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Articles by J. M Massaro
Total Records ( 8 ) for J. M Massaro
  M. J Pencina , R. B D'Agostino , M. G Larson , J. M Massaro and R. S. Vasan
 

Background— Present cardiovascular disease (CVD) risk prediction algorithms were developed for a ≤10-year follow up period. Clustering of risk factors at younger ages and increasing life expectancy suggest the need for longer-term risk prediction tools.

Methods and Results— We prospectively followed 4506 participants (2333 women) of the Framingham Offspring cohort aged 20 to 59 years and free of CVD and cancer at baseline examination in 1971–1974 for the development of "hard" CVD events (coronary death, myocardial infarction, stroke). We used a modified Cox model that allows adjustment for competing risk of noncardiovascular death to construct a prediction algorithm for 30-year risk of hard CVD. Cross-validated survival C statistic and calibration 2 were used to assess model performance. The 30-year hard CVD event rates adjusted for the competing risk of death were 7.6% for women and 18.3% for men. Standard risk factors (male sex, systolic blood pressure, antihypertensive treatment, total and high-density lipoprotein cholesterol, smoking, and diabetes mellitus), measured at baseline, were significantly related to the incidence of hard CVD and remained significant when updated regularly on follow-up. Body mass index was associated positively with 30-year risk of hard CVD only in models that did not update risk factors. Model performance was excellent as indicated by cross-validated discrimination C=0.803 and calibration 2=4.25 (P=0.894). In contrast, 30-year risk predictions based on different applications of 10-year functions proved inadequate.

Conclusions— Standard risk factors remain strong predictors of hard CVD over extended follow-up. Thirty-year risk prediction functions offer additional risk burden information that complements that of 10-year functions.

  O. H Franco , J. M Massaro , J Civil , M. R Cobain , B O'Malley and R. B. D'Agostino
 

Background— We evaluated the progression of the metabolic syndrome (MetS) and its components, the trajectories followed by individuals entering MetS, and the manner in which different trajectories predict cardiovascular disease and mortality.

Methods and Results— Using data from 3078 participants from the Framingham Offspring Study (a cohort study) who attended examinations 4 (1987), 5 (1991), and 6 (1995), we evaluated the progression of MetS and its components. MetS was defined according to the Adult Treatment Panel III criteria. Using logistic regression, we evaluated the predictive ability of the presence of each component of the MetS on the subsequent development of MetS. Additionally, we examined the probability of developing cardiovascular disease or mortality (until 2007) by having specific combinations of 3 that diagnose MetS. The prevalence of MetS almost doubled in 10 years of follow-up. Hyperglycemia and central obesity experienced the highest increase. High blood pressure was most frequently present when a diagnosis of MetS occurred (77.3%), and the presence of central obesity conferred the highest risk of developing MetS (odds ratio, 4.75; 95% confidence interval, 3.78 to 5.98). Participants who entered the MetS having a combination of central obesity, high blood pressure, and hyperglycemia had a 2.36-fold (hazard ratio, 2.36; 95% confidence interval, 1.54 to 3.61) increase of incident cardiovascular events and a 3-fold (hazard ratio, 3.09, 95% confidence interval, 1.93 to 4.94) increased risk of mortality.

Conclusions— Particular trajectories and combinations of factors on entering the MetS confer higher risks of incident cardiovascular disease and mortality in the general population and among those with MetS. Intense efforts are required to identify populations with these particular combinations and to provide them with adequate treatment at early stages of disease.

  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
  Background—

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.

Conclusions—

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.

  A Dehghan , Q Yang , A Peters , S Basu , J. C Bis , A. R Rudnicka , M Kavousi , M. H Chen , J Baumert , G. D.O Lowe , B McKnight , W Tang , M de Maat , M. G Larson , S Eyhermendy , W. L McArdle , T Lumley , J. S Pankow , A Hofman , J. M Massaro , F Rivadeneira , M Kolz , K. D Taylor , C. M van Duijn , S Kathiresan , T Illig , Y. S Aulchenko , K. A Volcik , A. D Johnson , A. G Uitterlinden , G. H Tofler , C Gieger , Psaty Wellcome Trust Case Control Consortium , D. J Couper , E Boerwinkle , W Koenig , C. J O`Donnell , J. C Witteman , D. P Strachan , N. L Smith and A. R. Folsom
 

Background— Fibrinogen is both central to blood coagulation and an acute-phase reactant. We aimed to identify common variants influencing circulation fibrinogen levels.

Methods and Results— We conducted a genome-wide association analysis on 6 population-based studies, the Rotterdam Study, the Framingham Heart Study, the Cardiovascular Health Study, the Atherosclerosis Risk in Communities Study, the Monitoring of Trends and Determinants in Cardiovascular Disease/KORA Augsburg Study, and the British 1958 Birth Cohort Study, including 22 096 participants of European ancestry. Four loci were marked by 1 or more single-nucleotide polymorphisms that demonstrated genome-wide significance (P<5.0x10–8). These included a single-nucleotide polymorphism located in the fibrinogen β chain (FGB) gene and 3 single-nucleotide polymorphisms representing newly identified loci. The high-signal single-nucleotide polymorphisms were rs1800789 in exon 7 of FGB (P=1.8x10–30), rs2522056 downstream from the interferon regulatory factor 1 (IRF1) gene (P=1.3x10–15), rs511154 within intron 1 of the propionyl coenzyme A carboxylase (PCCB) gene (P=5.9x10–10), and rs1539019 on the NLR family pyrin domain containing 3 isoforms (NLRP3) gene (P=1.04x10–8).

Conclusions— Our findings highlight biological pathways that may be important in regulation of inflammation underlying cardiovascular disease.

  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
  Background—

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).

Conclusions—

Periaortic fat is associated with low ABI and intermittent claudication.

  G Thanassoulis , J. M Massaro , U Hoffmann , A. A Mahabadi , R. S Vasan , C. J O'Donnell and C. S. Fox
  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.

  R. S Lovely , S. C Kazmierczak , J. M Massaro , R. B D'Agostino , C. J O'Donnell and D. H. Farrell
 

Background: Studies of disease associations with ' fibrinogen, a newly emerging risk factor for cardiovascular disease, have been hampered by the lack of a standardized and well-characterized assay.

Methods: We developed an immunometric technique to measure ' fibrinogen concentrations in plasma and studied the clinical utility of this test in samples from healthy individuals enrolled in the Framingham Offspring Study and in a separate case/control study of coronary artery disease (CAD). Monoclonal antibody 2.G2.H9, specific for the unique carboxyl terminal peptide of the fibrinogen ' chain, was used as capture antibody. Sheep antihuman fibrinogen/horseradish peroxidase conjugate was used for detection, with 3,3',5,5'-tetramethylbenzidine as substrate. We evaluated the linearity, imprecision, analytical specificity, and lower limit of quantification of the assay. We determined the reference interval for ' fibrinogen in healthy individuals from the Framingham Offspring Study (n = 2879) and quantified associations between ' fibrinogen and cardiovascular disease risk factors. The sensitivity and specificity of ' fibrinogen in evaluating CAD patients (n = 133) was determined with ROC curve analysis.

Results: The ' fibrinogen ELISA had within-run CVs of 13.4% at 0.127 g/L and 4.8% at 0.416 g/L. The limit of quantification at an imprecision of 20% was 0.10 g/L. The reference interval for healthy individuals was 0.088–0.551 g/L. ROC curve analysis of results from patients with CAD yielded an area under the curve of 0.76, with a diagnostic accuracy of 0.78 at a decision threshold of 0.30 g/L.

Conclusions: ' Fibrinogen shows excellent utility for cardiovascular risk analysis.

  S. A Porter , J. M Massaro , U Hoffmann , R. S Vasan , C. J O`Donnel and C. S. Fox
  OBJECTIVE

Obesity is associated with increased metabolic and cardiovascular risk. The ectopic fat hypothesis suggests that subcutaneous fat may be protective, but this theory has yet to be fully explored.

RESEARCH DESIGN AND METHODS

Participants from the Framingham Heart Study (n = 3,001, 48.5% women) were stratified by visceral adipose tissue (VAT) into sex-specific tertiles. Within these tertiles, age-adjusted abdominal subcutaneous adipose tissue (SAT) tertiles were examined in relation to cardiometabolic risk factors.

RESULTS

In the lowest VAT tertile, risk factor prevalence was low, although systolic blood pressure in women and rates of high triglycerides, impaired fasting glucose, hypertension, and the metabolic syndrome in men increased with increasing SAT tertile (all P < 0.04). In contrast, in the top VAT tertile, lower triglycerides were observed in men with increasing SAT (64.4% high triglycerides in SAT tertile 1 vs. 52.7% in SAT tertile 3, P = 0.03). Similar observations were made for women, although results were not statistically significant (50.6% high triglycerides in SAT tertile 1 vs. 41.0% in tertile 3, P = 0.10). Results in the highest VAT tertile were notable for a lack of increase in the prevalence of low HDL in men and women and in rates of impaired fasting glucose in men with increasing subcutaneous fat, despite sizable differences in BMI across SAT tertiles (27.1 to 36.3 kg/m2[women]; 28.1 to 35.7 kg/m2[men]).

CONCLUSIONS

Although adiposity increases the absolute risk of metabolic and cardiovascular disease, abdominal subcutaneous fat is not associated with a linear increase in the prevalence of all risk factors among the obese, most notably, high triglycerides.

 
 
 
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