Irfan Zeb

Effect of statin treatment on coronary plaque progression - a serial coronary CT angiography study.

OBJECTIVES Statins have been shown to reduce plaque progression using data on intravascular ultrasound, carotid intima-media thickness and coronary artery calcium scans. However, there is little data on effects of statins on plaque progression using Coronary CTA. The objective is to evaluate the effect of statin therapy on plaque progression using serial Coronary CTA (CCTA). METHODS The study included 100 consecutive patients who underwent serial Coronary CTA (mean follow up: 406 ± 92 days) for evaluation of CAD without known prior heart disease or revascularization. We performed volumetric assessment of low attenuation plaque (LAP < 30 Hounsfield units), non-calcified (NCP) and calcified plaque volumes at baseline and follow up scans for vessels >2 mm in diameter. Patients who received statins were compared to those that did not. RESULTS Total plaque progression was significantly reduced among statin user compared to non-statin users (-33.3 mm(3) ± 90.5 vs. 31.0 mm(3) ± 84.5, p = 0.0006). Statin users had significantly reduced progression of NCP volume (-47.7 mm(3) ± 71.9 vs. 13.8 mm(3) ± 76.6, p < 0.001) and significantly reduced progression of LAP volume (-12.2 mm(3) ± 19.2 vs. 5.9 mm(3) ± 23.1, p < 0.0001). When we compared for remodeling index, no statistical difference was found between the two groups (p = 0.25) and a non-significant trend toward calcium progression (29.3 mm(3) ± 67.9 vs. 10.0 mm(3) ± 53.2, p = 0.133). After adjustment for cardiovascular risk factors, mean plaque volume difference between statin and non-statin users was statistically significant for both LAP and NCP volumes (-18.1, 95% CI: -26.4, -9.8 for LAP; -101.7, 95% CI: -162.1, -41.4 for NCP; p < 0.001) respectively. CONCLUSION Statin therapy resulted in significantly lower progression of LAP and NCP plaques compared to non-statin users.

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.

Computed Tomography Scans in the Evaluation of Fatty Liver Disease in a Population Based Study: The Multi-Ethnic Study of Atherosclerosis

RATIONALE AND OBJECTIVES Fatty liver disease is a common clinical entity in hepatology practice. This study evaluates the prevalence and reproducibility of computed tomography (CT) measures for diagnosis of fatty liver and compares commonly used CT criteria for the diagnosis of liver fat. MATERIALS AND METHODS The study includes 6814 asymptomatic participants from a population-based sample. The ratio of liver-to-spleen (L/S) Hounsfield units (HU) <1.0 and liver attenuation <40 HU were used for diagnosing and assessing the severity of liver fat content. Participants with heavy alcohol intake (>7 drinks/week for women and >14 drinks/week for men) were excluded. Final analysis was performed on participants where images of both liver and spleen were available on the scans. RESULTS The overall prevalence of fatty liver (4175 subjects included in final analysis) was 17.2% (using L/S ratio <1.0), with 6.3% (with <40 HU cutoff) of the population having moderate to severe steatosis (>30% liver fat content). The prevalence was high in participants with dyslipidemia (70.4%), hypertension (56.8%), and obesity (53%). Diabetic patients had 24.1% prevalence of fatty liver. The prevalence provided by L/S ratio <1.0 (17.2%) was comparable to prevalence provided by <51 HU (17.3%), whereas prevalence obtained by <40 HU (6.3%) cutoff corresponded to L/S ratio of <0.8 (6.5%). The measurements of liver and spleen HU attenuations were highly reproducible (0.96, 0.99 and 0.99, 0.99 for intra- and inter-reader variability, respectively) in a sample of 100 scans. CONCLUSION Fatty liver can be reliably diagnosed using nonenhanced CT scans.

Aged garlic extract and coenzyme Q10 have favorable effect on inflammatory markers and coronary atherosclerosis progression: A randomized clinical trial.

Background: Aged garlic extract (AGE) and coenzyme Q10 (CoQ10) have been shown to affect multiple cardiovascular risk factors. The current study evaluates the effect of AGE combined with CoQ10 on inflammatory markers and progression of coronary atherosclerosis compared with placebo. Methods and Results: In this placebo-controlled, double-blind, randomized trial, 65 intermediate risk firefighters (age 55 ± 6 years) were treated with a placebo capsule or a capsule containing AGE and CoQ10 (AGE+CoQ10, 1200 and 120 mg, respectively) daily for 1 year. All participants underwent coronary artery calcium (CAC) scanning and C-reactive protein (CRP) at baseline and at 12 months. At 1 year, mean CAC progression was significantly lower in AGE+CoQ10 (32 ± 6 vs. 58 ± 8, P = 0.01) than placebo. Similarly, CRP were significantly decreased in AGE+CoQ10 compared with placebo (-0.12 ± 0.24 vs. 0.91 ± 0.56 mg/L, P < 0.05). After adjustment for age, gender, conventional cardiac risk factors, and statin therapy, AGE+CoQ10 was associated with 3.99 fold (95% 1.3–12.2, P = 0.01) lack of CAC progression compared with the placebo. Conclusion: AGE+CoQ10 are associated with beneficial effects on inflammatory markers and reduced progression of coronary atherosclerosis.

Intra-thoracic fat, cardiometabolic risk factors, and subclinical cardiovascular disease in healthy, recently menopausal women screened for the Kronos Early Estrogen Prevention Study (KEEPS)

OBJECTIVE To examine the correlations between intra-hepatic and intra-thoracic (total, epicardial, and pericardial) fat deposition with cardiovascular disease (CVD) risk factors and subclinical atherosclerosis burden in healthy, recently postmenopausal women. METHODS Women screened for the Kronos Early Estrogen Prevention Study (mean age 52.9 years) who underwent electron beam or multidetector computed tomography (CT) imaging for the quantification of intra-hepatic fat and thoracic adipose tissue, and coronary artery calcification (CAC) were included (n=650). RESULTS Higher levels of intra-hepatic and thoracic fat were each associated with CVD risk markers. After adjustment for BMI, the associations for intra-hepatic fat with hs-CRP and insulin persisted (r=0.21 and 0.19, respectively; P<0.001), while those between thoracic fat indices and lipids persisted (r for total thoracic fat with HDL, LDL, and triglycerides=-0.16, 0.11, and 0.11, respectively, P<0.05). Total thoracic fat was associated with CAC after initial multivariable adjustment (odds ratio [OR] of 2nd, 3rd, and 4th vs. 1st quartile and [95% confidence intervals]: 0.8 [0.4-1.6], 1.5 [0.8-2.9], and 1.8 [1.0-3.4]; p for linear trend=0.017) and was only slightly attenuated after additional adjustment for BMI. Associations between total thoracic fat and CVD risk markers and CAC appeared due slightly more to associations with epicardial than pericardial fat. CONCLUSION While hepatic fat is related to hs-CRP and insulin, cardiac fat is associated with subclinical atherosclerosis as demonstrated by CAC. Cardiac fat may represent a useful marker for increased CVD risk beyond the standard adiposity measures of BMI and WC.

Computed tomography-derived cardiovascular risk markers, incident cardiovascular events, and all-cause mortality in nondiabetics: the Multi-Ethnic Study of Atherosclerosis:

Aim We assess the improvement in discrimination afforded by the addition of the computed tomography risk markers thoracic aorta calcium (TAC), aortic valve calcification (AVC), mitral annular calcification (MAC), pericardial adipose tissue volume (PAT), and liver attenuation (LA) to the Framingham risk score (FRS) + coronary artery calcium (CAC) for incident coronary heart disease (CHD) and incident cerebrovascular disease (CVD) in a multiethnic cohort. Methods and results A total of 5745 participants were enrolled, with 2710 at intermediate Framingham risk, 210 CVD events, and 155 CHD events). Over 9 years of follow up, 251 had adjudicated CHD, 346 had CVD events, and 321 died. The data were analysed using Cox proportional hazard, receiver operator curve (ROC), and net reclassification improvement (NRI) analyses. In the whole cohort and also when the analysis was restricted to only the intermediate-risk participants, CAC, TAC, AVC, and MAC were all significantly associated with incident CVD, incident CHD, and mortality, and CAC had the strongest association. When added to the FRS, CAC had the highest area under the curve (AUC) for the prediction of incident CVD and incident CHD; LA had the least. The addition of TAC, AVC, MAC, PAT, and LA to FRS + CAC all resulted in a significant reduction in AUC for incident CHD (0.712 vs. 0.646, 0.655, 0.652, 0.648, and 0.569; all p < 0.01, respectively) in participants with intermediate FRS. The addition of CAC to FRS resulted in an NRI of 0.547 for incident CHD in the intermediate-risk group. The NRI when TAC, AVC, MAC, PAT, and LA were added to FRS + CAC were 0.024, 0.026, 0.019, 0.012, and 0.012, respectively, for incident CHD in the intermediate-risk group. Similar results were obtained for incident CVD in the intermediate-risk group and also when the whole cohort was used instead of the intermediate FRS group. Conclusions The addition of CAC to the FRS provides superior discrimination especially in intermediate-risk individuals compared with the addition of TAC, AVC, MAC, PAT, or LA for incident CVD and incident CHD. Compared with FRS + CAC, the addition of TAC, AVC, MAC, PAT, or LA individually to FRS + CAC worsens the discrimination for incident CVD and incident CHD. These risk markers are unlikely to be useful for improving cardiovascular risk prediction.

Ethnic and sex differences in fatty liver on cardiac computed tomography: the multi-ethnic study of atherosclerosis.

OBJECTIVE To describe ethnic and sex differences in the prevalence and determinants of fatty liver in a multiethnic cohort. PATIENTS AND METHODS We studied participants of the Multi-Ethnic Study of Atherosclerosis who underwent baseline noncontrast cardiac computed tomography between July 17, 2000, and August 29, 2002, and had adequate hepatic and splenic imaging for fatty liver determination (n=4088). Fatty liver was defined as a liver/spleen attenuation ratio of less than 1. We compared the prevalence and severity of fatty liver, in 4 ethnicities (white, Asian, African American, and Hispanic), and the factors associated with fatty liver in each ethnicity, stratifying by obesity and metabolic syndrome. Multivariable ordinal logistic regression was used to determine the effect of cardiometabolic risk factors on the prevalence of fatty liver in different ethnicities. RESULTS The prevalence of fatty liver varied significantly by ethnicity (African American, 11%; white, 15%; Asian, 20%; and Hispanic, 27%; P<.001). Although African Americans had the highest prevalence of obesity, a smaller percentage of obese African Americans received a diagnosis of fatty liver than did other ethnicities (African American, 17%; white, 31%; Asian, 37%; and Hispanic 39%; P<.001). Hispanics had the highest prevalence of fatty liver, including the obese and metabolic syndrome population. An increase in insulin resistance predicted a 2-fold increased prevalence of fatty liver in all ethnicities after multivariable adjustment. CONCLUSION African Americans have a lower prevalence and Hispanics have a higher prevalence of fatty liver than do other ethnicities. There are distinct ethnic variations in the prevalence of fatty liver even in patients with the metabolic syndrome or obesity, suggesting that genetic factors may play a substantial role in the phenotypic expression of fatty liver.

Coronary computed tomography as a cost-effective test strategy for coronary artery disease assessment - a systematic review.

Cardiovascular imaging imparts a huge burden on healthcare spending. Coronary CT angiography (CCTA) may provide a cost effective means of diagnosing coronary artery disease (CAD) and reducing downstream cost of testing. We performed a systematic search of literature for randomized controlled trials or prospective or retrospective non-randomized comparative studies or case series, decision analytic models and technology reports in which some or all of the patients underwent CCTA and looking at the cost effectiveness, comparative effectiveness and downstream test utilization associated with the use of CCTA. We found 42 articles matching our criteria. CCTA either as first line or as a layering test may represent a cost effective strategy for initial evaluation of patients with CAD prevalence of 10%-50% in both near-term and long-term diagnostic periods. For CAD prevalence ≥70%, ICA as initial test may represent cost effective strategy for diagnosis of stable chest pain. CCTA may represent cost-effective strategy when performed as a layering test to equivocal initial stress imaging before performing ICA. Use of CCTA is cost- and time-effective strategy for evaluation of low risk (<30% CAD prevalence) acute chest pain patients in emergency department and can be used for safe exclusion of acute coronary syndrome (ACS). Use of coronary calcium score as an initial test may require further evidence to be deemed cost-effective strategy. CCTA may represent a cost effective and may be associated with less downstream testing for diagnosis of stable chest pain patients in low to intermediate risk patients whereas for low risk acute chest pain patients, use of CCTA is associated with expedited patient management, less cost and safe exclusion of ACS.

Beneficial effects of aged garlic extract and coenzyme Q10 on vascular elasticity and endothelial function: The FAITH randomized clinical trial

OBJECTIVE Aged garlic extract (AGE) is associated with a significant decrease in atherosclerotic plaque progression and endothelial function improvement. Similarly, coenzyme Q10 (CoQ10) has significant beneficial effects on endothelial function. A stressful lifestyle is a well-known risk factor for the presence and progression of atherosclerosis. This study investigated the effect of AGE plus CoQ10 on vascular elasticity measured by pulse-wave velocity (PWV) and endothelial function measured by digital thermal monitoring (DTM) in firefighters. METHODS Sixty-five Los-Angeles County firefighters who met the eligibility criteria were enrolled in this placebo-controlled, double-blinded randomized trial. The firefighters were randomized to four tablets of AGE (300 mg/tablet) plus CoQ10 (30 mg/tablet) or placebo. The participants underwent quarterly visits and 1-year follow-up. PWV and DTM were measured at baseline and at the 1-year follow-up. RESULTS There were no significant differences in age, cardiovascular risk factors, PWV, and DTM between the AGE/CoQ10 and placebo groups at baseline (P > 0.5). At 1-y, PWV and DTM significantly improved in the AGE/CoQ10 compared with the placebo group (P < 0.05). After an adjustment for cardiovascular risk factors and statin therapy, the mean decrease in vascular stiffness (PWV) was 1.21 m/s in the AGE/CoQ10 compared with the placebo group (P = 0.005). Similarly, the mean increase in the area under the temperature curve, the DTM index of endothelial function, was 31.3 in the AGE/CoQ10 compared with the placebo group (P = 0.01). CONCLUSION The combination of AGE and CoQ10 was independently associated with significant beneficial effects on vascular elasticity and endothelial function in firefighters with high occupational stress, highlighting the important role of AGE and CoQ10 in atherosclerotic prevention of such individuals.

Relation of vascular stiffness with epicardial and pericardial adipose tissues, and coronary atherosclerosis

OBJECTIVES Increased measured vascular stiffness is an early marker of atherosclerosis and is associated with cardiovascular risk factors. Coronary artery calcium (CAC) and adipose tissues are accurate markers of overall burden of coronary atherosclerosis and metabolic status, respectively. We evaluated the relation of vascular stiffness with epicardial (EAT) and pericardial (PAT) adipose tissues, as well as the presence and severity of CAC. METHODS One hundred and eleven consecutive subjects, mean age 59 ± 11 years, 78% male, underwent 64-multidetector row cardiac computed tomography (MDCT) and their carotid-radial pulse wave velocity (PWV) was measured using SphygmoCor tonometry. EAT and total thoracic adipose tissue (TAT) volumes were measured using MDCT. PAT was calculated as TAT-EAT. The highest tertile of EAT (≥111 ml) and PAT (≥103 ml) were defined as significant adipose tissue depots. RESULTS PWV was moderately associated with EAT (r = 0.46, p < 0.001), and PAT (r = 0.41, p < 0.001). PWV increased proportionally with the severity of CAC from 0 to 400+. The relative risk of highest vs. lowest tertile of PWV was 3.03 (95% CI 1.22-7.51, p = 0.01) for significant EAT, 2.34 (95% CI 1.10-4.90, p = 0.02) for significant PAT and 2.46 (95% CI 1.13-3.14, p = 0.01) for significant CAC (CAC 100+) after adjustment for conventional cardiovascular risk factors. This relative risk was increased after combination of CAC 100+ with each significant adipose tissue. CONCLUSIONS Increased vascular stiffness is associated with increase in EAT, PAT and coronary atherosclerosis. EAT was associated with higher relative risk of PWV, compared with CAC, suggesting a role of adipose tissue in vascular stiffness.