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Objectives: We examined mortality in relation to coronary artery disease (CAD) as assessed by ≥64-detector row coronary computed tomography angiography (CCTA). Background: Although CCTA has demonstrated high diagnostic performance for detection and exclusion of obstructive CAD, the prognostic findings of CAD by CCTA have not, to date, been examined for age- and sex-specific outcomes. Methods: We evaluated a consecutive cohort of 24,775 patients undergoing ≥64-detector row CCTA between 2005 and 2009 without known CAD who met inclusion criteria. In these patients, CAD by CCTA was defined as none (0% stenosis), mild (1% to 49% stenosis), moderate (50% to 69% stenosis), or severe (≥70% stenosis). CAD severity was judged on a per-patient, per-vessel, and per-segment basis. Time to mortality was estimated using multivariable Cox proportional hazards models. Results: At a 2.3 ± 1.1-year follow-up, 404 deaths had occurred. In risk-adjusted analysis, both per-patient obstructive (hazard ratio [HR]: 2.60; 95% confidence interval [CI]: 1.94 to 3.49; p < 0.0001) and nonobstructive (HR: 1.60; 95% CI: 1.18 to 2.16; p = 0.002) CAD conferred increased risk of mortality compared with patients without evident CAD. Incident mortality was associated with a dose-response relationship to the number of coronary vessels exhibiting obstructive CAD, with increasing risk observed for nonobstructive (HR: 1.62; 95% CI: 1.20 to 2.19; p = 0.002), obstructive 1-vessel (HR: 2.00; 95% CI: 1.43 to 2.82; p < 0.0001), 2-vessel (HR: 2.92; 95% CI: 2.00 to 4.25; p < 0.0001), or 3-vessel or left main (HR: 3.70; 95% CI: 2.58 to 5.29; p < 0.0001) CAD. Importantly, the absence of CAD by CCTA was associated with a low rate of incident death (annualized death rate: 0.28%). When stratified by age <65 years versus ≥65 years, younger patients experienced higher hazards for death for 2-vessel (HR: 4.00; 95% CI: 2.16 to 7.40; p < 0.0001 vs. HR: 2.46; 95% CI: 1.51 to 4.02; p = 0.0003) and 3-vessel (HR: 6.19; 95% CI: 3.43 to 11.2; p < 0.0001 vs. HR: 3.10; 95% CI: 1.95 to 4.92; p < 0.0001) CAD. The relative hazard for 3-vessel CAD (HR: 4.21; 95% CI: 2.47 to 7.18; p < 0.0001 vs. HR: 3.27; 95% CI: 1.96 to 5.45; p < 0.0001) was higher for women as compared with men. Conclusions: Among individuals without known CAD, nonobstructive and obstructive CAD by CCTA are associated with higher rates of mortality, with risk profiles differing for age and sex. Importantly, absence of CAD is associated with a very favorable prognosis. [Copyright &y& Elsevier]

Objectives: This study identified the incidence and predictors of conversion of a normal to abnormal coronary artery calcium (CAC) scan during serial CAC scanning over 5 years. Background: Although a normal CAC scan signifies absence of significant atherosclerosis and is used to identify individuals at low clinical risk, the “warranty period” of a normal CAC scan relative to its ability to predict sustained absence of coronary atherosclerosis remains unknown. Methods: We assessed frequency of and time to progression, as well as proportional increase of CAC in 422 individuals with normal CAC scan (CAC = 0) undergoing annual CAC scanning for 5 years. Results were compared with those of a referent cohort of 621 individuals with baseline CAC scan (CAC >0). Results: A total of 106 (25.1%) patients with CAC = 0 developed CAC during follow-up at a mean time to conversion of 4.1 ± 0.9 years. Incidence of conversion to CAC >0 was nonlinear and was highest in the fifth year. In multivariable analysis, progression to CAC >0 was associated with age, diabetes, and smoking (p < 0.01 for all). Among the 621 individuals with baseline CAC >0, only the presence of CAC itself, rather than CAD risk factors, was predictive of CAC progression. Among propensity score-matched individuals with CAC >0 versus CAC = 0, baseline CAC >0 emerged as the strongest predictor of CAC progression (hazard ratio [HR]: 12.50, 95% confidence interval [CI]: 9.31 to 16.77), followed by diabetes (HR: 2.07, 95% CI: 1.47 to 2.90) and smoking (HR: 1.29, 95% CI: 1.02 to 1.63, p < 0.05 for all). Conclusions: Among individuals with CAC = 0, conversion to CAC >0 is nonlinear and occurs at low frequency before 4 years. No clinical factor seems to mandate earlier repeat CAC scanning. [Copyright &y& Elsevier]

Objectives: We prospectively evaluated procedural costs and resource consumption patterns in the EISNER (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) study after coronary calcium (CAC) measurements. Background: Controversy surrounds expansion of cardiovascular disease (CVD) screening to include atherosclerosis imaging as the result of concern whether induced costs will outweigh any benefit. Methods: Detailed risk factor and CAC measurements with 4-year follow-up for CVD death or myocardial infarction and procedures were performed. Costs were estimated with the use of Medicare reimbursement rates (discounted and inflation corrected). Cox survival analysis was used to estimate procedures and events. Results: CAC scores varied widely but were skewed toward low scores with 56.7% of screened subjects having CAC scores ≤10 and only 8.2% having CAC scores ≥400. Noninvasive testing was infrequent and medical costs were low among subjects with low CAC scores, both rising progressively with increasing CAC scores (p < 0.001), particularly in the 31 (2.2% of subjects) that had CAC scores ≥1,000. Similarly, invasive coronary angiography rose progressively with increasing scores (p < 0.001) but occurred exclusively among subjects first undergoing noninvasive testing and overall, was performed in only 19.4% of subjects with CAC scores ≥1,000. Conclusions: CAC scanning is associated with a marked differential in downstream frequency of medical tests and costs, ranging from a very low frequency of testing and invasive procedures among a predominantly large percentage of subjects with low CAC scores, to selectively concentrated testing and procedures among a small number of subjects with CAC scores >400. Thus, CAC scanning appears to foster efficient selective testing patterns among asymptomatic individuals at risk for CVD. [Copyright &y& Elsevier]

Evaluation of coronary artery disease (CAD) using coronary computed tomography angiography (CCTA) has seen a paradigm shift in the last decade. Evidence increasingly supports the clinical utility of CCTA across various stages of CAD, from the detection of early subclinical disease to the assessment of acute chest pain. Additionally, CCTA can be used to noninvasively quantify plaque burden and identify high-risk plaque, aiding in diagnosis, prognosis, and treatment. This is especially important in the evaluation of CAD in immune-driven conditions with increased cardiovascular disease prevalence. Emerging applications of CCTA based on hemodynamic indices and plaque characterization may provide personalized risk assessment, affect disease detection, and further guide therapy. This review provides an update on the evidence, clinical applications, and emerging technologies surrounding CCTA as highlighted at the 2019 National Heart, Lung and Blood Institute CCTA Summit. [ABSTRACT FROM AUTHOR]

Background: Atherosclerotic plaque characteristics may affect downstream myocardial perfusion, as well as coronary lesion severity.Objectives: This study sought to evaluate the association between quantitative plaque burden and plaque morphology obtained using coronary computed tomography angiography (CTA) and quantitative myocardial perfusion obtained using [15O]H2O positron emission tomography (PET), as well as fractional flow reserve (FFR) derived invasively.Methods: Two hundred eight patients (63% men; age 58 ± 8.7 years) with suspected coronary artery disease were prospectively included. All patients underwent 256-slice coronary CTA, [15O]H2O PET, and invasive FFR measurements. Coronary CTA-derived plaque burden and morphology were assessed using commercially available software and compared with PET perfusion and FFR.Results: Atherosclerotic plaques were present in 179 patients (86%) and 415 of 610 (68%) evaluable coronary arteries. On a per-vessel basis, traditional coronary plaque burden indexes, such as plaque length and volume, minimal lumen area, and stenosis percentage, were significantly associated with impaired hyperemic myocardial blood flow (MBF) and FFR. In addition, morphological features, such as partially calcified plaques, positive remodeling (PR), and low attenuation plaque, displayed a negative impact on hyperemic MBF and FFR. Multivariable analysis revealed that the morphological feature of PR was independently related to impaired hyperemic MBF as well as an unfavorable FFR (p = 0.004 and p = 0.007, respectively), next to stenosis percentage (p = 0.001 and p < 0.001, respectively) and noncalcified plaque volume (p < 0.001 and p = 0.010, respectively).Conclusions: PR and noncalcified plaque volume are associated with detrimental downstream hyperemic myocardial perfusion and FFR, independent of lesion severity. [ABSTRACT FROM AUTHOR]

Objectives: We examined mortality risk in relation to extent and composition of nonobstructive plaques by 64-detector row coronary computed tomographic angiography (CCTA). Background: The prognostic significance of nonobstructive coronary artery plaques by CCTA is poorly understood. Methods: We prospectively evaluated consecutive adults from 2 centers undergoing 64-detector row CCTA without prior documented coronary artery disease (CAD) and without obstructive (≥50%) CAD by CCTA. Luminal diameter stenosis severity was classified for each segment as none (0%) or mild (1% to 49%), and plaque composition was classified as noncalcified, calcified, or mixed. Results: During 3.1 ± 0.5 years, 54 intermediate-term (≥90 days) deaths occurred among 2,583 patients (2.09%), with 4 early (<90 days) deaths. Adjusted for CAD risk factors, the presence of any nonobstructive plaque was associated with higher mortality (hazard ratio [HR]: 1.98, 95% confidence Interval [CI]: 1.06 to 3.69, p = 0.03), with the highest risk among those exhibiting nonobstructive CAD in 3 epicardial vessels (HR: 4.75, 95% CI: 2.10 to 10.75, p = 0.0002) or ≥5 segments (HR: 5.12, 95% CI: 2.16 to 12.10, p = 0.0002). Higher mortality for nonobstructive CAD was observed even among patients with low 10-year Framingham risk (3.4%, p < 0.0001) as well as those with no traditional, medically treatable CAD risk factors, including diabetes mellitus, hypertension, and dyslipidemia (6.7%, p < 0.0001). No independent relationship between plaque composition and incident mortality was observed. Importantly, patients without evident plaque experienced a low rate of incident death during follow-up (0.34%/year). Conclusions: The presence and extent of nonobstructive plaques augment prediction of incident mortality beyond conventional clinical risk assessment. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to determine the relationship between Rho-associated kinase (ROCK) activity and aortic stiffness in humans. Background: Epidemiologic studies have shown that there is a relationship between aortic stiffness and cardiovascular complications. Recent evidence suggests that ROCK plays an important role in the process of atherosclerosis. Methods: We evaluated the forearm blood flow (FBF) response to sodium nitroprusside (SNP), a nitric oxide donor, acetylcholine (ACh), an endothelium-dependent vasodilator, and fasudil, a specific ROCK inhibitor, in 51 healthy male subjects (mean age 45.6 ± 3.0 years). The FBF was measured by using a strain-gauge plethysmography. Carotid-femoral pulse wave velocity (cf-PWV) was measured to assess the aortic stiffness using a pulse wave velocimeter. Results: Intra-arterial infusion of SNP alone, ACh alone, or fasudil alone and after co-infusion of N G-monomethyl-L-arginine (L-NMMA), a nitric-oxide synthase inhibitor, significantly increased FBF in a dose-dependent manner (p < 0.01). Multivariate analysis showed that age and number of pack-years smoked were independent predictors of ROCK activity before or after co-infusion of L-NMMA (p < 0.01) and that age and ROCK activity before or after co-infusion of L-NMMA were independent predictors of cf-PWV (p < 0.01). The concentration of serum malondialdehyde-modified low-density lipoprotein, an index of oxidative stress, was significantly correlated with ROCK activity before and after co-infusion of L-NMMA and cf-PWV (p < 0.01). Conclusions: These findings suggest that aging and accumulating smoking habit, which might induce excessive oxidative stress, are involved in ROCK activity in the vasculature, leading to an increase in aortic stiffness in humans. [Copyright &y& Elsevier]