentration was associated with increased CAC, insulin resistance, and decreased high-density lipoprotein particle number. When added as an interaction term with ACC/AHA 10-year risk score plus high-sensitivity C-reactive protein, IgA anti-MAA antibody concentration improved the C-statistic for prediction of any CAC and high CAC compared to ACC/AHA 10-year risk score plus hs-CRP alone. IgA anti-MAA concentration is associated with multiple cardiovascular risk factors and modifies the relationship between ACC/AHA 10-year risk score and CAC in RA patients. IgA anti-MAA concentration could assist in prediction of atherosclerotic CVD and risk stratification when added to standard measures of cardiovascular risk.

1100-P: Endothelial Protein Expression and Its Association with Type 1 Diabetes

Introduction: People with type 1 diabetes (T1D) have an increased risk of developing cardiovascular disease. Endothelial cell dysfunction is thought to be a factor in this increased risk but underlying cellular mechanisms related to vasodilation, inflammation and oxidative stress are unknown. Methods: Participants with T1D (n= 25) and non-T1D (n=20) were categorized into groups of high (≥80) or low (&amp;lt;15 AU) coronary artery calcium (CAC) , measured by computed tomography. Protein expression was assessed for endothelial Nitric Oxide Synthase [eNOS], estrogen receptors (ER) α and ER-β (women only) , nuclear factor [NF]κβ and nicotinamide adenine dinucleotide phosphate [NADPH] using quantitative immunofluorescence in peripheral venous endothelial cells harvested by endovascular biopsy. SphygmoCor Pulse Wave Velocity (PWV) measured arterial stiffness. Linear regression was used to test associations of high vs. low CAC and T1D with proteins of interest. All models included age, sex, CAC and diabetes. Results: As shown in table 1, eNOS and NADPH were lower and NFκβ and Nitrotyrosine [NT] were higher in T1D compared to non-T1D participants with low CAC. Among T1D, PWV was higher in those with high vs. low CAC. Among non-T1D participants, eNOS was lower and NT and ER-α were lower in those with high vs. low CAC. Conclusions: T1D is associated with adverse endothelial proteins that may contribute to endothelial dysfunction and vascular disease. Disclosure H.K.Wise: None. A.Keshawarz: None. K.Moreau: None. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc.

Complex association of apolipoprotein E-containing HDL with coronary artery disease burden in cardiovascular disease.

BackgroundAlthough traditional lipid parameters and coronary imaging techniques are valuable for cardiovascular disease (CVD) risk prediction, better diagnostic tests are still needed.MethodsIn a prospective, observational study, 795 individuals had extensive cardiometabolic profiling, including emerging biomarkers, such as apolipoprotein E–containing HDL-cholesterol (ApoE-HDL-C). Coronary artery calcium (CAC) score was assessed in the entire cohort, and quantitative coronary computed tomography angiography (CCTA) characterization of total burden, noncalcified burden (NCB), and fibrous plaque burden (FB) was performed in a subcohort (n = 300) of patients stratified by concentration of ApoE-HDL-C. Total and HDL-containing apolipoprotein C-III (ApoC-III) were also measured.ResultsMost patients had a clinical diagnosis of coronary artery disease (CAD) (n = 80.4% of 795), with mean age of 59 years, a majority being male (57%), and about half on statin treatment. The low ApoE-HDL-C group had more severe stenosis (11% vs. 2%, overall P < 0.001), with higher CAC as compared with high ApoE-HDL-C. On quantitative CCTA, the high ApoE-HDL-C group had lower NCB (β = –0.24, P = 0.0001), which tended to be significant in a fully adjusted model (β = –0.32, P = 0.001) and altered by ApoC-III in HDL levels. Low ApoE-HDL-C was significantly associated with LDL particle number (β = 0.31; P = 0.0001). Finally, when stratified by FB, ApoC-III in HDL showed a more robust predictive value of CAD over ApoE-HDL-C (AUC: 0.705, P = 0.0001) in a fully adjusted model.ConclusionApoE-containing HDL-C showed a significant association with early coronary plaque characteristics and is affected by the presence of ApoC-III, indicating that low ApoE-HDL-C and high ApoC-III may be important markers of CVD severity.Trial RegistrationClinicalTrials.gov: NCT01621594.FundingThis work was supported by the NHLBI at the NIH Intramural Research Program.

MO982: Determinants of Coronary Artery Calcium Score in Stable Kidney Transplant Recipients 12 Months After Transplantation

Abstract BACKGROUND AND AIMS Cardiovascular disease remains the primary cause of death after kidney transplantation. Vascular calcification may at least in part explain excess cardiovascular morbidity and mortality, but little is known about the drivers of vascular calcification after kidney transplantation. Remarkably, some patients with kidney failure develop extensive calcifications, whereas others remain free of calcifications. This study aimed to assess the severity of CAC score and investigate potential determinants of vascular calcification in stable kidney transplant recipients (KTRs) at 12 months after transplantation. The second aim was to compare the characteristics of KTRs without any calcifications versus those with a relatively high CAC score. METHOD Adult KTRs with no prior coronary artery disease and eGFR &amp;gt;30 mL/min/1.73 m2 who visited our center between June 2018 and June 2021 underwent non-contrast computed tomography (CT) of the heart to quantify the coronary artery calcium (CAC)-score, calculated by the Agatston method. CAC-score percentiles were calculated using a CAC nomogram available at https://www.calciumscorecalculator.com. Clinical, laboratory, lifestyle and nutritional data, including bioimpedance analysis (BIA), were collected as part of the TransplantLines Biobank and Cohort Study1. The association between potential determinants and CAC-score percentiles was first studied in univariable multinomial logistic regression analysis and subsequently all variables with P &amp;lt; 0.10 were included in a multivariable multinomial logistic regression analysis to study independent determinants of CAC. We subsequently performed a case control analysis, comparing KTRs without calcifications (no-CAC, n = 36) versus those with relatively high calcium score (CAC ≥75th percentile, n = 36), matched by age, sex and dialysis vintage. RESULTS A total of 203 KTRs (54.0 ± 14.7 year old, 61.1% male) at 12 months after transplantation were included in the main analysis. Participants were categorized into three groups according to CAC-score percentiles {P = 0% (CAC = 0), n = 68; P ≥1%—P ≤ 75% [CAC = 67.5 (6.5–247.0)], n = 52; P &amp;gt; 75%, [CAC = 0], 581 (148.0–1652), n = 83}. Individuals in the highest CAC-score percentile group had lower educational level, heart rate, urinary protein excretion, urinary magnesium excretion, physical functioning score and phase angle assessed by BIA (a marker of both hydration status and body cell mass/integrity), and higher prevalence of diabetes mellitus, dialysis vintage, serum triglycerides, PTH, alkaline phosphatase, calcium, use of statins, use of antihypertensives and use of diuretics. In multivariable-adjusted multinomial logistic regression analysis, donor living status and phase angle were inversely associated with CAC-score &amp;gt;75% (Table 1). In the matched case control analysis, KTR with CAC-score &amp;gt;75% had lower plasma magnesium, albuminuria, and phase angle, and were less likely a recipient from a living donor (Table 2). CONCLUSION This study identifies phase angle, reflecting body cell integrity, as an independent determinant of CAC at 12 months after kidney transplantation. Interestingly, in two subgroups with similar dialysis vintage, KTRs with a CAC score of zero were more likely to have received a kidney from a living donor, and had higher plasma magnesium levels, compared with KTRs with relatively high CAC scores. Futures studies should address whether improving magnesium status could retard calcification progression after kidney transplantation.

Abstract 269: Coronary Artery Calcium As A Predictor For Stenting Outcomes: A Meta-analytic Comparison

Abstract: Coronary Artery Calcium (CAC) measurement and its usefulness to stratify patients by CAD risk remains an area of controversy. Current AHA/ACC guidelines recommend using CAC to guide management on patients with risk factors for CAD but not on optimal medical treatment. The purpose of this study is to investigate the impact of CAC on stenting outcomes. Methods: A systematic review of MEDLINE using PRISMA guidelines was conducted using the search terms CAC, Calcium, Coronary, and Stent. Studies were included if they had an appropriate control group and subdivided high coronary calcium and low coronary calcium measured using an approved imaging modality. Clinical characteristics of patients and outcomes were aggregated according to the Cochrane Manual. A random effects model was used to retrieve odds ratio values. Revman 5.3 was used to aggregate outcomes. Results: A total of 11 studies with 56,725 patients were included. The high CAC cohort included 14,390 patients and Low/No CAC included 42,335 patients. TLR was significantly higher in the high CAC cohort: Odds Ratio: 1.82 [1.37, 2.43], Test for overall effect: Z = 4.08 (P &lt; 0.0001). Heterogeneity was significant amongst the studies for TLR but not amongst TVR or Stent Thrombosis outcomes (Heterogeneity: Tau 2 = 0.14; Chi 2 = 84.08, df = 10 (P &lt; 0.00001); I 2 = 88%). TVR and Stent Thrombosis was significantly higher in the high CAC cohort: Odds Ratio 1.20 [1.14, 1.26] and Odds Ratio 1.42 [1.24, 1.62] Test for overall effect: Z = 5.01 (P &lt; 0.00001) respectively. Conclusion: TLR, TVR, and Stent Thrombosis were all significantly higher in the high CAC cohort as compared to control. Elevated CAC not only provides a description of coronary plaque morphology but also can be used to predict adverse interventional outcomes. Further prospective studies with standard imaging techniques are needed to eliminate any inter-imaging modality differences in CAC characterization.

Relationship Between Coronary Artery Calcium and Atherosclerosis Progression Among Patients With Suspected Coronary Artery Disease

BackgroundAmong symptomatic patients, it remains unclear whether a coronary artery calcium (CAC) score alone is sufficient or misses a sizeable burden and progressive risk associated with obstructive and nonobstructive atherosclerotic plaque. ObjectivesAmong patients with low to high CAC scores, our aims were to quantify co-occurring obstructive and nonobstructive noncalcified plaque and serial progression of atherosclerotic plaque volume. MethodsA total of 698 symptomatic patients with suspected coronary artery disease (CAD) underwent serial coronary computed tomographic angiography (CTA) performed 3.5 to 4.0 years apart. Atherosclerotic plaque was quantified, including by compositional subgroups. Obstructive CAD was defined as ≥50% stenosis. Multivariate linear regression models were used to measure atherosclerotic plaque progression by CAC scores. Cox proportional hazard models estimated CAD event risk (median of 10.7 years of follow-up). ResultsAcross baseline CAC scores from 0 to ≥400, total plaque volume ranged from 30.4 to 522.4 mm3 (P < 0.001) and the prevalence of obstructive CAD increased from 1.4% to 49.1% (P < 0.001). Of those with a 0 CAC score, 97.9% of total plaque was noncalcified. Among patients with baseline CAC <100, nonobstructive CAD was prevalent (40% and 89% in CAC scores of 0 and 1-99), with plaque largely being noncalcified. On the follow-up coronary CTA, volumetric plaque growth (P < 0.001) and the development of new or worsening stenosis (P < 0.001) occurred more among patients with baseline CAC ≥100. Progression varied compositionally by baseline CAC scores. Patients with no CAC had disproportionate growth in noncalcified plaque, and for every 1 mm3 increase in calcified plaque, there was a 5.5 mm3 increase in noncalcified plaque volume. By comparison, patients with CAC scores of ≥400 exhibited disproportionate growth in calcified plaque with a volumetric increase 15.7-fold that of noncalcified plaque. There was a graded increase in CAD event risk by the CAC with rates from 3.3% for no CAC to 21.9% for CAC ≥400 (P < 0.001). ConclusionsCAC imperfectly characterizes atherosclerotic disease burden, but its subgroups exhibit pathogenic patterns of early to advanced disease progression and stratify long-term prognostic risk.

Coronary artery calcifications and 6-month mortality in patients with COVID-19 without known atheromatous disease

Coronary artery calcium (CAC) is an independent risk factor for major adverse cardiovascular events; however, its impact on coronavirus disease 2019 (COVID-19) mortality remains unclear, especially in patients without known atheromatous disease. To evaluate the association between CAC visual score and 6-month mortality in patients without history of atheromatous disease hospitalized with COVID-19 pneumonia. A single-centre observational cohort study was conducted, involving 293 consecutive patients with COVID-19 in Paris, France, between 13 March and 30 April 2020, with a 6-month follow-up. Patients with a history of ischaemic stroke or coronary or peripheral artery disease were excluded. The primary outcome was all-cause mortality at 6 months according to CAC score, which was assessed by analysing images obtained after the first routine non-electrocardiogram-gated computed tomography scan performed to detect COVID-19 pneumonia. A total of 251 patients (mean age 64.8±16.7 years) were included in the analysis. Fifty-one patients (20.3%) died within 6 months. The mortality rate increased with the magnitude of calcifications, and was 10/101 (9.9%), 15/66 (22.7%), 10/34 (29.4%) and 16/50 (32.0%) for the no CAC, mild CAC, moderate CAC and heavy CAC groups, respectively (p=0.004). Compared with the no calcification group, adjusted risk of death increased progressively with CAC: hazard ratio (HR) 2.37 (95% confidence interval [CI] 1.06-5.27), HR 3.1 (95% CI 1.29-7.45) and HR 4.02 (95% CI 1.82-8.88) in the mild, moderate and heavy CAC groups, respectively. Non-electrocardiogram-gated computed tomography during the initial pulmonary assessment of patients with COVID-19 without atherosclerotic cardiovascular disease showed a high prevalence of mild, moderate and heavy CAC. CAC score was related to 6-month mortality, independent of conventional cardiovascular risk factors. These results highlight the importance of CAC scoring for patients hospitalized with COVID-19, and calls for attention to patients with high CAC.