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Although acute coronary syndrome culprit lesions occur more frequently in the proximal coronary artery, whether the proximal clustering of high-risk plaque is reflected in earlier-stage atherosclerosis remains unclarified. We evaluated the longitudinal distribution of stable atherosclerotic lesions on coronary computed tomography angiography (CCTA) in 1,478 patients (mean age, 61 years; men, 58%) enrolled from a prospective multinational registry of consecutive patients undergoing serial CCTA. Of 3,202 coronary artery lesions identified, 2,140 left lesions were classified (based on the minimal lumen diameter location) into left main (LM, n = 128), proximal (n = 739), and other (n = 1,273), and 1,062 right lesions were classified into proximal (n = 355) and other (n = 707). Plaque volume (PV) was the highest in proximal lesions (median, 26.1 mm3), followed by LM (20.6 mm3) and other lesions (15.0 mm3, p

Thoracic aortic calcium(TAC) is an important marker of extracoronary atherosclerosis with established predictive value for all-cause mortality. We sought to explore the predictive value of TAC for stroke mortality, independent of the more established coronary artery calcium (CAC) score. The CAC Consortium is a retrospectively assembled database of 66,636 patients aged ≥18 years with no previous history of cardiovascular disease, baseline CAC scans for risk stratification, and follow-up for 12 ± 4 years. CAC scans capture the adjacent thoracic aorta, enabling assessment of TAC from the same images. TAC was available in 41,066 (62%), and was primarily analyzed as present or not present. To account for competing risks for nonstroke death, we utilized multivariable-adjusted Fine and Gray competing risk regression models adjusted for traditional cardiovascular risk factors and CAC score. The mean age of participants was 53.8 ± 10.3 years, with 34.4% female. There were 110 stroke deaths during follow-up. The unadjusted subdistribution hazard ratio (SHR) for stroke mortality in those who had TAC present compared with those who did not was 8.80 (95% confidence interval [CI]: 5.97, 12.98). After adjusting for traditional risk factors and CAC score, the SHR was 2.21 (95% CI:1.39,3.49). In sex-stratified analyses, the fully adjusted SHR for females was 3.42 (95% CI: 1.74, 6.73) while for males it was 1.55 (95% CI: 0.83, 2.90). TAC was associated with stroke mortality independent of CAC and traditional risk factors, more so in women. The presence of TAC appears to be an independent risk marker for stroke mortality.

Retinopathy is a microvascular complication of diabetes mellitus (DM); however, it is also increasingly recognized in persons without DM. The microvascular diseases may play a prominent role in coronary heart disease (CHD) development in individuals with DM. We performed the study to evaluate the relation between non-DM retinopathy and CHD and also the association between baseline retinopathy and incidence and progression of CHD in individuals with and without DM. We included 5709 subjects with and without DM from the Multi-Ethnic Study of Atherosclerosis, who had retinal photos and coronary artery calcium score (CACS) available. We studied the association between baseline retinopathy and incidence and progression of coronary artery calcification (CAC) in subjects with and without DM. In DM group, the presence of retinopathy was significantly associated with an increased rate of CAC (RR 1.3 (95% CI [1.02, 1.66]) after adjusting for age, sex, race, follow-up time, and CHD risk factors. In non-DM group, the presence of retinopathy was not significantly associated with increased risk of CAC, however, the interaction between presence of retinopathy and DM status was not statistically significant. Within the DM group with CAC present at baseline, the presence of retinopathy was significantly associated with greater CAC progression (113 Agatson units (AU) greater, (95% CI [51-174]). In the non-DM group with present CAC at baseline; the presence of retinopathy was associated with 24 (95% CI [-0.69, 48.76]) AU higher CAC progression. All findings were adjusted for CHD risk factors. In conclusion, after adjustment for major CHD risk factors, retinopathy was associated with progression of CAC in both DM and non-DM individuals. However, the association was stronger in those with DM.

Calcific aortic valve disease, a condition of chronic inflammation, is associated with increased cardiovascular events and all-cause mortality. Omega-3 fatty acids (O3FAs) reduce both acute and chronic inflammation, but their associations with aortic valve calcium (AVC) have not been studied. The Multi-Ethnic Study of Atherosclerosis is a prospective cohort study of 6,814 adults without clinical cardiovascular disease. Plasma fatty acid levels and cardiac computed tomography (CT) scans were performed at baseline, and CT scans were performed at subsequent clinical visits over a median 9-year period. We assessed whether plasma levels of O3FAs and their species correlate with the presence, severity, and progression of AVC measured by CT in Multi-Ethnic Study of Atherosclerosis. The mean age of the 6,510 included participants with baseline fatty acid levels, AVC, and covariate data was 62.1 ± 10.2 years, and 47.1% of the participants were male. Race distribution was 38.6% White, 27.2% Black, 22.1% Hispanic/Latino, and 12.1% Chinese. Among the 6,510 participants, 5,884 had a subsequent CT scan, and 3,304 had a third CT scan with AVC measurements. At baseline, 862 participants (13.2%) had prevalent AVC (Agatston score0), and were more likely to be of older age, male, of the White race, have a lower education level, and have co-morbidities that are associated with a higher risk for AVC. Plasma tertiles of eicosapentaenoic acid, docosahexaenoic acid, and total O3FA were not associated with prevalent AVC at baseline, incident AVC, or change in AVC. In conclusion, plasma levels of O3FAs in subjects not routinely supplemented with O3FAs are not useful for predicting the presence or development of AVC. Whether high plasma O3FA levels, achievable by high-dose O3FA over-the-counter supplementation or pharmacotherapy, is associated with AVC requires further investigation.

The prognostic value of traditional atherosclerotic cardiovascular disease (ASCVD) risk factors may decrease with age. We sought to determine whether the association between traditional ASCVD risk factors and incident coronary artery calcium (CAC) differs for younger versus older persons. We included 5,108 participants with baseline CAC = 0. Repeat CAC scoring occurred over 3 to 11 years of follow-up. Multivariable Cox proportional hazards regression assessed the association between traditional risk factors and incident CAC in young (32 to 45 years), middle-aged (46 to 64 years), and older adults (65 to 84 years). A total of 61% of the participants were women and 37% were Black. The proportion with incident CAC ranged from 22% among young adults, 34% for middle-aged adults, and 45% for older adults. In young adults, traditional risk factors were significantly associated with incident CAC except for diastolic blood pressure and high-density lipoprotein (HDL) cholesterol, whereas only total cholesterol/HDL cholesterol ≥3.5 (p = 0.04) was significantly associated with incident CAC in older persons. Non-HDL cholesterol (p = 0.02) was more strongly associated with incident CAC in young (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09 to 1.31) and middle aged (HR 1.14, 95% CI 1.07 to 1.23) compared to older adults (HR 1.11, 95% CI 0.99 to 1.23). When added to demographics, traditional risk factors provided a greater C-statistic improvement for incident CAC prediction in young (0.752, +0.070, p0.001) versus middle-aged (0.645, +0.054, p0.001) and older adults (0.597,+0.025, p = 0.08). In conclusion, traditional risk factors more strongly predict incident CAC in young compared to older adults, underlining the importance of primordial prevention through middle age while identifying the challenges of ASCVD risk assessment in older persons.

Current risk stratification strategies do not fully explain cardiovascular disease (CVD) risk. We aimed to evaluate the association of low-density lipoprotein (LDL-P) and high-density lipoprotein (HDL-P) particles with progression of coronary artery calcium and carotid wall injury. All participants in the Multi-Ethnic Study Atherosclerosis (MESA) with LDL-P and HDL-P measured by ion mobility, coronary artery calcium score (CAC), carotid intima-media thickness (IMT), and carotid plaque data available at Exam 1 and 5 were included in the study. CAC progression was annualized and treated as a categorical or continuous variable. Carotid IMT and plaque progression were treated as continuous variables. Fully adjusted regression models included established CVD risk factors, as well as traditional lipids. Mean (±SD) follow-up duration was 9.6 ± 0.6 years. All LDL-P subclasses as well as large HDL-P at baseline were positively and significantly associated with annualized CAC progression, however, after adjustment for established risk factors and traditional lipids, only the association with medium and very small LDL-P remained significant (β -0.02, p = 0.019 and β 0.01, p = 0.003, per 1 nmol/l increase, respectively). Carotid plaque score progression was positively associated with small and very small LDL-P (p

The 2017 American blood pressure (BP) guidelines recommended a personalized risk-based approach to treatment in stage 1 hypertension. We sought to establish the utility of coronary artery or thoracic aortic calcium (CAC or TAC) as additional risk modifiers in this setting. We included 1859 Multiethnic Study of Atherosclerosis participants with stage 1 hypertension. We compared adjusted HR for the composite outcome of incident atherosclerotic cardiovascular disease or heart failure across predefined categories of either CAC or TAC (0, 1 to 100, or >100) in: (1) the full sample; (2) 4 high-risk subgroups recommended for pharmacotherapy to a BP goal 100. CAC >100 was independently associated with a higher relative risk of events compared with CAC = 0 (e.g., adjusted HR [9.5 (1.8 to 18.7)] in the low-risk subgroup). NNT10 for CAC = 0 were 3 to 5 times higher than those for CAC >100 in all analyses. TAC was not a reliable risk modifier in our study. In conclusion, CAC, but not TAC, can further guide risk-based allocation of treatment in stage 1 hypertension and should be considered as a risk modifier in future guidelines.

The role of NT-proBNP and hs-cTnT levels in predicting heart failure (HF) and cardiovascular disease (CVD) events in persons with prediabetes (pre-DM) and diabetes mellitus (DM) is not well-established. We examined the individual and combined relations of N-terminal natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) levels among asymptomatic adults with pre-DM and DM with the development of incident HF and CVD events. 5,584 participants with biomarker measures aged 45 to 84 years were included from the Multi-Ethnic Study of Atherosclerosis, of which 4,090 were normoglycemic, 799 had pre-DM, and 695 had DM at baseline and were followed for 12.4 ± 3.8 years. In those with DM, HF incidence rates per 1,000 person-years ranged from 3.2 to 39.4 across quartiles of NT-proBNP and 0.6 to 18.2 for hs-cTnT, respectively. Corresponding values for CVD incidence per 1,000 person-years ranged from 13.7 to 39.4 for NT-proBNP and 13.2 to 35.4 for hs-cTnT. Multivariate adjusted HRs were highest when both NT-proBNP and hs-cTnT were above versus below the median in those with pre-DM/DM (16.7 for incident HF and 2.1 for CVD events, both p

The prognostic utility of coronary artery calcium (CAC) for individuals taking statins is unclear. We hypothesized that CAC remains associated with atherosclerotic cardiovascular disease (ASCVD) events in individuals using statins at baseline or among those started on statin at follow-up. The Multi-Ethnic Study of Atherosclerosis is a prospective cohort study of 6,814 participants who were enrolled between 2000 and 2002 and were free of clinical ASCVD at baseline. Four follow-up visits were conducted in 2002 to 2004, 2004 to 2006, 2005 to 2007, and 2010 to 2012. CAC was assessed at baseline and follow-up using either an electron-beam CT scanner or a multidetector CT system. Statin use at baseline and follow up was self-reported. Among 6,811 participants with complete information on statin use, mean age was 62 (SD = 10) years, 53% were women, 38% white, 12% Chinese-American, 28% African American, and 22% Hispanic. In multivariable analyses, CAC >0 was associated with a significantly higher risk of ASCVD events regardless of baseline or incident statin use. For example, hazard ratios (95% confidence interval) for the association between CAC >0 and ASCVD were 2.46 (1.41, 4.28) for baseline statin users, 2.08 (1.68, 2.57) for baseline-statin nonusers, and 2.21 (1.56, 3.15) for those started on a statin at follow-up. In conclusion, current statin use does not weaken the prognostic utility of CAC. CAC is associated with incident ASCVD regardless of baseline or incident statin use.

The 2018 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guideline recommends risk enhancers in the borderline-risk and statin recommended/intermediate-risk groups. We determined the risk reclassification by the presence and severity of coronary computed tomography angiography (CCTA)-visualized coronary artery disease (CAD) according to statin eligibility groups. Of 35,281 individuals who underwent CCTA, 1,303 asymptomatic patients (age 59, 65% male) were identified. Patients were categorized as low risk, borderline risk, statin recommended/intermediate risk or statin recommended/high risk according to the guideline. CCTA-visualized CAD was categorized as no CAD, nonobstructive, or obstructive. Major adverse cardiovascular events (MACE) were defined as a composite outcome of all-cause mortality, nonfatal myocardial infarction, and late coronary revascularization (>90 days). We tested a reclassification wherein no CAD reclassifies downward, and the presence of any CAD reclassifies upward. During a median follow-up of 2.9 years, 93 MACE events (7.1%) were observed. Among the borderline-risk and statin-recommended/intermediate-risk groups eligible for risk enhancers, the presence or absence of any CCTA-visualized CAD led to a net increase of 2.3% of cases and 22.4% of controls correctly classified (net reclassification index [NRI] 0.27, 95% CI 0.13 to 0.41, p = 0.0002). The NRI was not significant among low- or statin-recommended/high-risk patients (all p > 0.05). The presence or absence of CCTA-visualized CAD, including both obstructive and nonobstructive CAD, significantly improves reclassification in patients eligible for risk enhancers in 2018 ACC/AHA guidelines. Patients in low- and high-risk groups derive no significant improvement in risk reclassification from CCTA. (C) 2019 Published by Elsevier Inc.

Cardiovascular services are the third largest source of Medicare spending. We examined the rate of cardiovascular service utilization in the community of Glendale, CA, compared with the nearest academic medical center, the University of Southern California. Publicly available utilization data released by Medicare for the years 2012 and 2013 were used to identify all inpatient and outpatient cardiology services provided in each practice setting. The analysis included 19 private and 17 academic cardiologists. In unadjusted analysis, academic physicians performed half as many services per Medicare beneficiary per year as those in private practice: 2.3 versus 4.8, p

Diastolic blood pressure has a J-curve relationship with coronary heart disease and death. Because this association is thought to reflect reduced coronary perfusion at low diastolic blood pressure, we hypothesized that the J-curve would be most pronounced among persons with coronary artery calcium. Among 6,811 participants from the Multi-Ethnic Study of Atherosclerosis, we used Cox models to examine if diastolic blood pressure category is associated with coronary heart disease events, stroke, and mortality. Analyses were conducted in the sample overall and after stratification by coronary artery calcium score. In multivariable-adjusted analyses, compared with diastolic blood pressure of 80 to 89 mmHg (reference), persons with diastolic blood pressure 0. Diastolic blood pressure

Nonalcoholic fatty liver disease (NAFLD) is considered a potential independent risk factor for cardiovascular disease (CVD). The Multi-Ethnic Study of Atherosclerosis cohort enrolled 6,814 adults without previous CVD. We excluded 2,692 participants who had missing variables, were heavy drinkers, or history of steroid use and/or chronic liver disease. NAFLD was defined using noncontrast cardiac CT and a liver/spleen Hounsfield Unit attenuation ratio1. Ultrasound-measured carotid arterial compliance and stiffness, was expressed as distensibility coefficient and Young's modulus. Common and internal carotid intima-media thickness (CIMT) and coronary artery calcium (CAC)0 were used as markers of subclinical CVD. A multivariate robust linear regression and logistic regression analysis were done to evaluate the association of NAFLD and this subclinical CVD markers. Our analysis of 4,123 participants showed 55% were female with a mean age of 63 (±10) years, 39% white, 10% Chinese, 28% black, and 23% were Hispanic. The prevalence of NAFLD was 17% (n = 729). Patients with NAFLD had higher distensibility coefficient and higher CIMT. Multivariate linear regression analysis showed the presence of NAFLD was associated with both the common carotid and internal carotid IMT and logCAC. Logistic analysis showed an independent association with CAC0 (odds ratio [OR] 1.44 95% confidence interval [CI] 1.18, 1.75) and CIMT1 mm (OR 1.30 95% 1.08, 1.56). When stratified by race the association with CIMT1 mm was significant in whites (OR 1.37 95% 1.00, 1.90) and Hispanic (OR 1.53 95% 1.08, 2. 17) and CAC0 was significant in Hispanics (OR 1.52 95% 1.06, 2.19). In conclusion, NAFLD is modestly associated with carotid IMT and coronary artery calcification in a multiethnic population.

Guidelines to evaluate patients for coronary artery disease (CAD) during preoperative evaluation for orthotopic liver transplantation (OLT) are conflicting. Cardiac catheterization is not without risk in patients with end-stage liver disease. No study to date has looked at the utility of non-electrocardiogram-gated chest computed tomography (CT) in the preliver transplant population. Our hypothesis was that coronary artery calcium scores (CACSs) from chest CT scans ordered during the liver transplant workup can identify patients who would benefit from invasive angiography. Nine hundred and fifty-three patients who underwent coronary angiography as part of their OLT workup were considered. Charts were randomly selected and reviewed for the presence of a chest CT performed before coronary angiography during the OLT workup. Agatston and Weston scores were calculated. CACS results were compared with coronary angiography findings. Nine of 54 patients were found to have obstructive CAD by angiography. Receiver-operating characteristic analysis demonstrated that an Agatston score of 251 and a Weston score of 6 maximized sensitivity and specificity for detection of obstructive coronary disease. An Agatston score

We hypothesized that anthropometric measures of abdominal obesity would have a stronger positive association with non-alcoholic fatty liver disease (NAFLD) measured by non-contrast computed tomography versus general measures of obesity. The Multi-Ethnic Study of Atherosclerosis (MESA) is comprised of participants aged 45–84 years free of known cardiovascular disease. We studied 4,088 participants with adequate liver and spleen CT-imaging and no prior use of oral steroids, class 3 anti-arrhythmics, moderately-heavy alcohol use, or cirrhosis. Prevalent NAFLD was defined as a liver:spleen Hounsfield attenuation ratio of

Although the traditional Agatston coronary artery calcium (CAC) score is a powerful predictor of mortality, it is unknown if the regional distribution of CAC further improves cardiovascular risk prediction. We retrospectively studied 23,058 patients referred for Agatston CAC scoring, of whom 61% had CAC (n=14,084). CAC distribution was defined as the number of vessels with CAC (0 to 4, including left main). For multivessel CAC, "diffuse" CAC was defined by decreasing percentage of CAC in the single most affected vessel and by ≤75% total Agatston CAC score in the most calcified vessel. All-cause mortality was ascertained through the social security death index. The mean age was 55±11 years, with 69% men. There were 584 deaths (2.5%) over 6.6±1.7 years. Considerable heterogeneity existed between the Agatston CAC score group and the number of vessels with CAC. In each CAC group, increasing number of vessels with CAC was associated with an increased mortality rate. After adjusting for age, gender, Agatston CAC score, and cardiovascular risk factors, increasing number of vessels with CAC was associated with higher mortality risk compared with single-vessel CAC (2-vessel: HR 1.61 [95% CI 1.14 to 2.25], 3-vessel: 1.99 [1.44 to 2.77], and 4-vessel: 2.22 [1.53 to 3.23]). "Diffuse" CAC was associated with a higher mortality rate in the CAC 101 to 400 and >400 groups. Left main CAC was associated with increased mortality risk. In conclusion, increasing number of vessels with CAC and left main CAC predict increased all-cause mortality and improve the prognostic power of the traditional Agatston CAC score.

Arterial calcification reflects an atherosclerotic process associated with vascular stiffness. Whether baseline coronary artery calcium (CAC) and extra-coronary calcium (ECC), measured using noncontrast computed tomography imaging, are associated with incident hypertension is poorly understood. We studied participants from the Multi-Ethnic Study of Atherosclerosis without measured or self-reported hypertension at baseline. Incident hypertension was defined by blood pressure criteria (BP, ≥140/90 mmHg), BP medication use, or both, and was assessed at in-person visits. We analyzed incident hypertension using multivariable-adjusted discrete-time proportional hazards models. Net reclassification improvement (NRI) assessed whether CAC reclassified hypertension risk when added to the Framingham hypertension risk score. Among 3,304 subjects analyzed, mean age was 59 ± 10 years; 48% were male and 42% were white. There were 1,283 incident hypertension cases over a median (interquartile range) follow-up time of 10.6 (4.5, 11.5) years. Each 1-unit increase in ln(CAC+1) was independently associated with a 12% higher risk of hypertension (95% confidence interval [CI] 9% to 16%). Relative to CAC = 0, patients with CAC >400 had a hazard ratio for incident hypertension of 2.2 (95% CI 1.8 to 2.9). There was no interaction by age, gender, or baseline BP (p = 0.43, 0.19, 0.09, respectively). Continuous NRI analyses demonstrated that CAC can reclassify risk of incident hypertension; NRI = 0.19 (95% CI 0.10 to 0.26). Furthermore, all measurements of ECC were significantly associated with incident hypertension, even after adjustment for CAC (hazard ratios ranging from 1.36 to 1.38). In conclusion, patients with CAC and ECC are at markedly higher risk of incident hypertension and may benefit from more intensified prevention efforts.

Previous studies demonstrated that blacks have less coronary artery calcification (CAC) than whites. We evaluated racial differences in plaque composition and stenosis in the Multicenter AIDS Cohort Study. HIV-positive and HIV-negative men underwent noncontrast cardiac computed tomography (CT) if they were aged 40 to 70 years, weighed136 kg, and had no history of cardiac surgery or revascularization and, if eligible, coronary CT angiography (CTA). There were 1,001 men who underwent CT scans and 759 men CTA. We measured CAC on noncontrast CT and identified total plaque, noncalcified plaque, calcified plaque, mixed plaque, and coronary stenosis50% on CTA. The association of presence and extent of plaque with race was determined after adjustment for HIV serostatus, cardiovascular risk factors, and measures of socioeconomic status. The prevalences of any plaque on CTA and noncalcified plaque were not different between black and white men; however, black men had lower prevalences of CAC (prevalence ratio [PR] 0.79, p = 0.01), calcified plaque (PR 0.69, p = 0.002), and stenosis50% (PR 0.59, p = 0.009). There were no associations between black race and extent of plaque in fully adjusted models. Using log-linear regression, black race was associated with a lower extent of any plaque on CTA in HIV-positive men (estimate = -0.24, p = 0.051) but not in HIV-negative men (0.12, p = 0.50, HIV interaction p = 0.005). In conclusion, a lower prevalence of CAC in black compared with white men appears to reflect less calcification of plaque and stenosis rather than a lower overall prevalence of plaque.

Patients with atrial fibrillation, who are referred for radiofrequency pulmonary vein antral isolation, frequently undergo transesophageal echocardiography (TEE) to detect and/or exclude left atrial or left atrial appendage (LAA) thrombus and cardiac computed tomographic angiography (CCTA) to define and/or evaluate left atrial and pulmonary venous anatomy. Previous studies have reported CCTA to have high sensitivity and negative predictive value (NPV) for detecting thrombus in the LAA. Previous studies determining an optimal LAA/ascending aorta (AA) Hounsfield unit (HU) density ratio for detection of LAA thrombus have been small, with limited numbers of thrombi. We thus sought to determine both the optimal cutoff for LAA HU density and LAA/AA HU density ratio in detecting LAA thrombus compared with TEE in a multicenter population. We included 84 patients who had undergone CCTA and TEE. LAA was evaluated by 64-row CCTA qualitatively (visual filling defect) and quantitatively (measurement of LAA HU density and LAA/AA HU density ratio), using a 1-cm area of interest in the same axial plane. Results were compared with TEE visualization of thrombus or spontaneous echo contrast. Qualitative identification of thrombus in LAA by CCTA compared with TEE detection of thrombus had a sensitivity of 100%, a specificity of 77.9%, a positive predictive value (PPV) of 51.6%, an NPV of 100%, and a total accuracy of 82.1%. The optimal LAA HU density cutoff for thrombus detection was 119 with a sensitivity of 88%, a specificity of 86%, PPV 56%, and an area under the curve of 0.923 (p = 0.0004). The optimal LAA/aorta HU ratio was 0.242 with a sensitivity of 87%, a specificity of 88%, a PPV of 64%, and an area under the curve of 0.921 (p = 0.0011). There is no significant difference (p = 0.72) between both areas under the curve, and both measurements improved the specificity and PPV compared with qualitative measures. Multidetector computed tomography is an imaging technique that can exclude LAA thrombus with very high NPV. Quantitative measurement of LAA HU density (cutoff 119) or LAA/aorta HU density ratio (cutoff 0.242) improves accuracy of positively detecting LAA thrombus. This technique is especially useful when delayed scanning is not performed and LAA is found incidentally after the patient scanning is complete.

Coronary artery calcium (CAC) is a marker of atherosclerosis, and CAC progression is independently associated with all-cause mortality in the general population but not convincingly in subjects with diabetes mellitus (DM). The aim of this study was to ascertain the differences in the rates of CAC progression, the effect of statin therapy, and all-cause mortality in subjects with and without DM. The study group consisted of 296 asymptomatic subjects with type 2 DM and 300 controls (mean age 59 ± 6 years, 29% women) who underwent baseline and follow-up CAC scans within a 2-year interval. Absolute annual CAC score change, percentage annual CAC progression(ΔCAC%), event-free survival, and the effect of statin therapy on survival were all assessed. The mean follow-up duration was 56 ± 11 months. Absolute annual CAC score change was 81 ± 10 in subjects with DM and 34 ± 5 in controls (p = 0.0001). Percentage annual CAC progression was 29 ± 9% in subjects with DM and 10 ± 7% in controls (p = 0.0001). The hazard ratios of death in 3 groups of subjects with DM compared to controls without DM were 1.88 (95% confidence interval [CI] 1.51 to 2.36, p = 0.0001) for ΔCAC of 10% to 20%, 2.29 (95% CI 1.56 to 3.38, p = 0.0001) for ΔCAC of 21% to 30%, and 6.95 (95% CI 2.23 to 11.53, p = 0.0001) for ΔCAC30%, all compared to ΔCAC10%. The adjusted hazard ratios of all-cause mortality in subjects receiving compared to those not receiving statin therapy were 0.29 (95% CI 0.13 to 0.56, p = 0.001) in those without DM and without CAC progression, 0.51 (95% CI 0.21 to 0.73, p = 0.001) in those with DM and without CAC progression, and 0.71 (95% CI 0.25 to 0.91, p = 0.003) in those without DM and with CAC progression, with all 3 groups compared to 1.0 (reference) in those with DM, with CAC progression and without statin therapy. In conclusion, CAC progression was greater and event-free survival lower in patients with DM compared to controls in proportion to the extent of CAC progression. These results suggest that CAC progression is an independent predictor of all-cause mortality in patients with DM.

Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). We examined the cross-sectional association between novel risk factors and coronary artery calcium (CAC) measured using electron beam computed tomography or multidetector computed tomography among 2,018 patients with CKD. Using the total Agatston scores, the participants were classified as having no (0), moderate (>0–100), or high (>100) CAC. After adjustment for age, gender, race, study sites, cigarette smoking, previous cardiovascular disease, hypertension, and diabetes, the use of lipid-lowering drugs, body mass index, waist circumference, and cystatin C, several novel risk factors were significantly associated with high CAC. For example, the odds ratios of high CAC associated with 1 SD greater level of risk factors were 1.20 (95% confidence interval 1.04 to 1.38) for serum calcium, 1.21 (95% confidence interval 1.04 to 1.41) for serum phosphate, 0.83 (95% confidence interval 0.71 to 0.97) for log (total parathyroid hormone), 1.21 (95% confidence interval 1.03 to 1.43) for log (homeostasis model assessment–insulin resistance), and 1.23 (95% confidence interval 1.04 to 1.45) for hemoglobin A1c. Additionally, the multivariate-adjusted odds ratio for 1 SD greater level of cystatin C was 1.31 (95% confidence interval 1.14 to 1.50). Serum high-sensitive C-reactive protein, interleukin-6, tumor necrosis factor-α, and homocysteine were not statistically significantly associated with high CAC. In conclusion, these data indicate that abnormal calcium and phosphate metabolism, insulin resistance, and declining kidney function are associated with the prevalence of high CAC, independent of the traditional risk factors in patients with CKD. Additional studies are warranted to examine the causal effect of these risk factors on CAC in patients with CKD.

Patients with mildly abnormal or equivocal results on myocardial perfusion imaging (MPI) typically undergo diagnostic angiography or receive medical management for coronary artery disease. Catheterization is often required for either appropriate diagnosis or management. With its very high negative predictive rate, coronary computed tomographic angiography (CCTA) has great potential to rule out clinically significant coronary artery disease in this setting. The aim of this study was to analyze the clinical utility and cost implications of CCTA before invasive angiography in patients with abnormal or equivocal results on MPI. Consecutive patients referred by their physicians to our center with abnormal or equivocal results on MPI were reviewed. Patients with histories of myocardial infarction or of revascularization (coronary artery bypass grafting or percutaneous coronary intervention) were excluded. All patients underwent CCTA. Of 241 participants, only 66 (27%) of the studies with abnormal or equivocal nuclear findings revealed obstructive disease on CCTA (50% stenosis). Fifty-five of 241 patients had normal coronary arteries, 97 patients had nonsignificant disease (30%), and 23 patients had mild disease (30% to 50% stenosis) on CCTA, leading to diagnoses of noncardiac chest pain. Selective catheterization (for50% stenosis on CCTA) demonstrated an average cost reduction of $1,295 per patient. Sensitivity analysis revealed cost savings to be preserved even if up to 70% of the patient cohort underwent catheterization after CCTA and across a wide range of procedural costs. In conclusion, CCTA after equivocal or mild or moderate abnormal MPI findings results in significant cost savings and a robust reduction in the need for cardiac catheterization and excludes obstructive coronary artery disease in almost 75% of patients.

Epicardial fat volume (EFV) quantified on noncontrast cardiac computed tomography relates to cardiovascular prognosis. We sought to define the upper normal limit of body surface area (BSA)-indexed EFV (EFVi) in a healthy population and to validate it as a predictor of major adverse cardiovascular events (MACE). We analyzed noncontrast cardiac computed tomography scans of 226 healthy subjects with a low Framingham Risk Score (FRS; ≤6%) performed for coronary calcium scoring (CCS). EFV was quantified using validated software and indexed to BSA. We defined the 95th percentile as the upper normal limit. Subsequently, we reanalyzed a separate cohort of 232 participants from a previously published case-control study with 4-year follow-up and 58 cases of MACE to test the additive value of an abnormally high EFVi for predicting MACE. Of the 226 healthy participants 51% were men (mean age 52 ± 9 years). EFV correlated to BSA (r = 0.373, p0.0001). Median, range, and 25th and 75th percentiles of the non-normally distributed EFVi were 33.3, 10.8 to 96.6, and 24.5 and 45.5 cm(3)/m(2). The 95th percentile definition of the upper normal limit of EFVi was 68.1 cm(3)/m(2). For prediction of MACE, EFVi values higher than the newly defined threshold emerged as a significant and independent predictor after controlling for confounders (odds ratio 2.8, 95% confidence interval 1.3 to 6.4, p = 0.012) and trended in its additive value to the combination of CCS ≥400 and FRS (area under the receiver operating characteristic curve 0.714 vs 0.675, p = 0.1277). In conclusion, in a healthy population we determined 68.1 cm(3)/m(2) as the 95th percentile threshold for abnormally high EFVi. EFVi exceeding this value independently predicted MACE and trended to add to CCS and FRS in this prediction.

Post-traumatic stress disorder (PTSD) is associated with increased risk of multiple medical problems including myocardial infarction. However, a direct link between PTSD and atherosclerotic coronary artery disease (CAD) has not been made. Coronary artery calcium (CAC) score is an excellent method to detect atherosclerosis. This study investigated the association of PTSD to atherosclerotic CAD and mortality. Six hundred thirty-seven veterans without known CAD (61 ± 9 years of age, 12.2% women) underwent CAC scanning for clinical indications and their psychological health status (PTSD vs non-PTSD) was evaluated. In subjects with PTSD, CAC was more prevalent than in the non-PTSD cohort (76.1% vs 59%, p = 0.001) and their CAC scores were significantly higher in each Framingham risk score category compared to the non-PTSD group. Multivariable generalized linear regression analysis identified PTSD as an independent predictor of presence and extent of atherosclerotic CAD (p0.01). During a mean follow-up of 42 months, the death rate was higher in the PTSD compared to the non-PTSD group (15, 17.1%, vs 57, 10.4%, p = 0.003). Multivariable survival regression analyses revealed a significant linkage between PTSD and mortality and between CAC and mortality. After adjustment for risk factors, relative risk (RR) of death was 1.48 (95% confidence interval [CI] 1.03 to 2.91, p = 0.01) in subjects with PTSD and CAC score0 compared to subjects without PTSD and CAC score equal to 0. With a CAC score equal to 0, risk of death was not different between subjects with and without PTSD (RR 1.04, 95% CI 0.67 to 6.82, p = 0.4). Risk of death in each CAC category was higher in subjects with PTSD compared to matched subjects without PTSD (RRs 1.23 for CAC scores 1 to 100, 1.51 for CAC scores 101 to 400, and 1.81 for CAC scores ≥400, p0.05 for all comparisons). In conclusion, PTSD is associated with presence and severity of coronary atherosclerosis and predicts mortality independent of age, gender, and conventional risk factors.

Hypertension has been identified as a risk factor for aortic valve calcium (AVC) but the magnitude of the risk relation with hypertension severity or whether age affects the strength of this risk association has not been studied. The relation of hypertension severity, as defined by Joint National Committee 7 (JNC-7) hypertension stages or blood pressure (BP), to computed tomographically assessed AVC prevalence and severity was examined in 4,274 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) without treated hypertension. Analyses were stratified by age65 or ≥ 65 years, were adjusted for common cardiovascular risk factors, and excluded those on antihypertensive medications. In age-stratified adjusted analyses, stage I/II hypertension was associated with prevalent AVC in those65 but not in those ≥ 65 years of age (odds ratio [OR] 2.31, 95% confidence interval [CI] 1.35 to 3.94, vs 1.33, 0.96 to 1.85, p for interaction = 0.041). Similarly, systolic BP and pulse pressure were more strongly associated with prevalent AVC in those65 than in those ≥ 65 years of age (OR 1.21, 95% CI 1.08 to 1.35, vs 1.07, 1.01 to 1.14, per 10-mm Hg increase in systolic BP, p for interaction = 0.006; and OR 1.41, 95% CI 1.21 to 1.64, vs 1.14, 1.05 to 1.23, per 10-mm Hg increase in pulse pressure). No associations were found between hypertension stage or BP and AVC severity. In conclusion, stage I/II hypertension and higher systolic BP and pulse pressure were associated with prevalent AVC. These risk associations were strongest in participants65 years of age.

Decreased arterial distensibility is an early manifestation of adverse structural and functional changes within the vessel wall. Its correlation with thoracic aortic calcium (TAC), a marker of atherosclerosis, has not been well demonstrated. We tested the hypothesis that decreasing aortic compliance and increasing arterial stiffness would be independently associated with increased TAC. We included 3,540 subjects (61 +/- 10 years, 46% men) from the Multi-ethnic Study of Atherosclerosis who had undergone an aortic distensibility (AD) assessment using magnetic resonance imaging. TAC was calculated using a modified Agatston algorithm on noncontrast cardiac computed tomographic scans. Multivariate regression models were calculated for the presence of TAC. Overall, 861 subjects (24%) had detectable TAC. Lower AD was observed among those with versus without TAC (2.02 +/- 1.34 vs 1.28 +/- 0.74, p0.0001). The prevalence of TAC increased significantly across decreasing quartiles of AD (7%, 17%, 31%, and 42%, p0.0001). Using multivariate analysis, TAC was independently associated with AD after adjusting for age, gender, ethnicity, and other covariates. In conclusion, our analysis has demonstrated that increased arterial stiffness is associated with increased TAC, independent of ethnicity and other atherosclerotic risk factors.

To date, sparse data are available with regard to gender differences in plaque morphology and composition. The aim of the present report was to assess the differences in coronary plaque burden and composition in a noninvasive manner between women and men using multidetector computed tomographic angiography. The study population consisted of 416 patients (61 +/- 13 years), with 148 women (36%). A stenosis ofor=70% in at least one coronary segment was found in 11% of women compared to 25% of men (p0.0001). Overall, women presented with a significantly lower mean number of segments containing calcified plaques (1.43 +/- 2.04 vs 2.25 +/- 2.30, p = 0.004) and mixed plaques (1.67 +/- 1.23 vs 2.25 +/- 2.30, p = 0.05). No such relation was seen with noncalcified plaques (0.72 +/- 1.01 vs 0.86 +/- 1.06, p = 0.21). In addition, the assessment of the overall proportion of the composition of plaque burden revealed relatively more noncalcified (40% vs 28%), less calcified (38% vs 43%), and mixed (23% vs 28%) plaques in women than in men (p0.0001). On multivariate analysis of the total plaque burden, the women had a 19% (95% confidence interval 11% to 28%, p0.0001) greater relative distribution of plaque that was noncalcified compared to the men, and the overall plaque burden was less likely to be calcified (p = 0.006) or mixed (p = 0.019). Similar results were seen in younger and older subjects. In conclusion, gender differences exist, not only in the atherosclerotic disease burden, but also in the underlying plaque composition. Women tended to have more exclusively noncalcified plaque and were less likely to have calcified or mixed plaques compared to men. Future studies are needed to elucidate whether these underlying differences in plaque composition might explain the reduced risk of cardiac events in women.

The aims of this study were to (1) determine the association between ethnicity and thoracic aortic calcium (TAC) and abdominal aortic calcium (AAC) and (2) investigate associations between cardiovascular disease (CVD) risk factors and TAC and AAC. Participants were 1,957 men and women enrolled in the Multi-Ethnic Study of Atherosclerosis who had computed tomographic scans of the chest and abdomen. These scans were obtained at the same clinic visit and calcium scores were computed using the Agatston method. Regression analyses were conducted using relative risk regression. Mean age was 65 years and 50% were women. Forty percent were white, 26% Hispanic, 21% African-American, and 13% Chinese. Whites had the highest prevalence of AAC (80%), which was significantly higher than Hispanics (68%, p

Thoracic aortic calcium (TAC) has been associated with a higher prevalence of coronary arterial calcium (CAC). The purpose of this study was to assess the relations between TAC and incident CAC and CAC progression in a cohort from the Multi-Ethnic Study of Atherosclerosis (MESA). MESA is a prospective cohort study of 6,814 participants free of clinical cardiovascular disease at entry who underwent noncontrast cardiac computed tomographic scanning at baseline examination and at a 2-year follow-up assessment. The independent associations between TAC and incident CAC in those without CAC at baseline and between TAC and CAC progression in those with CAC at baseline were investigated. The final study population consisted of 5,755 subjects (84%; mean age 62 +/- 10 years, 48% men) who had follow-up CAC scores an average of 2.4 years later. Incident CAC was significantly higher in those with TAC compared with those without TAC at baseline (11 per 100 patient-years vs 6 per 100 patient-years). Similarly, TAC was associated with a higher CAC change (p0.0001) in those with some CAC at baseline. In analysis adjusted for demographics and follow-up duration, TAC was associated with incident CAC (relative risk 1.72, p0.0001) as well as with a greater CAC change (first quartile: relative risk 2.89, 95% confidence interval -3.16 to 8.95; fourth quartile: relative risk 24.21, 95% confidence interval 18.25 to 30.18). In conclusion, TAC is associated with the incidence and progression of CAC. The detection of TAC may improve risk stratification efforts. Future clinical outcomes studies are needed to support such an approach.

It has been proposed that coronary artery calcium (CAC) can be used to estimate arterial age in adults. Supporting this concept is that chronologic age, as used in cardiovascular risk assessment, is a surrogate for atherosclerotic burden. This measure can provide patients with a more understandable version of their CAC scores (e.g., "You are 55 years old, but your arteries are more consistent with an arterial age of 65 years"). The aim of this study was to describe a method of calculating arterial age by equating estimated coronary heart disease (CHD) risk for observed age and CAC. Arterial age is then the risk equivalent of CAC. Data from the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort study of 6,814 participants free of clinical cardiovascular disease and followed for an average of 4 years, were used. Estimated arterial age was obtained as a simple linear function of log-transformed CAC. In a model for incident CHD risk controlling for age and arterial age, only arterial age was significant, indicating that observed age does not provide additional information after controlling for arterial age. Framingham risk calculated using this arterial age was more predictive of short-term incident coronary events than Framingham risk on the basis of observed age (area under the receiver-operating characteristic curve 0.75 for Framingham risk on the basis of observed age and 0.79 using arterial age, p = 0.006). In conclusion, arterial age provides a convenient transformation of CAC from Agatston units to a scale more easily appreciated by patients and treating physicians.

Women with coronary heart disease (CHD) have higher mortality compared with men. Atherosclerotic imaging risk markers are associated with higher mortality and relative risk of CHD events in women compared with men. However, data on the predictive accuracy of coronary artery calcium (CAC) in women are scarce. We performed a systematic review of the published literature from 2003 to 2006 on the prognostic value of CAC in women and men. Two investigators reviewed Medline for prospective registries on annual rates of CHD death or myocardial infarction (MI) by CAC results. Three studies in 6,481 women and 13,697 men reported results by gender. We also analyzed 2 observational registries for annual all-cause death rates by CAC scores in women (n = 17,779) and men (n = 17,850). Summary relative risk ratios and 95% confidence intervals were calculated using a random effects model. For all-cause mortality, rates were 0.1% to 1.6% per year for women and 0.1% to 2.6% for men with CAC scores from 0 to 10 toor =1,000, respectively (p0.0001). For CHD death or MI, annual rates were 0.2% to 1.3% in women and 0.3% to 2.4% for men with low- to high-risk CAC scores. For women with a CAC score of 0, annual CHD death or MI rates were 0.16%, similar to that of men (p = 0.55). Summary relative risk ratios increased 4.9-fold (p = 0.006), 5.5-fold (p = 0.002), and 8.7-fold (p0.0001) for mild-, moderate-, and high-risk CAC scores, respectively. A comparative analysis of gender differences showed no significant differences between women and men for mild- to high-risk CAC scores (p = 0.66), suggesting an equivalent ability to risk stratify by gender. In conclusion, this meta- and pooled analysis revealed that CAC screening is equally accurate in stratifying risk in women and men.

The relation between insulin resistance and coronary artery disease (CAD) in patients with HIV infection remains incompletely defined. Fasting serum insulin and glucose measurements from 448 HIV-infected and 306 uninfected men enrolled in the Multicenter AIDS Cohort Study (MACS) were collected at semi-annual visits between 2003 and 2013 and used to compute the homeostatic model assessment of insulin resistance (HOMA-IR). Coronary computed tomographic angiography (CTA) was performed at the end of the study period to characterize coronary pathology. Associations between HOMA-IR (categorized into tertiles and assessed near the time of the CTA and over the 10 year study period) and the prevalence of coronary plaque or stenosis ≥ 50% were assessed with multivariable logistic regression. HOMA-IR was higher in HIV-infected men than HIV-uninfected men when measured near the time of CTA (3.2 vs. 2.7, P = 0.002) and when averaged over the study period (3.4 vs. 3.0, P < 0.001). The prevalence of coronary stenosis ≥ 50% was similar between both groups (17% vs. 15%, P = 0.41). Both measures of HOMA-IR were associated with greater odds of coronary stenosis ≥ 50% in models comparing men with values in the highest versus the lowest tertiles, though the effect of mean HOMA-IR was stronger than the single measurement of HOMA-IR prior to CTA (OR 2.46, 95% CI 1.95–3.11, vs. OR 1.43, 1.20–1.70). This effect was not significantly modified by HIV serostatus. In conclusion, insulin resistance over nearly a decade was greater in HIV-infected men than HIV-uninfected men, and among both groups, was associated with significant coronary artery stenosis.

The ability to observe changes in atherosclerotic plaque burden over time should provide an accurate measure of efficacy for different cardiovascular therapies. Electron-beam computed tomography (EBCT), by quantification of coronary artery calcification, is a noninvasive measure of atherosclerosis burden. This article summarizes data from abstracts and publications related to coronary artery calcium measurement and its use in progression studies. The issues related to interscan variability and reproducibility of this measure are detailed. The limitations of multidetector spiral computed tomography (high radiation dose and poor reproducibility) are also addressed. Several studies of progression using 2 scans, administeredor =1 year apart, demonstrate significant annual progression (22% to 52% per year). All studies demonstrate that therapy with cholesterol-lowering agents slows the atherosclerotic process, and that it may lead to regression of coronary calcium over time. There are 2 small prognostic studies that demonstrate that coronary events predominantly occur in those patients who exhibit significant progression of coronary artery calcium. Large multicenter trials are underway to evaluate the prognostic significance of coronary artery calcium progression. The progression of coronary artery atherosclerosis can be observed noninvasively by monitoring the progression of coronary calcification with EBCT. With annual progression rates of 22% to 52% and a median interscan variability of only 5% to 8%, this technology provides an opportunity to noninvasively monitor patients to assess the clinical efficacy of medical therapies in studies as short as 1 year.

In this study, we sought to determine the rate of progression of atherosclerosis using coronary calcium scores derived from electron beam tomography (EBT). We studied a variety of disease states (hypertension, high cholesterol, tobacco use, diabetes mellitus) followed for 1 to 6.5 years. We evaluated 299 asymptomatic persons (227 men and 72 women) who underwent 2 consecutive EBT scans at least 12 months apart. The average change in the calcium score (Agatston method) for the entire group was 33.2 +/- 9.2%/year. The treated group (receiving statins) demonstrated an average increase in calcium scores of 15 +/- 8%/year compared with 39 +/- 12%/year for untreated patients (p0.001). Among the 60 patients on statin monotherapy, 37% had a decrease in the calcium score from baseline to follow-up scan. The relative increase in calcium scores did not vary significantly by gender or risk factors, with the exception of statin-treated hypercholesterolemic subjects. Scores of zero on the initial scan portend a low likelihood of significant calcific deposits on repeat scanning. Only 2 of 81 participants (2%) with scores of zero at baseline had scores10 on repeat study. In this study, statin therapy induced a 61% reduction in the rate of coronary calcium progression. This study demonstrates that EBT may be a useful tool in assessing efficacy of different interventions to retard progression of atherosclerosis, noninvasively, over relatively short time periods.

Coronary angiography remains the diagnostic standard for establishing the presence, site, and severity of coronary artery disease (CAD). Electron beam computed tomography (EBCT), with its 3-dimensional capabilities, is an emerging technology with the potential for obtaining essentially noninvasive coronary arteriograms. The purpose of this study was to (1) test the accuracy of intravenous coronary arteriography using the EBCT to conventional coronary arteriographic images; (2) establish the inter-reader variability of this procedure; (3) determine the limitations due to location within the coronary tree; and (4) identify factors that contributed to improved image quality of the 3-dimensional EBCT angiograms. Fifty-two patients underwent both EBCT angiography and coronary angiography within 2 weeks. The coronary angiogram and the EBCT 3-dimensional images were analyzed by 2 observers blinded to the results of the other techniques. EBCT correctly identified 43 of 55 significantly stenosed arteries (sensitivity 78%), and correctly identified 118 of 130 of the nonobstructed arteries, yielding a specificity of 91% (p

We recently demonstrated in subjects referred for the evaluation of cardiovascular disease that coronary atherosclerosis and coronary artery calcium (CAC) were reduced in Hispanics compared with non-Hispanic whites (NHWs). We now evaluate whether this ethnic disparity is present in a unselected healthy cohort of men. Despite the apparently worse risk factor profile, mean and median levels of CAC trended lower in Hispanic men, and the distribution of CAC scores differed from that of NHW (p0.05), with fewer Hispanic subjects having CAC scores that are generally equated with extensive atherosclerotic burden (400). These results demonstrate that healthy Hispanic men have reduced CAC compared with age-matched NHW men and this occurs despite evidence for a worse cardiovascular risk profile.

We conducted an observational study relating the occurrence of acute myocardial infarction (MI) to coronary artery calcium progression in 817 asymptomatic subjects referred for sequential electron beam tomographic imaging (average interval 2.2 +/- 1.3 years). A calcium volume score (CVS) was used for plaque quantification. The yearly mean absolute and percent CVS changes in the 45 patients who had a MI were 147 +/- 152 and 47 +/- 50%, respectively, compared with 63 +/- 128 and 26 +/- 32%, respectively (p

Firefighters are known to have an elevated rate of sudden cardiac death compared to the general population. It is unclear whether this finding is related to underlying cardiovascular risk factors or whether firefighting inherently carries additional risk. Our objective was to determine whether Los Angeles county firefighters have higher coronary artery calcium (CAC) scores and increased atherosclerosis as determined using 64-slice cardiac, multidetector computed tomography. A total of 647 asymptomatic firefighters evaluated as a part of a wellness protocol were referred for cardiac multidetector computed tomography to evaluate abnormal exercise treadmill test findings. They were matched by age and cardiovascular risk factors, with 2,533 asymptomatic subjects undergoing cardiac computed tomography because of abnormal electrocardiographic or exercise treadmill test findings. CAC and the prevalence of obstructive coronary artery disease by vessel were derived. Finally, the predictors of CAC were analyzed using regression analysis. Of the firefighters, 49% had detectable CAC compared to 43% of controls (p = 0.015). Although the lesions were most prevalent in the left anterior descending artery in both groups, more firefighters had any left anterior descending artery stenosis compared to the controls (p

The aim of this study was to compare coronary artery plaque burden, composition, distribution, and the degree of coronary artery stenosis in diabetic and nondiabetic patients with known or suspected coronary artery disease (CAD). The study group consisted of 594 patients with known or suspected CAD, including 122 diabetics, who underwent multidetector computed tomographic coronary angiography and traditional invasive coronary artery angiography. Coronary artery calcium scores were compared in different age subgroups. Noncalcified plaque, calcified plaque, and mixed plaque were analyzed by coronary segment on computed tomographic coronary angiography, as well as the degree of coronary stenosis on coronary artery angiography. Obstructive vessels were compared between the 2 groups. Total coronary artery calcium score was higher in patients with diabetes compared to those without (378.4 ± 613.0 vs 226.0 ± 408.4, p = 0.003). The percentage of patients with coronary artery calcium scores >400 among diabetics (22.1%) was higher than among nondiabetics (14.2%) (p = 0.032). Diabetics had a higher percentage of coronary segments with noncalcified plaque, calcified plaque, and mixed plaque than nondiabetics (35.3% vs 26.2%, p

Atherosclerosis is a complex diffuse disorder. The close correlation between coronary artery calcium (CAC) score on computed tomogram and extent and severity of coronary atherosclerosis is well established. It has been suggested that mitral annular calcification (MAC) may be a manifestation of generalized atherosclerosis. The MESA population included a population-based sample of 4 ethnic groups (12% Chinese, 38% white, 22% Hispanic, and 28% black) of 6,814 women and men 45 to 84 years of age. Computed tomographic scans were performed for all participants. The calcium score of each lesion was calculated by multiplying lesion area by a density factor derived from maximal Hounsfield units. A total calcium score was determined by summing individual lesion scores at each anatomic site. Relative risk regression was used to model the probability of MAC as a function of CAC0 and CAC categories (0, 1 to 99, 100 to 399, and ≥400) with the referent group being CAC 0. The final study population consisted of 6,814 subjects (mean age 62 ± 10 years, 47% men). Overall 9% and 50% had detectable MAC and CAC, respectively. Of those with absent CAC, only 4% had MAC, whereas 9%, 19%, and 15% had MAC scores with increasing CAC scores of 1 to 99, 100 to 399, and ≥400, respectively (p0.0001 for trend). After taking into account demographics and other risk factors, the prevalence ratio of MAC in those with mild CAC (1 to 99) was 2.13 (95% confidence interval 1.69 to 2.69) and increased to 7.57 (95% confidence interval 5.95 to 9.62) for CAC ≥400. Similar statistically significant increased risk of MAC was found when CAC was assessed as a continuous variable. In conclusion, we observed a strong association between MAC and increasing burden of CAC. This association weakened but persisted after adjustment for age, gender, and other traditional cardiovascular risk factors. These findings suggest that presence of MAC is an indicator of atherosclerotic burden rather than just a degenerative change of the mitral valve.

A risk-management approach based on the Framingham risk score (FRS), although useful in preventing future coronary artery disease (CAD) events, is unable to identify a considerable portion of patients with CAD who need aggressive medical management. Coronary artery calcium (CAC), an anatomic marker of atherosclerosis, correlates well with presence and extent of CAD. This study investigated mortality risk associated with CAC score and FRS in subjects classified as "low risk" versus "high risk" based on FRS. In total 730 veterans without known CAD (61 ± 10 years old, 12.8% women) underwent measurement of their FRS and CAC. Subjects were classified as "discordant low risk" (DLR) if their FRS was10% and CAC score was ≥ 100 (n = 108, 14.8%) or "discordant high risk" (DHR) if their FRS was ≥ 20% and CAC score was 0 (n = 104, 14.2%). Survival analysis was used to compare mortality rates associated with FRS and CAC in DLR versus DHR subjects. Mortality rate during the mean 48-month follow-up was 7.3% (n = 53) including 18.5% (n = 20) in the DLR group and 7.7% (n = 8) in the DHR group, respectively. Adjusted relative risks of mortality were 5.46 (95% confidence interval [CI] 2.44 to 12.20, p = 0.0001) in subjects with CAC score ≥ 100 compared to CAC score 0 and 1.35 (95% CI 1.01 to 4.32, p = 0.04) in subjects with FRS ≥ 20% compared to FRS10%. Adjusted relative risk of mortality was 3.6 (95% CI 1.57 to 8.34, p = 0.003) for DLR compared to DHR. Areas under the receiver operator curve to predict mortality were 0.72 for FRS, 0.82 for CAC score, and 0.92 for the combination. In conclusion, the prognostic value of CAC to predict future mortality is superior to the FRS. Addition of CAC score to FRS significantly improves the identification and prognostication of patients without known CAD.

It was previously reported that event-free survival rates of symptomatic patients with coronary artery disease (CAD) diagnosed by computed tomographic angiography decreased incrementally from normal coronary arteries to obstructive CAD. The aim of this study was to investigate the clinical outcomes of symptomatic patients with nonobstructive CAD with luminal stenoses of 1% to 49% on the basis of coronary plaque morphology in an outpatient setting. Among 3,499 consecutive symptomatic subjects who underwent computed tomographic angiography, 1,102 subjects with nonobstructive CAD (mean age 59 ± 14 years, 69.9% men) were prospectively followed for a mean of 78 ± 12 months. Coronary plaques were defined as noncalcified, mixed, and calcified per patient. Multivariate Cox proportional-hazards models were developed to predict all-cause mortality. The death rate of patients with nonobstructive CAD was 3.1% (34 deaths). The death rate increased incrementally from calcified plaque (1.4%) to mixed plaque (3.3%) to noncalcified plaque (9.6%), as well as from single- to triple-vessel disease (p0.001). In subjects with mixed or calcified plaques, the death rate increased with the severity of coronary artery calcium from 1 to 9 to ≥ 400. The risk-adjusted hazard ratios of all-cause mortality in patients with nonobstructive CAD were 3.2 (95% confidence interval 1.3 to 8.0, p = 0.001) for mixed plaques and 7.4 (95% confidence interval 2.7 to 20.1, p = 0.0001) for noncalcified plaques compared with calcified plaques. The areas under the receiver-operating characteristic curve to predict all-cause mortality were 0.75 for mixed and 0.86 for noncalcified coronary lesions. In conclusion, this study demonstrates that the presence of noncalcified and mixed coronary plaques provided incremental value in predicting all-cause mortality in symptomatic subjects with nonobstructive CAD independent of age, gender, and conventional risk factors.

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.

We studied 6,141 consecutive, asymptomatic, nondiabetic patients who underwent electron beam tomography and explored the interaction between metabolic risk factors (RFs) and premature family history (FH) of coronary heart disease (CHD) in predicting the presence and severity of coronary arterial calcium (CAC). In the presence of >2 metabolic RFs, patients with a positive FH of premature CHD had a significantly higher prevalence of any CAC, CAC ≥100, and CAC ≥75th age-gender percentile than those without a FH of CHD. Our study demonstrated that a familial propensity to subclinical atherosclerosis interacts with the presence of ≥2 metabolic RFs, magnifying the risks for those exposed to both.

Lack of physical activity (PA) increases risk of coronary heart disease. Metabolic risk factors increase the risk of coronary heart disease and development of advanced coronary artery calcium (CAC). We hypothesized that, in a population with multiple metabolic risk factors (or =2), the degree of PA would be inversely associated with the degree and prevalence of CAC. After excluding subjects who had known diabetes and coronary heart disease, we studied 779 asymptomatic patients referred for electron beam tomography. All patients hador =2 of the following metabolic risk factors: blood pressure130/85 mm Hg, serum triglycerides150 mg/dl, serum high-density lipoprotein40 and50 mg/dl in men and women, respectively, and body mass index30 kg/m(2). Advanced CAC was defined as a calcium score75th percentile based on gender and age. In the study, 37% patients were sedentary, 26% engaged in moderate-duration (30 minutes 1 to 2 times/week) PA, and 37% engaged in long-duration (or =30 minutesor =3 times/week) PA. The median CAC scores were 24 (sedentary), 18 (moderate PA), and 11 (long-duration PA; p0.002). Advanced CAC was prevalent in 26% of sedentary patients, 24% of patients who performed moderate PA, and 16% of patients who engaged in long-duration PA (p0.05). On logistic regression analysis, long-duration PA had an independent inverse association with advanced CAC. Thus, asymptomatic patients who haveor =2 metabolic risk factors and who regularly engage in long-duration PA have a lower prevalence of CAC than do those who are sedentary or participate in moderate-duration PA.

We developed age- and gender-specific normative tables of calcium volume scores by using data from 12,936 asymptomatic patients who underwent electron beam tomographic scanning and compared the volume with the Agatston scores obtained in the same subjects. The 2 scores increased as the number of atherosclerotic risk factors increased. The volume scores were statistically smaller than the Agatston scores at the upper quartile level.

Electron beam tomography (EBT) can accurately and noninvasively quantitate the amount of coronary artery calcium (CAC), thus, providing an index of atherosclerotic burden. We sought to evaluate whether ethnic differences exist in the prevalence and severity of coronary calcium in asymptomatic, highrisk patients.  We evaluated 1,426 minority participants (828 men, 598 women) who underwent EBT scanning. These patients were were age- and gender-matched 3:1 with Caucasians (2,484 men, 1,794 women). We utilized the mean age of the minority participants and percentages of men and women to match to our physician-referred Caucasian population. All participants (minorities and matched Caucasians) were asymptomatic and referred by their primary physician to evaluate the presence and amount of CAC. Physicians referred patients to assess their cardiovascular risk. Data on risk factors for coronary artery disease (CAD) were collected at interview before the EBT procedure. The presence and number of risk factors for a participant were calculated based on the National Cholesterol Education Program guidelines. 1 Risk factors included: men aged 45 years, women aged 55 years, current cigarette smokers, history of premature coronary disease in a first-degree relative (men 55 years, women 65 years), diabetes, hypertension, and hypercholesterolemia. Cigarette smoking was defined as smoking 10 cigarettes/day. Participants currently using insulin or oral hypoglycemic agents, or those with dietcontrolled diabetes were classified as diabetic. Systemic hypertension was defined by current use of antihypertensive medication or known and untreated hypertension; hypercholesterolemia was similarly defined by use of cholesterol-lowering medication or known but untreated serum total cholesterol 240 mg/dl. Participants were excluded from the study if they had documented CAD before entry into the study. The study protocol was approved by the institutional review board of the Harbor-UCLA Research and Education Institute. One thousand four hundred twenty-six minority and 4,278 Caucasian subjects at Harbor-UCLA Medical Center underwent EBT using an Imatron C-150XL Ultrafast computed tomographic scanner (Imatron, Inc., South San Francisco, California). Coronary artery visualization was obtained without contrast medium injection, and 30 consecutive images were obtained at 3-mm intervals beginning 1 cm below the carina and progressing caudally to include the entire coronary tree. Exposure time was 100 ms/image slice, and total skin irradiation dose was 600 mrads/ scan. Electrocardiographic triggering was used and adjusted such that image acquisition occurred at the same point in the cardiac cycle starting in late systole.2,3 A computed tomographic threshold of 2 pixels and 130 Hounsfield units was utilized for identification of a calcific lesion. Each focus exceeding the minimum criteria was scored using the algorithm developed by Agatston et al, 4 calculated by multiplying the lesion area by a density factor derived from the maximal Hounsfield unit within this area. A total coronary calcium score was determined by summing individual lesion scores from each of 4 anatomic sites (left main, left anterior descending, circumflex, and right coronary arteries). EBT scoring was performed by a cardiologist who was blinded to the clinical, electrocardiographic, and angiographic information. Categorical data are presented as number (percentages), and continuous data as mean value SD.

This blinded, single center study prospectively compares exercise electron beam computed tomography (EBCT) with stress technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) in 33 patients undergoing coronary angiography for evaluation of chest pain. Patients undergoing routine cardiac catheterization for the diagnosis of chest pain were imaged at rest using EBCT. Patients exercised on a semi-supine ergometer, and exercise EBCT was immediately followed by injection of Tc-99m sestamibi for assessment of myocardial ischemia. At peak exercise, Tc-99m SPECT, followed immediately by nonionic contrast material, was injected intravenously to directly compare these 2 imaging techniques. Patients were reimaged with Tc-99m SPECT at rest 24 to 48 hours after stress. Exercise EBCT, which was analyzed using a global ejection fraction measure, had a sensitivity of 81% and a specificity of 76%, compared with angiography. Using the development of a new regional wall motion abnormality as evidence of obstructive coronary artery disease (CAD), EBCT yielded a specificity of 100% and a sensitivity of 88%. Reversible perfusion defects identified by SPECT, as evidence of obstructive CAD, revealed a sensitivity of 75% and a specificity of 71%. The specificity of regional wall motion analysis by EBCT was significantly better than SPECT (p

Coronary arteriography was performed on 18 asymptomatic, apparently healthy adults with elevated coronary calcium scores. To extend the range of observation to subjects with low calcium scores, arteriograms from 18 patients with exertional dyspnea and/or valvular heart disease and low calcium scores were also analyzed; these 18 patients were considered asymptomatic from the point of view of coronary artery disease (CAD). For the comparison of symptomatic and asymptomatic persons, 3 age and sex-matched symptomatic patients were also selected for each of the original 18 asymptomatic subjects. Arteriograms were analyzed by computer-assisted quantitative coronary arteriography at a remote site without knowledge of the calcium score or any other patient characteristics. In the 18 asymptomatic subjects with elevated calcium scores, the mean calcium score was 573 +/- 504 (Agatston method) and the mean worst stenosis was 45% +/- 16%. For all 36 patients without symptoms of CAD, worst stenosis was closely correlated with the square root of the calcium score (r = 0.85, p0.0001). Patients with symptomatic coronary disease and calcium scores1,000 had stenoses more severe than asymptomatic persons with similar calcium scores. Most asymptomatic adults with elevated calcium scores have nontrivial, nonobstructive CAD or preclinical obstructive CAD, and the relation between coronary calcium score and severity of stenosis is highly significant. These data indicate that electron beam tomography can be used to estimate the severity of CAD in asymptomatic persons.