UNASSIGNED: Extent and progression of coronary artery calcification (CAC) are strong predictors of myocardial infarction and mortality.
UNASSIGNED: This study aims to investigate if vitamin K2 and D supplementation can reduce CAC progression.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.

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.

OBJECTIVE: 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).
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.
CONCLUSIONS: 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.

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.
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.
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.
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.

OBJECTIVE: 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.

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.
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.
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.
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.

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.

OBJECTIVE: 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.
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.
CONCLUSIONS: 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.

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.
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.
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.
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.

OBJECTIVE: 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).
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.
CONCLUSIONS: 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).