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

Unraveling the Role of microRNAs in Intralipid-induced Cardio-protection against Acute Myocardial Ischemia-Reperfusion Injury

Acute myocardial ischemic-reperfusion (IR) injury remains a widespread, unresolved clinical problem. While current therapies in animal IR injury models target delaying of the mitochondria permeability transition pore, none have shown success in human trials. Therefore, novel therapies are critical to limit IR injury and improve patient outcomes following reperfusion intervention. Our lab showed that intralipid (ILP), a safe fat emulsion, protects the heart against IR injury in rodent models. The exact molecular mechanisms by which ILP confers this cardioprotection is unclear and deciphering it could help develop more targeted effective reperfusion intervention for myocardial infarct. microRNAs are promising mediators in ILP cardioprotection as they regulate gene expression in IR injury molecular pathways. Here, we show that ILP normalizes miR-1 expression in hearts subjected to IR injury using a longer reperfusion time; this is associated with reduced infarct size and reduced apoptosis in cardiomyocytes subjected to hypoxia-reoxygenation. My findings will uncover mechanisms of ILP-mediated cardioprotection, which should lead to a novel therapeutic strategy against acute myocardial IR injury

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 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 (β = 0.38; p < 0.001), noncalcified plaque (β = 0.35; p = 0.001), fibrous plaque (β = 0.56; p < 0.001), and calcified plaque (β = 0.63; p = 0.001) volume progression, but not fibrous-fatty (β = 0.03; p = 0.28) or low-attenuation plaque (β = 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

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 current 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, 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

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 (β = 0.38; p &lt; 0.001), noncalcified plaque (β = 0.35; p = 0.001), fibrous plaque (β = 0.56; p &lt; 0.001), and calcified plaque (β = 0.63; p = 0.001) volume progression, but not fibrous-fatty (β = 0.03; p = 0.28) or low-attenuation plaque (β = 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

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

BackgroundCardiac 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.MethodsWe 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.ResultsThe 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 &gt; 0.38). The inter-observer correlation coefficient was 0.99 (p &lt; 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.ConclusionsOur 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 registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00154180; Keywords: Epicardial fat volume; intra-thoracic fat volume; computed tomography; intra-observer; inter-observer