Coronary artery calcium and bone mineral density by serial CTA: Does menopausal hormone therapy modify the association?

INTRODUCTION: Both osteoporosis and cardiovascular disease (CVD) increase in women after menopause. Estrogen deficiency is thought to be an underlying mechanism for both these conditions. METHODS: Healthy menopausal women (n = 374, age 42-58 years) underwent cardiac CT scans over four years as participants in the Kronos Early Estrogen Prevention Study (KEEPS), a randomized, controlled trial to Women randomized to either oral conjugated equine estrogens (o-CEE, n = 104), transdermal 17ß-estradiol (t-E2, n = 119) or placebo (n-115). CAC (Agatston units, AU), and BMD (mg/cm3) were measured from thoracic vertebrae at baseline and at the 4 years of the study using validated software. ANOVA and multiple linear regression analyzed the association between incident CAC or progression of CAC and BMD among the treatment groups. RESULTS: At baseline 374 women, 40 participants with CAC >0 had greater decrements in BMD than the 334 participants with CAC = 0 at baseline, The average change in BMD in o-CEE group with CAC was -9.6 ± 13.3 versus -3.1 ± 19.5 in those with zero CAC, p = 0.0018. With t-E2, BMD changed by -11.7 ± 26.2 in those with CAC versus +5.7 ± 26.2 in the zero CAC group, p ≤ 0. 0001. Similarly in the 66 participants that showed progression of CAC >1, had more BMD loss, than those with stable CAC regardless of the treatment. CONCLUSION: Progression of bone loss is reduced among women treated with o-CEE or t-E2. Progression of CAC is associated with greater BMD loss, a relationship that is differentially modified by t-E2 and o-CEE.

Role of miRNA-1 and miRNA-21 in Acute Myocardial Ischemia-Reperfusion Injury and Their Potential as Therapeutic Strategy.

Coronary artery disease remains the leading cause of death. Acute myocardial infarction (MI) is characterized by decreased blood flow to the coronary arteries, resulting in cardiomyocytes death. The most effective strategy for treating an MI is early and rapid myocardial reperfusion, but restoring blood flow to the ischemic myocardium can induce further damage, known as ischemia-reperfusion (IR) injury. Novel therapeutic strategies are critical to limit myocardial IR injury and improve patient outcomes following reperfusion intervention. miRNAs are small non-coding RNA molecules that have been implicated in attenuating IR injury pathology in pre-clinical rodent models. In this review, we discuss the role of miR-1 and miR-21 in regulating myocardial apoptosis in ischemia-reperfusion injury in the whole heart as well as in different cardiac cell types with special emphasis on cardiomyocytes, fibroblasts, and immune cells. We also examine therapeutic potential of miR-1 and miR-21 in preclinical studies. More research is necessary to understand the cell-specific molecular principles of miRNAs in cardioprotection and application to acute myocardial IR injury.

Coronary artery plaque progression and cardiovascular risk scores in men with and without HIV-infection.

OBJECTIVE: The aim of this study was to assess the association of cardiovascular disease (CVD) risk scores and coronary artery plaque (CAP) progression in HIV-infected participants. METHODS: We studied men with and without HIV-infection enrolled in the Multicenter AIDS Cohort Study (MACS) CVD study. CAP at baseline and follow-up was assessed with cardiac computed tomography angiography (CCTA). We examined the association between baseline risk scores including pooled cohort equation (PCE), Framingham risk score (FRS), and Data collect of Adverse effects of anti-HIV drugs equation (D:A:D) and CAP progression. RESULTS: We studied 495 men (211 HIV-uninfected, 284 HIV-infected). The adjusted odds ratio (aOR) of total plaque volume (TPV) and noncalcified plaque volume (NCPV) progression in the highest relative to lowest tertile was 9.4 [95% confidence interval (95% CI) 2.4-12.1, P < 0.001)] and 7.7 (95% CI 3.1-19.1, P < 0.001) times greater, respectively, among HIV-uninfected men in the PCE atherosclerotic cardiovascular disease (ASCVD) high vs. low-risk category. Among HIV-infected men, the association for TPV and NCPV progression for the same PCE risk categories, odds ratio (OR) 2.8 (95% CI 1.4-5.8, P < 0.01) and OR 2.4 (95% CI 1.2-4.8, P < 0.05), respectively (P values for interaction by HIV = 0.02 and 0.08, respectively). Similar results were seen for the FRS risk scores. Among HIV-uninfected men, PCE high risk category identified the highest proportion of men with plaque progression in the highest tertile, although in HIV-infected men, high-risk category by D:A:D identified the greatest percentage of men with plaque progression albeit with lower specificity than FRS and PCE. CONCLUSION: PCE and FRS categories predict CAP progression better in HIV-uninfected than in HIV-infected men. Improved CVD risk scores are needed to identify high-risk HIV-infected men for more aggressive CVD risk prevention strategies.

Aged garlic extract reduces low attenuation plaque in coronary arteries of patients with diabetes: A randomized, double-blind, placebo-controlled study.

Several previous studies have demonstrated that aged garlic extract (AGE) inhibits the progression of coronary artery calcification and non-calcified plaque (NCP) in the general population. However, its effects on plaque progression in patients with diabetes have not yet been investigated, at least to the best of our knowledge. This study investigated whether AGE reduces the coronary plaque volume measured by cardiac computed tomography angiography (CCTA) in patients with diabetes mellitus (DM). A total of 80 participants with DM with a median age of 57 years were prospectively assigned to consume 2,400 mg AGE/day (after completion, 37 participants) or placebo (after completion, 29 participants) orally. Both groups underwent CCTA at baseline and follow-up 365 days apart. In total, 66 participants completed the study. Coronary plaque volume, including total plaque (TP), dense calcium (DC), fibrous, fibro-fatty and low-attenuation plaque (LAP) volumes were measured based upon pre-defined intensity cut-off values using semi-automated software (QAngio CT). Changes in various plaque types were normalized to the total coronary artery length. The non-parametric Wilcoxon rank-sum test was performed to examine the differences in plaque formation between the 2 groups. No significant differences were found in the baseline characteristics between the AGE and placebo groups. Compared with the placebo group, the AGE group exhibited a statistically significant regression in normalized LAP [median and standard deviation (SD) -0.2 (18.8) vs. 2.5 (69.3), P=0.0415]. No differences were observed in TP, fibrous, or fibrofatty plaque volumes between the AGE and placebo group. On the whole, this study indicated that the %LAP change in the AGE group was significantly greater than that in the placebo group in patients with diabetes. However, further studies are warranted to evaluate whether AGE has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events.

Aged garlic extract reduces left ventricular myocardial mass in patients with diabetes: A prospective randomized controlled double-blind study.

Increased left ventricular myocardial mass (LVM) is a well known prognostic marker of poor cardiac outcomes. Decreases in LVM have been shown to decrease the cardiovascular risk. Aged garlic extract (AGE) has been shown to have an overall favorable effect on cardiac health; however, to the best of our knowledge, no study to date has specifically examined its effects on left ventricular mass. This study investigated whether AGE can affect LVM measured by cardiac computed tomography angiography (CCTA) in patients with diabetes mellitus (DM). This is a double-blind, placebo controlled randomized trial. In total, 65 participants with DM with a mean age of 58 years were prospectively assigned to consume 2,400 mg AGE/day or the placebo orally. Both groups underwent CCTA at baseline and follow-up at 1 year apart. LVM was measured using automated software. The baseline characteristics did not differ between the AGE and placebo groups. There was a trend towards a significant reduction in LVM at follow-up as compared to baseline in the AGE group (119.30±34.77 vs. 121.0±34.70, P=0.059). No change was observed in LVM in the placebo group at 1-year follow-up as compared to baseline (124.6±37.33 vs. 124.6±35.13, P=0.9). On the whole, this study indicated that AGE may decrease or stabilize LVM. Further studies however, with a larger sample size and longer follow-up times are required to evaluate the effects of AGE on hypertension and LVM.

Non-contrast cardiac CT-based quantitative evaluation of epicardial and intra-thoracic fat in healthy, recently menopausal women: Reproducibility data from the Kronos Early Estrogen Prevention Study.

BACKGROUND: Cardiac fat is emerging as an important parameter for cardiovascular risk stratification. Accurate and reproducible volumetric measurements can facilitate in the serial assessment of cardiac fat by computed tomography (CT). We assessed the intra- and inter-observer variability of cardiac fat volumetric measurements using a semi-automated CT software. METHODS: We used non-contrast coronary calcium CT scans to quantify epicardial and intra-thoracic fat volumes. Two expert readers analyzed baseline and follow up CT scans of 45 subjects by using a semi-automated CT software (QFAT 2.0, Cedars Sinai-Medical Center). Correlation and Bland-Altman analysis was performed for both intra- and inter-observer comparisons for each cardiac fat type. RESULTS: The intra-observer correlation coefficients ranged between 0.86 to 0.99 and 0.87 to 0.99 for epicardial (median fat per reader (cm3) 20.9 to 25.7) and intra-thoracic (median fat per reader (cm3) 27.1 to 31.6) fat volumes respectively, with no significant differences between individual data points (all p > 0.38). The inter-observer correlation coefficient was 0.99 (p < 0.0001 for correlation) for both epicardial and intra-thoracic fat. By Bland-Altman analysis for epicardial fat measurements, mean difference of intra-observer was 0.90 cm3 with 95% confidence intervals (0.22,1.7) and -1.8 cm3 for inter-observer, with 95% CI (-2.9, -0.69). Bland-Altman plots for intra-thoracic fat measurements were similarly impressive for both inter- and intra-observer reads. CONCLUSIONS: Our data showed that measuring epicardial and intra-thoracic fat volumes by CT using a semi-automated software has excellent intra-observer and inter-observer reliability. Cardiac fat volumes can be obtained easily and reproducibly from routine calcium scoring scans and may help in assessing cardiovascular risk. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00154180; Keywords: Epicardial fat volume; intra-thoracic fat volume; computed tomography; intra-observer; inter-observer.

Apixaban versus warfarin in evaluation of progression of atherosclerotic and calcified plaques (prospective randomized trial).

Warfarin has been showed to increase vascular calcification. Apixaban, a direct factor Xa inhibitor, has no interaction with vitamin K and its effect on coronary plaques is unknown. We randomized and compared warfarin and apixaban on progression of coronary atherosclerotic plaques measured by coronary computed tomographic angiography in 66 subjects with non-valvular atrial fibrillation over the period of one-year follow up. There was significant higher total, calcified and low attenuation plaque volume in the group randomized to warfarin as compared to apixaban (all P < .05). Greater volume of total (ß2 = 28.54; P = .03), low attenuation plaque (ß2 = 3.58; P = .02) and calcified (ß2 = 14.10; P = .005) plaque progression was observed in the VKA_group.

Comparison of Whole Heart Computed Tomography Scanners for Image Quality Lower Radiation Dosing in Coronary Computed Tomography Angiography: The CONVERGE Registry.

RATIONALE AND OBJECTIVES: Novel technology in coronary computed tomographic angiography allows assessment of coronary artery disease with high image quality (IQ). There are currently two wide detector "whole heart" coverage scanners available, which avoid misregistration artifacts. However, there are no data directly comparing IQ between the two scanners. The aim of the current study is to investigate if IQ is different between the most scanners of GE and Toshiba broad detector scanners. MATERIALS AND METHODS: Prospective, observational, multicenter international cohort study comparing 236 consecutive patients who underwent coronary computed tomographic angiography using whole-heart scanners; 126 patients on scanner S1 ( Aquilion ONE Vision, Toshiba), and 110 patients on scanner S2 (Revolution CT, GE Healthcare). Hounsfield units were measured using regions of interest in the descending aorta at 6 points (cranial slice, level of the visualized first, second, third, and fourth spines, and the caudal slice). We also compared the coverage length (z-axis) of the full width field of view between a single rotation of the two scanners. RESULTS: Evaluating mean CT attenuation values Hounsfield units through the scan range, are progressively reduced across the descending aorta in the S1 group, resulting in the larger difference of contrast brightness between the cranial and caudal slices compared to the S2 group (absolute difference: S2 13.0 ± 4.4 vs S1 141.9 ± 16.4, p < 0.0001; Percent difference: 19.3 ± 2.1 vs -3.4 ± 1.2, <0.0001). The standard deviation (SD) is similar at the cranial slice between the two scanners, however, the S1 group demonstrated higher SD-differential from cranial to caudal than S2 group. Median radiation exposure was significantly lower for the S2 scanner 1.50 ± 0.75 mSv vs the S1 system 1.9 mSv (IQR 1.7-2.7 mSv) (p = 0.01). Z-axis coverage was larger for the S2 scanner 152.5 mm (244 slices × 0.625 mm/slice) than 133 mm for S1 (266 slices × 0.5 mm/slice). CONCLUSION: Although both "volume" scanners cover the whole heart z-axis with one beat, scans using the S1 scanner have a larger variability in attenuation values throughout the scan range, resulting in 20% increase in nonuniformity from cranial to caudal slice. Additionally, SD variation across the field of view, a metric of noise, is larger when using the S1 scanner vs the S2 scanner. These results indicate that the GE Revolution CT has more uniform contrast enhancement and more coverage, lower radiation and lower image noise compared to the Toshiba Aquilion ONE Vision system.

Correlation of Arterial Stiffness With Left Atrial Volume Index and Left Ventricular Mass Index in Young Adults: Evaluation by Coronary Computed Tomography Angiography.

BACKGROUND: Increased arterial stiffness is reportedly associated with cardiac remodelling, including the left atrium and left ventricle, in middle-aged and older adults. However, little is known about this association in young adults. METHODS: In total, 73 patients (44 (60%) men) aged 25 to 45 years with suspected coronary artery disease were included in the analysis. The left atrial volume index (LAVI), left ventricular volume index (LVVI), and left ventricular mass index (LVMI) were measured using coronary computed tomography angiography (CCTA). Arterial stiffness was assessed with the cardio-ankle vascular index (CAVI). An abnormally high CAVI was defined as that above the age- and sex-specific cut-off points of the CAVI. RESULTS: Compared with patients with a normal CAVI, those with an abnormally high CAVI were older and had a greater prevalence of diabetes mellitus, higher diastolic blood pressure, greater coronary artery calcification score, and a greater LAVI (33.5±10.3 vs. 43.0±10.3mL/m2, p <0.01). In contrast, there were no significant differences in the LVVI or LVMI between the subgroups with a normal CAVI and an abnormally high CAVI. Multivariate linear regression analysis showed that the LAVI was significantly associated with an abnormally high CAVI (standardised regression coefficient=0.283, p=0.03). CONCLUSIONS: The present study demonstrated that increased arterial stiffness is associated with the LAVI, which reflects the early stages of cardiac remodelling, independent of various comorbidity factors in young adults with suspected coronary artery disease.

Randomized trial of rivaroxaban versus warfarin in the evaluation of progression of coronary atherosclerosis.

Warfarin, a vitamin K antagonist, is associated with systemic vascular calcification. We evaluated whether rivaroxaban (a direct oral factor Xa inhibitor with no interaction with vitamin K) will slow the progression in coronary plaque volumes compared with warfarin in patients with nonvalvular atrial fibrillation using coronary computed tomography angiography.

Automated estimation of image quality for coronary computed tomographic angiography using machine learning.

OBJECTIVES: Our goal was to evaluate the efficacy of a fully automated method for assessing the image quality (IQ) of coronary computed tomography angiography (CCTA). METHODS: The machine learning method was trained using 75 CCTA studies by mapping features (noise, contrast, misregistration scores, and un-interpretability index) to an IQ score based on manual ground truth data. The automated method was validated on a set of 50 CCTA studies and subsequently tested on a new set of 172 CCTA studies against visual IQ scores on a 5-point Likert scale. RESULTS: The area under the curve in the validation set was 0.96. In the 172 CCTA studies, our method yielded a Cohen's kappa statistic for the agreement between automated and visual IQ assessment of 0.67 (p < 0.01). In the group where good to excellent (n = 163), fair (n = 6), and poor visual IQ scores (n = 3) were graded, 155, 5, and 2 of the patients received an automated IQ score > 50 %, respectively. CONCLUSION: Fully automated assessment of the IQ of CCTA data sets by machine learning was reproducible and provided similar results compared with visual analysis within the limits of inter-operator variability. KEY POINTS: • The proposed method enables automated and reproducible image quality assessment. • Machine learning and visual assessments yielded comparable estimates of image quality. • Automated assessment potentially allows for more standardised image quality. • Image quality assessment enables standardization of clinical trial results across different datasets.

Multicenter AIDS Cohort Study Quantitative Coronary Plaque Progression Study: rationale and design.

BACKGROUND AND AIM: The association of HIV with coronary atherosclerosis has been established; however, the progression of coronary atherosclerosis over time among participants with HIV is not well known. The Multicenter AIDS Cohort Study Quantitative Coronary Plaque Progression Study is a large prospective multicenter study quantifying progression of coronary plaque assessed by serial coronary computed tomography angiography (CTA). PATIENTS AND METHODS: HIV-infected and uninfected men who were enrolled in the Multicenter AIDS Cohort Study Cardiovascular Substudy were eligible to complete a follow-up contrast coronary CTA 3-6 years after baseline. We measured coronary plaque volume and characteristics (calcified and noncalcified plaque including fibrous, fibrous-fatty, and low attenuation) and vulnerable plaque among HIV-infected and uninfected men using semiautomated plaque software to investigate the progression of coronary atherosclerosis over time. CONCLUSION: We describe a novel, large prospective multicenter study investigating incidence, transition of characteristics, and progression in coronary atherosclerosis quantitatively assessed by serial coronary CTAs among HIV-infected and uninfected men.

Coronary Artery Calcium Progression Is Associated With Coronary Plaque Volume Progression: Results From a Quantitative Semiautomated Coronary Artery Plaque Analysis.

OBJECTIVES: The aim of this study was to determine whether coronary artery calcium (CAC) progression was associated with coronary plaque progression on coronary computed tomographic angiography. BACKGROUND: CAC progression and coronary plaque characteristics are associated with incident coronary heart disease. However, natural history of coronary atherosclerosis has not been well described to date, and the understanding of the association between CAC progression and coronary plaque subtypes such as noncalcified plaque progression remains unclear. METHODS: Consecutive patients who were referred to our clinic for evaluation and had serial coronary computed tomography angiography scans performed were included in the study. Coronary artery plaque (total, fibrous, fibrous-fatty, low-attenuation, densely calcified) volumes were calculated using semiautomated plaque analysis software. RESULTS: A total of 211 patients (61.3 ± 12.7 years of age, 75.4% men) were included in the analysis. The mean interval between baseline and follow-up scans was 3.3 ± 1.7 years. CAC progression was associated with a significant linear increase in all types of coronary plaque and no plaque progression was observed in subjects without CAC progression. In multivariate analysis, annualized and normalized total plaque (ß = 0.38; p < 0.001), noncalcified plaque (ß = 0.35; p = 0.001), fibrous plaque (ß = 0.56; p < 0.001), and calcified plaque (ß = 0.63; p = 0.001) volume progression, but not fibrous-fatty (ß = 0.03; p = 0.28) or low-attenuation plaque (ß = 0.11; p = 0.1) progression, were independently associated with CAC progression. Plaque progression did not differ between the sexes. A significantly increased total and calcified plaque progression was observed in statin users. CONCLUSIONS: In a clinical practice setting, progression of CAC was significantly associated with an increase in both calcified and noncalcified plaque volume, except fibrous-fatty and low-attenuation plaque. Serial CAC measurements may be helpful in determining the need for intensification of preventive treatment.