Thoracic versus coronary calcification for atherosclerotic cardiovascular disease events prediction.

This study compared the prognostic value of quantified thoracic artery calcium (TAC) including aortic arch on chest CT and coronary artery calcium (CAC) score on ECG-gated cardiac CT. METHODS: A total of 2412 participants who underwent both chest CT and ECG-gated cardiac CT at the same period were included in the Multi-Ethnic Study of Atherosclerosis Exam 5. All participants were monitored for incident atherosclerotic cardiovascular disease (ASCVD) events. TAC is defined as calcification in the ascending aorta, aortic arch and descending aorta on chest CT. The quantification of TAC was measured using the Agatston method. Time-dependent receiver-operating characteristic (ROC) curves were used to compare the prognostic value of TAC and CAC scores. RESULTS: Participants were 69±9 years of age and 47% were male. The Spearman correlation between TAC and CAC scores was 0.46 (p<0.001). During the median follow-up period of 8.8 years, 234 participants (9.7%) experienced ASCVD events. In multivariable Cox regression analysis, TAC score was independently associated with increased risk of ASCVD events (HR 1.31, 95% CI 1.09 to 1.58) as well as CAC score (HR 1.82, 95% CI 1.53 to 2.17). However, the area under the time-dependent ROC curve for CAC score was greater than that for TAC score in all participants (0.698 and 0.641, p=0.031). This was particularly pronounced in participants with borderline/intermediate and high 10-year ASCVD risk scores. CONCLUSION: Our study demonstrated a significant association between TAC and CAC scores but a superior prognostic value of CAC score for ASCVD events. These findings suggest TAC on chest CT provides supplementary data to estimate ASCVD risk but does not replace CAC on ECG-gated cardiac CT.

Iron Status and Risk of Heart Disease, Stroke, and Diabetes: A Mendelian Randomization Study in European Adults.

BACKGROUND: The relevance of iron status biomarkers for coronary artery disease (CAD), heart failure (HF), ischemic stroke (IS), and type 2 diabetes (T2D) is uncertain. We compared the observational and Mendelian randomization (MR) analyses of iron status biomarkers and hemoglobin with these diseases. METHODS AND RESULTS: Observational analyses of hemoglobin were compared with genetically predicted hemoglobin with cardiovascular diseases and diabetes in the UK Biobank. Iron biomarkers included transferrin saturation, serum iron, ferritin, and total iron binding capacity. MR analyses assessed associations with CAD (CARDIOGRAMplusC4D [Coronary Artery Disease Genome Wide Replication and Meta-Analysis Plus The Coronary Artery Disease Genetics], n=181 522 cases), HF (HERMES [Heart Failure Molecular Epidemiology for Therapeutic Targets), n=115 150 cases), IS (GIGASTROKE, n=62 100 cases), and T2D (DIAMANTE [Diabetes Meta-Analysis of Trans-Ethnic Association Studies], n=80 154 cases) genome-wide consortia. Observational analyses demonstrated J-shaped associations of hemoglobin with CAD, HF, IS, and T2D. In contrast, MR analyses demonstrated linear positive associations of higher genetically predicted hemoglobin levels with 8% higher risk per 1 SD higher hemoglobin for CAD, 10% to 13% for diabetes, but not with IS or HF in UK Biobank. Bidirectional MR analyses confirmed the causal relevance of iron biomarkers for hemoglobin. Further MR analyses in global consortia demonstrated modest protective effects of iron biomarkers for CAD (7%-14% lower risk for 1 SD higher levels of iron biomarkers), adverse effects for T2D, but no associations with IS or HF. CONCLUSIONS: Higher levels of iron biomarkers were protective for CAD, had adverse effects on T2D, but had no effects on IS or HF. Randomized trials are now required to assess effects of iron supplements on risk of CAD in high-risk older people.

Evaluating the association between opium abuse, blood lead levels, and the complexity of coronary artery disease.

Opium abuse and exposure to heavy metals elevate the risk of coronary artery disease (CAD). Therefore, we aimed to determine the association between opium abuse and blood lead levels (BLLs) and the CAD complexity. We evaluated patients with acute coronary symptoms who underwent coronary angiography, and those with >50% stenosis in at least one of the coronary arteries were included. Furthermore, Synergy between PCI with Taxus and Cardiac Surgery I (SYNTAX I) score and BLLs were measured. Based on the opium abuse, 95 patients were subdivided into opium (45) and control (50) groups. Differences in demographics and CAD risk factors were insignificant between the two groups. The median BLLs were remarkably higher in the opium group than in controls (36 (35.7) and 20.5 µg/dL (11.45), respectively, p = 0.003). We also revealed no significant differences in SYNTAX score between the two groups (15.0 (9.0) and 17.5 (14.0), respectively, p = 0.28). Additionally, we found no significant correlation between BLLs and the SYNTAX scores (p = 0.277 and r = -0.113). Opium abuse was associated with high BLLs. Neither opium abuse nor high BLLs were correlated with the complexity of CAD. Further studies are warranted to establish better the relationship between opium abuse, BLLs, and CAD.

Medicinal herbs consumption in relation to cardiometabolic indices and coronary artery stenosis in participants undergoing coronary angiography: A cross-sectional study.

Few studies have investigated the association between herbal medicine consumption and coronary artery disease severity. This cross-sectional study aimed to investigate the association between the frequency of medicinal herbs consumption and coronary artery stenosis (CAS), lipid profile, fasting blood sugar (FBS), and blood pressure level in participants undergoing coronary angiography. This study was conducted on 662 participants aged 35-75 years. Serum cardiometabolic markers were measured using standard kits. The extent and severity of CAS were evaluated using the Gensini score (GS) and syntax score (SS). Higher consumption of Thymus vulgaris and Sumac was associated with decreased odds of artery-clogging according to the GS. A higher intake of Thymus vulgaris and Mentha was associated with lower levels of serum cholesterol and triglyceride. Monthly intake of Thymus vulgaris, and weekly/daily intake of Mentha, Nigella Sativa, and Cuminum Cyminum were associated with lower low-density lipoprotein. Weekly/daily intake of Turmeric and Thymus vulgaris were associated with lower high-density lipoprotein levels and monthly intake of Mentha was related to lower serum FBS levels. Higher consumption of Mentha, Mentha pulegium L, Lavandula angustifolia, and Nigella Sativa was associated with lower levels of systolic blood pressure. According to the results of the present study, herbs consumption might be related to a reduction in CAS risk factors.

Relation Between Calcium-Phosphorus Product and Total Coronary Artery Occlusion in a Nonchronic Kidney Disease Population: A Cross-Sectional Study.

Excessive calcium-phosphorus product (Ca-P product) in patients with chronic kidney disease (CKD) is associated with coronary artery calcification and coronary artery disease, but the relation between Ca-P product and coronary artery disease in non-CKD populations has rarely been reported. Therefore, we designed a cross-sectional study to investigate the role of Ca-P product in total coronary artery occlusion (TCAO) in a non-CKD population. We reviewed 983 patients who underwent coronary angiography at Guangyuan Central Hospital from February 2018 to January 2020. Ca-P product (mg2/dl2) was calculated as Ca (mmol/L) × 4 × P (mmol/L) × 3.1 and was analyzed as a continuous and tertiary variable. TCAO was defined as complete occlusion of any coronary artery by coronary angiography (thrombolysis in myocardial infarction flow grade 0). Statistical analysis was performed using univariate and multivariate logistic regression models and restricted cubic splines. Univariate logistic regression analysis showed a statistically significant association between Ca-P product and TCAO (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.95 to 0.99, p <0.001). After stepwise adjustment for covariates, the risk of TCAO was reduced by 40% in the high versus low Ca-P group (OR 0.6, 95% CI 0.38 to 0.95, p = 0.031), and the risk of TCAO was predicted to decrease by 4% (OR 0.96, 95% CI 0.94 to 0.99, p = 0.006) for each unit increase in Ca-P product. Restricted cubic splines showed a nonlinear relation between Ca-P product and TCAO, with a significant decrease in the risk of TCAO after reaching 27.46 (nonlinear p = 0.047). In conclusion, in non-CKD populations, a higher Ca-P product (≥27.46 mg2/dl2) may help avoid TCAO.

Effect of omega-3 fatty acids supplementation on the prognosis of coronary artery disease: A meta-analysis of randomized controlled trials.

AIMS: To evaluate whether omega-3 fatty acids (É·-3 FAs) supplementation can improve cardiovascular outcomes in patients with established coronary artery disease (CAD). DATA SYNTHESIS: Five electronic databases were searched for randomized controlled trials that evaluated the effect of É·-3 FAs on cardiovascular outcomes in patients with CAD. The language was restricted to English. The risk ratio was pooled. Subgroup analyses were conducted to evaluate whether study-level variables might act as effect modifiers. A total of 12 studies involving 29913 patients were included. É·-3 FAs had no effects on major adverse cardiovascular events (MACEs) (RR, 0.93; 95 % CI: 0.85 to 1.01, P = 0.09). While É·-3 FAs reduced the incidences of all-cause death (RR, 0.90; 95 % CI: 0.83 to 0.97, P = 0.005), cardiovascular death (RR, 0.82; 95 % CI: 0.75 to 0.90, P < 0.0001), myocardial infarction (RR, 0.77; 95 % CI: 0.68 to 0.86, P < 0.0001), revascularization (RR, 0.80; 95 % CI: 0.69 to 0.93, P = 0.003), sudden cardiac death (RR, 0.67; 95 % CI: 0.52 to 0.86, P = 0.002) and hospitalization for heart failure or unstable angina pectoris (RR, 0.75; 95 % CI: 0.58 to 0.97, P = 0.03) in CAD. It did not statistically reduce the risk of stroke (RR, 0.96; 95 % CI: 0.77 to 1.21, P = 0.76). The favorable effects of É·-3 FAs on MACEs were significant in subgroups of intervention with EPA and baseline triglyceride ≥1.7 mmol/L. CONCLUSION: É·-3 FAs supplementation, especially EPA, appears to be an effective adjunct therapy for improving the prognosis of CAD. REGISTRATION NUMBER: PROSPERO CRD42022311237.

Pharmacoscreening, molecular dynamics, and quantum mechanics of inermin from Panax ginseng: a crucial molecule inhibiting exosomal protein target associated with coronary artery disease progression.

Background: Exosomes, microvesicles, carry and release several vital molecules across cells, tissues, and organs. Epicardial adipose tissue exosomes are critical in the development and progression of coronary artery disease (CAD). It is hypothesized that exosomes may transport causative molecules from inflamed tissue and deliver to the target tissue and progress CAD. Thus, identifying and inhibiting the CAD-associated proteins that are being transported to other cells via exosomes will help slow the progression of CAD. Methods: This study uses a systems biological approach that integrates differential gene expression in the CAD, exosomal cargo assessment, protein network construction, and functional enrichment to identify the crucial exosomal cargo protein target. Meanwhile, absorption, distribution, metabolism, and excretion (ADME) screening of Panax ginseng-derived compounds was conducted and then docked against the protein target to identify potential inhibitors and then subjected to molecular dynamics simulation (MDS) to understand the behavior of the protein-ligand complex till 100 nanoseconds. Finally, density functional theory (DFT) calculation was performed on the ligand with the highest affinity with the target. Results: Through the systems biological approach, Mothers against decapentaplegic homolog 2 protein (SMAD2) was determined as a potential target that linked with PI3K-Akt signaling, Ubiquitin mediated proteolysis, and the focal adhesion pathway. Further, screening of 190 Panax ginseng compounds, 27 showed drug-likeness properties. Inermin, a phytochemical showed good docking with -5.02 kcal/mol and achieved stability confirmation with SMAD2 based on MDS when compared to the known CAD drugs. Additionally, DFT analysis of inermin showed high chemical activity that significantly contributes to effective target binding. Overall, our computational study suggests that inermin could act against SMAD2 and may aid in the management of CAD.

The Short-Term Effect of Olive Oil Extract Enriched with Hydroxytyrosol on Cardiovascular Function.

Olive is rich in polyphenols such as hydroxytyrosol (HT) that have antioxidative and anti-inflammatory effects. In this study, we examined the short-term effects of olive oil extract (OE) enriched with HT on left atrial function, left ventricular (LV) function, and arterial elastic properties in patients with chronic coronary artery disease (CAD). Sixty-one patients with chronic CAD were enrolled. This randomized study had a two-period, two-sequence crossover (AB/BA) design. Group AB (n = 32) initially received OE capsules (500 mg) enriched with HT (5 mg) (two capsules/day) for 30 days, and after a wash out of 48 h, placebo for another 30 days. The opposite occurred in Group BA (n = 29). Exclusion criteria included age >70 years, diabetes, anemia, hypertension, liver and thyroid disease, malignancy, autoimmune disease, kidney disease, use of corticosteroids, weight loss, excessive exercise dietary intervention, and use of antioxidant vitamins. Patients underwent echocardiography/Doppler and applanation tonometry applied to radial artery at the beginning and end of the study. No significant change regarding Vmax, Vp, Vmin, E wave, A wave, deceleration time, LV ejection fraction, central aortic systolic and pulse pressure, and augmentation index. However, a trend toward improvement of E/e' (P = .062) and pulse wave velocity (P = .091) was observed. Use of OE enriched with HT for a limited time period was associated with a trend toward improvement of LV diastolic function and aortic elastic properties in chronic CAD patients. Studies of longer duration are needed to delineate the effect of this promising agent on cardiovascular function and outcomes in chronic CAD.

Effectiveness of an online/offline mixed-mode Tai Chi cardiac rehabilitation program on microcirculation in patients with coronary artery disease: A randomized controlled study.

OBJECTIVE: We explored the effectiveness of an online/offline mixed-mode Tai Chi cardiac rehabilitation program on the microcirculation of patients with coronary artery disease (CAD). DESIGN: Prospective, randomized controlled study. SETTING: It was conducted in a tertiary hospital. SUBJECTS: Twenty-six patients who met the diagnostic criteria for coronary artery disease were recruited. INTERVENTIONS: Patients were randomized divided into a 12-week Tai Chi cardiac rehabilitation program(TCCRP) or a conventional exercise rehabilitation program(CERP) in a 1:1 fashion, 4 weeks of in-hospital rehabilitation and 8 weeks of online rehabilitation at home (a total of 12 weeks of intervention). MAIN OUTCOME MEASURES: Nailfold microcirculation (Morphological integrals, Blood flow integrals, Periphery capillary loop integrals, Overall integrals). MAIN OUTCOME MEASURES: Twenty patients completed the study. The Morphological integrals (baseline: 2.875±1.171 vs 12weeks: 1.863±0.414, t = 2.432, P = 0.045 < 0.05) and Overall integrals (baseline: 5.563±2.001 vs 12weeks: 3.688±1.167, t = 3.358, P = 0.012 < 0.05) decreased significantly in the TCCRP, The nailfold microcirculation integra decreased not significantly in the CERP (P > 0.05). The nailfold microcirculation integra was not significantly different between the two groups after the intervention (P > 0.05). CONCLUSIONS: The TCCRP improved the microcirculation of patients with CAD.

Reduction of Calcium Scores Using Intravenous Chelation: A Retrospective Pilot Study.

This pilot study presents a retrospective analysis of 10 asymptomatic patients with a positive calcium score who received a series of intravenous calcium ethylenediaminetetraacetic acid (EDTA) chelations. Current standards for cardiovascular risk stratification include assessments of cholesterol, blood pressure, blood sugar, lifestyle, obesity, and family history. Despite addressing traditional risk factors, myocardial infarctions and cerebrovascular accidents remain the leading causes of death and disability worldwide. Asymptomatic decay of the vascular system is a prelude to catastrophic events, and calcium scores are emerging as a significant adjunct for risk assessment. Positive calcium scores correlate with an increased risk of cardiovascular events. However, there are no therapies known to reliably reverse calcium scores. Previous studies have demonstrated that intravenous chelation therapy reduces cardiovascular morbidity and mortality in patients with a prior history of myocardial infarction; however, its mechanism of action is unknown. One theory is that chelation therapy would reverse calcium buildup in coronary arteries, which is known to have a positive correlation with the risk of having a cardiovascular event. The 10 patients had no prior history of coronary artery disease. Infusions were administered in an outpatient setting. Patients were encouraged to receive a treatment every month. No other supplements or prescriptions were required as part of the treatment. An average of 26.9 chelations were administered over an average of 37.9 months. Calcium scores decreased by an average of 27.38%, and all 10 patients experienced a reduction in scores.  This study demonstrates that chelation has the potential to reduce calcium scores. Since calcium scores correlate with cardiovascular risk, reducing the calcium score may reduce the risk of an event. If these results are supported by larger, placebo-controlled studies, chelation therapy may become an option that could be added to statins and other FDA-approved therapies for primary prevention in patients with a positive calcium score.

Should atrial fibrillation be considered a vascular disease? The need for a comprehensive vascular approach.

INTRODUCTION: Atrial fibrillation (AF) cannot be considered an isolated disease. Patients with AF should be managed using a comprehensive approach that is not limited to stroke prevention. AREAS COVERED: In this manuscript, the potential role of AF as a vascular disease that is managed as part of a holistic approach was reviewed. EXPERT OPINION: The residual risk of stroke in patients with AF reaches 1-2% annually, despite appropriate anticoagulation therapy. Additionally, patients with AF may develop cognitive impairment through stroke-independent pathways. Furthermore, patients with AF may have a higher risk of developing atherosclerotic vascular disease in various vascular beds and chronic kidney disease; conversely, patients with atherosclerotic disease may have an increased risk of developing AF. AF should be considered a truly systemic vascular disease, since it brings together several hemodynamic and systemic changes, including inflammation, oxidative stress, activation of the renin-angiotensin-aldosterone and sympathetic systems, as well as a prothrombotic state and endothelial dysfunction. In this regard, patients with AF should be treated based on a holistic approach that is not limited to oral anticoagulation but includes complete vascular protection.

Efficacy and safety of Qixue Tongzhi Granule in improving the exercise capacity of stable coronary artery disease: study protocol for a multicenter, randomized, double-blind, placebo-controlled trial.

Background: Despite optimal medical therapy, patients with stable coronary artery disease (SCAD) still have a high risk of recurrent cardiovascular events. Exercise capacity measured by cardiopulmonary exercise testing (CPET) is a good surrogate marker for the long-term prognosis of SCAD. Qixue Tongzhi Granule (QTG) is created by academician Chen Keji and has the function of tonifying qi, promoting blood circulation, and regulating qi-flowing. This trial aims to investigate the efficacy and safety of QTG in improving exercise tolerance, alleviating angina pectoris and anxiety/depression symptoms, promoting health-related quality of life, and reducing the risk of adverse cardiovascular events in subjects with SCAD. Methods: This is a randomized, double-blind, placebo-controlled trial. 150 SCAD patients with qi deficiency, blood stasis, and liver qi stagnation syndrome are enrolled. Patients will be randomly allocated to the QTG or placebo groups at a 1:1 ratio. QTG and placebo will be added to the modern guideline-directed medical therapy for 12 weeks and patients will be followed up for another 24 weeks. The primary outcome is the improvement of metabolic equivalents measured by CPET. The secondary outcomes are cumulative incidence of composite endpoint events, other indicators in CPET, changes in the Seattle Angina Questionnaire, traditional Chinese medicine syndrome scale, 12 items of Short Form Health Survey Questionnaire, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7, changes of ST-T segment in the electrocardiogram, improvement of left ventricular ejection fraction and left ventricular end-diastolic diameter in echocardiography. In addition, metabolomics analysis will be performed based on blood samples. Adverse events and safety evaluations will also be documented. A full analysis set, per protocol set, and safety analysis set will be conducted. Discussion: This clinical trial can enrich treatment options for CHD patients with low cardiorespiratory fitness and psychological imbalance, and it may also create a new situation for promoting the application of traditional Chinese medicine in cardiac rehabilitation.Clinical Trial Registration: [http://www.chictr.org.cn], identifier: [ChiCTR2200058988].

Role of Vitamins in Cardiovascular Health: Know Your Facts - Part 1.

Cardiovascular (CV) disease (CVD) is a major cause of morbidity and mortality world-wide, thus it is important to adopt preventive interventions. Observational data demonstrating CV benefits of vitamin supplements, advanced by self-proclaimed experts have resulted in ~50% of Americans reporting the use of multivitamins for health promotion; this practice has led to a multi-billion-dollar business of the multivitamin-industry. However, the data on the extensive use of multivitamins show no consistent benefit for CVD prevention or all-cause mortality, while the use of certain vitamins might prove harmful. Thus, the focus of this two-part review is on the attributes or concerns about specific vitamins on CVD. In Part 1, the CV effects of specific vitamins are discussed, indicating the need for further supportive evidence of potential benefits. Vitamin A preserves CV homeostasis as it participates in many biologic functions, including atherosclerosis. However, supplementation could potentially be harmful. Betacarotene, a pro-vitamin A, conveys pro-oxidant actions that may mitigate any other benefits. Folic acid alone and certain B-vitamins (e.g., B1/B2/B6/B12) may reduce CVD, heart failure, and/or stroke, while niacin might increase mortality. Vitamin C has antioxidant and cardioprotective effects. Vitamin D may confer CV protection, but all the data are not in agreement. Combined vitamin E and C have antiatherogenic effects but clinical evidence is inconsistent. Vitamin K seems neutral. Thus, there are individual vitamin actions with favorable CV impact (certain B-vitamins and vitamins C and D), but other vitamins (ß-carotene, niacin) may potentially have deleterious effects, which also holds true for high doses of fat-soluble vitamins (A/D/E/K).

Transcutaneous Electrical Acupuncture Point Stimulation Is Cardioprotective for Patients With Stable Ischemic Heart Disease.

We evaluated the effects of electroacupuncture (EA) at Neiguan and Ximen on the prognosis of patients with stable ischemic heart disease. A total of 240 patients symptomatic with suspected coronary artery disease referred for coronary angiography were analyzed, and 232 patients (62.3 ± 9.1 years) with stable ischemic heart disease were included. The primary end point was major adverse cardiovascular events (MACEs), defined as a composite of recurrent angina requiring hospitalization, nonfatal acute myocardial infarction, cardiogenic death, and death from any other causes. Over a mean follow-up of 12 months, 9 patients (8.4%) in the EA treatment group and 22 patients (19.3%) in the control group occurred. Patients treated with EA had a significantly smaller risk of MACE (p = 0.021), recurrence of unstable angina (p = 0.033), and nonfatal myocardial infraction (p = 0.038) than that of those treated without EA. Kaplan-Meier analysis revealed that the EA and control groups began to separate at approximately 5 months and continued to diverge up to study termination. Moreover, multivariate Cox analysis showed that treatment with EA was associated with decreased likelihood of MACE within 12 months of follow-up. The circulating levels of cluster of differentiation 40 ligand but hypersensitive C-reactive protein were lower (166.0 ± 92.6 pg/ml vs 197.3 ± 79.2 pg/ml, p = 0.012) in the EA group than in the control group and decreased significantly (-30.6 ± 47.2 pg/ml vs -1.1 ± 50.4 pg/ml, p <0.001) after 12 months of treatment. EA is an effective treatment method for supporting patients with stable ischemic heart disease.

The effect of magnesium sulfate on gene expression and serum level of inflammatory cytokines in coronary artery disease patients.

PURPOSE: To evaluate the effect of oral magnesium sulfate (MgSO4) on the gene expression and serum levels of inflammatory cytokines including TNF-α, IL-18, IL-1ß, IL-6, and IFN-γ in patients with moderate coronary artery disease (CAD). METHODS: 60 CAD patients were selected based on angiography findings and were randomly divided into two groups that received 300 mg/day MgSO4 (n = 30) or placebo (n = 30) for 3 months. Gene expression and serum levels of inflammatory cytokines were assessed. RESULTS: After 3 months of intervention, gene expression and serum levels of IL-18 and TNF-α in the MgSO4 group were significantly less than the placebo group (P < 0.05). However, no significant difference in gene expression and serum levels of IL-1ß, IL-6, and IFN-γ was observed between the two groups (P > 0.05). In addition, within group analysis demonstrate that Mg-treatment significantly decrease serum level of TNF-α and IL-18 as compared to pretreatment. CONCLUSION: The results of our study demonstrate that 3-month magnesium sulfate administration (300 mg/day) to CAD patients could significantly decrease serum concentration and gene expression levels of IL-18 and TNF-α. Our findings support the potential beneficial effect of magnesium supplementation on alleviating CAD complications through modulating inflammatory cytokines.

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

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

Role of Vitamins in Cardiovascular Health: Know Your Facts-Part 2.

Cardiovascular disease (CVD) is a major cause of morbidity/mortality world-wide, hence preventive interventions are crucial. Observational data showing beneficial CV effects of vitamin supplements, promoted by self-proclaimed experts, have led to ~50% of Americans using multivitamins; this practice has culminated into a multi-billion-dollar business. However, robust evidence is lacking, and certain vitamins might incur harm. This two-part review focuses on the attributes or concerns about specific vitamin consumption on CVD. The evidence for indiscriminate use of multivitamins indicates no consistent CVD benefit. Specific vitamins and/or combinations are suggested, but further supportive evidence is needed. Data presented in Part 1 indicated that folic acid and certain B-vitamins may decrease stroke, whereas niacin might raise mortality; beta-carotene mediates pro-oxidant effects, which may abate the benefits from other vitamins. In Part 2, data favor the anti-oxidant effects of vitamin C and the anti-atherogenic effects of vitamins C and E, but clinical evidence is inconsistent. Vitamin D may provide CV protection, but data are conflicting. Vitamin K appears neutral. Thus, there are favorable CV effects of individual vitamins (C/D), but randomized/controlled data are lacking. An important caveat regards the potential toxicity of increased doses of fat-soluble vitamins (A/D/E/K). As emphasized in Part 1, vitamins might benefit subjects who are antioxidant-deficient or exposed to high levels of oxidative-stress (e.g., diabetics, smokers, and elderly), stressing the importance of targeting certain subgroups for optimal results. Finally, by promoting CV-healthy balanced-diets, we could acquire essential vitamins and nutrients and use supplements only for specific indications.