Although coronary computed tomographic angiography (CCTA) has been a robust diagnostic tool to identify anatomical significance of coronary artery disease (CAD), the utility of CCTA to assess hemodynamic significance of CAD remains unclear. We investigated the diagnostic performance of transluminal attenuation gradient (TAG) and fractional flow reserve derived from CCTA (FFRCT) to predict lesion-specific ischemia by invasive FFR. We identified 103 patients with suspected or known CAD enrolled from the DISCOVER-FLOW and DeFACTO studies who underwent invasive coronary angiography with FFR and high quality ≥64-slice CCTA. Diagnostic performance for predicting abnormal invasive FFR (≤0.80) was assessed for TAG [≤−1.1 HU/mm by the area under the curve (AUC) by receiver-operating characteristic curve analysis (ROC)], FFRCT (≤0.80), and CCTA stenosis (≥50 %). On a per-vessel analysis (n = 146), 52 vessels (35.6 %) had ischemia by invasive FFR. The sensitivity, specificity, positive predictive value and negative predictive value were 53.8, 45.7, 35.4, 64.2 % for TAG, 82.7, 74.5, 64.2, 88.6 % for FFRCT, 84.6, 39.4, 43.6, 82.2 % for CCTA stenosis, respectively. The AUC by ROC curve analysis for FFRCT (0.79) demonstrated greater discrimination of hemodynamic ischemia compared to TAG (0.50, p < 0.0001 vs. FFRCT), CCTA stenosis (0.62, p = 0.0004 vs. FFRCT) and the combination of the two (0.63, p = 0.004 vs. FFRCT). These results remained consistent regardless of the number of CCTA slices. FFRCT allows identification of lesion-specific ischemia using invasive FFR as a reference standard with greater diagnostic accuracy than TAG, CCTA stenosis, or the combination of the two.

STATEMENT OF FINDINGS: The kinetics of apoptosis and the apoptosis-regulating gene p53 in adjuvant arthritis (AA) were investigated to assess the value of the AA rat model for testing apoptosis-inducing therapies. Very few terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end-labeling (TUNEL)-positive cells were detected during the early phases of AA, but on day 23 (chronic arthritis) the percentage of TUNEL-positive cells was significantly increased. Expression of p53 in synovial tissue gradually increased from days 5-23, which was markedly higher than p53 levels in rheumatoid arthritis (RA) synovium. Significant apoptosis only occurs late in rat AA and is concordant with marked p53 overexpression, making it useful model for testing proapoptotic therapies, but rat AA is not the best model for p53 gene therapy because dramatic p53 overexpression occurs in the latter stages of the disease.

Background and aims

We aimed at investigating whether diabetes is associated with progression in coronary plaque components.

Methods

We identified 142 study subjects undergoing serial coronary computed tomography angiography. The resulting propensity score was applied 1:1 to match diabetic patients to non-diabetic patients for clinical risk factors, prior coronary stenting, coronary artery calcium (CAC) score and the serial scan interval, resulting in the 71 diabetes and 71 non-diabetes patients. Coronary plaque (total, calcified, non-calcified including fibrous, fibrous-fatty and low attenuation plaque [LAP]) volume normalized by total coronary artery length was measured using semi-automated plaque software and its change overtime between diabetic and non-diabetic patients was evaluated.

Results

The matching was successful without significant differences between the two groups in all matched variables. The baseline volumes in each plaque also did not differ. During a mean scan interval of 3.4 ± 1.8 years, diabetic patients showed a 2-fold greater progression in normalized total plaque volume (TPV) than non-diabetes patients (52.8 mm³vs. 118.3 mm³, p = 0.005). Multivariable linear regression model revealed that diabetes was associated with normalized TPV progression (β 72.3, 95%CI 24.3-120.3). A similar trend was observed for the non-calcified components, but not calcified plaque (β 3.8, 95%CI -27.0-34.7). Higher baseline CAC score was found to be associated with total, non-calcified and calcified plaque progression. However, baseline non-calcified volume but not CAC score was associated with LAP progression.

Conclusions

The current study among matched patients indicates diabetes is associated with a greater plaque progression. Our results show the need for strict adherence of diabetic patients to the current preventive guidelines.

Although coronary computed tomographic angiography (CCTA) has been a robust diagnostic tool to identify anatomical significance of coronary artery disease (CAD), the utility of CCTA to assess hemodynamic significance of CAD remains unclear. We investigated the diagnostic performance of transluminal attenuation gradient (TAG) and fractional flow reserve derived from CCTA (FFRCT) to predict lesion-specific ischemia by invasive FFR. We identified 103 patients with suspected or known CAD enrolled from the DISCOVER-FLOW and DeFACTO studies who underwent invasive coronary angiography with FFR and high quality ≥64-slice CCTA. Diagnostic performance for predicting abnormal invasive FFR (≤0.80) was assessed for TAG [≤-1.1 HU/mm by the area under the curve (AUC) by receiver-operating characteristic curve analysis (ROC)], FFR(CT) (≤0.80), and CCTA stenosis (≥50%). On a per-vessel analysis (n = 146), 52 vessels (35.6%) had ischemia by invasive FFR. The sensitivity, specificity, positive predictive value and negative predictive value were 53.8, 45.7, 35.4, 64.2% for TAG, 82.7, 74.5, 64.2, 88.6% for FFR(CT), 84.6, 39.4, 43.6, 82.2% for CCTA stenosis, respectively. The AUC by ROC curve analysis for FFR(CT) (0.79) demonstrated greater discrimination of hemodynamic ischemia compared to TAG (0.50, p < 0.0001 vs. FFR(CT)), CCTA stenosis (0.62, p = 0.0004 vs. FFR(CT)) and the combination of the two (0.63, p = 0.004 vs. FFR(CT)). These results remained consistent regardless of the number of CCTA slices. FFR(CT) allows identification of lesion-specific ischemia using invasive FFR as a reference standard with greater diagnostic accuracy than TAG, CCTA stenosis, or the combination of the two.

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.

Serial measurements of coronary plaque volume have been used to evaluate drug efficacy in atherosclerotic progression. However, the usefulness of computed tomography for this purpose is unknown. We investigated whether the change in total plaque volume on coronary computed tomographic angiography is associated with the change in segment plaque volume on intravascular ultrasound. We prospectively enrolled 11 consecutive patients (mean age, 56.3 ± 5 yr; 6 men) who were to undergo serial invasive coronary angiographic examinations with use of grayscale intravascular ultrasound and coronary computed tomography, performed <180 days apart at baseline and from 1 to 2 years later. Subjects underwent 186 serial measurements of total plaque volume on coronary computed tomography and 22 of segmental plaque volume on intravascular ultrasound. We used semiautomated software to examine percentage relationships and changes between total plaque and segmental plaque volumes. No significant correlations were found between percentages of total coronary and segment coronary plaque volume, nor between normalized coronary plaque volume. However, in the per-patient analysis, there were strong correlations between the imaging methods for changes in total coronary and segment coronary plaque volume (r=0.62; P=0.04), as well as normalized plaque volume (r=0.82; P=0.002). Per-patient change in plaque volume on coronary computed tomography is significantly associated with that on intravascular ultrasound. Computed tomographic angiography may be safer and more widely available than intravascular ultrasound for evaluating atherosclerotic progression in coronary arteries. Larger studies are warranted.

Background

Although several previous studies have demonstrated that aged garlic extract (AGE) inhibits the progression of coronary artery calcification, its effect on noncalcified plaque (NCP) has been unclear.

Objective

This study investigated whether AGE reduces coronary plaque volume measured by cardiac computed tomography angiography (CCTA) in patients with metabolic syndrome (MetS).

Methods

Fifty-five patients with MetS (mean ± SD age: 58.7 ± 6.7 y; 71% men) were prospectively assigned to consume 2400 mg AGE/d (27 patients) or placebo (28 patients) orally. Both groups underwent CCTA at baseline and follow-up 354 ± 41 d apart. Coronary plaque volume, including total plaque volume (TPV), dense calcium (DC), NCP, and low-attenuation plaque (LAP), were measured based upon predefined intensity cutoff values. Multivariable linear regression analysis, adjusted for age, gender, number of risk factors, hyperlipidemia medications, history of coronary artery disease, scan interval time, and baseline %TPV, was performed to examine whether AGE affected each plaque change.

Results

The %LAP change was significantly reduced in the AGE group compared with the placebo group (-1.5% ± 2.3% compared with 0.2% ± 2.0%, P = 0.0049). In contrast, no difference was observed in %TPV change (0.3% ± 3.3% compared with 1.6% ± 3.0%, P = 0.13), %NCP change (0.2% ± 3.3% compared with 1.4% ± 2.9%, P = 0.14), and %DC change (0.2% ± 1.4%, compared with 0.2% ± 1.7%, P = 0.99). Multivariable linear regression analysis found a beneficial effect of AGE on %LAP regression (β: -1.61; 95% CI: -2.79, -0.43; P = 0.008).

Conclusions

This study indicates that the %LAP change was significantly greater in the AGE group than in the placebo group. Further studies are needed to evaluate whether AGE has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events. This trial was registered at clinicaltrials.gov as NCT01534910.

Prevention and management of coronary artery disease (CAD) is of great concern in patients with diabetes mellitus. Although the impact of coronary atherosclerosis is described well for subjects older than 40 years, the prevalence and types of coronary atherosclerosis in young patients are not well known. The aim of this study was to evaluate the prevalence, extent, severity, and volumes of coronary plaque in type 2 diabetes mellitus (T2DM) population younger than of 40 years. This prospective study enrolled 181 subjects (25-40 year old) undergoing coronary computed tomography angiography, with 86 T2DM and 95 nondiabetic age/gender-matched subjects. Coronary artery calcium (CAC), plaque assessment including total segment stenosis (sum of individual segmental stenosis), total plaque scores (sum of semiquantitative segmental plaque burden), segment involvement scores (number of segments with plaque) were evaluated. In addition, we quantitatively measured plaque volumes in total, fibrous, fibrous fatty, dense calcified, and low-attenuation plaque using novel plaque software. Compared with nondiabetic patients, the prevalence of CAD, calcified, and noncalcified plaques was higher in patients with T2DM (19% vs 58%; p <0.001). In patients with a zero CAC, T2DM had a higher prevalence (46%) of noncalcified plaque (p <0.0001). In multivariate linear regression models after adjusting for traditional cardiovascular risk factors, increased total segmental stenosis, total plaque scores, and segment involvement scores were associated with T2DM. Regarding quantitative plaque assessment, all volumes in noncalcified plaque type were approximately threefold higher in patients with T2DM. In conclusion, young patients with T2DM are susceptible to premature CAD with more calcified and noncalcified plaques. Early prevention program using computed tomography angiography might be helpful in identifying young diabetic patients with subclinical atherosclerosis.