Objectives The purpose of this study was to evaluate the diagnostic accuracy of electrocardiographically gated 64-multidetector row coronary computed tomographic angiography (CCTA) in individuals ...without known coronary artery disease (CAD). Background CCTA is a promising method for detection and exclusion of obstructive coronary artery stenosis. To date, no prospective multicenter trial has evaluated the diagnostic accuracy of 64-multidetector row CCTA in populations with intermediate prevalence of CAD. Methods We prospectively evaluated subjects with chest pain at 16 sites who were clinically referred for invasive coronary angiography (ICA). CCTAs were scored by consensus of 3 independent blinded readers. The ICAs were evaluated for coronary stenosis based on quantitative coronary angiography (QCA). No subjects were excluded for baseline coronary artery calcium score or body mass index. Results A total of 230 subjects underwent both CCTA and ICA (59.1% male; mean age: 57 ± 10 years). On a patient-based model, the sensitivity, specificity, and positive and negative predictive values to detect ≥50% or ≥70% stenosis were 95%, 83%, 64%, and 99%, respectively, and 94%, 83%, 48%, 99%, respectively. No differences in sensitivity and specificity were noted for nonobese compared with obese subjects or for heart rates ≤65 beats/min compared with >65 beats/min, whereas calcium scores >400 reduced specificity significantly. Conclusions In this prospective multicenter trial of chest pain patients without known CAD, 64-multidetector row CCTA possesses high diagnostic accuracy for detection of obstructive coronary stenosis at both thresholds of 50% and 70% stenosis. Importantly, the 99% negative predictive value at the patient and vessel level establishes CCTA as an effective noninvasive alternative to ICA to rule out obstructive coronary artery stenosis. (A Study of Computed Tomography CT for Evaluation of Coronary Artery Blockages in Typical or Atypical Chest Pain; NCT00348569 )
Abstract This expert consensus statement summarizes the available data regarding the prognostic value of CAC in the asymptomatic population and its ability to refine individual risk prediction, ...addresses the limitations identified in the current traditional risk factor-based treatment strategies recommended by the 2013 ACC/AHA Prevention guidelines including use of the Pooled Cohort Equations (PCE), and the US Preventive Services Task Force (USPSTF) Recommendation Statement for Statin Use for the Primary Prevention of Cardiovascular Disease in Adults. It provides CAC based treatment recommendations both within the context of the shared decision making model espoused by the 2013 ACC/AHA Prevention guidelines and independent of these guidelines.
Objectives The aim of this study was to further explore the interplay between smoking status, coronary artery calcium (CAC), and all-cause mortality. Background Prior studies have not directly ...compared the relative prognostic impact of CAC in smokers versus nonsmokers. In particular, although a calcium score of zero (CAC = 0) is a known favorable prognostic marker, whether smokers with CAC = 0 have as good a prognosis as nonsmokers with CAC = 0 is unknown. Given that computed tomography (CT) screening for lung cancer appears effective in smokers, the relative prognostic implications of visualizing any CAC versus no CAC on such screening also deserve study. Methods Our study cohort consisted of 44,042 asymptomatic individuals referred for noncontrast cardiac CT (age 54 ± 11 years, 54% men). Subjects were followed for a mean of 5.6 years. The primary endpoint was all-cause mortality. Results Approximately 14% (n = 6,020) of subjects were active smokers at enrollment. There were 901 deaths (2.05%) overall, with increased mortality in smokers versus nonsmokers (4.3% vs. 1.7%, p < 0.0001). Smoking remained a risk factor for mortality across increasing strata of CAC scores (1 to 100, 101 to 400, and >400). At each stratum of elevated CAC score, mortality in smokers was consistently higher than mortality in nonsmokers from the CAC stratum above. In multivariable analysis within these strata, we found mortality hazard ratios of 3.8 (95% confidence interval CI: 2.8 to 5.2), 3.5 (95% CI: 2.6 to 4.9), and 2.7 (95% CI: 2.1 to 3.5), respectively, in smokers compared with nonsmokers. However, among the 19,898 individuals with CAC = 0, the mortality hazard ratio for smokers without CAC was 3.6 (95% CI: 2.3 to 5.7), compared with nonsmokers without CAC. Conclusions Smoking is a risk factor for death across the entire spectrum of subclinical coronary atherosclerosis. Smokers with any CAC had significantly higher mortality than smokers without CAC, a finding with implications for smokers undergoing lung cancer CT-based screening. However, the absence of CAC might not be as useful a “negative risk factor” in active smokers, because this group has mortality rates similar to nonsmokers with mild-to-moderate atherosclerosis.
Objectives We sought to quantify the mortality rates associated with absent and low positive (CAC 1 to 10) coronary artery calcium (CAC). Background There is increasing interest in the absence of CAC ...as a “negative” cardiovascular risk factor. However, published event rates for individuals with no CAC vary, likely owing to differences in baseline risk, follow-up period, and outcome ascertainment. The prognostic significance of low CAC (CAC 1 to 10) is not well described. Methods Annualized all-cause mortality rates were assessed in 44,052 consecutive asymptomatic patients referred for CAC testing. Mean follow-up of the cohort was 5.6 ± 2.6 years (range 1 to 13 years). Results A total of 19,898 patients (45%) had no CAC on screening electron beam tomography, whereas 5,388 (12%) had low levels of CAC (CAC 1 to 10), and 18,766 (43%) had CAC >10. There were 104 deaths in those with no CAC (0.52%), 58 deaths in those with CAC 1 to 10 (1.06%), and 739 deaths in those with CAC >10 (3.96%). Annualized all-cause mortality rates for CAC = 0, CAC 1 to 10, and CAC >10 were 0.87, 1.92, and 7.48 deaths/1,000 person-years, respectively. The hazard ratio (HR) for all-cause mortality among CAC 1 to 10 versus CAC = 0 after adjustment for traditional risk factors was 1.99 (95% confidence interval CI: 1.44 to 2.75). Smoking (HR: 3.97, 95% CI: 2.75 to 5.41) and diabetes mellitus (HR: 3.36, 95% CI: 2.09 to 5.41) were associated with few events observed in CAC = 0 group. Conclusions In appropriately selected asymptomatic patients, the absence of CAC predicts excellent survival with 10-year event rates of approximately 1%. A finding of 0 CAC might be used as a rationale to emphasize lifestyle therapies rather than pharmacotherapy and to forgo repeated imaging studies. Individuals with low CAC score (CAC 1 to 10) are at increased risk above individuals with a 0 score and could be considered a distinct risk group by physicians and investigators.
Abstract Background Cardiovascular calcification outside of the coronary tree, known as extracoronary calcification (ECC), is highly prevalent, often occurs concurrently in multiple sites, and yet ...its prognostic value is unclear. Objective To determine whether multisite ECC is associated with coronary heart disease (CHD) events, CHD mortality, and all-cause mortality. Methods We evaluated 5903 participants from the Multi-Ethnic Study of Atherosclerosis without diabetes who underwent CT imaging for calcification of the aortic valve, aortic root, mitral valve, and thoracic aorta. Participants were followed for 10.3 years. Multivariable adjusted hazard ratios estimated risk of outcomes for increasing numbers of ECC sites (0, 1, 2, 3, and 4), and receiver operator characteristic analysis assessed model discrimination. Results Prevalence of any ECC was 45%; median age was 62 years. Compared with those without ECC, those with ECC in 4 sites had increased hazards of 4.5, 7.1 and 2.3 for CHD events, CHD mortality, and all-cause mortality, respectively, independent of traditional risk factors (TRF; all P ≤ .05), and had ≥2-fold increased hazards for outcomes independent of coronary artery calcification (CAC). Each additional site of ECC was positively associated with each outcome in a graded fashion. When added to TRF, ECC significantly increased the area under the receiver operator characteristic curve for all outcomes and modestly increased the area under the curve for mortality beyond TRF + CAC (0.799 to 0.802; P = .03). Conclusion Increasing multisite ECC has a graded association with higher CHD and mortality risk, contributing information beyond TRF. Multisite ECC incidentally identified on imaging can be used to improve individualized risk prediction.
Aortic valve calcium (AVC) can be quantified on the same computed tomographic scan as coronary artery calcium (CAC). Although CAC is an established predictor of cardiovascular events, limited ...evidence is available for an independent predictive value for AVC. We studied a cohort of 8,401 asymptomatic subjects (mean age 53 ± 10 years, 69% men), who were free of known coronary heart disease and were undergoing electron beam computed tomography for assessment of subclinical atherosclerosis. The patients were followed for a median of 5 years (range 1 to 7) for the occurrence of mortality from any cause. Multivariate Cox regression models were developed to predict all-cause mortality according to the presence of AVC. A total of 517 patients (6%) had AVC on electron beam computed tomography. During follow-up, 124 patients died (1.5%), for an overall survival rate of 96.1% and 98.7% for those with and without AVC, respectively (hazard ratio 3.39, 95% confidence interval 2.09 to 5.49). After adjustment for age, gender, hypertension, dyslipidemia, diabetes mellitus, smoking, and a family history of premature coronary heart disease, AVC remained a significant predictor of mortality (hazard ratio 1.82, 95% confidence interval 1.11 to 2.98). Likelihood ratio chi-square statistics demonstrated that the addition of AVC contributed significantly to the prediction of mortality in a model adjusted for traditional risk factors (chi-square = 5.03, p = 0.03) as well as traditional risk factors plus the presence of CAC (chi-square = 3.58, p = 0.05). In conclusion, AVC was associated with increased all-cause mortality, independent of the traditional risk factors and the presence of CAC.
Objectives This study examined a large cohort to assess whether progression of coronary artery calcium (CAC) was associated with all-cause mortality, and which among 3 different methods to assess CAC ...progression provided the best estimate of risk. Background Serial assessment of CAC scores has been proposed as a method to follow progression of coronary artery disease, and it has been suggested that excessive CAC progression may be a useful noninvasive predictor of the patient's risk of future events. However, the optimal method to measure calcium progression has not been well established. Methods The study sample consisted of 4,609 consecutive asymptomatic individuals referred by primary physicians for CAC measurement with electron beam tomography, who underwent repeat screening. Three general statistical approaches were taken: 1) the absolute difference between follow-up and baseline CAC score; 2) percent annualized differences between follow-up and baseline CAC score; and 3) difference between square root of baseline and square root of follow-up CAC score >2.5 (the “SQRT method”). Results The average interscan time was 3.1 years, and there were 288 deaths. Progression of CAC was significantly associated with mortality regardless of the method used to assess progression (p < 0.0001). After adjusting for baseline score, age, sex, and time between scans, the best CAC progression model to predict mortality was the SQRT method (hazard ratio HR: 3.34; 95% confidence interval CI: 2.65 to 4.21; p < 0.0001), followed by a >15% yearly increase (HR: 2.98; 95% CI: 2.20 to 4.95; p < 0.0001). Progression was very limited and did not predict mortality in patients with baseline CAC = 0. Conclusions The CAC progression added incremental value in predicting all-cause mortality over baseline score, time between scans, demographics, and cardiovascular risk factors. Serial assessment may have clinical value in assessing plaque progression and future cardiovascular risk.
We hypothesized that anthropometric measures of abdominal obesity would have a stronger positive association with nonalcoholic fatty liver disease (NAFLD) measured by noncontrast computed tomography ...versus general measures of obesity. The Multiethnic Study of Atherosclerosis comprised participants aged 45 to 84 years free of known cardiovascular disease. We studied 4,088 participants with adequate liver and spleen computed tomography imaging and no previous use of oral steroids, class 3 antiarrhythmics, moderately heavy alcohol use, or cirrhosis. Prevalent NAFLD was defined as a liver:spleen Hounsfield attenuation ratio of <1. Multivariable log-linear regression modeled the association of 4 obesity measures—weight, body mass index (BMI), waist circumference, and waist-to-hip ratio—with prevalent NAFLD. Receiver-operator curve analysis compared NAFLD discrimination. Median age was 63 years, and 55% were women. For each obesity measure, adjusted prevalence ratios for NAFLD were fourfold to fivefold greater in the highest versus the lowest quartile (p <0.001). Waist circumference and BMI had the highest prevalence ratios, and waist circumference had the best discrimination, for NAFLD in the total population, although an abnormal BMI categorized subjects with NAFLD as well if not better than waist circumference. In ethnic-specific analysis, whites and Chinese had the strongest association of obesity and NAFLD compared with other ethnicities. In conclusion, although waist circumference provided the best discrimination for NAFLD, BMI may perform similarly well in clinical settings to screen for NAFLD.
To describe ethnic and sex differences in the prevalence and determinants of fatty liver in a multiethnic cohort.
We studied participants of the Multi-Ethnic Study of Atherosclerosis who underwent ...baseline noncontrast cardiac computed tomography between July 17, 2000, and August 29, 2002, and had adequate hepatic and splenic imaging for fatty liver determination (n=4088). Fatty liver was defined as a liver/spleen attenuation ratio of less than 1. We compared the prevalence and severity of fatty liver, in 4 ethnicities (white, Asian, African American, and Hispanic), and the factors associated with fatty liver in each ethnicity, stratifying by obesity and metabolic syndrome. Multivariable ordinal logistic regression was used to determine the effect of cardiometabolic risk factors on the prevalence of fatty liver in different ethnicities.
The prevalence of fatty liver varied significantly by ethnicity (African American, 11%; white, 15%; Asian, 20%; and Hispanic, 27%; P<.001). Although African Americans had the highest prevalence of obesity, a smaller percentage of obese African Americans received a diagnosis of fatty liver than did other ethnicities (African American, 17%; white, 31%; Asian, 37%; and Hispanic 39%; P<.001). Hispanics had the highest prevalence of fatty liver, including the obese and metabolic syndrome population. An increase in insulin resistance predicted a 2-fold increased prevalence of fatty liver in all ethnicities after multivariable adjustment.
African Americans have a lower prevalence and Hispanics have a higher prevalence of fatty liver than do other ethnicities. There are distinct ethnic variations in the prevalence of fatty liver even in patients with the metabolic syndrome or obesity, suggesting that genetic factors may play a substantial role in the phenotypic expression of fatty liver.
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