Fully automated epicardial adipose tissue volume quantification with deep learning and relationship with CAC score and micro/macrovascular complications in people living with type 2 diabetes: the multicenter EPIDIAB study.

BACKGROUND: The aim of this study (EPIDIAB) was to assess the relationship between epicardial adipose tissue (EAT) and the micro and macrovascular complications (MVC) of type 2 diabetes (T2D). METHODS: EPIDIAB is a post hoc analysis from the AngioSafe T2D study, which is a multicentric study aimed at determining the safety of antihyperglycemic drugs on retina and including patients with T2D screened for diabetic retinopathy (DR) (n = 7200) and deeply phenotyped for MVC. Patients included who had undergone cardiac CT for CAC (Coronary Artery Calcium) scoring after inclusion (n = 1253) were tested with a validated deep learning segmentation pipeline for EAT volume quantification. RESULTS: Median age of the study population was 61 [54;67], with a majority of men (57%) a median duration of the disease 11 years [5;18] and a mean HbA1c of7.8 ± 1.4%. EAT was significantly associated with all traditional CV risk factors. EAT volume significantly increased with chronic kidney disease (CKD vs no CKD: 87.8 [63.5;118.6] vs 82.7 mL [58.8;110.8], p = 0.008), coronary artery disease (CAD vs no CAD: 112.2 [82.7;133.3] vs 83.8 mL [59.4;112.1], p = 0.0004, peripheral arterial disease (PAD vs no PAD: 107 [76.2;141] vs 84.6 mL[59.2; 114], p = 0.0005 and elevated CAC score (> 100 vs < 100 AU: 96.8 mL [69.1;130] vs 77.9 mL [53.8;107.7], p < 0.0001). By contrast, EAT volume was neither associated with DR, nor with peripheral neuropathy. We further evidenced a subgroup of patients with high EAT volume and a null CAC score. Interestingly, this group were more likely to be composed of young women with a high BMI, a lower duration of T2D, a lower prevalence of microvascular complications, and a higher inflammatory profile. CONCLUSIONS: Fully-automated EAT volume quantification could provide useful information about the risk of both renal and macrovascular complications in T2D patients.

Circulating isomiRs May Be Superior Biomarkers Compared to Their Corresponding miRNAs: A Pilot Biomarker Study of Using isomiR-Ome to Detect Coronary Calcium-Based Cardiovascular Risk in Patients with NAFLD.

Circulating miRNAs are increasingly being considered as biomarkers in various medical contexts, but the value of analyzing isomiRs (isoforms of canonical miRNA sequences) has not frequently been assessed. Here we hypothesize that an in-depth analysis of the full circulating miRNA landscape could identify specific isomiRs that are stronger biomarkers, compared to their corresponding miRNA, for identifying increased CV risk in patients with non-alcoholic fatty liver disease (NAFLD)-a clinical unmet need. Plasma miRNAs were sequenced with next-generation sequencing (NGS). Liver fat content was measured with magnetic-resonance spectrometry (MRS); CV risk was determined, beyond using traditional biomarkers, by a CT-based measurement of coronary artery calcium (CAC) score and the calculation of a CAC score-based CV-risk percentile (CAC-CV%). This pilot study included n = 13 patients, age > 45 years, with an MRS-measured liver fat content of ≥5% (wt/wt), and free of overt CVD. NGS identified 1103 miRNAs and 404,022 different isomiRs, of which 280 (25%) and 1418 (0.35%), respectively, passed an abundance threshold. Eighteen (sixteen/two) circulating miRNAs correlated positively/negatively, respectively, with CAC-CV%, nine of which also significantly discriminated between high/low CV risk through ROC-AUC analysis. IsomiR-ome analyses uncovered 67 isomiRs highly correlated (R ≥ 0.55) with CAC-CV%. Specific isomiRs of miRNAs 101-3p, 144-3p, 421, and 484 exhibited stronger associations with CAC-CV% compared to their corresponding miRNA. Additionally, while miRNAs 140-3p, 223-3p, 30e-5p, and 342-3p did not correlate with CAC-CV%, specific isomiRs with altered seed sequences exhibited a strong correlation with coronary atherosclerosis burden. Their predicted isomiRs-specific targets were uniquely enriched (compared to their canonical miRNA sequence) in CV Disease (CVD)-related pathways. Two of the isomiRs exhibited discriminative ROC-AUC, and another two showed a correlation with reverse cholesterol transport from cholesterol-loaded macrophages to ApoB-depleted plasma. In summary, we propose a pipeline for exploring circulating isomiR-ome as an approach to uncover novel and strong CVD biomarkers.

Performance of the 2019 ESC/EASD guideline strategy for the screening of silent coronary artery disease in patients with diabetes.

BACKGROUND: The 2019 guidelines for cardiovascular risk stratification by the European Society of Cardiology and European Association for the Study of Diabetes (ESC-EASD) suggested screening for silent coronary disease in very high risk patients with severe target organ damage (TOD) (i.e. peripheral occlusive arterial disease or severe nephropathy) or high coronary artery calcium (CAC) score. This study aimed to test the validity of this strategy. METHODS: In this retrospective study, we included 385 asymptomatic patients with diabetes and no history of coronary disease but with TOD or ≥ 3 risk factors in addition to diabetes. CAC score was measured using computed tomography scan and a stress myocardial scintigraphy was performed to detect silent myocardial ischemia (SMI), with subsequent coronary angiography in those with SMI. Various strategies to select patients to be screened for SMI were tested. RESULTS: CAC score was ≥ 100 Agatston units (AU) in 175 patients (45.5%). SMI was present in 39 patients (10.1%) and among the 30 patients who underwent angiography, 15 had coronary stenoses and 12 had a revascularization procedure. The most effective strategy consisted in performing myocardial scintigraphy in the 146 patients with severe TOD and, among the 239 other patients without severe TOD, in those with CAC ≥ 100 AU: this strategy provided 82% sensitivity for SMI diagnosis, and identified all the patients with stenoses. CONCLUSION: The ESC-EASD guidelines suggesting SMI screening in asymptomatic patients with very high risk assessed by severe TOD or high CAC score appears effective and could identify all the patients with stenoses eligible for revascularization.

Association Between Sonographically Diagnosed Nephrolithiasis and Subclinical Coronary Artery Calcification in Adults.

BACKGROUND: Although recent studies suggest an association between nephrolithiasis and clinical cardiovascular events, this association has been underexplored. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 62,091 asymptomatic adults without known coronary heart disease who underwent a screening health examination that included cardiac tomography. PREDICTOR: Nephrolithiasis. OUTCOME: Coronary artery calcification (CAC). MEASUREMENTS: Nephrolithiasis assessed using ultrasonography of the abdomen. CAC scoring assessed using cardiac computed tomography. RESULTS: The prevalence of CAC scores > 0 was 13.1% overall. Participants with nephrolithiasis had a higher prevalence of coronary calcification than those without (19.1% vs 12.8%). In Tobit models adjusted for age and sex, the CAC score ratio comparing participants with nephrolithiasis with those without nephrolithiasis was 1.56 (95% CI, 1.19-2.05). After further adjustment for screening center, year of screening examination, physical activity, alcohol intake, smoking status, education level, body mass index, family history of cardiovascular disease, total energy intake, glucose concentration, systolic blood pressure, triglyceride concentration, high-density lipoprotein cholesterol concentration, uric acid concentration, and estimated glomerular filtration rate, the CAC score ratio was attenuated, but remained significant (CAC score ratio, 1.31; 95% CI, 1.00-1.71). LIMITATIONS: Computed tomographic diagnosis of nephrolithiasis was unavailable. CONCLUSIONS: Nephrolithiasis was associated with the presence of CAC in adults without known coronary heart disease, supporting the hypothesis that these 2 health conditions share a common pathophysiology.

Left ventricle size quantification using non-contrast-enhanced cardiac computed tomography--association with cardiovascular risk factors and coronary artery calcium score in the general population: The Heinz Nixdorf Recall Study.

BACKGROUND: Increased left ventricular (LV) size is associated with cardiovascular mortality and morbidity. Once non-contrast cardiac computed tomography (CT) is performed for other purposes, information of LV size is readily available. PURPOSE: To determine the association of gated CT-derived LV size with cardiovascular risk factors and coronary artery calcification (CAC) and to describe age- and gender-specific normative values in a general population cohort. MATERIAL AND METHODS: LV area was quantified from non-contrast-enhanced CT in axial, end-diastolic images at a mid-ventricular slice in participants of the population-based Heinz Nixdorf Recall Study, free of known cardiovascular disease. LV index (LVI) was calculated by the quotient of LV area and body surface area (BSA). Crude and adjusted regression analyses were used to determine the association of LVI with risk factors and CAC. RESULTS: Overall, 3926 subjects (age 59 ± 8 years, 53% women) were included in this analysis. From quantification in end-diastolic phase, men had larger LV index (2232 ± 296 mm(2)/m(2) vs. 2088 ± 251 mm(2)/m(2), both P < 0.0001). LVI was strongly correlated systolic blood pressure (men, PE [95% CI]: 22.8 [15.5-30.2] mm(2)/10 mmHg; women, 23.4 [18.1-28.6]), and antihypertensive medication (men, 45.2 [14.7-75.8] mm(2); women: 46.5 [22.7-70.2], all P < 0.005). Cholesterol levels were associated with LVI in univariate analysis, however, correlations were low (R(2) ≤ 0.04). In multivariable regression, blood pressure, antihypertensive medication and cholesterol levels, remained associated with LVI (P < 0.05). LVI was linked with CAC in unadjusted (men, increase of CAC + 1 by 13.0% [1.4-25.8] with increased LVI by 1 standard deviation of LVI, P = 0.03; women, 20.7% [10.0-32.3], P < 0.0001) and risk factor adjusted models (men, 14.6% [3.7-26.6], P = 0.007); women, 17.4% [7.8-27.8], P = 0.0002). CONCLUSION: Non-contrast cardiac CT derived LV index is associated with body size and hypertension. LVI is weakly linked with CAC-score. Further studies need to evaluate whether assessment of LV dimensions from cardiac CT helps identifying subjects with increased cardiovascular risk.

HDL-C levels modify the association between C-reactive protein and coronary artery calcium score.

BACKGROUNDS AND AIMS: C-reactive protein (CRP) levels predict incident and recurrent cardiovascular disease (CVD) events; however, associations between CRP and pre-clinical atherosclerosis is less certain. Since high concentrations of high-density lipoprotein cholesterol (HDL-C) are inversely associated with CVD risk, we investigated whether HDL-C modified the association between CRP concentration and measures of preclinical atherosclerosis. METHODS AND RESULTS: Data were analyzed from a Korean occupational cohort of 12,030 male subjects who underwent a cardiac computed tomography (CT) estimation of coronary artery calcification (CAC) score and an assessment of CVD risk factors. Logistic regression was used to describe associations between CRP and measures of pre-clinical atherosclerosis, such as CAC scores >0. As many as 1351 (11.2%) participants had a CAC score>0. CRP was stratified into 3 groups based on clinical category: <1 mg/L, 1 to <2 mg/L, and ≥ 2 mg/dL. In the bottom CRP group, 907/8697 (10.4%) of subjects had a CAC score >0, compared with 242/1943 (12.5%) in the middle group and 202/1396 (14.5%) in the top CRP group (p < 0.0001). After adjustment for multiple CVD risk factors, there was a positive association between CRP and CAC score>0 (OR between top and bottom CRP groups, 1.41 [1.04, 1.90], p = 0.027) in the lowest HDL-C quartile but not in the highest HDL-C (OR between top and bottom CRP group, 0.80 [0.46, 1.39], p = 0.425). CONCLUSION: The association between CRP concentration and CAC score differed according to HDL-C levels.

Metabolically healthy obese subjects are at risk of fatty liver but not of pre-clinical atherosclerosis.

BACKGROUNDS AND AIMS: Whether obesity increases risk of cardiovascular disease (CVD) and fatty liver because of the co-existence of other risk factors is uncertain. We investigated odds ratios (ORs) for: a) a measure of pre-clinical atherosclerosis and b) fatty liver, in metabolically healthy obese (MHO) subjects, metabolically abnormal obese (MAO) subjects and metabolically abnormal non obese subjects (MANO), using a metabolically healthy non obese (MHNO) group as the reference. METHODS AND RESULTS: 14,384 South Koreans from an occupational cohort underwent cardiac computed tomography (CT) estimation of CAC score, liver ultrasound determination of fatty liver, and measurement of cardiovascular risk factors. Pre-clinical atherosclerosis was defined by a CAC score >0. We used logistic regression to determine ORs for CAC >0, and fatty liver in MHO, MAO and MANO subjects (reference group MHNO). There was no increase in OR for CAC score >0 (OR = 0.93, [95% CIs 0.67,1.31], p = 0.68), in the MHO group, whereas there was an increase in the ORs for CAC score >0 in the MAO, and MANO groups (OR = 1.64 [95% CI 1.36,1.98], p < 0.001) and (OR = 1.38 [95% CI 1.17,1.64], p < 0.001), respectively. In contrast, for fatty liver, there was an increase in OR in each group (OR = 3.63 [95% CI 3.06, 4.31] p < 0.001); (OR = 5.89 [5.18,6.70] p < 0.001); and (OR = 1.83 [95% CI 1.69,2.08]) in the MHO, MAO group and MANO groups respectively. CONCLUSION: MHO subjects are at risk of fatty liver but attenuated risk of pre-clinical atherosclerosis. Both MAO and MANO subjects are at risk of fatty liver and pre-clinical atherosclerosis.

The Effect of Eicosapentaenoic and Docosahexaenoic Acid Supplementation on Coronary Artery Calcium Progression in Subjects With Diabetes and Coronary Artery Disease: A Secondary Analysis of a Randomized Trial.

Higher coronary artery calcium (CAC) scores and progression of CAC are associated with higher mortality. We previously reported that subjects with coronary artery disease randomly allocated to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation or none had similar significant increases in CAC score over 30 months. Whether these findings are influenced by diabetes status is unknown. A total of 242 subjects with coronary artery disease who were on statin therapy were randomly allocated to to 1.86 g EPA and 1.5 g DHA daily or none (control). The CAC score was measured at baseline and 30-month follow-up using noncontrast, cardiac computed tomography. A significant interaction term between diabetes status and treatment arm was noted in the prediction of the CAC score (p <0.001). A total of 176 subjects (85.8% men) had no diabetes and 66 subjects (80.3% men) had diabetes. The mean age was 62.9 ± 7.9 versus 63.2 ± 7.1 years, respectively. The mean low-density lipoprotein cholesterol and median triglyceride levels were not significantly different between those without and with diabetes: 77.7 ± 25.9 versus 77.1 ± 30.2 mg/100 ml, respectively, and 117.0 (78.0 to 158.0) versus 119.0 (84.5 to 201.5) mg/100 ml, respectively. Subjects with diabetes on EPA+DHA had a greater increase in CAC score than subjects with diabetes in the control group (median 380.7 vs 183.5, respectively, p = 0.021). In contrast, no difference occurred between the EPA+DHA and control groups in subjects without diabetes (175.7 vs 201.1, respectively, p = 0.41). In conclusion, EPA+DHA supplementation was associated with greater CAC progression in subjects with diabetes than subjects with diabetes in the control group over a 30-month period; whether this indicates progression of the disease burden or plaque stabilization requires further study.

Predictive improvement of adding coronary calcium score and a genetic risk score to a traditional risk model for cardiovascular event prediction.

AIMS: Coronary artery calcium score (CACS) and polygenic risk score have been used as novel markers to predict cardiovascular (CV) events of asymptomatic individuals compared with traditional scores. No previous studies have directly compared the additive capacity of these two markers relative to conventional scores. The aim of the study was to evaluate the change in CV risk prediction ability when CACS, genetic risk score (GRS), or both are added to Systematic Coronary Risk Evaluation 2 (SCORE2). METHODS AND RESULTS: In a prospective, observational population-based study, 1002 asymptomatic subjects (mean age 53.1 ± 6.8 years, 73.8% male), free of clinical coronary disease and diabetes, were selected from GENEMACOR-study controls. SCORE2, CACS, and GRS were estimated to evaluate CV events' predictive and discriminative ability through Harrell's C-statistics. Net reclassification improvement (NRI) and integrated discrimination index were used to reclassify the population. Multivariable Cox proportional hazard ratio (HR) analysis assessed the variables independently associated with CV events. C-statistic demonstrated that the discriminative value for CV event occurrence was 0.608 for SCORE2, increasing to 0.749 (P = 0.001) when CACS was added, and improved to 0.802 (P = 0.0008) with GRS, showing a better discriminative capacity for CV events. Continuous NRI reclassified >70% of the population. Cox proportional analysis showed that the highest categories of SCORE2, CACS, and GRS remained in the equation with an HR of 2.9 (P = 0.003), 5.0 (P < 0.0001), and 3.2 (P = 0.003), respectively, when compared with the lowest categories. CONCLUSION: In our population, CACS added to SCORE2 had better ability than GRS in CV event risk prediction, discrimination, and reclassification. However, adding the three scores can become clinically relevant, especially in intermediate-risk persons.

Our study highlights the impact of including coronary artery calcium score (CACS) and genetic risk score (GRS) alongside Systematic Coronary Risk Evaluation 2 (SCORE2) for enhancing cardiovascular (CV) risk assessment in primary prevention. In our population, adding CACS to SCORE2 exhibited a superior discriminative capacity for CV events compared with GRS alone in terms of risk prediction, discrimination, and reclassification. Our results emphasize the potential clinical relevance of using all three scores to identify high-risk individuals who would benefit from earlier and more stringent cardiovascular risk management strategies to prevent future cardiovascular events.

Lipoprotein (a), metabolic syndrome and coronary calcium score in a large occupational cohort.

BACKGROUND AND AIMS: Whether lipoprotein (a) [Lp(a)] concentration is associated with metabolic syndrome (MetS) and pre-clinical atherosclerosis in different ethnic groups is uncertain. The association between Lp(a), MetS and a measure of pre-clinical atherosclerosis was studied in a large Asian cohort. METHODS AND RESULTS: Data were analyzed from a South Korean occupational cohort who underwent a cardiac computed tomography (CT) estimation of CAC score and measurements of cardiovascular risk factors (n = 14,583 people). The key exposure was an Lp(a) concentration in the top quartile (>38.64 mg/dL)) with a CAC score >0 as the outcome variable and measure of pre-clinical atherosclerosis. Logistic regression was used to describe the associations. 1462 participants had a CAC score >0. In the lowest Lp(a) quartile (<11.29 mg/dL), 25.8% had MetS, compared with 16.1% in the highest Lp(a) quartile (>38.64 mg/dL (p < 0.001). MetS, and component features, were inversely related to Lp(a) concentration (all p < 0.0001). In the highest Lp(a) quartile group, there was an association between Lp(a) and CAC score >0 in men (OR 1.21[1.05, 1.40], p = 0.008), and women (OR 1.62[1.03, 2.55], p = 0.038), after adjustment for age, sex, lipid lowering therapy, and multiple cardiovascular risk factors. There was no evidence of an interaction between highest quartile Lp(a) and either high LDLc (>147 mg/dL) (p = 0.99), or MetS (p = 0.84) on the association with CAC score >0. CONCLUSION: Lp(a) levels are inversely related to MetS and its components. There was a robust association between Lp(a) concentration >38.6 mg/dL and marker of early atherosclerosis in both men and women, regardless of LDLc, level MetS or other cardiovascular risk factors.

Eicosapentaenoic and docosahexaenoic acid supplementation and coronary artery calcium progression in patients with coronary artery disease: A secondary analysis of a randomized trial.

BACKGROUND AND AIMS: We previously reported that an omega-3 fatty acid index ≥4% with high-dose eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) prevented progression of noncalcified plaque. Higher coronary artery calcium (CAC) scores and progression of CAC are associated with increased cardiovascular events and mortality. We examined the effect of EPA + DHA on CAC score. METHODS: A total of 242 patients with coronary artery disease (CAD) on statin therapy were randomized to 1.86 g EPA and 1.5 g DHA daily or none (control) for 30 months. The CAC score was measured at baseline and 30-months with non-contrast, cardiac computed tomography. RESULTS: Both EPA + DHA and control groups had significant progression in CAC scores over 30 months (median change:183.5 vs 221.0, respectively, p < 0.001) despite a 13.6% reduction in triglyceride level with EPA + DHA. No significant difference was observed between groups for the total group, by baseline CAC scores of <100, 100-399, 400-999 and ≥1000 or quartiles of achieved levels of EPA, DHA and the omega-3 fatty acid index. Similar rates of CAC progression were noted in those on high-intensity statin compared to low- and moderate-intensity statin. CONCLUSIONS: EPA and DHA added to statin resulted in similar CAC progression over 30 months regardless of baseline CAC categories, statin intensity and achieved levels of EPA, DHA and the omega-3 fatty acid index.

Effects of Vitamin K2 and D Supplementation on Coronary Artery Disease in Men: A RCT.

Background: Extent and progression of coronary artery calcification (CAC) are strong predictors of myocardial infarction and mortality. Objectives: This study aims to investigate if vitamin K2 and D supplementation can reduce CAC progression. Methods: A total of 389 participants were randomized to supplementation with vitamin K2 (720 µg/day) and D (25 µg/day) vs placebo in a multicenter double-blinded randomized controlled trial. The primary endpoint (progression of aortic valve calcification) has been reported. This study reports CAC progression in participants with no ischemic heart disease. CT scans were performed at baseline, 12, and 24 months. ΔCAC and coronary plaque volume were evaluated in the entire group and in 2 subgroups. A safety endpoint was the composite of myocardial infarction, coronary revascularization, and all-cause mortality. Results: In total, 304 participants (male, mean age 71 years) were identified. The intervention and placebo group both increased in mean CAC scores from baseline to 24-month follow-up (Δ203 vs Δ254 AU, P = 0.089). In patients with CAC scores ≥400 AU, CAC progression was lower by intervention (Δ288 vs Δ380 AU, P = 0.047). Plaque analyses showed no significant difference in progression of noncalcified plaque volume (Δ-6 vs Δ46 mm3, P = 0.172). Safety events were fewer in participants receiving supplementation (1.9% vs 6.7%, P = 0.048). Conclusions: Patients with no prior ischemic heart disease randomized to vitamin K2 and D supplementation had no significant reduction in mean CAC progression over a 2-year follow-up compared to placebo. Although the primary endpoint is neutral, differential responses to supplementation in those with CAC scores ≥400 AU and in safety endpoints are hypothesis-generating for future studies.

Standardized Radiomics Analysis of Clinical Myocardial Perfusion Stress SPECT Images to Identify Coronary Artery Calcification.

PURPOSE: Myocardial perfusion (MP) stress single-photon emission computed tomography (SPECT) is an established diagnostic test for patients suspected of coronary artery disease (CAD). Meanwhile, coronary artery calcification (CAC) scoring obtained from diagnostic CT is a highly sensitive test, offering incremental diagnostic information in identifying patients with significant CAD yet normal MP stress SPECT (MPSS) scans. However, after decades of wide utilization of MPSS, CAC is not commonly reimbursed (e.g. by the CMS), nor widely deployed in community settings. We studied the potential of complementary information deduced from the radiomics analysis of normal MPSS scans in predicting the CAC score. METHODS: We collected data from 428 patients with normal (non-ischemic) MPSS (99mTc-sestamibi; consensus reading). A nuclear medicine physician verified iteratively reconstructed images (attenuation-corrected) to be free from fixed perfusion defects and artifactual attenuation. Three-dimensional images were automatically segmented into four regions of interest (ROIs), including myocardium and three vascular segments (left anterior descending [LAD]-left circumference [LCX]-right coronary artery [RCA]). We used our software package, standardized environment for radiomics analysis (SERA), to extract 487 radiomic features in compliance with the image biomarker standardization initiative (IBSI). Isotropic cubic voxels were discretized using fixed bin-number discretization (eight schemes). We first performed blind-to-outcome feature selection focusing on a priori usefulness, dynamic range, and redundancy of features. Subsequently, we performed univariate and multivariate machine learning analyses to predict CAC scores from i) selected radiomic features, ii) 10 clinical features, and iii) combined radiomics + clinical features. Univariate analysis invoked Spearman correlation with Benjamini-Hotchberg false-discovery correction. The multivariate analysis incorporated stepwise linear regression, where we randomly selected a 15% test set and divided the other 85% of data into 70% training and 30% validation sets. Training started from a constant (intercept) model, iteratively adding/removing features (stepwise regression), invoking the Akaike information criterion (AIC) to discourage overfitting. Validation was run similarly, except that the training output model was used as the initial model. We randomized training/validation sets 20 times, selecting the best model using log-likelihood for evaluation in the test set. Assessment in the test set was performed thoroughly by running the entire operation 50 times, subsequently employing Fisher's method to verify the significance of independent tests. RESULTS: Unsupervised feature selection significantly reduced 8×487 features to 56. In univariate analysis, no feature survived the false-discovery rate (FDR) to directly correlate with CAC scores. Applying Fisher's method to the multivariate regression results demonstrated combining radiomics with the clinical features to enhance the significance of the prediction model across all cardiac segments.  Conclusions: Our standardized and statistically robust multivariate analysis demonstrated significant prediction of the CAC score for all cardiac segments when combining MPSS radiomic features with clinical features, suggesting radiomics analysis can add diagnostic or prognostic value to standard MPSS for wide clinical usage.

Predictive values of coronary artery calcium and arterial stiffness for long-term cardiovascular events in patients with stable coronary artery disease.

BACKGROUND: Subclinical atherosclerosis detected by increased coronary artery calcium (CAC) or arterial stiffness as reflected by cardio-ankle vascular index (CAVI) has been associated with major adverse cardiovascular events (MACEs). However, comparative data from these two assessments in the same population are still limited. METHODS: From 2005 to 2013, patients with stable coronary artery disease (CAD), both asymptomatic and symptomatic who underwent both coronary computed tomography and CAVI were enrolled and followed for occurrence of MACEs (cardiovascular [CV] death, nonfatal myocardial infarction [MI], and nonfatal stroke) until December 2019. A cause-specific hazard model was applied to assess the associations of CAC score, and CAVI with long-term MACEs. RESULTS: A total of 8687 patients participated. Of them, CAC scores were 0, 1-99, 100-399, and ≥400 in 49.7%, 31.9%, 12.3%, and 6.1%, respectively. Arterial stiffness (CAVI ≥ 9.0) was associated with the magnitude of CAC in 23.8%, 36.3%, 44.5%, and 56.2%, respectively. During an average of 9.9 ± 2.4 years follow-up, MACEs occurred in 8.0% (95% CI: 7.4%, 8.6%) of subjects. After adjusting for covariables, CAC scores of 100-399 and ≥400, and CAVIs of ≥9.0 were found to independently predict the occurrence of MACEs with the hazard ratios (95% CI) of 1.70 (1.13, 1.98), 1.87 (1.33, 2.63), and 1.27 (1.06, 1.52), respectively. Other risk predictors were hypertension, diabetes mellitus (DM), chronic kidney disease (CKD), aspirin, and statin therapy. CONCLUSIONS: A CAC score ≥100 or a CAVI ≥ 9.0 predicts the long-term occurrence of MACEs in both asymptomatic and symptomatic patients with stable CAD. These two noninvasive tests can be used as screening tools to guide treatment for the prevention of future CV events.

Prevalence and extent of coronary artery calcification in the middle-aged and elderly population.

AIMS: Coronary artery calcification (CAC) measured on cardiac computed tomography (CT) is an important risk marker for cardiovascular disease (CVD) and has been included in the prevention guidelines. The aim of this study was to describe CAC score reference values in the middle-aged and elderly population and to develop a freely available CAC calculator. METHODS AND RESULTS: All participants from two population-based cardiac CT screening cohorts (DanRisk and DANCAVAS) were included. The CAC score was measured as a part of a screening session. Positive CAC scores were log-transformed and non-parametrically regressed on age for each gender, and percentile curves were transposed according to proportions of zero CAC scores. Men had higher CAC scores than women, and the prevalence and extend of CAC increased steadily with age. An online CAC calculator was developed, http://flscripts.dk/cacscore. After entering sex, age, and CAC score, the CAC score percentile and the coronary age are depicted including a figure with the specific CAC score and 25%, 50%, 75%, and 90% percentiles. The specific CAC score can be compared to the entire background population or only those without prior CVD. CONCLUSION: This study provides modern population-based reference values of CAC scores in men and woman and a freely accessible online CAC calculator. Physicians and patients are very familiar with blood pressure and lipids, but unfamiliar with CAC scores. Using the calculator makes it easy to see if a CAC value is low, moderate, or high, when a physician in the future communicate and discusses a CAC score with a patient.

Automatic coronary artery calcium scoring on routine chest computed tomography (CT): comparison of a deep learning algorithm and a dedicated calcium scoring CT.

Background: The aim of this study was to investigate the reliability and accuracy of automatic coronary artery calcium (CAC) scoring and risk classification in non-gated, non-contrast chest computed tomography (CT) of different slice thicknesses using a deep learning algorithm. Methods: This retrospective study was performed at 2 tertiary hospitals. Paired, dedicated calcium-scoring CT scans and non-gated, non-contrast chest CT scans taken within a month from the same patients were included. Chest CT images were grouped according to the slice thickness (group A: 1 mm; group B: 3 mm). For internal scans, the CAC score manually measured on dedicated calcium scoring CT images was used as the gold standard. The deep learning algorithm for group A was trained using 150 chest CT scans and tested using 144 scans, and that for group B was trained using 170 chest CT scans and tested using 144 scans. The intraclass correlation coefficient (ICC) was used to evaluate the correlation between the algorithm and the gold standard. Agreement between the deep learning algorithm, the manual results on chest CT, and the gold standard was determined by Bland-Altman analysis. Cardiac risk categories were compared. External validation was performed on 334 paired scans from a different organization. Results: A total of 608 internal paired scans (1 mm: 294; 3 mm: 314) of 406 individuals and 334 external paired scans (1 mm: 117; 3 mm: 117) of 117 individuals were included in the analysis. The ICCs between the deep learning algorithm and the gold standard were excellent in both group A (0.90; 95% CI: 0.85-0.93) and group B (0.94; 95% CI: 0.92-0.96). The Bland-Altman plots showed good agreement in both groups. For the cardiovascular risk category, the deep learning algorithm accurately classified 71% of cases in group A and 81% of cases in group B. The Kappa values for risk classification were 0.72 in group A and 0.82 in group B. External validation yielded equally good results. Conclusions: The automatic calculation of CAC score and cardiovascular risk stratification on non-gated chest CT using a deep learning algorithm was reliable and accurate on both 1 and 3 mm scans. Chest CT with a slice thickness of 3 mm was slightly more accurate in CAC detection and risk classification.

Association of Carotid Artery Plaque With Cardiovascular Events and Incident Coronary Artery Calcium in Individuals With Absent Coronary Calcification: The MESA.

BACKGROUND: Absence of coronary artery calcium (CAC) identifies asymptomatic individuals at low cardiovascular disease risk. Carotid artery plaque is a marker of increased risk, but its association with cardiovascular risk and incident CAC in people without CAC is unclear. METHODS: Multi-Ethnic Study of Atherosclerosis participants with CAC score of 0 at enrollment who also underwent carotid plaque measurement using B-mode ultrasonography were prospectively followed for incident coronary heart disease, stroke, and cardiovascular disease events, and CAC (score >0 on up to 3 serial computed tomography scans). The association of carotid plaque presence and plaque score (Ln[score+1]) at baseline with cardiovascular events and incident CAC was evaluated with Cox proportional hazards regression models adjusted for demographics, risk factors, and statin use. RESULTS: Among these 2673 participants (58 years, 64% women, 34% White, 30% Black, 24% Hispanic, and 12% Chinese), carotid plaque at baseline was observed in 973 (36%) and the median plaque score (range, 1-12) among those with plaque was 1. A total of 79 coronary heart disease, 80 stroke, and 151 cardiovascular disease events were observed during 16.1 years of follow-up. Carotid plaque presence and plaque score were independently associated with coronary heart disease risk (HRs, 1.66 [95% CI, 1.04-2.66]; and 1.48 [95% CI, 1.01-2.17], respectively) but not with stroke and cardiovascular disease risk. A total of 973 (36.4%) participants developed CAC over the evaluation period (median 9.3 years). Carotid plaque presence and plaque score were independently associated with incident CAC (HRs, 1.34 [95% CI, 1.18-1.54]; and 1.37 [95% CI, 1.21-1.54]), respectively. CONCLUSIONS: The presence and extent of carotid plaque are associated with long-term coronary heart disease risk and incident CAC among middle-aged asymptomatic individuals with an initial CAC score of 0.

Locking and loading the bullet against micro-calcification.

AIMS: Despite recent medical advances, cardiovascular disease remains the leading cause of death worldwide. As (micro)-calcification is a hallmark of atherosclerosis, this review will elaborately discuss advantages of sodium fluoride positron emission tomography (PET) as a reliable cardiovascular imaging technique for identifying the early onset of vascular calcification (i.e. locking onto the target). We assess state-of-the-art meta-analysis and clinical studies of possible treatment options and evaluate the concept of vitamin K supplementation to preserve vascular health (i.e. loading the bullet). METHODS AND RESULTS: After a structured PubMed search, we identified 18F-sodium fluoride (18F-NaF) PET as the most suitable technique for detecting micro-calcification. Presenting the pros and cons of available treatments, vitamin K supplementation should be considered as a possible safe and cost-effective option to inhibit vascular (micro)-calcification. CONCLUSION: This review demonstrates need for more extensive research in the concept of vitamin K supplementation (i.e. loading the bullet) and recommends monitoring the effects on vascular calcification using 18F-NaF PET (i.e. locking onto the target).

The association between periodontitis and cardiovascular risks in asymptomatic healthy patients.

BACKGROUND: Periodontitis is a chronic multifactorial inflammatory disease of the supportive tissues of the teeth. Pathophysiological evidence suggests a possible common inflammatory background between periodontitis and cardiovascular diseases (CVD). Pathological and epidemiological associations between these two diseases have been presented, but are still debated. This study aimed to investigate the association between the inflammatory burden of periodontitis and the presence and extent of coronary calcification. Secondary aims were to study other cardiovascular parameters and cardiovascular risk predictors in relation to periodontitis and dental health. METHODS: Healthy periodontitis or non-periodontitis patients 45-70 years of age were included in a prospective cross-sectional study. Full-mouth examinations were performed by a periodontist to determine their Periodontal Inflamed Surface Area (PISA) score and other dental parameters. To assess the cardiovascular conditions, Coronary Artery Calcium (CAC) scores, endothelial function assessments by the EndoPAT ™, and several physical and biochemical examinations were performed. RESULTS: Seventy-one patients were included. Elevated CAC scores and endothelial dysfunction were not significantly related to PISA or dental health. PISA was significantly related to the Framingham and Reynolds CVD risk predictors, but were no longer significant after correction for confounders. The same applied to the significant relations between tooth loss, dental plaque and bleeding scores and the CVD risk predictors. CONCLUSIONS: Periodontitis is associated with increased CVD risk, but is not an independent risk factor. This link is still important to make to bridge the gap between dentistry and general medicine and to identify patients at risk for CVD in an earlier stage.

Coronary Artery Calcium Score - A Reliable Indicator of Coronary Artery Disease?

Coronary artery disease (CAD) is caused by atheromatous blockage of coronary vessels leading to acute coronary events that usually occur when a plaque ruptures and a thrombus forms. CAD is a known cause of significant cardiovascular events, accounting for more than 50% of the deaths in western countries, and most of the patients with CAD remain asymptomatic. The coronary artery calcium (CAC) score has been created as a measure of coronary atherosclerosis. This article has compiled various studies that conclude the clinical relationship between coronary artery calcium and the development of cardiovascular (CV) events by using the CAC score as a reliable indicator of CAD. This article has reviewed the pathophysiology and risk factors of CAD, along with various methods of CAC scoring. It also underlined the reliability of CAC scoring for early detection of CAD in asymptomatic individuals. We emphasized the importance of age-dependent risk factor analysis combined with practical screening tools like CAC scoring for early diagnosis of CAD can help direct the treatment and prevent deaths in asymptomatic individuals.