Vahid Nabavi

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.

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.

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.

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.

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= 30%), moderate (stenosis 31%-69%), and severe (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.

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.

Aged Garlic Extract with Supplement is Associated with Beneficial Effect on Bone Mineral Density and Predicts Lack of Progression of Atherosclerosis: A Prospective Double Blinded Randomized Trial

Aged Garlic Extract with Supplement is Associated with Beneficial Effect on Bone Mineral Density and Predicts Lack of Progression of Atherosclerosis: A Prospective Double Blinded Randomized Trial Low levels of bone-mineral-density (BMD) are independently associated with the presence and severity of coronary-arterycalcium (CAC). This study evaluates the beneficial-effects of aged-garlic-extract therapy with-supplements (AGE-S) on levels of BMD, vascular-function, inflammation and CAC. Sixty subjects, randomized to four daily capsules of placebo vs. AGE-S inclusive of aged garlic extract (1000 mg) plus VitaminB12 (400 mcg or µg), folic-acid (1200 mcg or µg), Vitamin-B6 (50 mg) and L-arginine (400 mg) underwent CAC, thoracicBMD (mg/cc), lipid-profile, lipoprotein a (Lp-a), homocysteine and vascular-function measurement at baseline and 12- months. The postcuff-deflation temperature-rebound (TR), digital-thermal-monitoring index of vascular-function was assessed using a reactive-hyperemia-procedure. At 1-year, the mean increase in CAC and decrease in BMD was significantly lower in the AGE-S as compared to the placebo (p<0.05). After adjustment for risk-factors, the risk of CAC progression and reduced BMD was 65% and 68% less in AGE-S as compared to placebo (P<0.05). From baseline to 12 months, a significant correlation was noted between increase in CAC and decreases in BMD. Similarly, a significant correlation was noted between increase in TR and decrease in homocysteine as well as increase in Lp-a with lack of decrease in BMD. The maximum beneficial effect of AGE-S was noted with increase in TR, lack of decrease in BMD and lack of progression of CAC. In conclusion, this study demonstrates AGE-S is independently associated with favorable effect on A strong direct relation between increases in vascular-function, decrease in inflammation with lack of lowering in BMD levels as well as lack of CAC-progression in response to AGE-S was noted.

Statin Therapy is Associated with Reduction of Epicardial Adipose Tissues and Coronary Plaque Volumes with Vulnerable Composition, Measured by Computed Tomography Angiography

Statin Therapy is Associated with Reduction of Epicardial Adipose Tissues and Coronary Plaque Volumes with Vulnerable Composition, Measured by Computed Tomography Angiography Background: Increased coronary plaque volume and epicardialadipose-tissue (EAT) are independently predicting major-adversecardiovascular-events. This study evaluates the changes in EAT, total and composition-specific plaque-volume measured noninvasively by computed-tomography-angiography (CTA) in subjects with and without statin-therapy. Methods: This is a study of 106 consecutive-subjects (age 67 ± 9years, 80.7% men) who underwent serial clinically-indicated CTAs with median-interval of 1.2-year. Clinical and demographicfindings of 31 with statin-therapy and 75 without statin-therapy were evaluated. Changes in indexed total and composition-specific plaque-volume of target-segment with luminal-stenosis 0.05). At follow-up, there were significant absolute-decrease in total plaque-volume (-38.2%) and EAT (-18.4%) in individuals with statin-therapy as compared to those without statin-therapy (p=0.0001). Similarly, significant decrease in non-calcified and mixed plaque-volume as well as lack of progression of calcified plaque-volume in statin-therapy group was noted (p<0.05). Risk adjusted median-decrease in total, mixed, calcified, non-calcified plaque-volumes, and EAT were 56%, 12%, 43%,144% and 76% more in statin-therapy as compared to those with diet-therapy (p<0.05). Furthermore, a significant directcorrelation between decrease in LDL-C and reduction in noncalcified plaque-volume (r2=0.64,p=0.0001) and decrease in EAT and non-calcified plaque-volume was noted (r2=0.69,p=0.0001). Conclusions: Statin therapy is associated with concomitant decreases in LDL-C, EAT and coronary plaque volumes especially non-calcified and mixed coronary plaques, which the latter suggesting plaque stabilization. This highlights that CTA can accurately and quantitatively measure the changes in EAT and coronary plaque volumes over time and monitor response to therapies.

THE BENEFICIAL EFFECTS OF STATIN THERAPY ON EPICARDIAL ADIPOSE TISSUE AND CORONARY PLAQUE VOLUMES WITH VULNERABLE CHARACTERISTICS MEASURED BY COMPUTED TOMOGRAPHY ANGIOGRAPHY

Increased epicardial adipose tissue(EAT) and progression of noncalcified plaque volumes(NCPV)are directly associated with coronary artery disease and independently predict cardiovascular mortality. This study evaluates the relation of change in EAT and NCPV measured by computed tomography