Coronary Calcium Research Articles

A novel marker of cardiovascular risk stratification: the role of total cardiovascular calcium score using cardiac CT

Abstract Introduction It is widely accepted that coronary and valve calcification measured by cardiac CT, individually, are associated with cardiovascular events and mortality. However, the role of an encompassing marker of cardiovascular atherosclerosis could be more representative of the real cardiovascular risk. Objectives To determine the prognostic value of a combined coronary, valvular and aortic calcium score to predict long-term major adverse cardiac and cerebrovascular events (MACCE). Methods We conducted a single center study on 316 consecutive patients who underwent cardiac CT scan between January 2018 and December 2019. We excluded patients with poor imaging quality, constrictive pericarditis, prosthetic valves and/or devices. The calcium score of coronary arteries (CA), mitral valve (MV), aortic valve (AoV), ascending aorta (AAo) and aortic arch (AAc) were calculated from non-contrast ECG-gated CT using the Agatston method and were combined to derive a valvular (VA=MV+AoV), total cardiac (TC=CA+VA) and total cardiovascular (TCV=TC+AAo+AAc) calcium scores (Fig.1A). The primary endpoint was a composite of MACCE, defined as all-cause death, stroke, myocardial infarction and hospital admission for heart failure. Results A total of 275 CT scans were suitable for analysis. Mean age was 59.6±12.3 years, 48.4% were female. A total of 183 (66.7%) patients presented calcification in at least one location. Patients with calcification on any of the prespecified locations had higher prevalence of hypertension, dyslipidemia and type 2 diabetes mellitus (DM) than those without any calcium (p<0.05). After a median follow-up of 3.18 [IQR 2.84-3.69] years, 40 (14.5%) patients had met the primary endpoint. Regression analyses demonstrated that all CA, VA, TC and TCV scores were independent predictors of MACCE (p<0.05 for all). The best prediction models included calcium score (all combinations), age, sex, type 2 DM and smoking status (Fig.1B). The model with TCV score was the most powerful predictor of MACCE (χ2 47.8), followed by TC score (χ2 43.1). Of interest, the model with CA score had the poorest performance (χ2 35.4). Conclusion Coronary calcium score is a quick way to stratify risk in clinical practice, but its performance is too focused on coronary events. Total cardiovascular calcium score, however, is more encompassing, also quick to measure, and a more truthful depiction of the patient’s cardiac and cerebrovascular risk, potentially allowing a more tailored and timely approach to risk factors in clinical practice.

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 (<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.

Does initial use of large versus small burr size in left main stem bifurcation impact clinical and procedural outcomes?

Abstract Background Coronary calcifications, detected in up to 25% of treated coronary lesions nowadays, has a well-known association with complications during PCI, particularly for left main stem (LMS) interventions. Current guidelines recommend coronary artery bypass grafting for patients with LMS disease, particularly with high SYNTAX score ≥ 33. However, in those with increased surgical risk, PCI can be used particularly with use of rota-ablation (RA). RA is a well-established treatment for heavily calcified disease particularly in non LMS sites. However, data on the safety and efficacy of use of RA in LMS bifurcation management is limited. Current guidelines recommend using a small burr size at the start, with upsizing burrs if required. Whether upfront use of large burr size ≥ 1.75 versus smaller burr size in this context in is safe or effective is unknown. Methods This was a retrospective, single centre, study. Included patients undergoing RA to LMS bifurcation disease. Standard procedures for RA were applied to each case, following current national and international intraprocedural standards. The main study outcomes were overall mortality at 1 year, and a comparison of mortality at 1 and 4 years between groups and repeat target lesion revascularization at 4 years. Results To our knowledge, this is the largest series of LMS rota-ablation cases, with the longest available follow up. Between June 2009 and October 2021, we included 243 patients with a mean age of 74.7±9 years. Males formed 80% of the cases. 51.4% of patients were treated with a large bur size ≥ 1.75mm, with more males being treated with large burr size. Most treated lesions were true bifurcations (85.6%). Treated lesions were complex (Syntax score = 35.3 ± 10.6). Radial access was used in almost two thirds of patients, with size 7F sheath being the most used. Intravascular ultrasound was more commonly used with large burr size (p = 0.017). Upfront 2-stent techniques, predominantly culotte, was employed more often with large burr size. Provisional technique was used more often in the small burr size group. The burr size to vessel size was 0.4 in small burr group versus 0.48 in large burr size using stent size as a surrogate for vessel size. Post dilatation balloons were larger as well as stent size in the large burr group. The overall 1-year mortality for the group was 12.7% similar to international literature. Importantly, procedural complications were not different between groups, and similarly mortality at 1 and 4 years, p = 0.082 and p = 0.384 respectively. There was no difference between groups in terms of repeat vessel revascularization at 4 years p=0.487. Conclusions Upfront use of large burr size ≥ 1.75 is feasible and safe to treat LMS bifurcation disease with no increase in procedural complications or mortality and target lesion revascularization on long term follow up. It is notable that in-hospital mortality for this cohort was low at 1.6% in comparison to previous studies.1 and 4 year mortality KM curves

Impact of ultra-high-resolution on cardiac CT assessment of coronary artery stenoses, plaque burden/composition, and pericoronary adipose tissue attenuation

Abstract Background Conventional coronary computed tomography angiography (CCTA) overestimates stenoses within stents and calcified arteries due to "blooming" artifacts. Ultra-high-resolution coronary CT (UHR-CT) may overcome this limitation because of higher spatial resolution. Purpose To investigate differences in coronary arterial lumen volume, stenosis severity, and plaque composition, between CCTA and UHRCT in patients with stents and/or high coronary calcium scores. Methods As part of a prospective pilot study, 14 patients referred for invasive coronary angiography for evaluation of obstructive CAD underwent UHRCT (Canon Precision, 160 x 0.25mm slices) prior to catheterization. Images of identical cardiac phases were reconstructed in two badges for comparison: 1) Ultra-high resolution using a 1,024 x 1,024 matrix, 0.25 mm, and 2) conventional resolution with a 524 x 524 matrix, 0.5 mm. All images were reconstructed using iterative reconstruction algorithm (AIDR 3D) and a sharp kernel (FC05). For the left main and three coronary arteries, an automated contour analysis using a dedicated software (QAngioCT RE 3.2, Medis, Netherlands) was performed to compare conventional CCTA vs. UHR-CT resolution images across common vascular and plaque metrics, including lumen and vessel volume, plaque burden/volume, plaque composition based upon predefined fixed intensity cut-off values of CT attenuation, minimal and maximal plaque thickness, pericoronary adipose tissue attenuation (PCAT), minimal lumen area and diameter, and diameter stenosis. All lumen and vessel contours were generated by the software, without manual editing. The segment model proposed by the SCCT was used as reference and the lesions classified as greater than 25% stenosis by visual assessment were recorded. The quality of the images was subjectively assessed using a 5-point Likert scale. Vessel segments with scores 1 (severe artifacts) and 2 (pronounced artifacts) were not included in the analysis. Results The mean patient age was 68.5 years (±6.8), 2 were female (14.3%), 6 patients had stents (11 stented segments) and the mean Agatston score was 947.6 (±449) among the 8 non-stented patients. A total of 56 vessels, 133 segments, and 57 lesions were analyzed. Eight segments (6%) were excluded from the analysis due to poor quality. Results on a per segment and per lesion basis were summarized in the table. The mean PCAT value was significantly lower for the UHRCT images compared to NR reconstruction in both segment (p<0.001) and lesion based (p=0.002) analyses. Plaque differentiation varied by UHRCT resulted in a lower fibrous plaque volumes but higher necrotic (low attenuation) plaque volumes. Conclusions Ultra-high-resolution CT image analysis results in significantly different coronary artery plaque volume and PCAT assessment vs. conventional resolution CCTA. These findings have implications for evaluating high-risk plaque features and perivascular inflammation in patients.Table 1

Sex differences in coronary atherosclerotic plaque activity using 18F-sodium fluoride positron emission tomography

Abstract Background There are sex differences in the extent, severity, and outcomes of coronary artery disease. Purpose To assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men. Methods In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men. Results Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27-434] versus 205 [51-571] Agatston units; p=0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p=0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p=0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n=80) and 48.3% (n=73); p=0.42), or CMA values >1.56 (21.8% (n=33) and 21.8% (n=33); p=1.00). Over a median follow-up of 4.5 [4.0-6.0] years, myocardial infarction occurred in 6.6% of women (n=10) and 7.8% of men (n=66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p=0.04) and men (HR: 5.29; 95% CI:2.28-12.28; p<0.001). Conclusions Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex.Sex differences in CAD activityCase examples

Functional and prognostic impacts of serum albumin with thoracic arterial calcification among asymptomatic individuals

Although several studies have demonstrated the cardiovascular (CV) implication of hypoalbuminemia and arterial calcification among hemodialysis patients, little is known regarding their cardiac correlates and relevant CV outcomes in asymptomatic individuals. We assessed the potential CV interrelation between serum albumin (SA) and aortic calcification. Among 2,723 asymptomatic individuals underwent cardiovascular health check-up, we assessed serum albumin (SA) level, thoracic aortic calcification (TAC) and coronary artery calcification (CAC) by multi-detector computed tomography, and ultrasound-determined carotid plaque burden. We related these measures to cardiac structure/function and CV outcomes. Lower SA level was associated with higher TAC score and volume rather than carotid plaque or coronary calcification burden in fully adjusted models. By categorizing the study population into 4 groups by SA (>, ≤ 4.6 mg/dL) and presence of TAC, subjects classified into low SA/TAC(+) category were oldest with highest prevalent CV disease. Both lower SA and TAC(+) were independently associated with impaired myocardial systolic/diastolic mechanics and higher CV events during a median of 6.6 years (IQR: 5.1, 6.8 years) follow-up. Participants classified into low SA/TAC(+) category showed highest risk for CV events (adjusted HR: 3.78 [95% CI: 2.11, 6.77], high SA/TAC[-] as reference) in fully adjusted Cox model. Among symptom-free individuals, TAC was closely associated with low SA concentration in relation to unfavorable cardiac mechanics and may serve as a useful prognosticator for adverse CV events.

In-Depth Review of the Influence of Renal Insuficiency on Major Adverse Cardiovascular Event (MACE) and Mortality in Patients with Acute St-Segment Elevation Myocardial In- farction (STEMI)

The widespread implementation of invasive procedures such as coronary angiography and primary percutaneous coronary intervention (PCI) into the routine management of patients with acute ST-segment elevation myocardial infarction (STEMI) in the last 10 years has led to a significant improvement in patient prognosis. At the same time, this also raises new problems and questions, mostly related to the fact that there are many elderly patients and/or patients with comorbidities who need to undergo this invasive procedure. One of the most important comorbidities is renal insufficiency. STEMI patients with renal insufficiency typically present with more extensive atherosclerotic lesions, including diffuse coronary calcification, which poses a challenge to the interventional cardiologist due to a higher risk of periprocedural complications, higher risk of restenosis, major adverse cardiovascular event (MACE) , and patient mortality. This review discusses in depth the influence of renal insufficiency on MACE and mortality in STEMI patients. Keywords: renal insufficiency, STEMI, MACE, mortality.

PERFIL DOS RESULTADOS DE ESCORE DE CÁLCIO DE CORONÁRIAS EM UM SERVIÇO PRIVADO DE ARACAJU

INTRODUCTION: Cardiovascular diseases (CVD) are responsible for one third of all deaths worldwide, with immutable risk factors such as age and gender, but also mutable factors such as sedentary lifestyles, obesity, hypertension and alcohol consumption. Given this scenario, there is a need to stratify the risk of individuals. The Coronary Calcium Score (CCS) is a tool used in non-contrast CT scans to stratify cardiovascular risk by quantifying the amount of calcium in the coronary arteries. OBJECTIVE: To analyze the coronary calcium score profile of patients at a private service in Aracaju/SE. METHODS: This is a quantitative, cross-sectional, documentary, descriptive and retrospective study, produced by evaluating tomography reports for calcium score, performed on outpatients, in a private service in Aracaju-SE, between January 1 and December 31, 2023. A total of 227 examination reports were obtained. The inclusion criteria were imaging reports from January to December 2023. Duplicate exams, exams of other areas of the body and exams outside the period listed for the research were excluded. RESULTS: Our sample consisted of 125 women and 102 men, with no difference in mean age between them, whose mean calcification was 215.46. Men had higher overall mean values for calcium score and calcification volume than women, as well as for the arterial territories (DA, CX and CD), with the exception of the TCE, for which there was no difference between the genders. CONCLUSION: These data reveal a higher proportion of women undergoing examinations compared to men. Although most of the individuals in the study did not have significant coronary calcification, it was observed that, among the cases of significant calcification, men were more affected than women.

Automated AI-based coronary calcium scoring using retrospective CT data from SCAPIS is accurate and correlates with expert scoring.

Evaluation of the correlation and agreement between AI and semi-automatic evaluations of calcium scoring CT (CSCT) examinations using extensive data from the Swedish CardioPulmonary bio-Image study (SCAPIS). In total, 5057 CSCT examinations were performed on one CT system at Linköping University Hospital between October 8, 2015, and June 12, 2018. AI evaluations were compared to semi-automatic CSCT results from expert reader evaluations rendered within SCAPIS. Pearson correlation, intraclass correlation coefficients (ICC), and Bland-Altman analysis were applied for Agatston (AS), volume (VS), mass scores (MS), number of lesions and lesion location. Agreement of Agatston score classifications into cardiovascular (CV) risk categories was evaluated with weighted kappa analysis. The evaluation included 4567 subjects, 2229 (48.8%) male, 2338 (51.2%) female, 50-64 years of age (mean 57.3 ± 4.4). The AS ranged from 0 to 2871 in the cohort, with 2846 subjects having an AS of 0. Mean and median AS were 51.4 and 0.0, respectively. Total AS, VS, MS and number of lesions ICCs were 0.994, 0.994, 0.994, 0.960 (p < 0.001), respectively. Bland-Altman analyses rendered mean differences ± 1.96 SD upper and lower limits of agreement for AS -0.04, -52.5 to 52.4, VS -0.44, -46.51 to 45.63, and MS -0.07, -9.62 to 9.48. Weighted kappa analysis for CV risk category classifications was 0.913, and overall accuracy was 91.2%. There was excellent correlation and agreement between AI and semi-automatic evaluations for all calcium scores, number of lesions and lesion location. High degrees of agreement and accuracy were found for the CV risk categorization. Question Can AI function as a tool for enhancing the efficiency and accuracy of Coronary Artery Calcium Score (CACS) evaluations in clinical radiology practice? Findings This study confirms the robustness of AI-derived CACS results across extensive datasets, though its generalizability is limited by data acquisition from a single CT system. Clinical relevance This study suggests that AI holds significant promise as a tool for enhancing the efficiency and accuracy of CACS evaluations, with implications for improving patient diagnostics and reducing radiologist workload in clinical practice.

The value of coronary calcium score in predicting clinical outcomes in patients with chronic coronary syndrome

BackgroundCoronary artery atherosclerosis and calcification are the precursors to the development of coronary artery disease and its complications. Coronary artery calcium scoring (CACS) is useful as a risk-stratification tool in coronary artery disease.ObjectiveThe current study was designed to identify the relationship between CACS and major adverse cardiovascular outcomes in patients with stable coronary artery disease.MethodsThe study was conducted on 435 patients with stable ischemic heart disease. The patients were classified into two groups according to their coronary artery calcium score (CACS): group I (n = 220 patients), whose calcium score was mild to moderate (< 400), and group II (n = 215 patients), whose calcium score was high (≥ 400). All patients were closely monitored for two years to assess major adverse cardiovascular events (MACE).ResultsAfter 2 years of follow-up, MACE drastically increased in Group II in the form of unstable angina, myocardial infarction, demand for percutaneous coronary intervention, and heart failure. Multivariate regression analysis showed that age ≥ 55 years, Framingham risk score > 10, CACS ≥ 400, body mass index ≥ 30 kg/m2, and the proximal lesions of the vessels were the independent risk factors for major cardiac events.ConclusionThe coronary calcium score is a distinct feature of coronary atherosclerosis, and a score of 400 or higher is a reliable, noninvasive predictor of the progression of coronary artery diseases and their consequences, including MACE.

Association of Cardiovascular Risk Factors and Coronary Calcium Burden with Epicardial Adipose Tissue Volume Obtained from PET-CT Imaging in Oncological Patients.

Whole-body positron emission tomography (PET)-computed tomography (CT) imaging performed for oncological purposes may provide additional parameters such as the coronary artery calcium (CAC) and epicardial adipose tissue (EAT) volume with cost-effective prognostic information in asymptomatic people beyond traditional cardiovascular risk factors. We evaluated the feasibility of measuring the CAC score and EAT volume in cancer patients without known coronary artery disease (CAD) referred to whole-body 18F-FDG PET-CT imaging, regardless of the main clinical problem. We also investigated the potential relationships between traditional cardiovascular risk factors and CAC with EAT volume. A total of 109 oncological patients without overt CAD underwent whole-body PET-CT imaging with 18F-fluorodeoxyglucose (FDG). Unenhanced CT images were retrospectively viewed for CAC and EAT measurements on a dedicated platform. Overall, the mean EAT volume was 99 ± 49 cm3. Patients with a CAC score ≥ 1 were older than those with a CAC = 0 (p < 0.001) and the prevalence of hypertension was higher in patients with detectable CAC as compared to those without (p < 0.005). The EAT volume was higher in patients with CAC than in those without (p < 0.001). For univariable age, body mass index (BMI), hypertension, and CAC were associated with increasing EAT values (all p < 0.005). However, the correlation between the CAC score and EAT volume was weak, and in multivariable analysis only age and BMI were independently associated with increased EAT (both p < 0.001), suggesting that potential prognostic information on CAC and EAT is not redundant. This study demonstrates the feasibility of a cost-effective assessment of CAC scores and EAT volumes in oncological patients undergoing whole-body 18F-FDG PET-CT imaging, enabling staging cancer disease and atherosclerotic burden by a single test already included in the diagnostic work program, with optimization of the radiation dose and without additional costs.

Automated segment-level coronary artery calcium scoring on non-contrast CT: a multi-task deep-learning approach

ObjectivesTo develop and evaluate a multi-task deep-learning (DL) model for automated segment-level coronary artery calcium (CAC) scoring on non-contrast computed tomography (CT) for precise localization and quantification of calcifications in the coronary artery tree.MethodsThis study included 1514 patients (mean age, 60.0 ± 10.2 years; 56.0% female) with stable chest pain from 26 centers participating in the multicenter DISCHARGE trial (NCT02400229). The patients were randomly assigned to a training/validation set (1059) and a test set (455). We developed a multi-task neural network for performing the segmentation of calcifications on the segment level as the main task and the segmentation of coronary artery segment regions with weak annotations as an auxiliary task. Model performance was evaluated using (micro-average) sensitivity, specificity, F1-score, and weighted Cohen’s κ for segment-level agreement based on the Agatston score and performing interobserver variability analysis.ResultsIn the test set of 455 patients with 1797 calcifications, the model assigned 73.2% (1316/1797) to the correct coronary artery segment. The model achieved a micro-average sensitivity of 0.732 (95% CI: 0.710–0.754), a micro-average specificity of 0.978 (95% CI: 0.976–0.980), and a micro-average F1-score of 0.717 (95% CI: 0.695–0.739). The segment-level agreement was good with a weighted Cohen’s κ of 0.808 (95% CI: 0.790–0.824), which was only slightly lower than the agreement between the first and second observer (0.809 (95% CI: 0.798–0.845)).ConclusionAutomated segment-level CAC scoring using a multi-task neural network approach showed good agreement on the segment level, indicating that DL has the potential for automated coronary artery calcification classification.Critical relevance statementMulti-task deep learning can perform automated coronary calcium scoring on the segment level with good agreement and may contribute to the development of new and improved calcium scoring methods.Key PointsSegment-level coronary artery calcium scoring is a tedious and error-prone task.The proposed multi-task model achieved good agreement with a human observer on the segment level.Deep learning can contribute to the automation of segment-level coronary artery calcium scoring.Graphical

Nesfatin-1 enhances vascular smooth muscle calcification through facilitating BMP-2 osteogenic signaling

Vascular calcification (VC) arises from the accumulation of calcium salts in the intimal or tunica media layer of the aorta, contributing to higher risk of cardiovascular events and mortality. Despite this, the mechanisms driving VC remain incompletely understood. We previously described that nesfatin-1 functioned as a switch for vascular smooth muscle cells (VSMCs) plasticity in hypertension and neointimal hyperplasia. In this study, we sought to investigate the role and mechanism of nesfatin-1 in VC. The expression of nesfatin-1 was measured in calcified VSMCs and aortas, as well as in patients. Loss- and gain-of-function experiments were evaluated the roles of nesfatin-1 in VC pathogenesis. The transcription activation of nesfatin-1 was detected using a mass spectrometry. We found higher levels of nesfatin-1 in both calcified VSMCs and aortas, as well as in patients with coronary calcification. Loss-of-function and gain-of-function experiments revealed that nesfatin-1 was a key regulator of VC by facilitating the osteogenic transformation of VSMCs. Mechanistically, nesfatin-1 promoted the de-ubiquitination and stability of BMP-2 via inhibiting the E3 ligase SYTL4, and the interaction of nesfatin-1 with BMP-2 potentiated BMP-2 signaling and induced phosphorylation of Smad, followed by HDAC4 phosphorylation and nuclear exclusion. The dissociation of HDAC4 from RUNX2 elicited RUNX2 acetylation and subsequent nuclear translocation, leading to the transcription upregulation of OPN, a critical player in VC. From a small library of natural compounds, we identified that Curculigoside and Chebulagic acid reduced VC development via binding to and inhibiting nesfatin-1. Eventually, we designed a mass spectrometry-based DNA-protein interaction screening to identify that STAT3 mediated the transcription activation of nesfatin-1 in the context of VC. Overall, our study demonstrates that nesfatin-1 enhances BMP-2 signaling by inhibiting the E3 ligase SYTL4, thereby stabilizing BMP-2 and facilitating the downstream phosphorylation of SMAD1/5/9 and HDAC4. This signaling cascade leads to RUNX2 activation and the transcriptional upregulation of MSX2, driving VC. These insights position nesfatin-1 as a potential therapeutic target for preventing or treating VC, advancing our understanding of the molecular mechanisms underlying this critical cardiovascular condition.

Genetic risk score for coronary artery calcification and its predictive ability for coronary artery disease

AimThe modest added predictive value of the existing genetic risk scores (GRSs) for coronary artery disease (CAD) could be partly due to missing genetic components, hidden in the genetic architecture of intermediate phenotypes such as coronary artery calcification (CAC). In this study, we investigated the predictive ability of CAC GRS for CAD. Materials and methodsWe investigated the association of CAC GRSs with CAD and coronary calcification among the participants in the Ludwigshafen Risk and Cardiovascular Health study (LURIC) (n = 2742), the Tampere Vascular Study (TVS) (n = 133), and the Tampere Sudden Death Study (TSDS) (n = 660) using summary data from the largest multi-ancestry GWAS meta-analysis of CAC to date. Added predictive value of the CAC GRS over the traditional CVD risk factors as well as metaGRS, a GRS for CAD constructed with 1.7 million genetic variants, was tested with standard train–test machine learning approach using the LURIC data, which had the largest sample size. ResultsCAC GRS was significantly associated with CAD in LURIC (OR=1.41, 95 % CI [1.28–1.55]), TVS (OR=1.79, 95 % CI [1.05–3.21]) as well as in TSDS (OR=4.20, 95 % CI [1.74–10.52]). CAC GRS showed strong association with calcification areas in left (OR=1.78, 95 % CI [1.16–2.74]) and right (OR=1.71, 95 % CI [1.98–2.67]) coronary arteries. There was statistically significant added predictive value of the CAC GRS for CAD over the used traditional CVD risk factors (AUC 0.734 vs 0.717, p-value = 0.02). Furthermore, CAC GRS improved the prediction accuracy for CAD when combined with metaGRS. ConclusionsThis study showed that CAC GRS is a new risk marker for CAD in three European cohorts, with added predictive value over the traditional CVD risk factors.

Potency of lysine and tryptophan protect from lysosomal dysfunction and from phenylketonuria, and Mitochondrial disorder mediated by activating lysosomes and OPA1

The phenylketonuria due to decreasing in lysine “AAG” and in Lys/ phosphorylation (which necessary for lysosomal digestive function), and associated with sever decreasing in Trp “TGG” , followed by mitochondrial dysfunction and lysosomal dysfunction, that followed by sever decreasing in phe /hydroxylase and in Tyr/ hydroxylase , and followed by decreasing in lysine acylation and in SFACs productiin which followed by decreasing in RA productive pathway and associated with increasing in both of TNFa and cholesterol accumulation, which reflect decreasing in estrogen synthesis and in dopamine production, that followed by increasing in the risk of ischemic damage and diabetes. And we can conclude that both of Lys “AAG” and Trp “TGG” are so necessary for activating mitochondrial oxidative functions and necessary for promoting transport system where Mitochondria is so necessary to activate antioxidant function and promoting all of Phe hydroxylase, Tyr hydroxylase, and Lys acylation production which necessary for dopamine and RA synthesis respectively, where the PKU characterized by sever decreasing in antioxidant function, and sever decreasing in both Phe/ hydroxylase &amp; Trp/ hydroxylase production, followed by decreasing in dopamine production and decreasing in retinoic acid production (which due to the reduction in SFACs synthesis). Retionic acid “RA” synthesis is activated by lysine acylation and is regulated by lysine acylation mediated by short fatty acid synthesis, which regulate aminoacyl-tRNAs production regulated by mitochondrial enzymes and regulate the mRNA production by E coli (regulated by phenylalanine) that necessary to run antioxidant functions and cellular biosynthesis. The antihypertensive pathway mechanism is : the Lysine ¬¬&gt; activate ATPase and both lysosomes and Mitochondrial oxidative functions which activate lysine acylation ¬¬&gt; which activate short fatty acid synthesis ¬¬&gt; which stimulate retinoic acid “RA” synthesis - ¬¬¬&gt; where both Lys and Trp activate mitochondria repair and oxidative functions, which activate, Phe/ hydroxylase, and activate Tyr/ hydroxylase which activate dopamine , and Trp /oxygenases followed by protection against PKU, pulmonary disease ischemic damage and CVD. The activation of antihypertensive pathway associated by activating lysosomes and Mitochondrial oxidative functions, that associated by activating NR4As pathway which responsible for activating GC-beta and both of Oxytocin and Nrf2, followed by Ang2-AT2 and VEGF-A productive functions and heme oxygenase production (notice dopamine regulate heme oxygenase mediated by dopamine beta-hydroxylase which regulated by Mitochondrial oxidative functions) followed by activating anti-inflammatory growth and processes. Lysine Methylation has important role to enhance and adopt hypertension through activating RA and pervious Antihypertensive pathway mediated by Phe /hydroxylase synthesis and Tyr /hydroxylase production followed by activating both of dopamine and NR4As pathway. Where dopamine synthesis reflect its productive functions to activate Antioxidant functions that prevent cholesterol accumulation, and in turn increase the estrogen production (which it’s synthesis reflect potential protection from pulmonary disease), and activate the NR4As pathway which regulate all of Oxytocin, Nrf2 production, followed by Ang2-AT2 and VEGF-A production, which followed by activating heme oxygenase and anti-inflammatory growth and processes that prevent LV-hypertrophy, and prevent coronary calcification . Also, the increasing in Lys AAA with decreasing in Lys AAG and decreasing Trp TGG will cause decreasing in lysosome proper function, and cause Decreasing in GTPase and decreasing in the Mitochondrial oxidative functions, that will cause decreasing in Phe hydroxylase and in Tyr hydroxylase followed by decreasing in lysine acylation, and associated with increasing in cholesterol accumulation, and also associated with decreasing in both of IL17 production and estrogen functional pathway , that will increase the risk of T2D, pulmonary disease, and increase the risk of PKU and CVD. Both Lys and Trp are necessary to activate transport system across cells membranes that activate antibacterial function and anti-atherosclerosis. Both Lys and Trp are having the Potency to activate lysosomes and Mitochondrial oxidative functions which activate lipid and protein digestion and enhance Phe hydroxylase and Tyr hydroxylase followed by activating lysine acylation which activate SFACs production and promote the RA synthesis and enhance antioxidant functions followed by dopamine synthesis and protection from ischemic damage and from both of diabetes and PKU

Relation of JAK2 V617F allele burden and coronary calcium score in patients with essential thrombocythemia.

JAK2 V617F (JAK2) mutation is associated with clonal hemopoiesis in myeloproliferative neoplasms as well as with faster progression of cardiovascular diseases. Little is known about the relationship between allele burden and the degree of atherosclerotic alteration of coronary vasculature. We previously reported that carotid artery stiffness progressed faster in patients with JAK2 positive essential thromocythemia (ET) patients. After a four-year follow-up we investigated whether mutation burden of a JAK2 allele correlates with a higher coronary calcium score. Thirty-six patients with JAK2 positive ET and 38 healthy matched control subjects were examined twice within four years. At each visit clinical baseline characteristics and laboratory testing were performed, JAK2 mutation burden was determined, and coronary calcium was measured. JAK2 allele burden decreased in 19 patients, did not change in 5 patients, and increased in 4 patients. The coronary calcium Agatston score increased slightly in both groups. Overall, there was no correlation between JAK2 allele burden and calcium burden of coronary arteries. However, in patients with the JAK2 mutation burden increase, the coronary calcium score increased as well. The average JAK2 allele burden decreased in our patients with high-risk ET during the four-year period. However, in the small subgroup whose JAK2 mutation burden increased the Agatston coronary calcium score increased as well. This finding, which should be interpreted with caution and validated in a larger group, is in line with emerging evidence that JAK2 mutation accelerates atherosclerosis and can be regarded as a non-classical risk factor for cardiovascular disease.

Intraindividual Comparison of Ultrahigh-Spatial-Resolution Photon-Counting Detector CT and Energy-Integrating Detector CT for Coronary Stenosis Measurement.

A recent simulation study proposed that stenosis measurements on coronary computed tomography (CT) angiography are influenced by the improved spatial resolution of photon-counting detector (PCD)-CT. The aim of the current study was to evaluate the impact of ultrahigh-spatial-resolution (UHR) on coronary stenosis measurements and Coronary Artery Disease Reporting and Data System (CAD-RADS) reclassification rates in patients undergoing coronary CT angiography on both PCD-CT and energy-integrating detector (EID)-CT and to compare measurements against quantitative coronary angiography. Patients with coronary calcification on EID-CT (collimation, 192×0.6 mm) were prospectively enrolled for a research coronary CT angiography with UHR PCD-CT (collimation, 120×0.2 mm) within 30 days (between April 1, 2023 and January 31, 2024). PCD-CT was acquired with the same or lower CT dose index and equivalent contrast media volume as EID-CT. Percentage diameter stenosis (PDS) for calcified, partially calcified, and noncalcified lesions were compared between scanners. Patient-level reclassification rates for CAD-RADS were evaluated. The accuracy of PDS measurements was validated against quantitative coronary angiography in patients who underwent invasive coronary angiography. In total, PDS of 278 plaques were quantified in 49 patients (calcified, 202; partially calcified, 51; noncalcified, 25). PCD-CT-based PDS values were lower than EID-CT measurements for calcified (45.1±20.7 versus 54.6±19.2%; P<0.001) and partially calcified plaques (44.3±19.6 versus 54.9±20.0%; P<0.001), without significant differences for noncalcified lesions (39.1±15.2 versus 39.0±16.0%; P=0.98). The reduction in stenosis degrees led to a 49.0% (24/49) reclassification rate to a lower CAD-RADS with PCD-CT. In a subset of 12 patients with 56 lesions, UHR-based PDS values showed higher agreement with quantitative coronary angiography (mean difference, 7.3%; limits of agreement, -10.7%/25.2%) than EID-CT measurements (mean difference, 17.4%; limits of agreement, -6.9%/41.7%). Compared with conventional EID-CT, UHR PCD-CT results in lower PDS values and more accurate stenosis measurements in coronary plaques with calcified components and leads to a substantial Coronary Artery Disease Reporting and Data System reclassification rate in 49.0% of patients.

Road-traffic noise exposure and coronary atherosclerosis in the Swedish CArdioPulmonary bioImage Study (SCAPIS).

Road-traffic noise may influence the development of cardiovascular events such as stroke and myocardial infarction, but etiological mechanisms remain unclear. This study aimed to assess the relationship between long-term road-traffic noise exposure and coronary atherosclerosis in Sweden. In the Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort, including 30,154 subjects aged 50-65 years, recruited between 2013 and 2018, coronary atherosclerosis was measured based on computer tomography (CT) scans as coronary artery calcium score, segment involvement score (SIS), and non-calcified plaques (NCP) at enrollment. Based on modified Nordic model, road-traffic noise exposure was modeled for 2000, 2013, and 2018 with interpolation for intermediate years. We investigated the association between time-weighted long-term exposure to road-traffic noise (Lden) and the prevalence of atherosclerosis using ordinal logistic regression models adjusting for potential socioeconomic, behavioral, and environmental confounders, including air pollution. No clear associations were found between road-traffic noise and coronary atherosclerosis. The odds ratio for coronary artery calcium score was 1.00 (95% confidence interval [CI] = 0.96, 1.04), SIS 0.99 (0.96, 1.03), and NCP 0.98 (0.90, 1.03) per interquartile range (9.4 dB Lden) for road-traffic noise exposure during 10 years before enrollment. No consistent associations were observed in site-specific analyses or using shorter exposure periods. Furthermore, exposure-response analyses revealed no clear trends, and there were no strong interactions between road-traffic noise and cardiovascular risk factors in relation to the atherosclerosis markers. Long-term exposure to road-traffic noise was not linked to coronary atherosclerosis or calcification in relatively healthy, middle-aged populations in Sweden.

Impact of serum cholinesterase on calcified nodules in patients with stable coronary artery disease.

Calcified nodules (CNs) are an advanced stage of coronary calcification that can have significant clinical implications. We investigated factors associated with CNs, the etiology of which is not fully understood. We retrospectively evaluated 619 patients with stable coronary artery disease who underwent intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI). CNs in the culprit lesion were evaluated via IVUS, and all-cause mortality and major cardiovascular and cerebrovascular events (MACCEs) were compared between the CN and non-CN groups. The CN group (n = 40 patients) had a significantly lower survival rate and a higher incidence of MACCE than the non-CN group (P = 0.020 and P < 0.001, respectively). Multivariate logistic regression analysis models revealed that chronic kidney disease and serum cholinesterase (ChE) level were associated with CN formation [odds ratio (OR): 3.15, 95% confidence interval (CI): 1.30-7.69, P = 0.001 and OR: 0.94, 95% CI: 0.88-0.99, P = 0.042]. The optimal cutoff of serum ChE level as per the receiver operating characteristic curve was 309 units/l (Area under the curve = 0.67, sensitivity = 93%, specificity = 40%, P = 0.001). The low-ChE group divided according to the optimal cutoff value showed significantly higher cumulative incidence of MACCEs after PCI than the high-ChE group as per Kaplan-Meier analysis. The presence of CNs is significantly associated with a poor prognosis and MACCE after PCI among patients with stable coronary artery disease. Serum ChE levels may affect CN formation.

Association between cumulative intake of sugar-sweetened and artificially sweetened beverages and progression of coronary calcification: Insights from the CARDIA study

Background and aimsThis study investigates the relationship between the cumulative intake of artificially sweetened beverages (ASBs) and sugar-sweetened beverages (SSBs) during young adulthood and the progression of coronary artery calcium (CAC) by midlife, using data from the Coronary Artery Risk Development in Young Adults study. Methods and resultsWe included 2,466 participants with CAC measurement via computed tomography at the 15th, 20th, and 25th year follow-ups. Dietary intake was assessed using the CARDIA Diet History at baseline and years 7. Cumulative average beverage intake was calculated and categorized. Multivariable Cox regression models adjusted for demographic, lifestyle, and cardiovascular risk factors assessed associations between beverages consumption and CAC progression. Among the included participants, 1107 (44.9 %) were male, 1439 (58.4 %) were white, and the average age was 40.4 years with a standard deviation of 3.5 years. Over a 9.2±1.8-year follow-up, CAC progression was recorded in 715 participants. Higher cumulative ASBs intake was associated with increased CAC progression risk, with hazard ratios (95%CI, P-value) for low and high ASBs consumption being 1.35 (1.14, 1.60; P < 0.001) and 1.54 (1.15, 2.07; P < 0.001) compared to non-consumers. Participants consuming >2 servings/day of SSBs had a 37 % higher CAC progression risk (HR 1.37, 95 % CI 1.14–1.64, P < 0.001). However, no significant association was found between SSB consumption and CAC progression after adjusting for confounders. ConclusionsProlonged consumption of beverages, especially ASBs, in young adults is linked to an increased risk of CAC progression.