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Introduction: High left ventricular ejection fraction (LVEF) has been associated with excess cardiovascular disease (CVD) morbidity and mortality among women with CVD. We sought to determine if high EF is associated with incident heart failure (HF) in a community-dwelling cohort of adults. Secondarily, we examined relationships between various adiposity measures and high EF, as obesity is associated with HF with preserved EF. Methods: 1794 participants aged 65±9y (53% women) of the Framingham Offspring cohort underwent cardiac MRI 2002-2006 to determine LV EF and mass (LVM). Anthropometric measures and clinical covariates were collected at the adjacent Offspring cycle 7 visit. Adiposity measures included body mass index (BMI) and waist circumference (WC). A healthy referent subset (no hypertension, diabetes, smoking, or history of CVD) was used to determine sex-specific upper 90 th percentile cutpoints (P90) for high EF. Cox proportional hazards regression models were used to assess event-free survival for the outcome of HF (adjudicated by 3 physician investigators). Multivariable-adjusted (MV) logistic regression analysis was used to determine clinical factors associated with high EF. Adiposity measures were considered categorically (as BMI≥30kg/m 2 and WC > 102 or 88 cm (men, women)) and as continuous variables. Results: P90 cutpoints for high EF were 72.5% (men) and 75.1% (women). Prevalence of high EF was 16.0% (men) and 14.7% (women). Over median 13.2 years of follow up there were 68 incident HF events. In MV-adjusted Cox models accounting for age, sex, hypertension, smoking, diabetes, and indexed LVM, the HF outcome was associated with greater age (hazard ratio, HR=3.13/10y, 95%CI 2.30 - 4.27), LVMi (HR=1.24/5g per m 2 , CI 1.12 - 1.36) and high EF (HR=2.26, CI 1.35 - 3.77). MV-adjusted logistic regression models showed high EF was associated with each measure of adiposity. High BMI (≥30) had odds ratio (OR) = 1.38 (CI 1.04 - 1.84), high WC (>102 or 88): OR=1.55 (1.12 - 2.09), continuous BMI: OR=1.03 (CI 1.01 - 1.06), continuous WC: OR=1.02 (1.01 - 1.03). In each of these models ORs for age ranged 1.52 to 1.54, hypertension 1.74 to 1.86. Conclusion: High EF was associated with greater hazard of incident heart failure in middle-aged and older adults. High EF was associated with increasing age, hypertension, and greater adiposity (measured by either BMI or WC). This work extends prior findings in women with CVD to a community-dwelling cohort of both sexes. Further work is needed to determine whether general or central measures of obesity are more strongly associated with high EF.

Introduction: Increased left ventricular mass (LVM) predicts excess cardiovascular morbidity and mortality. LVM is often indexed to height (HT) or body surface area (BSA). HT-indexation ignores weight and thus obesity. The relationship of indexed LVM with weight, obesity, and adiposity is unclear. We investigated the association of LVM with total-body mass (TBM, i.e. weight) and fat-free mass (FFM), hypothesizing that LVM scales better to FFM than TBM. Methods: From the 1794 members of Framingham Offspring cohort who underwent cardiac magnetic resonance (CMR), we identified 845 (aged 65±9y) without any history of hypertension, myocardial infarction, heart failure, or CMR wall-motion abnormality. LVM was measured from cine bSSFP images and indexed to HT, BSA, TBM and FFM (by DEXA). Participants were stratified by sex and body mass index (BMI) category (NL=BMI 18.5 - 24.9; OW=25.0 - 29.9; OB=30.0+ kg/m 2 ). We used sex-specific ANCOVA to test for linear trend across BMI categories, and determined sex-specific Pearson correlation coefficients of LVM with BMI; both sets of analyses were adjusted for age and systolic blood pressure. Data are summarized as mean ± SD. Results: The Table shows that LVM and LVM/HT increase with greater BMI-category in both sexes. LVM/BSA was similar across BMI-categories, while LVM/TBM decreased. There was no linear trend across BMI-categories for LVM/FFM in either sex. On a continuous basis, LVM and LVM/HT were positively correlated with BMI in both sexes (r=0.20 to 0.35, p Conclusion: LVM as a proportion of TBM (weight) actually decreases with greater BMI, while LVM/FFM is not associated with BMI. Whether LVM is better scaled to FFM vs HT, BSA or TBM for risk stratification purposes remains to be determined.

Introduction: Greater burden of pericardial fat is associated with increased body mass index (BMI). Obesity is associated with unfavorable metabolic characteristics such as hypertension, dyslipidemia, and glucose intolerance. We sought to determine whether increased pericardial fat thickness (PFT) was associated with unfavorable metabolic profile alone, in the absence of excess BMI. Methods: From the 1,794 Framingham Offspring cohort adults who underwent cardiac magnetic resonance (CMR), we identified 446 free of non-skin cancer and prevalent clinical cardiovascular disease (CVD) who had 18.5≤BMI2 and complete covariates. We calculated a metabolic score (MS) based on ATPIII criteria where 1 point was assigned for each of: a) fasting plasma glucose≥100 mg/dL or diabetes; b) SBP≥130 or DBP≥85 mm Hg or antihypertensive treatment; c) triglycerides≥150 mg/dL; d) HDL cholesterol Results: PFT increased with worsening metabolic score (see Table) at the fixed locations of the apical and mid-level RV, as well as at maximal PFT. On pairwise comparisons, only the MS3+ group had PFT that was consistently significantly greater than that of MS0 (all p Conclusions: In a community-dwelling cohort, among participants who were free of cancer and clinical CVD and had normal-range or “healthy” BMI, worsening metabolic profile was associated with increased pericardial fat thickness.

Introduction: Persons with normal-range body mass index (BMI) but adverse metabolic characteristics associated with obesity have been described as metabolically-obese normal weight (MONW). We sought to determine whether adverse metabolic profile is associated with alterations in left ventricular (LV) structure or function among adults with normal BMI. Methods: From the 1794 Framingham Offspring cohort adults who underwent cardiac magnetic resonance (CMR), we identified 446 free of non-skin cancer and prevalent clinical cardiovascular disease (CVD) who had 18.5≤BMI Results: LV concentricity increased with worsening metabolic status (see Table); this was driven by lower LV EDV, not increased LVM. LVM did not differ across (trend) or between MS-groups. LVEDV decreased across groups but only MS2 differed significantly from MS0. LVEF increased slightly but significantly across MS-groups. Conclusions: In a community-dwelling cohort, among participants who were free of cancer and clinical CVD and had normal BMI, worsening metabolic profile was associated with adverse remodeling of the left ventricle, reflected by greater LV concentricity.

Introduction: Aortic plaque can be seen on noncontrast cardiovascular magnetic resonance (CMR) imaging. We sought to determine the prevalence, distribution and burden, or quantitative amount, of CMR-detected thoracic (TAP) and abdominal (AAP) aortic plaque in a community-dwelling cohort of adults. Methods: 1794 Framingham Offspring cohort members underwent ECG-gated, fat-suppressed, T2-weighted TSE black blood aortic CMR at 1.5T: 1.03 x 0.64-mm pixels, 5-mm slice thickness. We obtained 12 thoracic (above diaphragm, 1-cm interslice gap) slices and 24 abdominal (below diaphragm/above aortic bifurcation, 5-mm gap) slices. Plaque protruding ≥1mm into the lumen was traced on each slice and summed to determine AAP and TAP burdens. Participants were stratified by sex and 10-year age groups. We tabulated number of persons with prevalent (i.e. >0) AAP and TAP and tested for trend (Cochrane-Armitage) across age groups. Among those with plaque>0, we determined upper 90th percentile (P90) plaque burden, if the sex/age-group had ≥20 persons with prevalent plaque (we felt calculations based on N Results: Complete aortic studies were available on 1726 adults aged 65±9y (47% men). AAP was more prevalent than TAP: 359/806 (44.5%) men and 430/920 (46.7%) women had AAP, p=0.26; 72/806 (8.9%) men and 65/920 (7.1%) women had TAP, p=0.15. The Table shows sex-specific distributions and burdens of plaque by age-group, where +AAP (+TAP) indicates abdominal (thoracic) aortic plaque is present. Prevalence of both AAP and TAP increased monotonically with age (p Conclusions: Among middle-aged and older community dwelling adults, AAP is seen on noncontrast CMR in 45.7%, while TAP is less prevalent at 7.9%. Prevalence of aortic plaque did not differ between men and women and increases with age in both sexes. Burden (amount) of AAP also increases with greater age.