Increased epicardial adipose tissue is associated with coronary artery disease and major adverse cardiovascular events.

BACKGROUND: Increased-epicardial-adipose tissue (EAT) is associated with the presence and severity of subclinical-atherosclerosis. This study investigates the long-term clinical-outcome of subjects with and without increased-EAT. METHODS: Two hundred and forty-five subjects, aged 61 ± 9 years and 34% women underwent clinically-indicated computed-tomography-angiography (CTA), and body-surface-area adjusted EAT was measured and were followed prospectively. CTA-diagnosed coronary-artery-disease (CAD) was defined as obstructive (luminal-stenosis ≥ 50%), non-obstructive (luminal-stenosis: 1-49%) and zero-obstruction. Major-adverse-cardiac-event (MACE) was defined as myocardial-infarction or cardiovascular-death. RESULTS: EAT increased significantly from subjects with zero-obstruction-coronaries (93 ± 37 cm(3)/m(2)) to non-obstructive-CAD (132 ± 25 cm(3)/m(2)) to obstructive-CAD (145 ± 35 cm(3)/m(2)) (P = 0.01). During the 48-month follow-up, the event-rate was 8.6% (21). The event free survival-rate decreased significantly from 99% in the lowest-quartile to 86.6% in the highest-quartile of EAT. After adjustment for risk-factors, the hazard ratio of MACE was 1.4, 3.1 and 5.7 in lower mid-, upper mid- and highest-quartiles of EAT as compared to lowest-quartile of EAT (P < 0.05). CONCLUSION: Increased EAT is directly associated with CAD and predicts MACE independent of the age, gender and conventional-risk-factors.

Aged garlic extract with supplement is associated with increase in brown adipose, decrease in white adipose tissue and predict lack of progression in coronary atherosclerosis.

BACKGROUND: Aged garlic extract with supplement (AGE-S) significantly reduces coronary artery calcium (CAC). We evaluated the effects of AGE-S on change in white (wEAT) and brown (bEAT) epicardial adipose tissue, homocysteine and CAC. METHODS: Sixty subjects, randomized to a daily capsule of placebo vs. AGE-S inclusive of aged garlic-extract (250 mg) plus vitamin-B12 (100 µg), folic-acid (300 µg), vitamin-B6 (12.5mg) and L-arginine (100mg) underwent CAC, wEAT and bEAT measurements at baseline and 12 months. The postcuff deflation temperature-rebound index of vascular function was assessed using a reactive-hyperemia procedure. Vascular dysfunction was defined according to the tertiles of temperature-rebound at 1 year of follow-up. CAC progression was defined as an annual-increase in CAC>15%. RESULTS: From baseline to 12 months, there was a strong correlation between increase in wEAT and CAC (r(2)=0.54, p=0.0001). At 1 year, the risks of CAC progression and increased wEAT and homocysteine were significantly lower in AGE-S to placebo (p<0.05). Similarly, bEAT and temperature-rebound were significantly higher in AGE-S as compared to placebo (p<0.05). Strong association between increase in temperature-rebound and bEAT/wEAT ratio (r(2)=0.80, p=0.001) was noted, which was more robust in AGE-S. Maximum beneficial effect of AGE-S was noted with increase in bEAT/wEAT ratio, temperature-rebound, and lack of progression of homocysteine and CAC. CONCLUSIONS: AGE-S is associated with increase in bEAT/wEAT ratio, reduction of homocysteine and lack of progression of CAC. Increases in bEAT/wEAT ratio correlated strongly with increases in vascular function measured by temperature-rebound and predicted a lack of CAC progression and plaque stabilization in response to AGE-S.

Increased carotid wall thickness measured by computed tomography is associated with the presence and severity of coronary artery calcium.

BACKGROUND: Previous studies have shown that increase in carotid wall thickness (CWT) is associated with cardiovascular risk factors. However, simultaneous systemic and local involvement of atherosclerosis in subjects with high risk of coronary atherosclerosis is not well studied. This study investigates the relation of carotid subclinical atherosclerosis assessed by CWT with the presence and severity of coronary artery calcium(CAC). METHODS: One hundred and twenty nine subjects (age of 69±10 years, 72% male) underwent CAC, carotid CT angiography, and their metabolic status was evaluated. CAC was defined as 0, 1-100, 101-400, 401-1000 and 1000+. CWT (mm) was calculated as: [mean of both right and left CT-measured CWT 10-mm below the common carotid bifurcation]. RESULTS: Modest correlation between CWT and CAC was noted (r=0.48, p=0.0001). CWT increased substantially with the severity of CAC from CAC 0 to CAC 1000+ (p<0.05). Increased CWT (1.0 mm+) was more prevalent in subjects with significant CAC (100+) as compared to CAC 0 (44.7% vs. 3.3%, p<0.05). Increase in CWT was associated with increased rates of metabolic syndrome and diabetes mellitus. After adjustment for cardiovascular risk factors, the risk of metabolic syndrome and DM was 1.7 and 2.3 respectively for each standard deviation (SD) increase in CWT. Similarly, the risk for each SD increase in CWT increased with severity of CAC as compared to CAC 0 (RR:CAC 1-100:1.2, CAC 101-400:1.5, CAC 400-1000:2.1, and CAC 1000+:3.4, respectively). CONCLUSION: Increased CWT is associated with the presence and severity of CAC, metabolic syndrome and DM independent of conventional cardiovascular risk factors; highlighting the important role of comprehensive carotid and coronary atherosclerotic assessment to identify at-risk individuals.

Mortality incidence of patients with non-obstructive coronary artery disease diagnosed by computed tomography angiography.

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 (p <0.001). 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.

Impaired aortic distensibility measured by computed tomography is associated with the severity of coronary artery disease.

Impaired aortic distensibility index (ADI) is associated with cardiovascular risk factors. This study evaluates the relation of ADI measured by computed tomographic angiography (CTA) with the severity of coronary atherosclerosis in subjects with suspected coronary artery disease (CAD). Two hundred and twenty-nine subjects,age 63 ± 9 years, 42% female, underwent coronary artery calcium (CAC) scanning and CTA, and their ADI and Framingham risk score (FRS) were measured. End-systolic and end-diastolic (ED) cross-sectional-area(CSA) of ascending-aorta (AAo) was measured 15-mm above the left-main coronary ostium. ADI was defined as: [(Δlumen-CSA)/(lumen-CSA in ED × systemic-pulse-pressure) × 10(3)]. ADI measured by 2D-trans-thoracic echocardiography (TTE) was compared with CTA-measured ADI in 26 subjects without CAC. CAC was defined as 0, 1-100, 101-400 and 400+. CAD was defined as luminal stenosis 0, 1-49% and 50%+. There was an excellent correlation between CTA- and TTE-measured ADI (r(2)=0.94, P=0.0001). ADI decreased from CAC 0 to CAC 400+; similarly from FRS 1-9% to FRS 20% + (P<0.05). After adjustment for risk factors, the relative risk for each standard deviation decrease in ADI was 1.66 for CAC 1-100, 2.26 for CAC 101-400 and 2.32 for CAC 400+ as compared to CAC 0; similarly, 2.36 for non-obstructive CAD and 2.67 for obstructive CAD as compared to normal coronaries. The area under the ROC-curve to predict significant CAD was 0.68 for FRS, 0.75 for ADI, 0.81 for CAC and 0.86 for the combination (P<0.05). Impaired aortic distensibility strongly correlates with the severity of coronary atherosclerosis. Addition of ADI to CAC and traditional risk factors provides incremental value to predict at-risk individuals.

Progression of coronary artery calcium predicts all-cause mortality.

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.

Increased epicardial, pericardial, and subcutaneous adipose tissue is associated with the presence and severity of coronary artery calcium.

RATIONALE AND OBJECTIVES: Epicardial adipose tissue (EAT), pericardial adipose tissue (PAT), and subcutaneous adipose tissue (SAT) are mediators of metabolic risk and may be involved in the pathogenesis of coronary artery disease. The aim of this study was to investigate the association of visceral and subcutaneous fat depots with the presence and severity of coronary artery calcium (CAC) in asymptomatic individuals. MATERIALS AND METHODS: One hundred eleven consecutive subjects underwent CAC assessment, and their Framingham risk scores were measured. EAT, total thoracic adipose tissue, and SAT volumes were measured from slice level 15 mm above to 30 mm below the ostium of the left main coronary artery. PAT was calculated as thoracic adipose tissue - EAT. SAT was defined as the volume of fat depot anterior to the sternum and posterior to the vertebra. CAC was defined as 0, 1 to 100, 101 to 400, or ≥ 400. Relative risk regression analysis was used to assess the association between fat depots and CAC. RESULTS: There were modest correlations between EAT (r = 0.58), PAT (r = 0.47), SAT (r = 0.34), and CAC (P < .01). EAT, PAT, and SAT increased proportionally with the severity of CAC in both genders (P < .05). After adjustment for cardiovascular risk factors and body mass index, the relative risks for each standard deviation increase in EAT, PAT, and SAT were 3.3 (95% confidence interval, 1.9-5.6), 2.7 (95% confidence interval, 1.6-3.9), and 2.6 (95% confidence interval, 1.5-4.4) for CAC ≥ 100 compared to CAC 0, respectively (P < .05). The area under the receiver-operating characteristic curve to predict CAC ≥ 100 was higher in each fat depot compared to Framingham risk score, and addition of fat depots to Framingham risk score provided maximum prognostication value to detect CAC ≥ 100. CONCLUSIONS: Increased EAT, PAT, and SAT are associated with the severity of CAC independent of risk factors.

Coronary distensibility index measured by computed tomography is associated with the severity of coronary artery disease.

BACKGROUND: Atherosclerotic changes within the coronary artery wall can affect vessel distensibility. OBJECTIVE: This study evaluated the relationship between the coronary distensibility index (CDI) and the severity of coronary artery disease (CAD) measured by computed tomographic angiography (CTA). METHODS: One hundred thirteen subjects, age 63 +/- 10 years, 32% women, who underwent coronary artery calcium (CAC) scanning and CTA, were studied. Early diastolic and mid diastolic (MD) cross-section area (CSA) of the left anterior descending (LAD) artery were measured 5 mm distal to the left main bifurcation. CDI was defined as Deltalumen CSA/[lumen CSA in MD x estimated central pulse pressure (eCPP)] x 10(3) {eCPP = 0.77 x peripheral pulse pressure}. LAD diameter measured by CTA and quantitative coronary angiography (QCA) was compared in 19 subjects without CAD. CAD was defined as normal (no stenosis and CAC 0), mild (stenosis or= 70%) on CTA. RESULTS: Excellent correlation was observed between CTA and QCA measured by CDI (r(2) = 0.96, P = 0.0001). CDI decreased from normal coronaries (6.75 +/- 1.43) to arteries with mild (5.78 +/- 1.45), moderate (3.96 +/- 1.06), and severe (3.31 +/- 1.06) disease (P = 0.004). The risk factor adjusted odds ratio of lowest versus 2 upper tertiles of CDI was 1.28 for mild, 8.47 for moderate, and 10.59 for severe CAD compared with the normal cohort. The area under the ROC curve to predict obstructive CAD (stenosis >or= 50%) increased significantly from 0.71 to 0.84 by addition of CDI to CAC (P < 0.05). CONCLUSION: CTA-measured CDI is inversely related to the severity of CAD independent of age, sex, cardiovascular risk factors, and CAC.

Relation of oxidative biomarkers, vascular dysfunction, and progression of coronary artery calcium.

The relation between oxidative stress and coronary artery calcium (CAC) progression is currently not well described. The present study evaluated the relation among the biomarkers of oxidative stress, vascular dysfunction, and CAC. Sixty asymptomatic subjects participated in a randomized trial evaluating the effect of aged garlic extract plus supplement versus placebo and underwent measurement of CAC. The postcuff deflation temperature-rebound index of vascular function was assessed using a reactive hyperemia procedure. The content of oxidized phospholipids (OxPL) on apolipoprotein B-100 (apoB) particles detected by antibody E06 (OxPL/apoB), lipoprotein(a), IgG and IgM autoantibodies to malondialdehyde-low-density lipoprotein and apoB-immune complexes were measured at baseline and after 12 months of treatment. CAC progression was defined as an annual increase in CAC >15%. Vascular dysfunction was defined according to the tertiles of temperature-rebound at 1 year of follow-up. From baseline to 12 months, a strong inverse correlation was noted between an increase in CAC scores and increases in temperature-rebound (r(2) = -0.90), OxPL/apoB (r(2) = -0.85), and lipoprotein(a) (r(2) = -0.81) levels (p <0.0001 for all). The improvement in temperature-rebound correlated positively with the increases in OxPL/apoB (r(2) = 0.81, p = 0.0008) and lipoprotein(a) (r(2) = 0.79, p = 0.0001) but inversely with autoantibodies to malondialdehyde-low-density lipoprotein and apoB-immune complexes. The greatest CAC progression was noted with the lowest tertiles of increases in temperature-rebound, OxPL/apoB and lipoprotein(a) and the highest tertiles of increases in IgG and IgM malondialdehyde-low-density lipoprotein. In conclusion, the present results have documented a strong relation among markers of oxidative stress, vascular dysfunction, and progression of coronary atherosclerosis. Increases in OxPL/apoB and lipoprotein(a) correlated strongly with increases in vascular function and predicted a lack of progression of CAC.

Low fingertip temperature rebound measured by digital thermal monitoring strongly correlates with the presence and extent of coronary artery disease diagnosed by 64-slice multi-detector computed tomography.

Previous studies showed strong correlations between low fingertip temperature rebound measured by digital thermal monitoring (DTM) during a 5 min arm-cuff induced reactive hyperemia and both the Framingham Risk Score (FRS), and coronary artery calcification (CAC) in asymptomatic populations. This study evaluates the correlation between DTM and coronary artery disease (CAD) measured by CT angiography (CTA) in symptomatic patients. It also investigates the correlation between CTA and a new index of neurovascular reactivity measured by DTM. 129 patients, age 63 +/- 9 years, 68% male, underwent DTM, CAC and CTA. Adjusted DTM indices in the occluded arm were calculated: temperature rebound: aTR and area under the temperature curve aTMP-AUC. DTM neurovascular reactivity (NVR) index was measured based on increased fingertip temperature in the non-occluded arm. Obstructive CAD was defined as >or=50% luminal stenosis, and normal as no stenosis and CAC = 0. Baseline fingertip temperature was not different across the groups. However, all DTM indices of vascular and neurovascular reactivity significantly decreased from normal to non-obstructive to obstructive CAD [(aTR 1.77 +/- 1.18 to 1.24 +/- 1.14 to 0.94 +/- 0.92) (P = 0.009), (aTMP-AUC: 355.6 +/- 242.4 to 277.4 +/- 182.4 to 184.4 +/- 171.2) (P = 0.001), (NVR: 161.5 +/- 147.4 to 77.6 +/- 88.2 to 48.8 +/- 63.8) (P = 0.015)]. After adjusting for risk factors, the odds ratio for obstructive CAD compared to normal in the lowest versus two upper tertiles of FRS, aTR, aTMP-AUC, and NVR were 2.41 (1.02-5.93), P = 0.05, 8.67 (2.6-9.4), P = 0.001, 11.62 (5.1-28.7), P = 0.001, and 3.58 (1.09-11.69), P = 0.01, respectively. DTM indices and FRS combined resulted in a ROC curve area of 0.88 for the prediction of obstructive CAD. In patients suspected of CAD, low fingertip temperature rebound measured by DTM significantly predicted CTA-diagnosed obstructive disease.