Is metabolic syndrome predictive of prevalence, extent, and risk of coronary artery disease beyond its components? results from the multinational coronary ct angiography evaluation for clinical outcome: An international multicenter registry (confirm)

Although metabolic syndrome is associated with increased risk of cardiovascular disease and events, its added prognostic value beyond its components remains unknown. This study compared the prevalence, severity of coronary artery disease (CAD), and prognosis of patients with metabolic syndrome to those with individual metabolic syndrome components. The study cohort consisted of 27125 consecutive individuals who underwent ≥64-detector row coronary CT angiography (CCTA) at 12 centers from 2003 to 2009. Metabolic syndrome was defined as per NCEP/ATP III criteria. Metabolic syndrome patients (n=690) were matched 1:1:1 to those with 1 component (n=690) and 2 components (n=690) of metabolic syndrome for age, sex, smoking status, and family history of premature CAD using propensity scoring. Major adverse cardiac events (MACE) were defined by a composite of myocardial infarction (MI), acute coronary syndrome, mortality and late target vessel revascularization. Patients with 1 component of metabolic syndrome manifested lower rates of obstructive 1-, 2-, and 3-vessel/left main disease compared to metabolic syndrome patients (9.4% vs 13.8%, 2.6% vs 4.5%, and 1.0% vs 2.3%, respectively; p0.05). At 2.5 years, metabolic syndrome patients experienced a higher rate of MACE compared to patients with 1 component (4.4% vs 1.6%; p=0.002), while no difference observed compared to individuals with 2 components (4.4% vs 3.2% p=0.25) of metabolic syndrome. In conclusion, Metabolic syndrome patients have significantly greater prevalence, severity, and prognosis of CAD compared to patients with 1 but not 2 components of metabolic syndrome

Prognostic implications of coronary artery calcium in the absence of coronary artery luminal narrowing

Background and aims: Coronary artery calcium (CAC) scoring is a predictor of future adverse clinical events, and a surrogate measure of overall coronary artery plaque burden. Coronary computed tomographic angiography (CCTA) is a contrast-enhanced method that allows for visualization of plaque as well as whether that plaque causes luminal narrowing. To date, the prognosis of individuals with CAC but without stenosis has not been reported. We explored the prevalence of CAC>0 and its prognostic utility for future mortality for patients without luminal narrowing by CCTA. Methods: From 17 sites in 9 countries, we identified patients without known coronary artery disease, who underwent CAC scoring and CCTA, and were followed for >3 years. CCTA was graded for % stenosis according to a modified American Heart Association 16-segment model. We calculated hazard ratios (HR) with 95% confidence intervals (95% CI) for incident mortality and compared risk of death for patients as a function of presence or absence of CAC and presence or absence of luminal narrowing by CCTA. Results: Among 6656 patients who underwent CCTA and CAC scoring, 399 patients (6.0%) had no coronary luminal narrowing but CAC>0. During a median follow-up of 5.1 years (IQR: 3.9-5.9 years), 456 deaths occurred. Compared to individuals without luminal narrowing or CAC, individuals without luminal narrowing but CAC>0 were older, more likely to be male and had higher rates of diabetes, hypertension, and dyslipidemia. Individuals without luminal narrowing but CAC experienced a 2-fold increased risk of mortality, with increasing risk of mortality with higher CAC score. Following adjustment, incident death persisted (HR, 1.8; 95% CI, 1.1-2.9, p = 0.02) among patients without luminal narrowing but with CAC>0 compared with patients whose CACS = 0. Individuals without luminal narrowing but CAC ≥100 had mortality risks similar to individuals with non-obstructive CAD (0 < stenosis<50%) by CCTA [HR 2.5 (95% CI 1.3-4.9) and 2.2 (95% CI 1.6-3.0), respectively]. Conclusions: Patients without luminal narrowing but with CAC experienc

Coronary dominance and prognosis in patients undergoing coronary computed tomographic angiography: Results from the CONFIRM (COronary CTAngiography EvaluatioN for Clinical Outcomes: An InteRnational Multicenter) registry

Aims: Coronary computed tomographic angiography (CCTA) has become an important tool for non-invasive diagnosis of coronary artery disease (CAD). Coronary dominance can be assessed by CCTA; however, the predictive value of coronary dominance is controversially discussed. The aim of this study was to evaluate the prevalence and prognosis of coronary dominance in a large prospective, international multicentre cohort of patients undergoing CCTA. Methods and results: The study population consisted of 6382 patients with or without CAD (47% females, 53% males, mean age 56.9±12.3 years) who underwent CCTA and were followed over a period of 60 months. Right or left coronary dominance was determined. Right dominance was present in 91% (n = 5817) and left in 9% (n = 565) of the study population. At the end of follow-up, outcome in patients with obstructive CAD (>50% luminal stenosis) and right dominance was similar compared with patients with left dominance [hazard ratio (HR) 0.46, 95% CI 0.16-1.32, P = 0.15]. Furthermore, no differences were observed for the type of coronary dominance in patients with non-obstructive CAD(HR 0.95, 95% CI 0.41-2.21, P = 0.8962) or normal coronary arteries (HR 1.04, 95% CI 0.68-1.59, P = 0.9). Subgroup analysis in patients with left main disease revealed an elevated hazard of the combined endpoint for left dominance (HR 6.45, 95% CI 1.66-25.0, P = 0.007), but not for right dominance. Conclusion: In our study population, survival after 5 years of follow-up did not differ significantly between patientswith left or right coronary dominance. Thus, assessment of coronary vessel dominance by CCTA may not enhance risk stratification in patients with normal coronary arteries or obstructive CAD, but may add prognostic information for specific subpopulations

Incremental prognostic value of coronary computed tomography angiography over coronary calcium scoring for major adverse cardiac events in elderly asymptomatic individuals

Aims Coronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults. Methods and results Of 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1-49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18-41 months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, P-value = 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; P-value <0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles. Conclusion CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults

Impact of age and sex on left ventricular function determined by coronary computed tomographic angiography

__Background__ Left ventricular (LV) volumetric and functional parameters measured with cardiac computed tomography (cardiac CT) augment risk prediction and discrimination for future mortality. Gender- and age-specific standard values for LV dimensions and systolic function obtained by 64-slice cardiac CT are lacking __Methods and results __ 1155 patients from the Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenterregistry (54.5% males, mean age 53.1 + 12.4 years, range: 18 – 92 years) without known coronary artery disease (CAD), structural heart disease, diabetes, or hypertension who underwent cardiac CT for various indications were categorized according to age and sex. A cardiac CT data acquisition protocol was used that allowed volumetric measuring of LV function. Image interpretation was performed at each site. Patients with significant CAD (.50% stenosis) on cardiac CT were excluded from the analysis. Overall, mean left ventricular ejection fraction (LVEF) was higher in women when compared with men (66.6 + 7.7% vs. 64.6 + 8.1%, P, 0.001). This gender-difference in overall LVEF was caused by a significantly higher LVEF in women ≥70 years when compared with men ≥70 years (69.95 + 8.89% vs. 65.50 + 9.42%, P ¼ 0.004). Accordingly, a significant increase in LVEF was observed with age (P ¼ 0.005 for males and P, 0.001 for females), which was more pronounced in females (5.21%) than in males (2.6%). LV end-diastolic volume decreased in females from 122.48+27.87 (,40 years) to 95.56+23.17 (.70 years; P, 0.001) and in males from 155.22+35.07 (,40 years) to 130.26+27.18 (.70 years; P, 0.001). __Conclusion__ Our findings indicate that the LV undergoes a lifelong remodelling and highlight the need for age and gender adjusted reference values

Cardiovascular risk among stable individuals suspected of having coronary artery disease with no modifiable risk factors: results from an international multicenter study of 5262 patients

Purpose: To assess the prevalence, extent, severity, and risk of coronary artery disease (CAD) in patients suspected of having CAD but with no medically modifiable risk factors. Materials and Methods: Institutional review board approval or waiver of consent was obtained at each center. This study was HIPAA compliant. From an international multicenter cohort study of 27 125 subjects undergoing coronary computed tomographic (CT) angiography from 12 centers, 5262 patients without known CAD and without modifiable risk factors were identified. CAD severity was defined as none (0%), mild (1%-49%), or obstructive (≥50%) on a per-patient, per-vessel, and per-segment basis. CAD presence, extent, and severity were related to incidence of major adverse cardiovascular event (MACE) by using Cox proportional hazards models. Results: At a mean follow-up of 2.3 years ± 1.2 (standard deviation), MACE occurred in 106 patients. CAD was common for nonobstructive (n = 1452, 27%) and obstructive (n = 629, 12%) CAD. In risk-adjusted analysis, per-patient obstructive CAD (hazard ratio [HR], 6.64; 95% confidence interval [CI]: 3.68, 12.00; P ≤ .001) was related to MACE. MACE was associated with a dose-response relationship to the number of vessels exhibiting obstructive CAD, increasing risk for obstructive one-vessel (HR, 6.11; 95% CI: 3.22, 11.6; P ≤ .001), two-vessel (HR, 5.86; 95% CI: 2.75, 12.5; P ≤ .0001), or three-vessel or left main (HR, 11.69; 95% CI: 5.38, 25.4; P ≤ .001) CAD. The increased hazard for MACE of obstructive disease holds true for symptomatic (HR, 11.9; 95% CI: 4.81, 29.6; P ≤ .001) and asymptomatic (HR, 6.3; 95% CI: 2.4, 16.7; P ≤ .001) patients. No CAD at coronary CT angiography was associated with a low annualized MACE rate: 0.31% versus 2.06% with obstructive disease. Conclusion: Among individuals suspected of having CAD but without modifiable risk factors, CAD is common, with significantly increased hazards for MACE and mortality. © RSNA, 2013

Gender differences in the prevalence, severity, and composition of coronary artery disease in the young: A study of 1635 individuals undergoing coronary CT angiography fromthe prospective, multinational confirm registry

Objective: Prior studies examining coronary atherosclerosis in the young have been limited by retrospective analyses in small cohorts. We examined the relationship between cardiovascular risk factors (RFs) and prevalence and severity of coronary atherosclerosis in a large, prospective, multinational registry of consecutive young individuals undergoing coronary computerized tomographic angiography (CCTA). Method and results: Of 27 125 patients undergoing CCTA, 1635 young (<45 years) individuals without known coronary artery disease (CAD) or coronary anomalies were identified. Coronary plaque was assessed for any CAD, obstructive CAD (≥50% stenosis), and presence of calcified plaque (CP) and non-calcified plaque (NCP). Among 1635 subjects (70% men, age 38±6 years), any CAD, obstructive CAD, CP, and NCP were observed in 19, 4, 5, and 8%, respectively. Compared with women, men demonstrated higher rates of any CAD (21 vs. 12%, P < 0.001), CP (6 vs. 3%, P = 0.01), and NCP (9 vs. 5%, P = 0.008), although no difference was observed for rates of obstructive CAD (5 vs. 4%, P = 0.46). Any CAD, obstructive CAD, and NCP were higher for young individuals with diabetes, hypertension, dyslipidaemia, current smoking, or family history of CAD; while only diabetes and dyslipidaemia were associated with CP. Increasing cardiovascular RFs was associated with a greater prevalence and extent and severity of CAD, with individuals with 0, 1, 2, ≥3 RFs manifesting a dose-response increase in any CAD (P < 0.001, for trend), obstructive CAD (P < 0.001, for trend), NCP (P < 0.001, for trend), and CP (P < 0.001, for trend). In multivariable analysis adjusting for sex and cardiovascular RFs, male sexwas the strongest predictor for anyCAD(odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.43-2.66, P < 0.001), CP (OR = 1.46, 95% CI = 1.08-1.98, P = 0.01), and NCP (OR = 1.33, 95% CI = 1.06-1.67, P = 0.01); family history of CAD was the strongest predictor for obstructive CAD (OR = 2.71, 95% CI = 1.65-4.45, P < 0.001). Conclusion: Any and obstructiveCADis present in 1 in 5 and 1 in 20 young individuals, respectively, with family history associated with the greatest risk of obstructive CAD

Improved 5-year prediction of all-cause mortality by coronary CT angiography applying the CONFIRM score

Aims To investigate the long-term performance of the CONFIRM score for prediction of all-cause mortality in a large patient cohort undergoing coronary computed tomography angiography (CCTA). Methods and results Patients with a 5-year follow-up from the international multicentre CONFIRM registry were included. The primary endpoint was all-cause mortality. The predictive value of the CONFIRM score over clinical risk scores (Morise, Framingham, and NCEP ATP III score) was studied in the entire patient population as well as in subgroups. Improvement in risk prediction and patient reclassification were assessed using categorical net reclassification index (NRI) and integrated discrimination improvement (IDI). During a median follow-up period of 5.3 years, 982 (6.5%) of 15 219 patients died. The CONFIRM score outperformed the prognostic value of the studied three clinical risk scores (c-indices: CONFIRM score 0.696, NCEP ATP III score 0.675, Framingham score 0.661, Morise score 0.606; c-index for improvement CONFIRM score vs. NCEP ATP III score 0.650, P 5 years after CCTA. These findings are consistent in a large variety of patient subgroups

Medical History for Prognostic Risk Assessment and Diagnosis of Stable Patients with Suspected Coronary Artery Disease

Objective To develop a clinical cardiac risk algorithm for stable patients with suspected coronary artery disease based upon angina typicality and coronary artery disease risk factors. Methods Between 2004 and 2011, 14,004 adults with suspected coronary artery disease referred for cardiac imaging were followed: 1) 9093 patients for coronary computed tomography angiography (CCTA) followed for 2.0 years (CCTA-1); 2) 2132 patients for CCTA followed for 1.6 years (CCTA-2); and 3) 2779 patients for exercise myocardial perfusion scintigraphy (MPS) followed for 5.0 years. A best-fit model from CCTA-1 for prediction of death or myocardial infarction was developed, with integer values proportional to regression coefficients. Discrimination was assessed using C-statistic. The validated model was tested for estimation of the likelihood of obstructive coronary artery disease, defined as ≥50% stenosis, as compared with the method of Diamond and Forrester. Primary outcomes included all-cause mortality and nonfatal myocardial infarction. Secondary outcomes included prevalent angiographically obstructive coronary artery disease. Results In CCTA-1, best-fit model discriminated individuals at risk of death or myocardial infarction (C-statistic 0.76). The integer model ranged from 3 to 13, corresponding to 3-year death risk or myocardial infarction of 0.25% to 53.8%. When applied to CCTA-2 and MPS cohorts, the model demonstrated C-statistics of 0.71 and 0.77, respectively. Both best-fit (C = 0.76; 95% confidence interval [CI], 0.746-0.771) and integer models (C = 0.71; 95% CI, 0.693-0.719) performed better than Diamond and Forrester (C = 0.64; 95% CI, 0.628-0.659) for estimating obstructive coronary artery disease. Conclusions For stable symptomatic patients with suspected coronary artery disease, we developed a history-based method for prediction of death and obstructive coronary artery disease