Coronary artery calcium and cardiovascular outcomes in patients with lymphoma undergoing autologous hematopoietic cell transplantation.

BACKGROUND: Patients undergoing autologous hematopoietic cell transplantation (HCT) have a >2-fold risk of developing cardiovascular disease (CVD; heart failure, myocardial infarction, and stroke), compared to the general population. Coronary artery calcium (CAC) is predictive of CVD in nononcology patients but is not as well studied in patients who underwent HCT and survivors of HCT.The objective of this study was to examine the association between CAC and CVD risk and outcomes after HCT in patients with lymphoma. METHODS: This was a retrospective cohort study of 243 consecutive patients who underwent a first autologous HCT for lymphoma between 2009 and 2014. CAC (Agatston score) was determined from chest computed tomography obtained <60 days from HCT. Multivariable Cox regression analysis was used to calculate hazard ratio (HR) estimates and 95% confidence intervals (CIs), adjusted for covariates (age, conventional risk factors [e.g., hypertension and dyslipidemia], and cancer treatment). RESULTS: The median age at HCT was 55.7 years (range, 18.5-75.1 years), 59% were male, and 60% were non-Hispanic White. The prevalence of CAC was 37%. The 5-year CVD incidence for the cohort was 12%, and there was an incremental increase in the incidence according to CAC score: 0 (6%), 1-100 (20%), and >100 (32%) (p = .001). CAC was significantly associated with CVD risk (HR, 3.0; 95% CI, 1.2-7.5) and worse 5-year survival (77% vs. 50%; p < .001; HR, 2.0; 95% CI, 1.1-3.4), compared to those without CAC. CONCLUSIONS: CAC is independently associated with CVD and survival after HCT. This highlights the importance of integrating readily available imaging information in risk stratification and decision-making in patients undergoing HCT, which sets the stage for strategies to optimize outcomes after HCT.

Immune checkpoint inhibitors in cancer: the increased risk of atherosclerotic cardiovascular disease events and progression of coronary artery calcium.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have contributed to a significant advancement in the treatment of cancer, leading to improved clinical outcomes in many individuals with advanced disease. Both preclinical and clinical investigations have shown that ICIs are associated with atherosclerosis and other cardiovascular events; however, the exact mechanism underlying this relationship has not been clarified. METHODS: Patients diagnosed with stages III or IV non-small cell lung cancer (NSCLC) at the Wuhan Union Hospital from March 1, 2020, to April 30, 2022, were included in this retrospective study. Coronary artery calcium (CAC) volume and score were assessed in a subset of patients during non-ECG-gated chest CT scans at baseline and 3, 6, and 12 months after treatment. Propensity score matching (PSM) was performed in a 1:1 ratio to balance the baseline characteristics between the two groups. RESULTS: Overall, 1458 patients (487 with ICI therapy and 971 without ICI therapy) were enrolled in this cardiovascular cohort study. After PSM, 446 patients were included in each group. During the entire period of follow-up (median follow-up 23.1 months), 24 atherosclerotic cardiovascular disease (ASCVD) events (4.9%) occurred in the ICI group, and 14 ASCVD events (1.4%) in the non-ICI group, before PSM; 24 ASCVD events (5.4%) occurred in the ICI group and 5 ASCVD events (1.1%) in the non-ICI group after PSM. The CAC imaging study group comprised 113 patients with ICI therapy and 133 patients without ICI therapy. After PSM, each group consisted of 75 patients. In the ICI group, the CAC volume/score increased from 93.4 mm3/96.9 (baseline) to 125.1 mm3/132.8 (at 12 months). In the non-ICI group, the CAC volume/score was increased from 70.1 mm3/68.8 (baseline) to 84.4 mm3/87.9 (at 12 months). After PSM, the CAC volume/score was increased from 85.1 mm3/76.4 (baseline) to 111.8 mm3/121.1 (12 months) in the ICI group and was increased from 74.9 mm3/76.8 (baseline) to 109.3 mm3/98.7 (12 months) in the non-ICI group. Both cardiovascular events and CAC progression were increased after the initiation of ICIs. CONCLUSIONS: Treatment with ICIs was associated with a higher rate of ASCVD events and a noticeable increase in CAC progression.

Non-alcoholic fatty liver disease biomarkers estimate cardiovascular risk based on coronary artery calcium score in type 2 diabetes: a cross-sectional study with two independent cohorts.

BACKGROUND: Studies have demonstrated that coronary artery calcification on one hand and non-alcoholic fatty liver disease (NAFLD) on the other hand are strongly associated with cardiovascular events. However, it remains unclear whether NAFLD biomarkers could help estimate cardiovascular risk in individuals with type 2 diabetes (T2D). The primary objective of the present study was to investigate whether the biomarkers of NAFLD included in the FibroMax® panels are associated with the degree of coronary artery calcification in patients with T2D. METHODS: A total of 157 and 460 patients with T2D were included from the DIACART and ACCoDiab cohorts, respectively. The coronary artery calcium score (CACS) was measured in both cohorts using computed tomography. FibroMax® panels (i.e., SteatoTest®, FibroTest®, NashTest®, and ActiTest®) were determined from blood samples as scores and stages in the DIACART cohort and as stages in the ACCoDiab cohort. RESULTS: CACS significantly increased with the FibroTest® stages in both the DIACART and ACCoDiab cohorts (p-value for trend = 0.0009 and 0.0001, respectively). In DIACART, the FibroTest® score was positively correlated with CACS in univariate analysis (r = 0.293, p = 0.0002) and remained associated with CACS independently of the traditional cardiovascular risk factors included in the SCORE2-Diabetes model [ß = 941 ± 425 (estimate ± standard error), p = 0.028]. In the ACCoDiab cohort, the FibroTest® F3-F4 stage was positively correlated with CACS in point-biserial analysis (rpbi = 0.104, p = 0.024) and remained associated with CACS after adjustment for the traditional cardiovascular risk factors included in the SCORE2-Diabetes model (ß = 234 ± 97, p = 0.016). Finally, the prediction of CACS was improved by adding FibroTest® to the traditional cardiovascular risk factors included in the SCORE2-Diabetes model (goodness-of-fit of prediction models multiplied by 4.1 and 6.7 in the DIACART and ACCoDiab cohorts, respectively). In contrast, no significant relationship was found between FibroMax® panels other than FibroTest® and CACS in either cohort. CONCLUSIONS: FibroTest® is independently and positively associated with the degree of coronary artery calcification in patients with T2D, suggesting that FibroTest® could be a relevant biomarker of coronary calcification and cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT02431234 and NCT03920683.

Coronary Artery Calcium Score-Weighted Clinical Likelihood Model Performance in Patients with Stable Chest Pain and Coronary Artery Calcium Scores of Zero.

Background: For individuals with persistent stable chest pain (SCP) and a coronary artery calcium score (CACS) of 0, it might be challenging to establish the best risk assessment method for determining the individuals who will not benefit from further cardiovascular imaging testing (CIT). Thus, we investigated the CACS-weighted clinical likelihood (CACS-CL) model in SCP patients with a CACS of 0. Methods: Thus, to assess SCP, we originally enrolled 14,232 individuals for CACS and coronary computed tomography angiography (CCTA) scans between January 2016 and January 2018. Finally, patients with a CACS of 0 were included and followed up ​until January 2022. According to the established CACS-CL cutoffs of 15% and 5%, the associations between coronary artery disease (CAD) and major adverse cardiovascular events (MACEs) in risk groups were evaluated, alongside the net reclassification improvement (NRI). Results: Of the 6689 patients with a CACS of 0, the prevalence of CAD increased significantly (p < 0.0001) in patients with higher CACS-CL. However, there was no significant difference in the CAD distribution (p = 0.0637) between patients with CACS-CL < 5% and 5-15%. The association between the CACS-CL = 15%-determined risk groups and the occurrence of MACEs was stronger than for a CACS-CL = 5% (adjusted hazard ratio (HR): 7.24 (95% CI: 1.93-16.42) versus 3.68 (95% CI: 1.50-8.26)). Compared with the cutoff for CACS-CL = 5%, the NRI was 10.61% when using a cutoff for CACS-CL = 15%. Conclusions: Among patients with an SCP and CACS of 0, the CACS-CL model provided accurate predictions of CAD and MACEs. Compared to the cutoff for CACS-CL = 5%, the cutoff for CACS-CL = 15% seemed to be more effective and safer for deferring further CIT. Clinical Trial registration: NCT04691037.

Artificial Intelligence in Cardiovascular Disease Prevention: Is it Ready for Prime Time?

PURPOSE OF REVIEW: This review evaluates how Artificial Intelligence (AI) enhances atherosclerotic cardiovascular disease (ASCVD) risk assessment, allows for opportunistic screening, and improves adherence to guidelines through the analysis of unstructured clinical data and patient-generated data. Additionally, it discusses strategies for integrating AI into clinical practice in preventive cardiology. RECENT FINDINGS: AI models have shown superior performance in personalized ASCVD risk evaluations compared to traditional risk scores. These models now support automated detection of ASCVD risk markers, including coronary artery calcium (CAC), across various imaging modalities such as dedicated ECG-gated CT scans, chest X-rays, mammograms, coronary angiography, and non-gated chest CT scans. Moreover, large language model (LLM) pipelines are effective in identifying and addressing gaps and disparities in ASCVD preventive care, and can also enhance patient education. AI applications are proving invaluable in preventing and managing ASCVD and are primed for clinical use, provided they are implemented within well-regulated, iterative clinical pathways.

Subclinical Atherosclerosis to Guide Treatment in Dyslipidemia and Diabetes Mellitus.

PURPOSE OF REVIEW: Dyslipidemia and type 2 diabetes mellitus are two common conditions that are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). In this review, we aimed to provide an in-depth and contemporary review of non-invasive approaches to assess subclinical atherosclerotic burden, predict cardiovascular risk, and guide appropriate treatment strategies. We focused this paper on two main imaging modalities: coronary artery calcium (CAC) score and computed tomography coronary angiography. RECENT FINDINGS: Recent longitudinal studies have provided stronger evidence on the relationship between increased CAC, thoracic aorta calcification, and risk of cardiovascular events among those with primary hypercholesterolemia, highlighting the beneficial role of statin therapy. Interestingly, resilient profiles of individuals not exhibiting atherosclerosis despite dyslipidemia have been described. Non-conventional markers of dyslipidemia have also been associated with increased subclinical atherosclerosis presence and burden, highlighting the contribution of apolipoprotein B-100 (apoB)-rich lipoprotein particles, such as remnant cholesterol and lipoprotein(a), to the residual risk of individuals on-target for low-density lipoprotein cholesterol (LDL-C) goals. Regarding type 2 diabetes mellitus, variability in atherosclerotic burden has also been found, and CAC testing has shown significant predictive value in stratifying cardiovascular risk. Non-invasive assessment of subclinical atherosclerosis can help reveal the continuum of ASCVD risk in those with dyslipidemia and diabetes mellitus and can inform personalized strategies for cardiovascular disease prevention in the primary prevention setting.

Cardiovascular Risk Estimation and Stratification Among Individuals with Hypercholesterolemia.

PURPOSE OF THE REVIEW: This review aims to assess the variability in considering hypercholesterolemia for cardiovascular risk stratification in the general population. Recent literature on the integration of hypercholesterolemia into clinical risk scores and its interaction with other risk factors will be explored. RECENT FINDINGS: The impact of hypercholesterolemia on risk estimation varies among different cardiovascular risk calculators. Elevated lipid levels during early life stages contribute to atherosclerotic plaque development, influencing disease severity despite later treatment initiation. The interplay between low-density lipoprotein cholesterol (LDLc), inflammatory markers and non-LDL lipid parameters enhances cardiovascular risk stratification. Studies have also examined the role of coronary artery calcium (CAC) score as a negative risk marker in populations with severe hypercholesterolemia. Furthermore, polygenic risk scores (PRS) may aid in diagnosing non-monogenic hypercholesterolemia, refining cardiovascular risk stratification and guiding lipid-lowering therapy strategies. Understanding the heterogeneity in risk estimation and the role of emerging biomarkers and imaging techniques is crucial for optimizing cardiovascular risk prediction and guiding personalized treatment strategies in individuals with hypercholesterolemia.

When Does Primary Prevention Encroach on Secondary Prevention?

PURPOSE OF REVIEW: The risk of incident atherosclerotic cardiovascular disease (ASCVD) in primary prevention is typically lower than in secondary prevention. However, there is a spectrum of risk among individuals undergoing primary prevention with the risk in some individuals approaching those of secondary prevention. We review the clinical conditions wherein the risk in primary prevention is similar to that observed in secondary prevention. RECENT FINDINGS: Among individuals without established ASCVD, coronary artery calcium (CAC) scores ≥ 300 AU are associated with ASCVD event rates similar to secondary prevention populations. CAC score ≥ 1,000 AU are associated with an ASCVD risk seen in very high-risk secondary prevention populations. Interpretation of these observations must however consider differences in the risk reduction strategies. Current guidelines dichotomize ASCVD prevention into primary and secondary prevention, but certain primary prevention patients have an ASCVD risk equivalent to that of secondary prevention populations. Identifying higher risk primary prevention populations will allow for better risk mitigation strategies.

Low HDL-C/ApoA-I index is associated with cardiometabolic risk factors and coronary artery calcium: a sub-analysis of the genetics of atherosclerotic disease (GEA) study.

BACKGROUND: The high-density lipoprotein cholesterol to apolipoprotein A-I index (HDL-C/ApoA-I) may be practical and useful in clinical practice as a marker of atherosclerosis. This study aimed to investigate the association between the HDL-C/ApoA-I index with cardiometabolic risk factors and subclinical atherosclerosis. METHODS: In this cross-sectional sub-analysis of the GEA study, 1,363 individuals, women (51.3%) and men (48.7%) between 20 and 75 years old, without coronary heart disease or diabetes mellitus were included. We defined an adverse cardiometabolic profile as excess adipose tissue metrics, non-alcoholic liver fat measured by non-contrasted tomography, metabolic syndrome, dyslipidemias, and insulin resistance. The population was stratified by quartiles of the HDL-C/Apo-AI index, and its dose-relationship associations were analysed using Tobit regression, binomial, and multinomial logistic regression analysis. RESULTS: Body mass index, visceral and pericardial fat, metabolic syndrome, fatty liver, high blood pressure, and CAC were inversely associated with the HDL-C/ApoA-I index. The CAC > 0 prevalence was higher in quartile 1 (29.2%) than in the last quartile (22%) of HDL-C/ApoA-I index (p = 0.035). The probability of having CAC > 0 was higher when the HDL-C/ApoA-I index was less than 0.28 (p < 0.001). This association was independent of classical coronary risk factors, visceral and pericardial fat measurements. CONCLUSION: The HDL-C/ApoA-I index is inversely associated with an adverse cardiometabolic profile and CAC score, making it a potentially useful and practical biomarker of coronary atherosclerosis. Overall, these findings suggest that the HDL-C/ApoA-I index could be useful for evaluating the probability of having higher cardiometabolic risk factors and subclinical atherosclerosis in adults without CAD.

Comparing coronary artery cross-sectional area among asymptomatic South Asian, White, and Black participants: the MASALA and CARDIA studies.

BACKGROUND: South Asian individuals have high risk of atherosclerotic cardiovascular disease (ASCVD). Some investigators suggest smaller coronary artery size may be partially responsible. METHODS: We compared the left anterior descending (LAD) artery cross-sectional area (CSA) (lumen and arterial wall) among South Asians in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study with White and Black participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, adjusting for BMI, height, and other ASCVD risk factors. We used thin-slice non-contrast cardiac computed tomography to measure LAD CSA. We used linear regression models to determine whether race/ethnicity was associated with LAD CSA after adjusting for demographic factors, BMI, height, coronary artery calcium (CAC), and traditional cardiovascular risk factors. RESULTS: Our sample included 3,353 participants: 513 self-identified as South Asian (44.4% women), 1286 as Black (59.6% women), and 1554 as White (53.5% women). After adjusting for age, BMI, height, there was no difference in LAD CSA between South Asian men and women compared to White men and women, respectively. After full adjustment for CVD risk factors, LAD CSA values were: South Asian women (19.9 mm2, 95% CI [18.8 - 20.9]) and men (22.3 mm2, 95% CI [21.4 - 23.2]; White women (20.0 mm2, 95% CI [19.4-20.5]) and men (23.6 mm2, 95% CI [23.0-24.2]); and Black women (21.6 mm2, 95% CI [21.0 - 22.2]) and men (26.0 mm2, 95% CI [25.3 - 26.7]). Height, BMI, hypertension, CAC, and age were positively associated with LAD CSA; current and former cigarette use were inversely associated. CONCLUSIONS: South Asian men and women have similar LAD CSA to White men and women, and smaller LAD CSA compared to Black men and women, respectively, after accounting for differences in body size. Future studies should determine whether LAD CSA is associated with future ASCVD events.

Improving cardiovascular risk prediction with machine learning: a focus on perivascular adipose tissue characteristics.

BACKGROUND: Timely prevention of major adverse cardiovascular events (MACEs) is imperative for reducing cardiovascular diseases-related mortality. Perivascular adipose tissue (PVAT), the adipose tissue surrounding coronary arteries, has attracted increased amounts of attention. Developing a model for predicting the incidence of MACE utilizing machine learning (ML) integrating clinical and PVAT features may facilitate targeted preventive interventions and improve patient outcomes. METHODS: From January 2017 to December 2019, we analyzed a cohort of 1077 individuals who underwent coronary CT scanning at our facility. Clinical features were collected alongside imaging features, such as coronary artery calcium (CAC) scores and perivascular adipose tissue (PVAT) characteristics. Logistic regression (LR), Framingham Risk Score, and ML algorithms were employed for MACE prediction. RESULTS: We screened seven critical features to improve the practicability of the model. MACE patients tended to be older, smokers, and hypertensive. Imaging biomarkers such as CAC scores and PVAT characteristics differed significantly between patients with and without a 3-year MACE risk in a population that did not exhibit disparities in laboratory results. The ensemble model, which leverages multiple ML algorithms, demonstrated superior predictive performance compared with the other models. Finally, the ensemble model was used for risk stratification prediction to explore its clinical application value. CONCLUSIONS: The developed ensemble model effectively predicted MACE incidence based on clinical and imaging features, highlighting the potential of ML algorithms in cardiovascular risk prediction and personalized medicine. Early identification of high-risk patients may facilitate targeted preventive interventions and improve patient outcomes.

Absolute iron deficiency, coronary artery calcification and cardiovascular mortality in maintenance haemodialysis patients.

AIM: The effects of iron on vascular calcification in rats and vascular smooth muscle cells were recently reported, but clinical studies on iron and vascular calcification are scant. We studied the associations of absolute iron deficiency, coronary artery calcification and mortality in patients with maintenance haemodialysis (MHD). METHODS: Transferrin saturation (TSAT), ferritin, mean corpuscular haemoglobin (MCH) and Agatston coronary artery calcium score (CACS) were studied at baseline in MHD patients and followed up for 3 years. Cox proportional hazard analyses for mortality and linear regression analyses for CACS were performed. RESULTS: In 306 patients, the median age was 67 (56-81) years, dialysis duration was 76 (38-142) months, and diabetes prevalence was 42.5%. Fifty-two patients had died by 3 years. Patients with absolute iron deficiency (TSAT <20% and ferritin <100 ng/mL) (n = 102) showed significantly higher CACS (p = .0266) and C-reactive protein (p = .0011), but a lower frequency of iron formulation administration compared with patients without absolute iron deficiency at baseline (n = 204). Absolute iron deficiency was a significant predictor for 3-year cardiovascular (CV) mortality (hazard ratio: 2.08; p = .0466), but not for 3-year all-cause mortality. CACS was significant predictor for both 3-year CV and all-cause mortality (p <.05). Absolute iron deficiency and MCH were significant determinants of CACS (p < .05). CONCLUSION: MHD patients with absolute iron deficiency showed significantly higher CACS than others, and absolute iron deficiency was a significant risk factor for coronary artery calcification and 3-year CV mortality in MHD patients, but was not a significant predictor for 3-year all-cause mortality.

Effects of overhydration, Kt/Vurea, ß2-microglobulin on coronary artery calcification and mortality in haemodialysis patients.

AIM: We studied the effects of overhydration (OH), Kt/Vurea and ß2-microglobulin (ß2-MG) on coronary artery calcification and mortality in patients undergoing haemodialysis (HD). METHODS: The Agatston coronary artery calcium score (CACS), postdialysis body composition using bioimpedance analysis, single-pool Kt/Vurea and predialysis ß2-MG at baseline were assessed and followed up for 3 years in patients undergoing HD. We performed logistic regression analyses for a CACS ≥400 and Cox proportional hazard analyses for all-cause and cardiovascular mortality. RESULTS: The study involved 338 patients with a median age of 67 (56-74) years, dialysis duration of 70 (33-141) months and diabetes prevalence of 39.1% (132/338). Patients with a CACS ≥400 (n = 222) had significantly higher age, dialysis duration, male prevalence, diabetes prevalence, C-reactive protein, predialysis ß2-MG, OH, extracellular water/total body water and overhydration/extracellular water (OH/ECW) but significantly lower Kt/Vurea than patients with a CACS <400 (n = 116) (p < .05). OH/ECW, Kt/Vurea and predialysis ß2-MG were significant predictors of a CACS ≥400 (p < .05) after adjusting for age, dialysis duration, serum phosphate and magnesium. In all patients, cut-off values of OH/ECW, Kt/Vurea and predialysis ß2-MG for a CACS ≥400 were 16%, 1.74 and 28 mg/L, respectively. After adjusting for dialysis duration, OH/ECW ≥16%, Kt/Vurea ≥1.74 and ß2-MG ≥28 mg/L were significant predictors of 3-year all-cause mortality but not 3-year cardiovascular mortality. CONCLUSION: Higher OH/ECW, higher predialysis ß2-MG and lower Kt/Vurea values are significant risk factors for a CACS ≥400 and 3-year all-cause mortality in patients undergoing maintenance HD.

The relationship between coronary artery calcium and layer-specific global longitudinal strain in patients with suspected coronary artery disease.

PURPOSE: Layer-specific global longitudinal strain (GLS) may provide important insights in patients with suspected coronary artery disease (CAD). We aimed to investigate the association between layer-specific GLS and coronary artery calcium score (CACS) in patients suspected of CAD. METHODS: We performed a retrospective study of patients suspected of CAD who underwent both an echocardiogram and cardiac computed tomography (median 42 days between). Layer-specific (endocardial-, whole-layer-, and epicardial-) GLS was measured using speckle tracking echocardiography. We assessed the continuous association between layer-specific GLS and CACS by negative binomial regression, and the association with high CACS (≥400) using logistic regression. RESULTS: Of the 496 patients included (mean age 59 years, 56% male), 64 (13%) had a high CACS. Those with high CACS had reduced GLS in all layers compared to those with CACS < 400 (endocardial GLS: -20.5 vs. -22.7%, whole-layer GLS: -17.7 vs. -19.4%, epicardial GLS: -15.3 vs. -16.9%, p < .001 for all). Negative binomial regression revealed a significant continuous association showing increasing CACS with worsening GLS in all layers, which remained significant after multivariable adjustment including SCORE chart risk factors. All layers of GLS were associated with high CACS in univariable analyses, which was consistent after multivariable adjustment (endocardial GLS: OR = 1.11 (1.03-1.20); whole-layer GLS: OR = 1.14 (1.04-1.24); epicardial GLS: OR = 1.16 (1.05-1.29), per 1% absolute decrease). CONCLUSION: In this study population with patients suspected of CAD and normal systolic function, impaired layer-specific GLS was continuously associated with increasing CACS, and decreasing GLS in all layers were associated with presence of high CACS.

A CNN-based denoising method trained with images acquired with electron density phantoms for thin-sliced coronary artery calcium scans.

PURPOSE: This work proposed a convolutional neural network (CNN)-based method trained with images acquired with electron density phantoms to reduce quantum noise for coronary artery calcium (CAC) scans reconstructed with slice thickness less than 3 mm. METHODS: A DenseNet model was used to estimate quantum noise for CAC scans reconstructed with slice thickness of 0.5, 1.0 and 1.5 mm. Training data was acquired using electron density phantoms in three different sizes. The label images of the CNN model were real noise maps, while the input images of the CNN model were pseudo noise maps. Image denoising was conducted by subtracting the CNN output images from thin-sliced CAC scans. The efficacy of the proposed method was verified through both phantom study and patient study. RESULTS: By means of phantom study, the proposed method was proven effective in reducing quantum noise in CAC scans reconstructed with 1.5-mm slice thickness without causing significant texture change or variation in HU values. With regard to patient study, calcifications were more clear on the denoised CAC scans reconstructed with slice thickness of 0.5, 1.0 and 1.5 mm than on 3-mm slice images, while over-smooth changes were not observed in the denoised CAC scans reconstructed with 1.5-mm slice thickness. CONCLUSION: Our results demonstrated that the electron density phantoms can be used to generate training data for the proposed CNN-based denoising method to reduce quantum noise for CAC scans reconstructed with 1.5-mm slice thickness. Because anthropomorphic phantom is not a necessity, our method could make image denoising more practical in routine clinical practice.

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.

Coronary artery calcium score as independent risk factor of obstructive coronary artery disease.

OBJECTIVE: Aim: To prove an independence of CAC score comparatively to conventional risk factors such as age, and dyslipidemia especially in patients under forty years of age. PATIENTS AND METHODS: Materials and Methods: Thirty-four asymptomatic adult patients with no prior established atherosclerotic cardiovascular disease, diabetes mellitus or severe comorbidities, except of complex clinical examination, underwent CT scan with evaluation of coronary artery calcium score. RESULTS: Results: The average total cholesterol level in the group was (5.62±1.02) mmol/l, indicating the presence of dyslipidemia. The average HDL level was (1.26±0.24) mmol/l, suggesting an average risk of atherosclerosis. The average LDL levels were within the borderline range at (3.63±1.01) mmol/l. The average triglyceride level was within the safe range at (1.93±1.08) mmol/l. The atherogenicity coefficient indicated a moderate risk of atherosclerosis with an average value of 3.64±1.31. The average coronary artery calcium score was 56.71±143.85, indicating minor plaques and a moderate risk of coronary artery disease. Correlation analysis revealed no significant correlation between age and the CAC score (r=0.1, p>0.05). However, reliable direct correlation of weak strength was found between the CAC score and LDL level (r=0.35, p<0.05). Direct correlations of weak strength were also observed between age and the levels of total cholesterol, LDL and the atherogenicity coefficient (r=0.43, 0.49, 0.42 respectively, p<0.05). CONCLUSION: Conclusions: Coronary artery calcium score is a valuable screening tool for identifying potential obstructive coronary artery disease, not only for individuals aged forty and above, but also for younger asymptomatic patients.

Coronary Artery Calcium Score Improves Risk Assessment of Symptomatic Patients in Low-Risk Group Based on Current Guidelines.

Background: The guidelines for evaluation and diagnosis of stable chest pain (SCP) released by American societies in 2021 (2021 GL) and European Society of Cardiology (ESC) in 2019 both recommended the estimation of pretest probability (PTP) by ESC-PTP model. Further risk assessment for the low-risk group according to 2021 GL (ESC-PTP ≤ 15%) is important but still remains unclear. Thus, the present study intended to comprehensively investigate the diagnostic and prognostic value of coronary artery calcium score (CACS) in these low-risk patients. Methods: From January 2017 to June 2019, we initially enrolled 8265 patients who were referred for CACS and coronary computed tomography angiography (CCTA) for the assessment of SCP. PTP of each patient was estimated by ESC-PTP model. Patients with ESC-PTP ≤ 15% were finally included and followed up for major adverse cardiovascular event (MACE) and utilization of invasive procedures until June 2022. The degree of coronary artery disease (CAD) on CCTA was defined as no CAD (0%), nonobstructive CAD (1-49%) and obstructive CAD ( ≥ 50%). Multivariate Cox proportional hazards and Logistic regression models were used to calculate adjusted hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs), respectively. Results: A total of 5183 patients with ESC-PTP ≤ 15% were identified and 1.6% experienced MACE during the 4-year follow-up. The prevalence of no CAD and obstructive CAD decreased and increased significantly (p < 0.0001) in patients with higher CACS, respectively, and 62% had nonobstructive CAD among those with CACS > 0, resulting in dramatically increasing ORs for any stenosis ≥ 50% and > 0% across CACS strata. Higher CACS was also associated with an elevated risk of MACE (adjusted HR of 3.59, 13.47 and 6.58 when comparing CACS = 0-100, CACS > 100 and CACS > 0 to CACS = 0, respectively) and intensive utilization of invasive procedures. Conclusions: In patients for whom subsequent testing should be deferred according to 2021 GL, high CACS conveyed a significant probability of substantial stenoses and clinical endpoints, respectively. These findings support the potential role of CACS as a further risk assessment tool to improve clinical management in these low-risk patients.

Interplay between Risk Factors and Coronary Artery Calcium in Middle-Aged and Elderly Symptomatic Patients.

Background: The prognostic value of coronary artery calcium (CAC) combined with risk factor burdens in middle-aged and elderly patients with symptoms is unclear. Methods: A cohort study comprising 7432 middle-aged and elderly symptomatic patients (aged above 55 years) was conducted between December 2013 and September 2020. All patients had undergone coronary computed tomography angiography, and the Agatston score were used to measure CAC scores. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), which was defined as a composite outcome of nonfatal myocardial infarction, revascularization (percutaneous coronary intervention or coronary artery bypass graft), stroke, and cardiovascular death. Congestive heart failure, cardiogenic shock, malignant arrhythmia, and all-cause mortality were defined as the secondary outcomes. Results: There are 970 (13%) patients with CAC 0-10, 2331 (31%) patients with CAC 11-100, and 4131 (56%) patients with CAC ≥ 101. The proportion of patients aged 55-65 years, 65-75 years and ≥ 75 years was 40.7%, 38.1% and 21.2%, respectively. The total number of MACCEs over the 3.4 years follow-up period was 478. The percentage of CAC ≥ 101 was higher among the 75-year-old group than the 55-65-year-old group, increasing from 46.5% to 68.2%. With the increase in the CAC score, the proportion of patients aged ≥ 75 years increased from 12.9% to 25.8%, compared to those aged 55-65 years. The number of risk factors gradually increased as the CAC scores increased in the symptomatic patients aged over 55 years and the similar tendencies were observed among the different age subgroups. The proportion of non-obstructive coronary artery disease (CAD) was comparable between the three age groups (53.5% vs 51.9% vs 49.1%), but obstruction CAD increased with age. The incidence of MACCE in the group with CAC ≥ 101 and ≥ 4 risk factors was 1.71 times higher (95% confidence interval (CI) 1.01-2.92; p = 0.044) than the rate in the group with CAC ≥ 101 and 1 risk factor. In the CAC 0-10 group, the incidence of MACCE in patients aged ≥ 75 years was 12.65 times higher (95% CI: 6.74-23.75; p < 0.0001) than that in patients aged 55-65 years. By taking into account the combination of CAC score, age, and risk factor burden, the predictive power of MACCE can be increased (area under the curve (AUC) = 0.614). Conclusions: In symptomatic patients aged 55 or above, a rise in age, CAC scores, and risk factor burden was linked to a considerable risk of future MACCE. In addition, combining CAC scores, age and risk factors can more accurately predict outcomes for middle-aged and elderly patients with symptoms.

Application of Targeted Coronary Angiography in the Diagnosis of Sudden Cardiac Death.

OBJECTIVES: To diagnose coronary artery stenosis by using the postmortem computed tomography angiography (PMCTA), and to explore the diagnostic value of PMCTA in sudden cardiac death. METHODS: Six death cases were selected, and the contrast medium iohexol was injected under high pressure through femoral artery approach with 5F pigtail catheter to obtain coronary image data and then the data was analyzed. The results of targeted coronary imaging and coronary artery calcium score (CaS) were compared with the results of conventional autopsy and histopathological examination. RESULTS: The autopsy and histopathological examination of cases with coronary artery stenosis obtained similar results in targeted coronary angiography, with a diagnostic concordance rate of 83.3%. Targeted coronary angiography could effectively show coronary artery diseases, and the CaS was consistent with the results of conventional autopsy and histopathological examination. CONCLUSIONS: Targeted coronary angiography can be used as an effective auxiliary method for conventional autopsy in cases of sudden cardiac death.