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Articles by C. S Fox
Total Records ( 4 ) for C. S Fox
  G Thanassoulis , J. M Massaro , C. J O'Donnell , U Hoffmann , D Levy , P. T Ellinor , T. J Wang , R. B Schnabel , R. S Vasan , C. S Fox and E. J. Benjamin

Obesity represents an important risk factor for atrial fibrillation (AF). We tested the hypothesis that pericardial fat, a unique fat deposit in close anatomic proximity to cardiac structures and autonomic fibers, is associated with prevalent AF.

Methods and Results—

Participants from the Framingham Heart Study underwent multidetector computed tomography from 2002 to 2005. We estimated the association between quantitative pericardial, intrathoracic and visceral adipose tissue volumes (per standard deviation of volume) with prevalent AF adjusting for established AF risk factors (age, sex, systolic blood pressure, blood pressure treatment, PR interval, and clinically significant valvular disease). Of the 3217 eligible participants (mean age, 50.6±10.1 years; 48% women), 54 had a confirmed diagnosis of AF. Pericardial fat but not intrathoracic or visceral abdominal fat was associated with prevalent AF in multivariable-adjusted models (odds ratio per standard deviation of pericardial fat volume, 1.28; 95% confidence intervals, 1.03 to 1.58). Further adjustments for body mass index, heart failure, myocardial infarction, and intrathoracic fat volume did not materially change the association between pericardial fat and AF.


Pericardial fat was associated with prevalent AF even after adjustment for AF risk factors, including body mass index. If this association is replicated, further investigations into the mechanisms linking pericardial fat to AF are merited.

  R. S Velagaleti , P Gona , M. L Chuang , C. J Salton , C. S Fox , S. J Blease , S. B Yeon , W. J Manning and C. J. O'Donnell

Background— Data regarding the relationships of diabetes, insulin resistance, and subclinical hyperinsulinemia/hyperglycemia with cardiac structure and function are conflicting. We sought to apply volumetric cardiovascular magnetic resonance (CMR) in a free-living cohort to potentially clarify these associations.

Methods and Results— A total of 1603 Framingham Heart Study Offspring participants (age, 64±9 years; 55% women) underwent CMR to determine left ventricular mass (LVM), LVM to end-diastolic volume ratio (LVM/LVEDV), relative wall thickness (RWT), ejection fraction, cardiac output, and left atrial size. Data regarding insulin resistance (homeostasis model, HOMA-IR) and glycemia categories (normal, impaired insulinemia or glycemia, prediabetes, and diabetes) were determined. In a subgroup (253 men, 290 women) that underwent oral glucose tolerance testing, we related 2-hour insulin and glucose with CMR measures. In both men and women, all age-adjusted CMR measures increased across HOMA-IR quartiles, but multivariable-adjusted trends were significant only for LVM/ht2.7 and LVM/LVEDV. LVM/LVEDV and RWT were higher in participants with prediabetes and diabetes (in both sexes) in age-adjusted models, but these associations remained significant after multivariable adjustment only in men. LVM/LVEDV was significantly associated with 2-hour insulin in men only, and RWT was significantly associated with 2-hour glucose in women only. In multivariable stepwise selection analyses, the inclusion of body mass index led to a loss in statistical significance.

Conclusions— Although insulin and glucose indices are associated with abnormalities in cardiac structure, insulin resistance and worsening glycemia are consistently and independently associated with LVM/LVEDV. These data implicate hyperglycemia and insulin resistance in concentric LV remodeling.

  C. S Fox , J. M Massaro , C. L Schlett , S. J Lehman , J. B Meigs , C. J O'Donnell , U Hoffmann and J. M. Murabito

Central obesity is associated with peripheral arterial disease, suggesting that ectopic fat depots may be associated with localized diseases of the aorta and lower-extremity arteries. We hypothesized that persons with greater amounts of periaortic fat are more likely to have clinical PAD and a low ankle-brachial index.

Methods and Results—

We quantified periaortic fat surrounding the thoracic aorta using a novel volumetric quantitative approach in 1205 participants from the Framingham Heart Study Offspring cohort (mean age, 65.9 years; women, 54%); visceral abdominal fat also was measured. Clinical peripheral arterial disease was defined as a history of intermittent claudication, and ankle-brachial index was dichotomized as low (≤0.9) or lower-extremity revascularization versus normal (>0.9 to <1.4). Regression models were created to examine the association between periaortic fat and intermittent claudication or low ankle-brachial index (n=66). In multivariable logistic regression, per 1 SD increase in periaortic fat, the odds ratio for the combined end point was 1.52 (P=0.004); these results were strengthened with additional adjustment for body mass index (odds ratio, 1.69; P=0.002) or visceral abdominal fat (odds ratio, 1.67; P=0.009), whereas no association was observed for visceral abdominal fat (P=0.16). Similarly, per SD increase in body mass index or waist circumference, no association was observed after accounting for visceral abdominal fat (body mass index, P=0.35; waist circumference, P=0.49).


Periaortic fat is associated with low ABI and intermittent claudication.

  A. P Carson , C. S Fox , D. K McGuire , E. B Levitan , M Laclaustra , D. M Mann and P. Muntner

Among individuals without diabetes, elevated hemoglobin A1c (HbA1c) has been associated with increased morbidity and mortality, but the literature is sparse regarding the prognostic importance of low HbA1c.

Methods and Results—

National Health and Nutrition Examination Survey III (NHANES III) participants, 20 years and older, were followed up to 12 years (median follow-up, 8.8 years) for all-cause mortality. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association between HbA1c levels and all-cause mortality for 14 099 participants without diabetes. There were 1825 deaths during the follow-up period. Participants with a low HbA1c (<4.0%) had the highest levels of mean red blood cell volume, ferritin, and liver enzymes and the lowest levels of mean total cholesterol and diastolic blood pressure compared with their counterparts with HbA1c levels between 4.0% and 6.4%. An HbA1c <4.0% versus 5.0% to 5.4% was associated with an increased risk of all-cause mortality (HR, 3.73; 95% CI, 1.45 to 9.63) after adjustment for age, race-ethnicity, and sex. This association was attenuated but remained statistically significant after further multivariable adjustment for lifestyle, cardiovascular factors, metabolic factors, red blood cell indices, iron storage indices, and liver function indices (HR, 2.90; 95% CI, 1.25 to 6.76).


In this nationally representative cohort, low HbA1c was associated with increased all-cause mortality among US adults without diabetes. Additional research is needed to confirm these results and identify potential mechanisms that may be underlying this association.

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