Coronary Artery Calcium Score Research Articles

Prognostic value of computed tomography-derived fractional flow reserve in patients with diabetes mellitus and unstable angina

BackgroundCoronary artery calcification is commonly found in patients with type 2 diabetes mellitus (T2DM), which may compromise the diagnostic accuracy of coronary computed tomography angiography (CTA). Computed tomography-derived fractional flow reserve (CT-FFR), which integrates coronary anatomy with functional assessment, holds the potential to become a powerful diagnostic tool for evaluating calcified lesions.ObjectiveWe aim to assess the prognostic value of CT-FFR for calcific lesions in patients with T2DM and unstable angina (UA).MethodsWe conducted a retrospective study involving 3,392 patients who were diagnosed with T2DM and UA who underwent coronary CTA, with at least one visible calcification site. Of those, 1,091 patients and 1,372 vessels were recommended by cardiovascular specialists and completed invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR) measurements. Simultaneously, those patients also underwent CT-FFR measurements and were divided into two groups based on CT-FFR values: one group with CT-FFR > 0.80 and the other with CT-FFR ≤ 0.80. Demographics, clinical data, the diagnostic performance of CT-FFR, analysis of calcified lesions on CTA, and major adverse events during follow-up were recorded.ResultsThe diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the curve (AUC) of CT-FFR were 84.8%, 84.6%, 85.1%, 84.7%, 85.0%, and 84.8%, respectively, per patient, and 82.2%, 80.3.2%, 81.8%, 79.7%, 81.1%, and 82.9% respectively, per vessel. For lesion and calcification characteristics, the degree of stenosis, lesion length, rate of bifurcation lesions, diffusive lesions, occlusion, calcium volume, and coronary artery calcification score (CACS) were significantly higher in the CT-FFR ≤ 0.8 group compared to the CT-FFR > 0.8 group. In contrast, the minimum cross-sectional area was smaller in the CT-FFR ≤ 0.8 group than in the CT-FFR > 0.8 group. Major adverse cardiovascular and cerebrovascular events (MACCE) at the 3-year follow-up was significantly higher in the CT-FFR ≤ 0.8 group compared to the CT-FFR > 0.8 group. The CT-FFR value is an independent predictor of MACCE at the 3-year follow-up.ConclusionCT-FFR demonstrated significant diagnostic performance using invasive FFR as the reference standard and proved to be an important predictive tool for assessing prognosis not only in calcified lesions but also in lesions with a CACS score of zero in patients with T2DM and UA. CT-FFR may serve as a valuable tool for guiding treatment decisions in these patients.Graphical abstract

Prognostic Value of Coronary Flow Capacity by 82Rb PET in Patients With Suspected Coronary Artery Disease and Normal Myocardial Perfusion at Semiquantitative Imaging Analysis.

Coronary flow capacity (CFC) is a measure that integrates hyperemic myocardial blood flow and myocardial flow reserve to quantify the pathophysiological impact of coronary artery disease on vasodilator capacity. We assessed the prognostic value of CFC derived from 82Rb positron emission tomography/computed tomography in patients with suspected coronary artery disease and normal myocardial perfusion imaging. We studied 1967 patients with suspected coronary artery disease and normal myocardial perfusion at the semiquantitative analysis of stress/rest cardiac 82Rb positron emission tomography/computed tomography imaging. Coronary artery calcium scores were calculated and categorized into 3 groups: 0, 0.1 to 99.9, and ≥100. Patients were classified as having myocardial steal, severely reduced CFC, moderately reduced CFC, mildly reduced CFC, minimally reduced CFC, or normal flow using previously defined thresholds. The outcome end points were myocardial infarction and cardiac death, whichever occurred first. During a mean time of 41±27 months, 49 events occurred (2.5% cumulative event rate, with an annualized event rate of 0.5% person-years). At multivariable Cox analysis, coronary artery calcium score categories and impaired CFC resulted as independent predictors of events (both P<0.001). The annualized event rate was higher in patients with impaired CFC compared with those with normal CFC (P<0.05). Kaplan-Meier analysis showed that patients with impaired CFC were at the highest risk of events. In patients with suspected coronary artery disease and normal myocardial perfusion, impaired CFC is associated with a higher risk of cardiac events. Evaluating CFC can help identify patients' candidates for additional therapies to prevent future events.

Leveraging calcium score CT radiomics for heart failure risk prediction.

Studies have used extensive clinical information to predict time-to-heart failure (HF) in patients with and without diabetes mellitus (DM). We aimed to determine a screening method using only computed tomography calcium scoring (CTCS) to assess HF risk. We analyzed CTCS scans from 1,998 patients (336 with type 2 diabetes) from a no-charge coronary artery calcium score registry (CLARIFY Study, Clinicaltrials.gov NCT04075162). We used deep learning to segment epicardial adipose tissue (EAT) and engineered radiomic features of calcifications ("calcium-omics") and EAT ("fat-omics"). We developed models incorporating radiomics to predict risk of incident HF in patients with and without type 2 diabetes. At a median follow-up of 1.7 years, 5% had incident HF. In the overall cohort, fat-omics (C-index: 77.3) outperformed models using clinical factors, EAT volume, Agatston score, calcium-omics, and calcium-and-fat-omics to predict HF. For DM patients, the calcium-omics model (C-index: 81.8) outperformed other models. In conclusion, CTCS-based models combining calcium and fat-omics can predict incident HF, outperforming prediction scores based on clinical factors.Please check article title if captured correctly.YesPlease check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.Yes.

Can Artificial Intelligence Help Us in the Evaluation of Coronary Artery Calcification Scores by Acting as a Prognosticator in Patients That Are Operated on Due to Non-Small Cell Lung Cancer? A Pivotal Study

Background: Non-small cell lung cancer (NSCLC) is the leading cause of death from malignancies, and surgical resection is the most effective form of treatment. Coronary artery disease (CAD) is a common comorbidity in patients with NSCLC. A coronary artery calcium (CAC) score correlates with the extent of CAD. We aimed to test whether an automated assessment of CAC scores helps to identify the population of patients with a higher risk of postoperative complications and worse overall survival (OS) after the surgical treatment of NSCLC. Methods: In this retrospective cohort study, the data of the patients who were surgically treated for NSCLC were matched with the reassessed preoperative CT images. The postoperative complication rates and overall survival were analyzed. The CAC score was evaluated automatically using the Syngo.via Siemens Healthcare software. Cardiac age was assessed according to Hoff et al. 2001. The prognosticators of postoperative complications and of OS were tested. Results: The data of 193 patients with complete data, an adherence to the inclusion and exclusion criteria, and that were operated between 2018 and 2019, were included. Cardiac age was a predictor of the cardiovascular and pulmonary complications rate (95%CI −0.007–0.203, p = 0.066, beta coefficient 0.098). In a multivariable stepwise regression analysis, operative access was a predictor of cardiovascular and pulmonary complications (95%CI −0.290–−0.111, p &lt; 0.001, beta coefficient −0.200), cardiovascular complications (95%CI −0.161–−0.022, p = 0.011, beta coefficient −0.036), and the general complication rate (95%CI −0.370–−0.194, p &lt; 0.001, beta coefficient −0.286). Kaplan–Meier curves were separated in the survival analysis of groups of patients with a cardiac age 0–69 years vs. an age of 70+ (92 vs. 92 patients) (in Cox regression analysis, HR = 1.678, 95%CI 0.847–3.292 p = 0.138). Conclusions: An automated CAC score assessment may be a potential and clinically meaningful prognosticator of both postoperative complications and OS in patients that are operated on due to NSCLC. Further studies are required.

Prognostic value of left ventricular mass measured on coronary computed tomography angiography

BackgroundLeft ventricular (LV) mass is a well-established prognostic indicator for cardiovascular risk. Measurement of LV mass on coronary computed tomography angiography (CCTA) is considered optional. We aimed to assess for associations between LV mass measured on CCTA with all-cause mortality (ACM) risk and to determine age- and sex-specific distributions. MethodsWe evaluated patients without known coronary artery disease (CAD) who underwent CCTA at a single center. We assessed age- and sex-specific distributions (10th, 25th, 50th, 75th, and 90th percentiles) of LV mass index. ACM, the primary endpoint, was recorded over a median period of 5.1 [interquartile range: 1.4–8.4] years. The association between LV mass and mortality risk was assessed using multivariable Cox models adjusted for age, sex, medical history, coronary artery calcium (CAC) score and CCTA stenosis. Results4187 patients (mean age: 61.9 ​± ​11.7, 63 ​% male) were included. Male sex, African American ethnicity, Hypertension, CAC>400, and smoking were independent predictors of increased LV mass index. During the median 5.1 years of study follow, 265 (6.3 ​%) deaths occurred. Increased LV mass index percentiles were associated with increased risk of ACM. The addition of LV mass index percentiles improved discrimination and reclassification for mortality prediction over a model with age, sex, conventional risk factors, CAC score and CCTA stenosis severity (X2 improvement: 22.68, NRI: 28 ​%, both p ​< ​0.001). ConclusionIn a large sample of patients without known CAD who underwent CCTA, increased LV mass index provided independent and incremental prognostic value for all-cause mortality. Assessment of LV mass by CCTA, considering age and gender distribution, can be utilized clinically to identify patients with high myocardial mass.

Editorial commentary: Polygenic risk and coronary artery calcium score: joining forces in preventive cardiology.

Editorial commentary: Polygenic risk and coronary artery calcium score: joining forces in preventive cardiology.

Carotid plaque thickness predicts cardiovascular events and death in patients with chronic kidney disease

BackgroundClassical risk scoring systems underestimate the risk of cardiovascular disease in chronic kidney disease (CKD). Coronary artery calcium score (CACS) has improved prediction of cardiovascular events in patients with CKD. The maximal carotid plaque thickness (cPTmax) measured in ultrasound scans of the carotid arteries has demonstrated similar predictive value as CACS in the general population. This is the first study to investigate whether cPTmax can predict cardiovascular events in CKD and to compare the predictive value of cPTmax and CACS in CKD.MethodTwo hundred patients with CKD stage 3 from the Copenhagen CKD Cohort underwent ultrasound scanning of the carotid arteries. The assessment consisted of locating plaque and measuring the thickest part of the plaque, cPTmax. Based on the distribution of cPTmax, the participants were divided into 3 groups: No plaques, cPTmax 1.0–1.9 mm and cPTmax > 1.9 mm (median cPTmax = 1.9 mm among patients with plaques). To measure CACS, 175 of the patients underwent a non-contrast CT scan of the coronary arteries. The follow-up time spanned between the ultrasound scan and a predefined end-date or the time of first event, defined as a composite of major cardiovascular events or death of any cause (MACE).ResultsThe median follow-up time was 5.4 years during which 45 patients (22.5%) developed MACE. In a Cox-regression adjusted for classical cardiovascular risk factors, patients with cPTmax > 1.9 mm had a significantly increased hazard ratio of MACE (HR 3.2, CI: 1.1–9.3), p = 0.031) compared to patients without plaques. C-statistics was used to evaluate models for predicting MACE. The improvement in C-statistics was similar for the two models including classical cardiovascular risk factors plus cPTmax (0.247, CI: 0.181–0.312) and CACS (0.243, CI: 0.172–0.315), respectively, when compared to a model only controlled for time since baseline (a Cox model with no covariates).ConclusionOur results indicate that cPTmax may be useful for predicting MACE in CKD. cPTmax and CACS showed similar ability to predict MACE.

Exploring the Relationship Between Visceral Fat and Coronary Artery Calcification Risk Using Metabolic Score for Visceral Fat (METS-VF)

Background: Metabolic Score for Visceral Fat (METS-VF) is a novel indicator for estimating intra-abdominal fat, yet its connection with coronary artery calcification (CAC) remains uncharted. Our research aims to explore the novel METS-VF indicator’s link to CAC while comparing its performance against relevant anthropometric indices. Methods: This study enrolled participants who underwent health checkups and computed tomography scans for categorizing severity of CAC using the coronary artery calcium score. The METS-VF was calculated and compared with anthropometric indices in estimating the presence of CAC and different CAC severity using receiver operating characteristic curves. Results: Overall, 1217 participants (mean age 50.7 ± 9.9, 53.8% male) were included. METS-VF (odds ratio [OR], 1.506; 95% confidence interval [CI], 1.181–1.921; p = 0.001) was positively associated with the presence of CAC, even after accounting for cardiometabolic factors. Notably, METS-VF was positively associated with mild (OR, 1.450; 95% CI, 1.115–1.886; p = 0.006), moderate (OR, 1.865; 95% CI, 1.137–3.062; p = 0.014), and severe (OR, 2.316; 95% CI, 1.090–4.923; p = 0.029) CAC. Moreover, METS-VF yielded the highest area under curve (AUC) value in the estimation of the CAC presence (AUC = 0.710), mild (AUC = 0.682), moderate (AUC = 0.757), and severe (AUC = 0.807) CAC when compared with body mass index, waist circumference, visceral adiposity index, triglyceride–glucose index, and metabolic score for insulin resistance. The optimal METS-VF cut-off value was 6.4 for predicting CAC. Conclusions: METS-VF emerged as a strong independent marker for detecting CAC presence across mild, moderate, and severe CAC categories, outperforming major anthropometric indices in accurately estimating the presence of CAC and different severity of CAC.

The Paradox of Physical Activity and Coronary Artery Calcification: Implications for Cardiovascular Risk

The introduction of CT scans and the subsequent Agatston score in the 1990s drastically improved our ability to detect coronary artery calcification (CAC). This led to its incorporation into cardiovascular risk assessment guidelines set forth by organizations such as the American Heart Association (AHA) and the American College of Cardiology (ACC). Over time, these guidelines have evolved significantly, reflecting an increasing understanding of CAC. Physical activity has become a key factor in the management of cardiovascular disease. However, the relationship between physical activity and CAC remains complex. Although physical activity is generally beneficial for cardiovascular health, paradoxically, high levels of physical activity have been associated with elevated CAC scores. However, these higher CAC levels may indicate the presence of more stable, calcified plaques that provide protection against plaque rupture. These contradictory findings call for balanced interpretations that acknowledge the cardiovascular benefits of physical activity. This review examines the historical development of clinical guidelines for CAC, the paradoxical relationship between physical activity and CAC, and potential underlying mechanisms. It emphasizes the need for future research to utilize objective measures and consistent methodologies to better understand the relationship between physical activity and CAC.

The role of coronary artery calcium score and european score2 in primary prevention of cardiovascular disease

Abstract Background There is limited evidence about the role of using coronary artery calcium (CAC) score in conjunction with the European SCORE2 (systematic coronary risk evaluation) for the identification of individuals at higher risk of cardiovascular disease. Purpose To evaluate the relationship between CAC score and the European SCORE2 for cardiovascular risk stratification in an asymptomatic population in primary prevention. Methods This is a preliminary analysis from a single-centre, prospective, randomised 1:1, controlled trial assessing the use of CAC score vs standard preventive strategies in asymptomatic individuals undergoing primary cardiovascular prevention. The 10-year risk of cardiovascular events was assessed with either SCORE2 (ages 45-69) or SCORE2-OP (ages 70-89). Subjects were classified as 1) low to moderate risk, 2) high risk, and 3) very high risk according to SCORE2/SCORE2-OP. CAC score was assessed by ECG gated low-dose computed tomography with no contrast administration. A CAC score of zero was considered to reclassify risk one level downward in high or very-high risk patients. CAC score ≥ 100 was used to reclassify risk one level upward in patients with low to moderate risk and a CAC score &amp;gt; 1000 to reclassify risk upward in subjects with high risk. Results A total of 1,252 participants: 627 in the CAC group and 625 in the control group, median age 55 yrs, 25th-75th 50-61 yrs, with availability of SCORE2 and SCORE2-OP were included in this analysis. SCORE2/SCORE 2-OP was similar in the CAC and control groups. Among the subjects in the CAC group, there was a highly significant difference in SCORE2/SCORE 2-OP between participants with CAC score = zero and those with CAC &amp;gt; zero (median 5.6, 25th-75th 3.6-8.55 vs 2.9, 1.8-4.6, p&amp;lt; 0.001) as well as between those with CAC ≥ 100 and those with CAC score &amp;lt; 100 [median 6.8, 25th-75th (10.3-4.5) vs 3.3 (2.0-5.3), p&amp;lt;0.001]. The prevalence of CAC score = zero was 75% in the low to moderate risk group, 47% in the high risk, and 20% in the very high risk, p&amp;lt;0.001. By contrast the prevalence of CAC score ≥ 100 was 7% in the low to moderate risk group, 24% in the high risk, and 45% in the very high risk, p&amp;lt; 0.001. The proportion of patients classified as low to moderate risk group was 72% with CAC score vs 59% without CAC score, high risk 23% with CAC score vs 35% without CAC score, very high risk 5% vs 6% respectively, p&amp;lt;0.001. Using CAC score risk reclassification occurred in 48% downward and 2% upward in originally classified high risk subjects, 7% upward in originally classified low to moderate risk, and 20% downward in originally classified very high risk subjects. Conclusions CAC score may lead to risk reclassification in a substantial proportion of individuals, in particular among those originally classified as high risk by the SCORE2/SCORE2-OP. The cardiovascular risk prediction accuracy of adding CAC score to SCORE2/SCORE2-OP awaits validation at long-term follow-up.

AI-based algorithm for assessing coronary artery calcium score on contrast-enhanced cardiac computed tomography scans

Abstract Introduction In cardiac computed tomography (CT) examinations, non-contrast scans are often performed in addition to contrast-enhanced scans to quantify the coronary artery calcification (CAC) score. These calcium score scans are associated with additional exposure to ionizing radiation. Purpose We sought to develop a fully automated artificial intelligence (AI)-based algorithm capable of determining CAC score based solely on contrast-enhanced CT scans, eliminating the need for additional non-contrast scans. Methods An automated CAC scoring algorithm on contrast-enhanced CT scans was developed and trained using a dataset of 297 cardiac CT studies. Coronary artery calcifications were manually segmented in contrast-enhanced scans using a threshold of 2 standard deviations above the mean attenuation value of the ascending aorta. On non-contrast scans, CAC was manually assessed using a standard threshold of ≥130 Hounsfield Units. A correction factor for calcium score results assessed on contrast-enhanced scans was determined using linear regression. The algorithm was tested on an independent set of 90 contrast-enhanced CT scans (four manufacturers, eight scanner models). We compared automated CAC scores to manual expert reader reference assessments on non-contrast CT scans. CAC scores were categorized into four risk categories following the Society of Cardiovascular Computed Tomography recommendations: 0, 1-100, 101-300, and &amp;gt;300 Agatston Units. Results In the assessment of 90 CT studies (mean age 61.0±11.4 years, 46.7% males), the AI-model detected CAC in 69 contrast-enhanced scans (76.7%), comparable to the human reader's detection rate of CAC in 71 non-contrast scans (78.9%) (p = 0.63). The CAC score was initially calculated using AI-based segmentation of coronary calcification on contrast-enhanced scans and then the result was multiplied by established linear correction factor of 1.97. There was an excellent correlation between AI-model and manual reference total CAC scores (Pearson’s r = 0.96, 95% CI 0.94–0.97, p &amp;lt; 0.001). The model correctly classified 77 patients (85.6%) into the same CAC risk category as the human reader (Figure 1). Among 19 patients (21.1%) with a CAC score of zero, only 1 patient (5.3%) was reclassified with a non-zero CAC score by the AI-model. Cohen’s kappa value for CAC score risk categorization was 0.80 (p &amp;lt; 0.001), indicating very good agreement (Figure 2). Bland–Altman analysis revealed minimal bias of -9.7 Agatston Unit with 95% limits of agreement ranging from -184.8 to 165.5 Agatston Unit. Conclusions CAC score can be accurately quantified on contrast-enhanced cardiac CT scans using an automated AI-based algorithm. This approach has the potential to eliminate the necessity for an additional non-contrast CT scan, thereby reducing the patient's exposure to ionizing radiation.

The paradox of CAC score and plaque vulnerability

Abstract Introduction The effect of coronary artery calcification on plaque vulnerability remains unclear. The coronary artery calcium (CAC) score, quantified using coronary computed tomography, has a strong correlation with total atherosclerotic burden and risk of adverse cardiac events. Nevertheless, different patterns in the distribution of coronary artery calcium have been reported to convey different effects on plaque stability. Some biomechanical models suggest that microcalcifications can intensify stress in the fibrous cap, promoting plaque rupture. On the other hand, large calcium deposits are hypothesized to promote plaque stability, as statin therapy has been shown to promote the calcification of atherosclerotic lesions. The purpose of this study is to investigate the relationship between CAC score and vulnerable plaque using coronary computed tomographic angiography (CCTA) in patients with an acute coronary syndrome (ACS). Methods CCTA was performed in 444 patients; these patients were divided into two groups (those with vulnerable plaque and those without). CAC score of each patient was obtained. We calculated median value of CAC score of both groups and compared them using Two Sample Mann-Whitney U Test. All tests were 2-sided, p values below a threshold of 0.05 were considered to be significant. All statistical analyses were performed using IBM SPSS Statistics 29.0 (SPSS Inc, Chicago, IL). Results Out of 444 patients with an ACS and evaluated with CCTA, vulnerable plaques were found in 57 patients (13%). The median value of CAC score in patients with vulnerable plaques was significantly higher compared with patients without vulnerable plaques (mean CAC score 1065,07 AU (95% Confidence Intervals 526,26-2656,40 AU) vs 444,03 AU (95% CI 120,18-766,88 AU, p &amp;lt; 0.001). Using Mann–Whitney U test, we found a statistically significant difference between CAC score of patients with vulnerable plaques and those that did not have such plaques. Conclusion Although CAC score is a reliable marker of atherosclerosis it is still uncertain whether CAC score is an indicator of plaque vulnerability. In our study, CAC score was higher in patients with vulnerable plaque compared to those without such plaques. A highly statistically significant difference was found between the median value of CAC score between these two groups of patients.Boxplot

Relationship between coronary artery calcium score and plaque vulnerability in patients with established coronary artery disease

Abstract Introduction Coronary artery calcium (CAC) score is widely used for risk stratification. However, in patients with established coronary artery disease (CAD), its clinical implication and relationship with plaque vulnerability have not been fully investigated. Purpose We sought to investigate the relationship between CAC score and plaque vulnerability assessed by optical coherence tomography (OCT). Methods Patients with CAD who had both CAC score and OCT prior to percutaneous coronary intervention were included. The patients with a prior history of coronary revascularization were excluded. Patients were divided into five groups based on CAC score; CAC score of 0, 1-99, 100-399, 400-999, and over 1000. Vulnerable features in culprit plaque assessed by OCT were compared among these five groups. Results In 460 patients, the prevalence of lipid-rich plaque, macrophage, and cholesterol crystal significantly differed among the five groups: lowest in the patients with a CAC score of zero. The prevalence of thin-cap fibroatheroma (TCFA) tended to be lower in those with a CAC score of zero (Figure). In the two-group comparison between the group with a CAC score of zero and the other four groups, the prevalence of lipid-rich plaque (60.5 vs. 85.9%, p &amp;lt; 0.001), macrophage (48.8 vs. 74.1%, p &amp;lt; 0.001), TCFA (16.3 vs. 35.0%, p = 0.013), and cholesterol crystal (11.6 vs. 32.9%, p = 0.004) was significantly lower in the patients with CAC score of zero. No significant difference in vulnerable features was observed among the four groups with CAC scores &amp;gt; 0. CAC score of zero was independently negatively associated with the lipid-rich plaque (odds ratio [OR] 0.246, p &amp;lt; 0.001), macrophage (OR 0.348, p = 0.003), TCFA (OR 0.285, p = 0.006), and cholesterol crystal (OR 0.273, p = 0.010) after adjustment with patient characteristics. Conclusion This is the first study that investigated the relationship between CAC score and plaque vulnerability assessed by OCT in patients with known CAD. Patients with CAC score of zero have a significantly lower prevalence of vulnerable plaque features compared to those with CAC score &amp;gt; 0.

Incidental detection and quantification of coronary artery calcification in ungated thoracic computed tomography for prognostic assessment. Preliminary results from the ICARUS registry

Abstract Background Coronary artery calcium (CAC) score improves cardiovascular risk stratification in asymptomatic individuals. However, whether CAC can be quantified in ungated thoracic computed tomography (uTCT) performed for other indications, and if this CAC score associates with cardiovascular outcomes, hasn’t been confirmed yet. Purpose We aim to analyse the extension of CAC and its prognostic value in terms of major adverse cardiovascular events (MACE) in patients who underwent uTCT for other indications. Methods We analysed a preliminary sample of 115 uTCT performed in 2015 in our hospital. We studied the presence and extension of CAC and quantified the global CAC score by Agatston method using validated software. Patients were categorized according to Coronary Artery Calcium Data and Reporting System (CAC-DRS) categories. Cardiovascular risk factors, lipidic control and pharmacological therapy of the cohort were registered. We analysed the time to first 3P-MACE, defined as cardiovascular death, non-fatal myocardial infarction and non-fatal stroke, whichever occurred first. A p-value &amp;lt;0.05 was considered statistically significant. Results Mean age of the cohort was 60.8±16.1 years (53% male, 53% smokers). Mean LDL-cholesterol was 121.67±34.91 mg/dL, and 35.1% received lipid-lowering therapy. In more than half (n=59, 51.3%) of the population CAC was detected. Mean CAC score was 312.99±774.48 Agatston units, and patients were categorized in CAC-DRS category 1 (n=19, 16.5%), category 2 (n=15, 13%) and category 3 (n=25, 21.7%). Patients with CAC were older (71±10.1 vs. 50.1±14.2 years, p&amp;lt;0.001), had higher burden of cardiovascular risk factors and prevalence of chronic kidney disease (CKD; n=8, 13.6% vs. n=1, 1.8%, p=0.03) and higher levels of triglycerides (143.2±80.5 vs. 106.8±36.2 mg/dL, p=0.004), but not LDL-cholesterol. Eleven (9.6%) patients presented 3P-MACE during a mean follow-up of 6.55±2.82 years. CAC score independently predicted 3P-MACE (HR 1.06 [1.01-1.11] per 100 Agatston units, p=0.02) along with CKD (HR 6.94 [1.58-30.46], p=0.01) and basal glucose levels (HR 1.03 [1.02-1.04] per mg/dL, p&amp;lt;0.001). Conclusions CAC can be incidentally detected in more than half of our unselected cohort of patients undergoing uTCT for other indications. CAC score quantification by Agatston method is feasible in uTCT and associates with a higher risk of MACE during follow-up.Incidental CAC detection in uTCT

Comparison between coronary calcium score and segment involvement score when used in clinical routine

Abstract Data from a nationwide registry on coronary computer tomography angiography. Background The Coronary Artery Calcium Score (CACS) and segment involvement score (SIS) are crucial factors in assessing the severity of coronary artery disease (CAD) and determining the likelihood of future cardiovascular events. However, there are few large multicenter studies comparing the predictive value of CACS and SIS when used in the clinical routine. Objectives To compare CACS and SIS ability to predict cardiovascular outcomes when used in the clinical routine. Methods This retrospective cohort study included patients who underwent Coronary Computed Tomography Angiography (CCTA) for CAD evaluation between 2006-2022 in 29 different centers in Sweden. CACS was calculated using the Agatston method, and SIS was determined based on the number of coronary segments exhibiting plaque. For SIS, patients were categorized into SIS=0, SIS=1, SIS=2, SIS=3, SIS³4, for CACS patients were categorized into CACS=0, CACS=1-9, CACS=10-99, CACS=100-299, CACS³300. Patients were followed regarding the primary outcome of death or myocardial infarction. Multivariable Cox proportional hazards models were used for adjusting for potential confounders. Results A total of 23034 patients underwent CCTA and were followed for up to ten years. Median age (IQR) was 58 (49–67) years, 50% were women, 9% had diabetes mellitus, 42% had hypertension, 25% had hyperlipidemia, 5% had previously known CAD. There were 955 patients (4.1%) with myocardial infarction (MI) and 409 patients (2.2%) died during follow up. There was an increase in cardiovascular events with increasing SIS. When comparing SIS and presence of obstructive stenosis, SIS was a better predictor of outcome (Figure 1). There was also an increase cardiovascular events with increasing CACS (Figure 2). When adjusted for age, sex, risk factors, previous cardiovascular disease and intervention, both SIS and CACS were independently associated with outcome. When SIS and CACS were compared in a receiver operating characteristic curve, CACS had significantly larger AUC than SIS, (0.70[0.67-0.73] vs 0.62[0.60-0.63]). Conclusion Our findings show that both CACS and SIS are important and independent predictors of cardiovascular outcomes thereby offering a valuable tool for personalized risk stratification and management in clinical settings. When used in the clinical routine, CACS appears to be more strongly associated with outcome than SIS.Figure1 Survival SISFigure 2 Survival CACS

Progress in understanding the genetic underpinning of coronary artery disease: from genotype to phenotype

Abstract Background The functional dissection of genetic risk opens the door to strategies for pharmacological manipulation of molecular and cellular processes implicated in human diseases, including coronary artery disease (CAD). Aim To assess the relationship between a set of single nucleotide polymorphisms previously associated with CAD and coronary artery calcium (CAC) score in an asymptomatic population from Portugal. Methods Prospective study in a cohort of 1,284 subjects aged 59.3±8.9 years, 73.6% males without apparent CAD. The CAC score was performed by cardiac computed tomography and reported as Agatston units according to the Hoff nomogram. Anthropometric, conventional, and biochemical risk factors were evaluated. Thirty-three single nucleotide polymorphisms were genotyped by TaqMan real-time PCR. Bivariate and multivariate logistic regression analysis estimated variables associated with the CAC score. Results After bivariate analysis, PHACTR1 rs1332844 C&amp;gt;T, a downstream regulator of the endothelin-1 gene, showed a significant association with CAC score (p=0.015), together with CDKN2B-AS1 variants rs4977574 A&amp;gt;G in the locus 9p21.3 (p=0.002) and rs1333049 G&amp;gt;C (p=0.010). MTHFD1L gene encodes a mitochondrial enzyme responsible for homocysteine remethylating in methionine, and rs6922269 G&amp;gt;A showed protection against artery calcification (p=0.013). After multivariate logistic regression, PHACTR1 rs1332844 (CT+TT) (p=0.009) and CDKN2B-AS1 rs4977574 A&amp;gt;G (GG) (p=0.002) remained in the equation as independently associated with arterial calcification, together with male sex (p=0.039), age (p&amp;lt;0.0001), hypertension (p=0.001), diabetes (p&amp;lt;0.0001), smoking status (p&amp;lt;0.0001) and obesity (p=0.020). MTHFD1L rs6922269 AA also remained as significant protection from arterial calcification (p=0.027). Conclusion The present work showed two genetic variants, PHACTR1 and CDKN2B-AS1, linked to arterial wall calcification, herewith clinical and environmental risk factors. MTHFD1L showed protection. Understanding the genetic basis of vessel calcification can enable lifestyle changes or pharmacologic therapy to attenuate risk before the disease becomes clinic. More research in this field is critical to understanding the genetic basis of CAD through an intermediate phenotype, coronary arterial wall calcification.

Prevalence of high-risk plaque features on cardiac computed tomography scans in patients with a coronary artery calcium score of zero

Abstract Introduction Coronary artery calcium (CAC) score of zero (so-called "power of zero") is associated with a very low rate of major adverse cardiac events (MACE), especially during short and midterm follow-up. However, a CAC score of zero does not definitively exclude the presence of atherosclerotic plaques or obstructive coronary artery disease (CAD). The composition of atherosclerotic plaques and the frequency of high-risk plaque features in this population are not well described. Purpose We sought to characterize the composition of atherosclerotic plaques and assess the frequency of high-risk plaque features on contrast-enhanced computed tomography (CT) images in patients with a zero CAC score. Methods The study enrolled patients with stable chest pain suspected of CAD referred for coronary CT imaging and having a CAC score of zero. Coronary CT angiography images were assessed by an expert reader to identify atherosclerotic plaques and high-risk plaque features in all coronary arteries with a diameter ≥1.5mm. The coronary artery lumen and plaques were manually segmented, and the degree of stenosis was evaluated following the Coronary Artery Disease Reporting and Data System (CAD-RADS) criteria. The presence of four high-risk plaque features was identified: positive remodeling, spotty calcification, low-attenuation plaque, and napkin ring sign. Total plaque volume, percent atheroma volume, and plaque composition were quantified using dedicated software (Figure 1). Results A total of 145 patients (mean age 54.2±12.1 years, 35.9% males) were included in the analysis. At least one coronary artery plaque was identified in 30 individuals (20.7%). 22 (15.2%), 7 (4.8%), and 1 (0.7%) patients were categorized into CAD-RADS 1, CAD-RADS 2, and CAD-RADS 3 categories, respectively. Among 30 patients with any coronary artery plaque, at least one high-risk feature was found in 10 individuals (33.3%), while 3 individuals (10.0%) had two features. Positive remodeling was found in 7 (23.3%), spotty calcification in 3 (10.0%), low-attenuation plaque in 3 (10.0%), and napkin ring sign in 0 patients, respectively (Figure 1). The mean total plaque volume was 48.2±54.3mm³, and the mean percent atheroma volume was 1.2±0.8%. Total plaque volume comprised low-attenuation (0.4%), fibro-fatty (58.9%), fibrous (39.4%), and calcified (1.3%) plaque volumes. Notably, in 3 (10.0%) individuals, the presence of calcified plaque was identified, which on non-contrast CT images did not meet the Agatston criteria for the CAC score. Conclusions Our study demonstrates a significant prevalence of atherosclerotic plaques and high-risk plaque features in patients with a CAC score of zero. Specifically, one in every five study participants had identifiable atherosclerotic plaque, with one in every three of those exhibiting one or more high-risk plaque features. The prognostic significance of these findings warrants further evaluation in studies with longitudinal follow-up.

Reduced inflammation assessed by pericoronary adipose tissue is associated with coronary plaque calcification

Abstract Introduction Pericoronary adipose tissue attenuation (PCAT) quantified from coronary computed tomography angiography (CCTA) is increasingly recognized as an inflammation marker in coronary artery disease (CAD). Inflamed PCAT has been linked to non-calcified plaque (NCP) and cardiovascular morbidity and mortality. Nevertheless, gaps remain in understanding how PCAT behaves during plaque stabilization. Purpose We investigated associations between coronary artery inflammation assessed by PCAT and the presence and type of coronary plaques, plaque burden, and coronary calcification. Methods An observational study involving 506 patients with suspected chronic coronary syndrome who underwent CCTA. PCAT was averaged across the proximal 40 mm segments of all three coronary vessels to represent the patient level. Plaque presence and types (calcified, mixed, and soft) were assessed. Total, NCP, and calcified plaque (CP) burdens were measured as normalized atheroma volumes. Coronary calcification was quantified using Agatson coronary artery calcification (CAC) score and categorized based on cut-offs of 0, 100, 400. Results The mean PCAT was -81.1 ±6.3 Hounsfield Unit (HU) without plaque and -79.7 ±6.0 HU with plaque (p= 0.01). PCAT differed between calcified (-81.8 HU), mixed (-79.8 HU), and soft (-77.0 HU) plaques (p&amp;lt;0.0001). Multivariate linear analysis (adjusted for clinical risk factors, cardiovascular medication, and tube voltage) showed PCAT positively associated with total plaque burden (estimate= 1.1 [95% CI: 0.3-1.8], p=0.004) and NCP burden (estimate= 2.4 [95% CI: 1.4-3.4]; p&amp;lt;0.0001), while the association with CP burden was negative, but not statistically significant (estimate= -1.7 [95%CI : -4.1-0.7], p=0.2). Multivariate linear analysis, which accounted for both calcified and non-calcified plaque, reaffirmed the positive association to NCP burden (estimate= 2.7 [95% CI: 1.7-3.7]; p&amp;lt;0.0001) and a significant negative association between CP burden (estimate= - 3.3 [95% CI: -5.8- -1.0]; p=0.007) and PCAT. No significant differences in PCAT levels were found among patients with a CAC score of 0 and those with CAC scores exceeding 400, or across different stages of CAC score categories (p&amp;gt;0.8). Conclusion PCAT increased with plaque presence, rising from calcified to mixed to soft plaques. Increased NCP burden associated with higher PCAT, while higher CP burden seemed to reduce PCAT, though not statistical significant. Interestingly, when NCP was absent, higher levels of CP burden were associated with reduced inflammation. This supports the hypothesis of plaque stabilization, proposing that calcification might stabilize the vessel and indirectly contribute to reducing inflammation.Figure 1 PCAT by plaque typesTable 1 PCAT &amp; plaque burden

Association between high versus low cardiovascular risk in individuals with corresponding unexpected absent versus severe subclinical coronary atherosclerosis, a nationwide, multicenter study

Abstract Background It remains unclear as to why some individuals at low risk of cardiovascular disease (CVD) develop severe coronary atherosclerosis, while those at high CVD risk may remain free from coronary atherosclerosis. Purpose Using Coronary Computed Tomography Angiography (CCTA), we aimed to identify factors associated with absence and severe coronary atherosclerosis in subjects from the general population with very high and low-moderate CVD risk, respectively. Methods We assessed cross-sectionally a nationwide, multicenter population-based cohort, consisting of 30,154 individuals randomly recruited from the general population (age range 50-64 years, 51.4% women). Coronary calcified plaque burden was estimated by coronary artery calcium score (CACS) assessed by CCTA. Absent coronary atherosclerosis was defined as CACS 0 and severe coronary atherosclerosis was defined as CACS ≥301. We investigated only individuals with low-moderate (&amp;lt;5%) and very high CVD risk (≥10%) according to SCORE2 were included. Individuals with CACS 0 and prevalent CVD were excluded, as well as those with moderate CACS (1-300) or SCORE2 risk 5-9%. Out of 26 722 subjects with complete data on CACS and SCORE2, 13 075 were included. Logistic regression was performed adjusted for age and sex. Results The overall distribution of CACS in relation to SCORE2 CVD risk is illustrated in the Figure. Study characteristics are displayed in Table 1. Severe-extensive CACS in combination with low-moderate CVD risk was present in 2.3% (n=296). A further 2.3% (n=311) had very high CVD risk but CACS 0. Factors associated with CACS 0 despite a very-high estimated CVD risk included: lower age, being female, being born in Sweden, not having hypertension or hyperlipidemia, fewer pack-years of smoking, and lower waist circumference in men. On the contrary, severe-extensive CACS despite a low-moderate estimated CVD risk was associated with higher age, being male, being an ex-smoker, reporting more pack-years of smoking, having higher HbA1c, higher BMI, higher waist circumference, and prevalent hyperlipidemia and hypertension (Table 2). Conclusions We identified extreme cardiovascular risk phenotypes (subgroups) in the general population that either lacked coronary calcifications despite being at very high estimated CVD risk or had severe subclinical coronary atherosclerosis despite being at estimated low-moderate CVD risk. Further studies are warranted to elucidate putative enhancing or protective mechanisms explaining this unexpected phenomenon.

Detection of biventricular volume increase in overweight and obese by using a novel index of the ideal human - a single center non-contrast-enhanced cardiac CT study

Abstract The bi-ventricular volume (BVV) can be measured from non-contrast-enhanced CT images in patients referred for coronary artery calcium (CAC) scoring. Such determined BVV has been found to correlate with left ventricular mass and to predict increased risk of all-cause and CV mortality in patients with type 2 diabetes mellitus. Currently, no data are available that quantifying the effect of body size on BVV using NCE-CT. We used a new indexing parameter that consisted of two parts: height and the difference between numerical values of height and body surface area (BSA). In the "ideal human", the difference is zero. Any deviation from this value determines the share of body mass regardless of height. Aim We hypothesize that a novel indexation way allows for better discrimination of the increased bi-ventricular volume in overweight and obese patients. Method We retrospectively analyzed the CT data from 2466 patients with CAC scoring over the last 15 years. Among them 1606 women and 860 men with an average age of 64 ± 11 years (range 21-93). The fatless bi-ventricular volume was measured manually using commercial software on a dedicated workstation (Vitrea2). Values of the raw (measured, ml) BVV and BVV normalized for height, BSA, and the novel parameter i.e. [h+ (h-BSA)], were compared in patients taking into account body mass index (BMI) categories of normal weight (25% of patients), overweight (40%) and obese (35%). Results Overall, the measured BVV [ml] was significantly greater in males (414±97) than in females (297±66) (p&amp;lt;0.001). BVV decreased non-linearly from before 40ties to mid-60ties, and then remained nearly stable. In normal-weight males, the measured BVV (370±80ml) was greater than in normal-weight females (279±61ml) (p&amp;lt;0.001). In overweight males, the BVV was 411±89ml; in overweight females, the BVV reached 290±59ml (p&amp;lt;0.001). These differences were non-significantly different from the sample of patients with normal BMI. In obese patients, mean values significantly differed between males and females (442±106 vs 321±71 ml, p&amp;lt;0.001). As the absolute value of the BVV should be interpreted in the context of body habitus, normalization for height, BSA, and the novel index were used. The results of these examinations are given in the figure. Conclusions Commonly used methods of indexing the volumetric parameters of the ventricles, as well as the novel indexing approach showed similar results in patients with normal body weight. The proposed indexation allowed for discriminating the increase in BVV that is easy to overlook in overweight. The use of body surface area for volumetric normalization is misleading as it provides similar values in normal, overweight, and obese patients, and should therefore be avoided. We should consider whether ventricular size standards based on a study population under 50 years of age create reliable conditions for detecting ventricular enlargement at an older age.