Absence Of Coronary Artery Calcium Research Articles

Low density lipoprotein cholesterol and cardiovascular disease risk in patients with absence of coronary artery calcification: a multicenter cohort study

Abstract Background Low-density lipoprotein cholesterol (LDL-C) plays a central role in the development of coronary heart disease (CHD). Absence of coronary artery calcification (CAC 0), as assessed by coronary computed tomography angiography (CCTA), is associated with a favorable outcome as it indicates a low burden of atherosclerosis. However, questions remain regarding the risk of non-calcified plaque and CHD in younger patients with CAC zero, as atherosclerosis tends to be non-calcified in earlier stages. Purpose To assess if LDL-C is associated with presence of non-calcified plaque and future cardiovascular events in patients with CAC zero across the age spectrum. Methods This observational multicenter cohort study included patients aged 18 years or more who underwent CCTA between January 2008 and May 2021 with CAC zero. LDL-C was measured prior to CCTA. Patients were followed from date of CCTA to occurrence of cardiovascular event, death, or 1st of October 2022. No patients were lost to follow-up. We assessed the association between LDL-C and presence of non-calcified plaque on CCTA as adjusted odds ratios, and risk for myocardial infarction and CHD (myocardial infarction or coronary revascularization) as adjusted hazard ratios using Cox regression analyses, across different age groups. Results A total of 23,776 patients with CAC zero were included in the study. Median age was 54 years (IQR 47-61) and 14,605 (61%) were women. During median follow-up of 5.5 years, 165 (0.7%) and 427 (1.8%) experienced myocardial infarction and CHD, respectively. Overall, the prevalence of non-calcified plaque was 11.1% (n=2,650). Higher LDL-C was associated with presence of non-calcified plaque with an odds ratio of 1.21 (95% CI 1.16-1.27) per 1 mmol/L higher LDL-C. Individuals aged ≤45 years had a higher odds ratio for non-calcified plaque per 1 mmol/L higher LDL-C compared to individuals aged 46-60 and >60 years; 1.36 (95% CI 1.22-1.52), 1.22 (95% CI 1.15-1.30) and 1.13 (95% CI 1.04-1.22), respectively, p value for interaction between the youngest and oldest age group was <0.05. Overall, LDL-C was associated with higher risk for myocardial infarction and CHD with hazard ratios of 1.29 (95% CI 1.10-1.52) and 1.26 (95% CI 1.14-1.39) per 1 mmol/L higher LDL-C, despite CAC zero. Conclusions Particularly in younger patients with absence of CAC, elevated LDL-C is associated with presence of non-calcified plaque and increased risk for future cardiovascular events. These data are important for clinical practice, as they demonstrate the importance of managing LDL-C in younger individuals over the long-time horizon despite CAC zero.

Deep learning detection of subclinical cardiovascular dysfunction in type 2 diabetes through retinal photography

Abstract Background Type 2 diabetes (T2D) is associated with excess atherosclerotic coronary disease and heart failure risk, with several cardiac abnormalities described in asymptomatic patients. Routine digital retinal photography performed for screening of diabetic retinopathy (DR) has the potential to identify patients with underlying cardiovascular disease (CVD). We aimed to determine whether features extracted from digital retinal photographs could detect subclinical cardiovascular dysfunction in asymptomatic people with T2D. Methods We prospectively enrolled adults with T2D and no history or symptoms of CVD to undergo extensive phenotyping with multiparametric stress perfusion cardiac MRI and CT coronary artery calcium scoring. Digital retinal photographs acquired for routine diabetic eye screening and performed within one year of cardiac evaluation were interrogated for retinopathy grading and using four deep learning (DL) models (Xception, Inception, EfficientNet, and MobileNet) to capture complex patterns within the retinal vasculature. Each subject had four retinal photographs (two of each eye) for DL analysis. Cardiac image analysis was performed blinded to participant details and independent of retinal images. Subjects with and without DR were compared. Participants were divided into training (80%) and validation datasets (20%) prior to DL analysis. DL models employed to predict from retinal images: presence or absence of coronary artery calcium on non-contrast CT, myocardial perfusion reserve <2.5, left ventricular (LV) global longitudinal strain <16%, absolute stress and rest myocardial blood flood (mL/g/min) used as continuous variables. AUC was used to assess the ability of DL models to discriminate between those without and without subclinical CVD. Results An initial 254 subjects (comprising 1,016 retinal photographs) were included in the analysis: 212 (83%) with no DR, 42 (17%) with grade 1 (mild background) DR. Key cardiac imaging parameters in subjects with and without DR are displayed in Table 1. The groups were well matched for age, sex, body mass index and blood pressure. Overall, those with grade 1 DR had higher atheroma burden, evidence of increased LV filling pressures (E/e’) and poorer systolic function, but no differences in stress and rest myocardial blood flow or myocardial perfusion reserve. However, all four DL models failed to achieve sufficient discrimination of any of the evaluated cardiac imaging parameters, with the majority achieving AUC scores below 50% for all cardiac parameters. Conclusion Asymptomatic adults with grade 1 DR exhibit more subclinical atherosclerosis and cardiovascular dysfunction than those without DR. However, DL transfer models could not discriminate between subjects with and without cardiovascular disease. Further work is needed to better define whether retinal screening may be used to identify those people with T2D most at risk of underlying cardiovascular disease.Subjects demographics

ЗНАЧЕНИЕ ОФЭКТ/КТ В ОДНОВРЕМЕННОЙ ОЦЕНКЕ КАЛЬЦИНОЗА КОРОНАРНЫХ АРТЕРИЙ, ПЕРФУЗИИ И КОНТРАКТИЛЬНОЙ ФУНКЦИИ МИОКАРДА У МУЖЧИН С ИШЕМИЧЕСКОЙ БОЛЕЗНЬЮ СЕРДЦА

Purpose: To study the frequency of calcinosis of coronary arteries and its effect on myocardial perfusion and contractile function among men’s with coronary heart disease (CHD). Material and methods: A survey was conducted among 1175 men’s aged 30 to 83 years with coronary artery disease (CHD): simultaneous assessment of coronary artery calcinosis, perfusion and contractile function with 99m Tc-MIBI using SPECT/CT with ECG-synchronization and X-ray radiation attenuation correction, as well as comparison of data with the results of electrocardiography (ECG), echocardiography (ECHO-CG), clinical and biochemical blood tests. Results: Of the 1175 men examined using SPECT/CT, coronary artery calcification was detected in 426 (35 %): in the age group over 55 years old – in 142 (12 %), in the age group 46−55 years old – in 200 (17 %), in the age group 27–45 years old – in 74 (6 %). The interval of calcium index indicators in accordance with the Agatston scale was established as follows: at the maximum degree > 400 units – in 87 males (7 % of all examined); at 101−400 units – at 121 (10 %); at 11−100 units – at 162 (14 %); at 1−10 units – in 46 (4 %); with a minimum degree − of 0 units – in 759 men (65 % of all examined). In 34 men of whom 15 had coronary calcification and 19 did not have it, perfusion index (SPB) was either normal or corresponded to the initial degree of decrease in perfusion, and contractile function was slightly impaired, the ejection fraction was not reduced. Conclusion: The use of SPECT/CT technology with ECG-synchronization and CT-attenuation correction of radiation, in 1175 men with CHD made it possible to detect coronary calcification in 35 %: at the age of 55 years in 12 %, at the age of 46–55 years in 17 %, at the age of 27–45 years – in 6 %. In men with CHD without acute coronary events, both with and without coronary calcinosis, SPB was either normal or corresponded to the initial degree of reduced perfusion, and contractile function was slightly impaired, EF was not reduced. Three years later, in men whose coronary artery calcification was moderate despite its increase to a high degree, the perfusion (SPB) and contractile function indicators did not significantly change, and such indicators did not significantly change in the absence of coronary artery calcification.

Quantitative analysis of small coronary artery calcium detectability with an accurate simulation and validation on a clinical CT scanner.

The absence of coronary artery calcium (CAC) measured via CT is associated with very favorable prognosis, and current guidelines recommend low-density lipoprotein cholesterol (LDL-c) lowering therapy for individuals with any CAC. This motivates early detection of small granules of CAC; however, calcium scan sensitivity for detecting very low levels of calcium has not been quantified. In this work, the size limit of detectability of small calcium hydroxyapatite (CaHA) granules with clinical CAC scanning was assessed using validated simulations. CT projections of digital 3D mathematical phantoms containing small CaHA granules were simulated analytically; images were reconstructed using a filter designed to reproduce the point spread function of a specific commercial scanner, and a relationship of HU number versus diameter was derived. These simulation results were validated with experimental measurements of HU versus diameter from phantoms containing small granules of CaHA on a GE Revolution CT scanner in the clinic; ground truth measurements of the CaHA granule diameters were obtained using a Zeiss Xradia 510 Versa high-resolution 3D micro-CT imaging system. Using experimental measurements on the clinical CT scanner, detectability was quantified with a detectability index (d') using a non-prewhitened matched filter. The effect of changes to reconstruction slice thickness and reconstruction kernel on granule detectability was evaluated. Under typical clinical calcium scanning and reconstruction conditions, the minimum detectable diameter of a simulated spherical calcium granule with a clinically relevant CaHA density was 0.76mm. The minimum detectable volume was 2.4 times smaller on images reconstructed at a slice thickness of 0.625mm compared to 2.5mm. The detectability index d' increased by a factor of 1.7 when images were reconstructed with 0.625mm slices compared to 2.5mm slices. d' did not change when images were reconstructed with the high-resolution BONE filter compared to the less sharp STANDARD resolution filter on the GE Revolution CT. We have quantified detectability versus size of small calcium granules at the resolution limit of a widely available clinical CT scanner. Detectability increased significantly with reduced slice thickness and did not change with a sharper reconstruction kernel. The simulation can be used to calculate the trade-off between dose and CAC detectability.

Association of Cardiovascular Mortality with Concurrent Coronary Artery Calcification and Physical Activity: A Cohort Study

Background: Increased coronary artery calcification (CAC) has been reported in individuals with high levels of physical activity (PA). However, the association between increased CAC in a physically active population and cardiovascular mortality has not yet been well-established. This study aimed to investigate the association between PA levels and the presence or absence of CAC and cardiovascular mortality. Methods: A cohort study was conducted from 1 January 2011 to 30 December 2019. Mortality data were updated until 30 December 2020. The study population comprised 56,469 individuals who had completed the International Physical Activity Short Form Questionnaire and had undergone CAC score evaluation using a CT scan. We divided the participants into four groups: physically inactive individuals without CAC, physically inactive individuals with CAC, moderately active and health-enhancing physically active (HEPA) individuals without CAC, and moderately active and HEPA individuals with CAC. The primary outcome was cardiovascular mortality. The Cox proportional hazard model with confounding factor adjustment was conducted. Inverse probability of treatment weighting-based marginal-structural modelling was conducted. Results: The median follow-up duration was 6.60 years. The mean (SD) age of the study participants was 41.67 (±10.91) years, with 76.78% (n = 43,359) men. Compared with individuals without CAC, individuals with CAC demonstrated higher cardiovascular disease mortality regardless of PA level (Inactive and CAC > 0, HR 2.81, 95% CI: 1.76-19.19; moderately active and HEPA HR 3.27, 95% CI: 1.14-9.38). Conclusions: The presence of CAC might be associated with cardiovascular mortality regardless of PA level.

Abstract MP67: The Relationship of Cardiorespiratory Fitness, Physical Activity, and Coronary Artery Calcification to Incident Cardiovascular Disease Events in Cardia Participants

Introduction: Coronary artery calcification (CAC) score, physical activity (PA), and cardiorespiratory fitness (CRF) are all associated with cardiovascular disease (CVD) risk. While a U-shaped relationship between PA and CRF with CAC has been reported, CAC presence among highly fit individuals was suggested to be benign. Objective: To determine interactive associations of PA/CRF and CAC with outcomes in a cohort of middle-aged adults and to evaluate the relationship of PA/CRF with CAC incidence. Methods: CARDIA participants with CT-assessed CAC at year 20 (2005-06) were included (n=3141, mean age 45y, 57% female, 45% Black). Moderate to vigorous intensity PA (MVPA) was assessed by self-report and accelerometer. CRF was estimated with a treadmill test. Incident CVD events were adjudicated, and mortality data were obtained through 2019. CAC was reassessed at year 25 (2010-11). Cox models assessed hazard ratios (HRs) for CVD and mortality in groups defined by CAC and MVPA/CRF. Logistic models assessed associations with CAC incidence. Results: At baseline, more favorable CVD risk was found among participants with higher MVPA, higher CRF (> median sex-specific duration), and absence of CAC. During a mean follow-up of 13 years, 166 CVD events and 171 deaths occurred. After multivariable adjustment, compared with no CAC and higher CRF (ref), the HRs (95% CIs) for CVD were 5.04 (2.49-10.20) for CAC and higher CRF, 2.26 (1.24-4.12) for no CAC and lower CRF, and 4.27 (2.24-8.14) for CAC and lower CRF (Figure, left panel). The respective HRs for mortality were 1.12 (0.45-2.77), 1.54 (0.91-2.60), and 3.23 (1.82-5.72) (Figure, right panel). Similar findings were observed with self-reported or accelerometer MVPA replacing CRF. Higher CRF and accelerometer MVPA were dose-responsively associated with a lower probability of developing CAC in a 5-year follow-up (P < .01). Conclusions: PA and CRF were inversely associated with CAC incidence in middle-aged adults. CAC presence eliminated the cardiovascular risk advantage of high PA or high CRF.

Abstract P337: Determinants and Influence of Breast Arterial Calcifications on Risk of Cardiovascular Disease

Background: Breast arterial calcifications (BAC) are incidentally observed on screening mammography. BAC has been shown to be associated with the presence of coronary artery calcification (CAC) and increased risk of coronary artery disease (CAD). Given that population-based mammography is currently recommended to women, the evaluation of BAC may be important in identifying high-risk women without additional cost or radiation exposure. Aims: We sought to identify reproductive and cardiovascular risk factors associated with the presence of detectable BAC and CAC in women participated to mammography screening. Also, we aimed to determine the association between BAC and presence of CAC. Further, we investigated presence of BAC, CAC and estimated 10-year risk of atherosclerotic cardiovascular disease (ASCVD). Methods: In this cross-sectional study, reproductive history and CVD risk factors were obtained in 215 women ≥ 18 years of age that underwent mammography and cardiac computed tomographic angiography (CCTA) within 2 years of each other between January 2007 and September 2017 at Weill Cornell Medicine/ New York Presbyterian hospital (WCM/NYP). BAC was recorded in two ways: a binary scale (presence/absence) and a semi-quantitative scale (mild, moderate, severe). CAC was calculated using the Agatston method and was recorded as a binary variable (presence/absence). Information regarding reproductive history and CVD risk factors, medical history, and relevant demographics were obtained by chart review. Odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for age at study entry as a potential confounder, were estimated. The 10-year risk of atherosclerotic cardiovascular disease (ASCVD) was calculated using the Pooled Cohort Risk Equations. Results: The odds of presence of BAC increased with increasing age . Women age ≥60 had a near 6-fold higher odds of BAC (OR = 5.77; 95% CI = 2.45 to 16.00) compared with women <60 years old. Other factors associated with presence of BAC after controlling for age were diastolic blood pressure ≥80 ( P = 0.0008), systolic blood pressure ≥140 ( P = 0.0009), number of children (P = 0.01). Younger age at first birth (≤28 years) was associated with 3-fold higher odds of BAC compared with women with age at first birth >28 years. Except for age at study entry, the only factor associated with presence of CAC was hyperlipidemia ( P = 0.002). We found no association between presence of BAC with CAC. We observed women with presence of both BAC and CAC had the highest estimated 10-year risk of ASCVD: 18.54%, followed by presence of BAC but absence of CAC 11.65%, absence of BAC and presence of CAC 6.01%, and women with no BAC and no CAC presence had a mean 10-year risk of ASCVD of 5.25%. Conclusions: These findings support the value of BAC in identifying women at potentially increased risk of future cardiovascular disease without additional cost and radiation exposure.

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 (>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

Non-calcific atherosclerotic burden in HeFH: The FH-CALC study

Background and Aims : In heterozygous familial hypercholesterolemia (HeFH) phenotypic variability in subclinical atherosclerosis is observed. For instance, the absence of coronary artery calcium (CAC) accounts for 45% of HeFH subjects. The aim of this study was to investigate the prevalence and determinants of non-calcified coronary plaques in asymptomatic HeFH.

The Curious Case of Synergy between Lipoprotein (a), Coronary Calcification, and Cardiovascular Disease Risk.

Despite recent advances in cardiovascular interventions and preventive therapies, there remains a substantial residual risk of atherosclerotic cardiovascular disease (ASCVD), even among patients on maximal guideline-directed medical therapy. Growing epidemiological and genetic evidence supports the causal role that lipoprotein(a) [Lp(a)], an apolipoprotein-B–containing lipoprotein, plays in increasing the risk of ASCVD morbidity and mortality, and an elevated Lp(a) (≥50 mg/dL or ≥125 nmol/L) is considered a risk enhancer in recent national guidelines (1). Multiple proinflammatory, proatherogenic, procalcific, and cellular signaling mechanisms have been described that could mediate the association of Lp(a) with ASCVD clinical events, in particular due to the oxidized phospholipid content of Lp(a) (2). An intriguing finding has been that elevated Lp(a) concentrations do not associate with prevalent coronary artery calcification (CAC) despite being associated with more rapid progression of CAC and atherosclerotic plaque (3). But while prior studies have shown no association between prevalent Lp(a) and CAC, the joint association of Lp(a) and CAC with the risk of future ASCVD events is not well understood (4). CAC, measured on computed tomography, is an established risk enhancer incorporated into recent guidelines to favor initiation or intensification of statin therapy in patients with uncertain ASCVD risk. On the other hand, the absence of CAC has been used to favor withholding or delaying statin use in certain patients (1).

The Prognostic Value of CAC Zero Among Individuals Presenting With Chest Pain: A Meta-Analysis

BackgroundThere is little consensus on whether absence of coronary artery calcium (CAC) can identify patients with chest pain (CP) who can safely avoid additional downstream testing. ObjectivesThe purpose of this study was to conduct a systematic review and meta-analysis investigating the utility of CAC assessment for ruling out obstructive coronary artery disease (CAD) among patients with stable and acute CP, at low-to-intermediate risk of obstructive CAD undergoing coronary computed tomography angiography (CTA). MethodsThe authors searched online databases for studies published between 2005 and 2021 examining the relationship between CAC and obstructive CAD (≥50% coronary luminal narrowing) on coronary CTA among patients with stable and acute CP. ResultsIn this review, the authors included 19 papers comprising 79,903 patients with stable CP and 13 papers including 12,376 patients with acute CP undergoing simultaneous CAC and coronary CTA assessment. Overall, 45% (95% CI: 40%-50%) of patients with stable CP and 58% (95% CI: 50%-66%) of patients with acute CP had CAC = 0. The negative predictive values for CAC = 0 ruling out obstructive CAD were 97% (95% CI: 96%-98%) and 98% (95% CI: 96%-99%) among patients with stable and acute CP, respectively. Additionally, the prevalence of nonobstructive CAD among those with CAC = 0 was 13% (95% CI: 10%-16%) among those with stable CP and 9% (95% CI: 5%-13%) among those with acute CP. A CAC score of zero predicted a low incidence of major adverse cardiac events among patients with stable CP (0.5% annual event rate) and acute CP (0.8% overall event rate). ConclusionsAmong over 92,000 patients with stable or acute CP, the absence of CAC was associated with a very low prevalence of obstructive CAD, a low prevalence of nonobstructive CAD, and a low annualized risk of major adverse cardiac events. These findings support the role of CAC = 0 in a value-based health care delivery model as a “gatekeeper” for more advanced imaging among patients presenting with CP.

Prevalence and extent of coronary artery disease among patients with a zero calcium score

Background and objective: Coronary artery calcium is a specific indicator of and an independent risk factor for atherosclerosis. However, calcium scoring may miss non calcified plaques, which were indicated to be of clinical importance. This study aimed to identify the presence of non calcified plaques in patients with zero coronary artery calcium score who have been examined with computed tomography coronary angiography and find out any association between the presence of non-calcified plaques and risk factors and presenting symptoms in those patients. Methods: In this retrospective study, we analyzed the computed tomography images of 9826 consecutive patients attending the cardiac center in Erbil, Iraq, between January 2016 and September 2020. Of these patients, we included 2805 patients with a zero coronary artery calcium score in the study. Coronary calcium-scoring scans were followed by computed tomography coronary angiography (256 MSCT Philips ICT). The coronary artery calcium scores were calculated, and the presence of non calcified plaques and significant stenosis (>50% of vessel diameter) were evaluated. Results: Of the 2805 patients with a zero coronary artery calcium score, 896 (31.9%) had atherosclerotic plaques; 143 patients (5.1%) had significant coronary stenosis. Among coronary risk factors, diabetes mellitus (OR = 2.1; 95% CI 1.4-3.3), hypertension (OR = 1.3; 95% CI 1.07-1.58)), male sex (OR = 1.9; 95% CI 1.5-2.3) and old age (OR was 3.2 for the age group 35-44 years reaching 27.7 in the age group ≥ 75 years) were significantly correlated with the presence of atherosclerosis and obstructive coronary artery disease. Conclusion: Although coronary artery calcium scoring is a safe and reliable test to exclude obstructive coronary artery disease, the absence of coronary artery calcium does not absolutely exclude the presence of atherosclerosis. Computed tomography coronary angiography is mandatory for determining the atheroma burden from zero coronary artery calcium score plaques.

Computed tomography angiography versus Agatston score for diagnosis of coronary artery disease in patients with stable chest pain: individual patient data meta-analysis of the international COME-CCT Consortium

ObjectivesThere is conflicting evidence about the comparative diagnostic accuracy of the Agatston score versus computed tomography angiography (CTA) in patients with suspected obstructive coronary artery disease (CAD).PurposeTo determine whether CTA is superior to the Agatston score in the diagnosis of CAD.MethodsIn total 2452 patients with stable chest pain and a clinical indication for invasive coronary angiography (ICA) for suspected CAD were included by the Collaborative Meta-analysis of Cardiac CT (COME-CCT) Consortium. An Agatston score of > 400 was considered positive, and obstructive CAD defined as at least 50% coronary diameter stenosis on ICA was used as the reference standard.ResultsObstructive CAD was diagnosed in 44.9% of patients (1100/2452). The median Agatston score was 74. Diagnostic accuracy of CTA for the detection of obstructive CAD (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) was significantly higher than that of the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). Among patients with an Agatston score of zero, 17% (101/600) had obstructive CAD. Diagnostic accuracy of CTA was not significantly different in patients with low to intermediate (1 to < 100, 100–400) versus moderate to high Agatston scores (401–1000, > 1000).ConclusionsResults in our international cohort show CTA to have significantly higher diagnostic accuracy than the Agatston score in patients with stable chest pain, suspected CAD, and a clinical indication for ICA. Diagnostic performance of CTA is not affected by a higher Agatston score while an Agatston score of zero does not reliably exclude obstructive CAD.Key Points• CTA showed significantly higher diagnostic accuracy (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) for diagnosis of coronary artery disease when compared to the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001).• Diagnostic performance of CTA was not affected by increased amount of calcium and was not significantly different in patients with low to intermediate (1 to <100, 100–400) versus moderate to high Agatston scores (401–1000, > 1000).• Seventeen percent of patients with an Agatston score of zero showed obstructive coronary artery disease by invasive angiography showing absence of coronary artery calcium cannot reliably exclude coronary artery disease.

Association of Coronary Plaque With Low-Density Lipoprotein Cholesterol Levels and Rates of Cardiovascular Disease Events Among Symptomatic Adults

Atherosclerosis burden and coronary artery calcium (CAC) are associated with the risk for atherosclerotic cardiovascular disease (ASCVD) events, with absence of plaque and CAC indicating low risk. Whether this is true in patients with elevated levels of low-density lipoprotein cholesterol (LDL-C) is not known. Specifically, a high prevalence of noncalcified plaque might signal high risk. To determine the prevalence of noncalcified and calcified plaque in symptomatic adults and assess its association with cardiovascular events across the LDL-C spectrum. This cohort study included symptomatic patients undergoing coronary computed tomographic angiography from January 1, 2008, to December 31, 2017, from the seminational Western Denmark Heart Registry. Follow-up was completed on July 6, 2018. Data were analyzed from April 2 to December 2, 2021. Prevalence of calcified and noncalcified plaque according to LDL-C strata of less than 77, 77 to 112, 113 to 154, 155 to 189, and at least 190 mg/dL. Severity of coronary artery disease was categorized using CAC scores of 0, 1 to 99, and ≥100, where higher numbers indicate greater CAC burden. Atherosclerotic cardiovascular disease events (myocardial infarction and stroke) and death. A total of 23 143 patients with a median age of 58 (IQR, 50-65) years (12 857 [55.6%] women) were included in the analysis. During median follow-up of 4.2 (IQR, 2.3-6.1) years, 1029 ASCVD and death events occurred. Across all LDL-C strata, absence of CAC was a prevalent finding (ranging from 438 of 948 [46.2%] in patients with LDL-C levels of at least 190 mg/dL to 4370 of 7964 [54.9%] in patients with LDL-C levels of 77-112 mg/dL) and associated with no detectable plaque in most patients, ranging from 338 of 438 (77.2%) in those with LDL-C levels of at least 190 mg/dL to 1067 of 1204 (88.6%) in those with LDL-C levels of less than 77 mg/dL. In all LDL-C groups, absence of CAC was associated with low rates of ASCVD and death (6.3 [95% CI, 5.6-7.0] per 1000 person-years), with increasing rates in patients with CAC scores of 1 to 99 (11.1 [95% CI, 10.0-12.5] per 1000 person-years) and CAC scores of at least 100 (21.9 [95% CI, 19.9-24.4] per 1000 person-years). Among those with CAC scores of 0, the event rate per 1000 person-years was 6.3 (95% CI, 5.6-7.0) in the overall population compared with 6.9 (95% CI, 4.0-11.9) in those with LDL-C levels of at least 190 mg/dL. Across all LDL-C strata, rates were similar and low in those with CAC scores of 0, regardless of whether they had no plaque or purely noncalcified plaque. The findings of this cohort study suggest that in symptomatic patients with severely elevated LDL-C levels of at least 190 mg/dL who are universally considered to be at high risk by guidelines, absence of calcified and noncalcified plaque on coronary computed tomographic angiography was associated with low risk for ASCVD events. These results further suggest that atherosclerosis burden, including CAC, can be used to individualize treatment intensity in patients with severely elevated LDL-C levels.

Prognostic value of coronary artery calcium score in hospitalized COVID - 19 patients

Abstract Funding Acknowledgements Type of funding sources: None. Background The association of known cardiovascular risk factors with poor prognosis of coronavirus disease 2019 (COVID-19) has been recently emphasized (1). Coronary artery calcium (CAC) score is considered a risk modifier in primary prevention of cardiovascular disease and has shown to improve cardiovascular risk prediction in addition to classical risk factors (2). Purpose We hypothesized that the absence of CAC might have an additional predictive value for an improved cardiovascular outcome of hospitalized COVID-19 patients. Methods We prospectively included 310 consecutive hospitalized patients with COVID-19. Thirty patients with a history of coronary artery disease were excluded. Low dose non - contrast chest computed tomography (CT) was performed in all patients at admission. Visual assessment of CAC in every coronary artery was obtained by using an ordinal scoring of 0, 1, 2 or 3 corresponding to absent, mild, moderate or severe CAC score. A total score was calculated by summing the score of each vessel, which was further categorized as 0 (undetectable), 1-3 (mild), 4-5 (moderate) and ≥ 6 (severe). (Figure 1). Demographics, medical history, clinical characteristics, laboratory findings, imaging data, in-hospital treatment, and outcomes were retrospectively analyzed. A composite endpoint of major adverse cardiovascular events (MACE) was defined as all - cause mortality, heart failure, acute coronary syndrome, atrial fibrillation and stroke. Results Two hundred eighty patients (63.2 ± 16.7 years old, 57.5% male) were included in the analysis. One hundred thirty one (46.7%) patients had a CAC score of 0. MACE rate was 21.8% (61 patients). Multivariable logistic regression showed that the absence of CAC was inversely associated with MACE (OR 0.209, 95% CI 0.052–0.833, p = 0.027), with a negative predictive value of 84.5% (sensitivity 72%, specificity 55%), independent of age, risk factors or disease severity (Figure 2). Conclusion The absence of CAC had a high negative predictive value for MACE in patients hospitalized with COVID-19, independent of the presence of cardiac risk factors or disease severity. These findings reinforce the idea that the assessment of CAC could be a useful marker for risk stratification and management of COVID - 19 patients. Future directions should focus on the implementation of CAC score into mid - term and long - term follow - up of this particular population, to provide a more precise and earlier estimation of cardiovascular risk. Abstract Figure. Abstract Figure.

Determinants of Incident Atherosclerotic Cardiovascular Disease Events Among Those With Absent Coronary Artery Calcium: Multi-Ethnic Study of Atherosclerosis.

The 2018 American Heart Association/American College of Cardiology/Multisociety cholesterol guideline states that statin therapy may be withheld or delayed among intermediate-risk individuals in the absence of coronary artery calcium (CAC=0). We evaluated whether traditional cardiovascular risk factors are associated with incident atherosclerotic cardiovascular disease (ASCVD) events among individuals with CAC=0 over long-term follow-up. We included participants with CAC=0 at baseline from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals free of clinical ASCVD at baseline. We used multivariable-adjusted Cox proportional hazards models to study the association between cardiovascular risk factors (cigarette smoking, diabetes, hypertension, preventive medication use [aspirin and statin], family history of premature ASCVD, chronic kidney disease, waist circumference, lipid and inflammatory markers) and adjudicated incident ASCVD outcomes. We studied 3416 individuals (mean [SD] age 58 [9] years; 63% were female, 33% White, 31% Black, 12% Chinese American, and 24% Hispanic). Over a median follow-up of 16 years, there were 189 ASCVD events (composite of coronary heart disease and stroke) of which 91 were coronary heart disease, 88 were stroke, and 10 were both coronary heart disease and stroke events. The unadjusted event rates of ASCVD were ≤5 per 1000 person-years among individuals with CAC=0 for most risk factors with the exception of current cigarette smoking (7.3), diabetes (8.9), hypertension (5.4), and chronic kidney disease (6.8). After multivariable adjustment, risk factors that were significantly associated with ASCVD included current cigarette smoking: hazard ratio, 2.12 (95% CI, 1.32-3.42); diabetes: hazard ratio, 1.68 (95% CI, 1.01-2.80); and hypertension: hazard ratio, 1.57 (95% CI, 1.06-2.33). Current cigarette smoking, diabetes, and hypertension are independently associated with incident ASCVD over a 16-year follow-up among those with CAC=0.

Abstract 10246: Low Polygenic CAD Risk Score is Associated with Coronary Artery Calcium Score of Zero: A Real World Experience

Introduction: Genetic predisposition for CAD is well established. Polygenic risk scores are emerging as tools to quantify the genomic component of an individual’s risk for CAD. However, their clinical utility for individual risk stratification is unclear. Hypothesis: 180 SNPs previously identified in Caucasian Genome Wide-Association Studies for CAD were used to construct a weighted restricted polygenic risk score (PRS; normalized range 11.18 -17.58). This study hypothesizes that a low PRS (&lt;85th percentile) is associated with coronary calcium score (CAC) of zero. Methods: Between January 2018 &amp; March 2020, 21,784 patients underwent CAC screening and/or PRS testing. Caucasian patients with both PRS and CAC scores were identified. Fisher’s exact test was utilized to test the association between low PRS and CAC score of zero. Results: 3,197 Caucasian patients had both PRS and CAC calculated, 1597 (49.9%) of whom had CAC greater than zero. Characteristics are summarized in table 1. Odds ratio of low PRS associated with CAC zero was 1.34 (95% CI 1.08 - 1.67; p=0.0079). Conclusions: In our Caucasian cohort, there is a statistically significant correlation between a low PRS and absence of coronary artery calcium. This is a real-world analysis incorporating genomic data for individual CAD risk stratification. Further studies on a larger, ethnically diverse cohort are needed.

Statin Intolerance and Noncompliance: An Empiric Approach

Statin Intolerance and Noncompliance: An Empiric Approach

Prognostic value of coronary artery calcium score in hospitalized COVID-19 patients

Abstract Background The association between known cardiovascular risk factors and poor prognosis of patients diagnosed with coronavirus disease 2019 (COVID-19) has been recently emphasized (1). Coronary artery calcium (CAC) score assessed by computed tomography (CT) is considered a risk modifier in primary prevention of cardiovascular disease and has shown to improve cardiovascular risk prediction in addition to classical risk factors (2). Purpose We hypothesized that the absence of CAC might have an additional predictive value for an improved cardiovascular outcome of hospitalized COVID-19 patients. Methods We prospectively included 310 consecutive hospitalized patients with COVID-19. Thirty patients with a history of coronary artery disease were excluded.Low dose non-contrast chest CT was performed in all patients at admission. Visual assessment of CAC in every coronary artery was obtained by using an ordinal scoring of 0, 1, 2 or 3 corresponding to absent, mild, moderate or severe CAC score. A total score was calculated by summing the score of each vessel, which was further categorized as 0 (undetectable), 1–3 (mild), 4–5 (moderate) and ≥6 (severe). (Figure 1). Demographics, medical history, clinical characteristics, laboratory findings, imaging data, in–hospital treatment and outcomes were retrospectively analyzed. A composite endpoint of major adverse cardiovascular events (MACE) was defined as all-cause mortality and cardiovascular events (heart failure, myocarditis, arrhythmia, acute coronary syndrome, stroke, pulmonary embolism). Results Two-hundred eighty patients (63.2±16.7 years old, 57.5% male) were included in the analysis. One hundred thirty one (46.7%) patients had a CAC score of zero. MACE-rate was 24.2% (68 patients). Multivariate logistic regression showed that the absence of CAC was inversely associated with MACE (OR 0.264, 95% 0.071–0.981, p=0.047), with a negative predictive value (NPV) of 81.4%, sensitivity 70%, specificity 55%, independent of age, risk factors or disease severity (Table 1). Conclusion The absence of CAC translated into a low risk for MACE in COVID-19 patients, even in the presence of cardiac risk factors, which reinforces the idea that the assessment of CAC score in COVID-19 patients could be a useful marker for patients risk stratification and management. Future directions should focus on the implementation of CAC score into mid-term and long-term follow-up of this particular population, to provide a more precise and earlier estimation of cardiovascular risk Funding Acknowledgement Type of funding sources: None. Figure 1Table 1

Arteriosclerosis, Atherosclerosis, and Cardiovascular Health: Joint Relations to the Incidence of Cardiovascular Disease.

[Figure: see text].