Amir A. Mahabadi

Pericardial Fat, Visceral Abdominal Fat, Cardiovascular Disease Risk Factors, and Vascular Calcification in a Community-Based Sample : The Framingham Heart Study

Background— Pericardial fat may be an important mediator of metabolic risk. Correlations with cardiovascular disease risk factors and vascular calcification in a community-based sample are lacking. We sought to examine associations between pericardial fat, metabolic risk factors, and vascular calcification. Methods and Results— Participants free of cardiovascular disease from the Framingham Heart Study (n=1155, mean age 63 years, 54.8% women) who were part of a multidetector computed tomography study underwent quantification of intrathoracic fat, pericardial fat, visceral abdominal fat (VAT), coronary artery calcification, and aortic artery calcification. Intrathoracic and pericardial fat volumes were examined in relation to body mass index, waist circumference, VAT, metabolic risk factors, coronary artery calcification, and abdominal aortic calcification. Intrathoracic and pericardial fat were directly correlated with body mass index (r=0.41 to 0.51, P<0.001), waist circumference (r=0.43 to 0.53, P<0.001), and VAT (r=0.62 to 0.76, P<0.001). Both intrathoracic and pericardial fat were associated with higher triglycerides (P<0.0001), lower high-density lipoprotein (P<0.0001), hypertension (P<0.0001 to 0.01), impaired fasting glucose (P<0.0001 to 0.001), diabetes mellitus (P=0.0005 to 0.009), and metabolic syndrome (P<0.0001) after multivariable adjustment. Associations generally persisted after additional adjustment for body mass index and waist circumference but not after adjustment for VAT (all P>0.05). Pericardial fat, but not intrathoracic fat, was associated with coronary artery calcification after multivariable and VAT adjustment (odds ratio 1.21, 95% confidence interval 1.005 to 1.46, P=0.04), whereas intrathoracic fat, but not pericardial fat, was associated with abdominal aortic calcification (odds ratio 1.32, 95% confidence interval 1.03 to 1.67, P=0.03). Conclusions— Pericardial fat is correlated with multiple measures of adiposity and cardiovascular disease risk factors, but VAT is a stronger correlate of most metabolic risk factors. However, intrathoracic and pericardial fat are associated with vascular calcification, which suggests that these fat depots may exert local toxic effects on the vasculature.

Association of pericardial fat, intrathoracic fat, and visceral abdominal fat with cardiovascular disease burden: the Framingham Heart Study.

AIMS The aim of this study was to assess whether pericardial fat, intrathoracic fat, and visceral abdominal adipose tissue (VAT) are associated with the prevalence of cardiovascular disease (CVD). METHODS AND RESULTS Participants from the Framingham Heart Study Offspring cohort underwent abdominal and chest multidetector computed tomography to quantify volumes of pericardial fat, intrathoracic fat, and VAT. Relations between each fat depot and CVD were assessed using logistic regression. The analysis of 1267 participants (mean age 60 years, 53.8% women, 9.7% with prevalent CVD) demonstrated that pericardial fat [odds ratio (OR) 1.32, 95% confidence interval (CI) 1.11-1.57; P = 0.002] and VAT (OR 1.35, 95% CI 1.11-1.57; P = 0.003), but not intrathoracic fat (OR 1.14, 95% CI 0.93-1.39; P = 0.22), were significantly associated with prevalent CVD in age-sex-adjusted models and after adjustment for body mass index and waist circumference. After multivariable adjustment, associations were attenuated (P > 0.14). Only pericardial fat was associated with prevalent myocardial infarction after adjusting for conventional measures of adiposity (OR 1.37, 95% CI 1.03-1.82; P = 0.03). CONCLUSION Pericardial fat and VAT, but not intrathoracic fat, are associated with CVD independent of traditional measures of obesity but not after further adjustment for traditional risk factor. Taken together with our prior work, these findings may support the hypothesis that pericardial fat contributes to coronary atherosclerosis.

Association of epicardial fat with cardiovascular risk factors and incident myocardial infarction in the general population: the Heinz Nixdorf Recall Study.

OBJECTIVES This study sought to determine whether epicardial fat volume predicts coronary events in the general population. BACKGROUND Epicardial adipose tissue (EAT) is suggested to promote plaque development in the coronary artery tree. METHODS We quantified EAT volume in participants from the prospective population-based Heinz Nixdorf Recall cohort study free of cardiovascular disease. Incident coronary events were assessed during a follow-up period of 8.0 ± 1.5 years. Multivariable association of EAT with cardiovascular risk factors, coronary artery calcification (CAC), and coronary events was assessed using regression analysis. RESULTS From the overall 4,093 participants (age 59.4 years, 47% male), 130 subjects developed a fatal or nonfatal coronary event. Incidence of coronary events increased by quartile of EAT (0.9% vs. 4.7% for 1(st) and 4th quartile, respectively, p < 0.001). Doubling of EAT was associated with a 1.5-fold risk of coronary events when adjusting for cardiovascular risk factors (hazard ratio [HR] [95% confidence interval (CI)]: 1.54 [1.09 to 2.19]), which remained unaltered after further adjustment for CAC score (HR [95% CI]: 1.50 [1.07 to 2.11]). For discrimination of subjects with events from those without, we observed a trend for improvement of Harrells C and explained variance by EAT over traditional cardiovascular risk factors, which, however, did not reach statistical significance (0.720 to 0.730 for risk factors alone and with EAT added, respectively, p = 0.10, R(2) = 2.73% to R(2) = 2.92%, time-dependent integrated discrimination improvement = 0.196%). CONCLUSIONS Epicardial fat is associated with fatal and nonfatal coronary events in the general population independent of traditional cardiovascular risk factors and complements information from cardiac computed tomography above the CAC score.

10-Year Coronary Heart Disease Risk Prediction Using Coronary Artery Calcium and Traditional Risk Factors: Derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) With Validation in the HNR (Heinz Nixdorf Recall) Study and the DHS (Dallas Heart Study).

BACKGROUND Several studies have demonstrated the tremendous potential of using coronary artery calcium (CAC) in addition to traditional risk factors for coronary heart disease (CHD) risk prediction. However, to date, no risk score incorporating CAC has been developed. OBJECTIVES The goal of this study was to derive and validate a novel risk score to estimate 10-year CHD risk using CAC and traditional risk factors. METHODS Algorithm development was conducted in the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective community-based cohort study of 6,814 participants age 45 to 84 years, who were free of clinical heart disease at baseline and followed for 10 years. MESA is sex balanced and included 39% non-Hispanic whites, 12% Chinese Americans, 28% African Americans, and 22% Hispanic Americans. External validation was conducted in the HNR (Heinz Nixdorf Recall Study) and the DHS (Dallas Heart Study). RESULTS Inclusion of CAC in the MESA risk score offered significant improvements in risk prediction (C-statistic 0.80 vs. 0.75; p < 0.0001). External validation in both the HNR and DHS studies provided evidence of very good discrimination and calibration. Harrells C-statistic was 0.779 in HNR and 0.816 in DHS. Additionally, the difference in estimated 10-year risk between events and nonevents was approximately 8% to 9%, indicating excellent discrimination. Mean calibration, or calibration-in-the-large, was excellent for both studies, with average predicted 10-year risk within one-half of a percent of the observed event rate. CONCLUSIONS An accurate estimate of 10-year CHD risk can be obtained using traditional risk factors and CAC. The MESA risk score, which is available online on the MESA web site for easy use, can be used to aid clinicians when communicating risk to patients and when determining risk-based treatment strategies.

Association of pericoronary fat volume with atherosclerotic plaque burden in the underlying coronary artery: A segment analysis

OBJECTIVE We aimed to determine, whether the amount of local pericoronary fat volume is associated with the presence of plaque burden in the underlying coronary artery segment. METHODS We assessed 311 coronary segments from ECG-gated contrast-enhanced dual-source computed tomography for presence of plaque as well as segmental pericoronary fat volume. For pericoronary fat evaluation, regions of interest were manually traced containing any fat surrounding a coronary artery segment, with the myocardial wall, the pericardial sac and other coronary segments as outer border. RESULTS Per each doubling of pericoronary fat volume, we observed an 2.5-fold increase in the presence of plaque in the underlying coronary segment in unadjusted models (95% confidence interval [CI] 1.87-3.27, p<0.001), which remained after adjustment for traditional cardiovascular risk factors (odds ratio [OR] 3.07 [2.16-4.35], p<0.001) and when additionally accounting for overall pericardial fat volume (OR 2.68 [1.90-3.79], p<0.001). Associations were similar in all coronary artery segments and not related to the type of plaque (calcified or non-calcified, p<0.01 for all). CONCLUSION Pericoronary fat is associated with atherosclerosis in the coronary arteries. Our results support the hypothesis that perivascular fat depots may function as a local endocrine risk factor in atherosclerosis development.

Hybrid PET/MR Imaging of the Heart: Feasibility and Initial Results

PURPOSE To assess the feasibility of hybrid imaging of the heart with fluorine 18 fluorodeoxyglucose (FDG) on an integrated 3-T positron emission tomography (PET)/magnetic resonance (MR) imaging system. MATERIALS AND METHODS The present study was approved by the local institutional review board. Written informed consent was obtained from all patients before imaging. Twenty consecutive patients with myocardial infarction (n = 20) underwent cardiac PET/MR imaging examination. Ten patients underwent additional cardiac PET/computed tomography (CT) before PET/MR. Two-dimensional half-Fourier acquisition single-shot turbo spin-echo sequences, balanced steady-state free precession cine sequences, two-dimensional turbo inversion-recovery magnitude T2-weighted sequences, and late gadolinium-enhanced (LGE) segmented two-dimensional inversion-recovery turbo fast low-angle shot sequences were performed. According to the 17-segment model, PET tracer uptake, wall motion, and late gadolinium enhancement were visually assessed for each segment on a binary scale, and categorical intermethod agreement was calculated by using the Cohen κ. The maximum standardized uptake value was measured in corresponding myocardial locations on PET/CT and PET/MR images. RESULTS Agreement was substantial over all patients and segments between PET and LGE images (κ = 0.76) and between PET and cine images (κ = 0.78). In 306 segments, 97 (32%) were rated as infarcted on PET images, compared with 93 (30%) rated as infarcted on LGE images and with 90 (29%) rated as infarcted on cine images. In a subgroup of patients (n = 10) with an additional PET/CT scan, no significant difference in myocardial tracer uptake between PET/CT and PET/MR images was found (paired t test, P = .95). CONCLUSION Cardiac PET/MR imaging with FDG is feasible and may add complementary information in patients with ischemic heart disease.

Reference Values for Normal Pulmonary Artery Dimensions by Noncontrast Cardiac Computed Tomography: The Framingham Heart Study

Background— Main pulmonary artery diameter (mPA) and ratio of mPA to ascending aorta diameter (ratio PA) derived from chest CT are commonly reported in clinical practice. We determined the age- and sex-specific distribution and normal reference values for mPA and ratio PA by CT in an asymptomatic community-based population. Methods and Results— In 3171 men and women (mean age, 51±10 years; 51% men) from the Framingham Heart Study, a noncontrast, ECG-gated, 8-slice cardiac multidetector CT was performed. We measured the mPA and transverse axial diameter of the ascending aorta at the level of the bifurcation of the right pulmonary artery and calculated the ratio PA. We defined the healthy referent cohort (n=706) as those without obesity, hypertension, current and past smokers, chronic obstructive pulmonary disease, history of pulmonary embolism, diabetics, cardiovascular disease, and heart valve surgery. The mean mPA diameter in the overall cohort was 25.1±2.8 mm and mean ratio PA was 0.77±0.09. The sex-specific 90th percentile cutoff value for mPA diameter was 28.9 mm in men and 26.9 mm in women and was associated with increase risk for self-reported dyspnea (adjusted odds ratio, 1.31; P=0.02). The 90th percentile cutoff value for ratio PA of the healthy referent group was 0.91, similar between sexes but decreased with increasing age (range, 0.82–0.94), though not associated with dyspnea. Conclusions— For simplicity, we established 29 mm in men and 27 mm in women as sex-specific normative reference values for mPA and 0.9 for ratio PA.

Safety, Efficacy, and Indications of β-Adrenergic Receptor Blockade to Reduce Heart Rate prior to Coronary CT Angiography

For selected indications, coronary computed tomographic (CT) angiography is an established clinical technology for evaluation in patients suspected of having or known to have coronary artery disease. In coronary CT angiography, image quality is highly dependent on heart rate, with heart rate reduction to less than 60 beats per minute being important for both image quality and radiation dose reduction, especially when single-source CT scanners are used. β-Blockers are the first-line option for short-term reduction of heart rate prior to coronary CT angiography. In recent years, multiple β-blocker administration protocols with oral and/or intravenous application have been proposed. This review article provides an overview of the indications, efficacy, and safety of β-blockade protocols prior to coronary CT angiography with respect to different scanner techniques. Moreover, implications for radiation exposure and left ventricular function analysis are discussed.

Prevalence, Distribution, and Risk Factor Correlates of High Pericardial and Intrathoracic Fat Depots in the Framingham Heart Study

Background—Pericardial and intrathoracic fat depots may represent novel risk factors for obesity-related cardiovascular disease. We sought to determine the prevalence, distribution, and risk factor correlates of high pericardial and intrathoracic fat deposits. Methods and Results—Participants from the Framingham Heart Study (n=3312; mean age, 52 years; 48% women) underwent multidetector CT imaging in 2002 to 2005; high pericardial and high intrathoracic fat were defined on the basis of the sex-specific 90th percentile for these fat depots in a healthy reference sample. For men and women, the prevalence of high pericardial fat was 29.3% and 26.3%, respectively, and high intrathoracic fat was 31.4% and 35.3%, respectively. Overall, 22.1% of the sample was discordant for pericardial and intrathoracic fat depots: 8.3% had high pericardial but normal intrathoracic fat and 13.8% had high intrathoracic but normal pericardial fat. Higher body mass index, higher waist circumference, and increased prevalence of metabolic syndrome were more prevalent in participants with high intrathoracic fat depots than with high pericardial fat (P<0.05 for all comparisons). High abdominal visceral adipose tissue was more frequent in participants with high intrathoracic adipose tissue compared with those with high pericardial fat (P<0.001). Intrathoracic fat but not waist circumference was more highly correlated with visceral adipose tissue (r=0.76 and 0.78 in men and women, respectively; P<0.0001) than with subcutaneous adipose tissue (SAT) (r=0.46 and 0.54 in men and women, respectively; P<0.0001). Conclusions—Although prevalence of pericardial fat and intrathoracic fat were comparable at 30%, intrathoracic fat correlated more closely with metabolic risk and visceral fat. Intrathoracic fat may be a potential marker of metabolic risk and visceral fat on thoracic imaging.

Carotid intima-media thickness as a biomarker of subclinical atherosclerosis

Intima-media thickness of the carotid artery (CIMT) and its increase is associated with several cardiovascular risk factors and manifest cardiovascular diseases. CIMT is suggested to be an important biomarker of subclinical atherosclerosis. CIMT is measured in B-mode ultrasound images of the carotid tree as a typical double line of the arterial wall. CIMT is best visible in the measurement segment of the distal common carotid artery with lowest measurement variability. The measurement is most reliable over a one centimeter-segment with automatic or semi-automatic reading methods, which minimises reading errors. Further structured training of sonographer and reader is important for valid and reproducible results. CIMT is an accepted predictor for future cardiovascular events independent of age, gender and cardiovascular risk factors. Measurement seems to be best applicable in patients with intermediate risk in order to readjust cardiovascular risk. Plaques in the carotid tree and thickening of the CIMT are different atherosclerotic processes. From childhood to early adulthood CIMT is the only atherosclerotic marker of the carotid tree; plaques occur later in life. Both parameters contribute independently to risk assessment for future cardio-vascular events. Aims of this review are to outline measurement procedures, reproducibility, prognostic value and ability to discriminate healthy subject and patients with manifest disease in a practical and scientifically contemporary manner.