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.

Vitamin K and vitamin D status: associations with inflammatory markers in the Framingham Offspring Study.

In vitro data suggest protective roles for vitamins K and D in inflammation. To examine associations between vitamins K and D and inflammation in vivo, the authors used multiple linear regression analyses, adjusted for age, sex, body mass index, triglyceride concentrations, use of aspirin, use of lipid-lowering medication, season, menopausal status, and hormone replacement therapy. Participants were from the Framingham Offspring Study (1997-2001; n = 1,381; mean age = 59 years; 52% women).

Genetic correlates of brain aging on MRI and cognitive test measures: a genome-wide association and linkage analysis in the Framingham Study.

Background: Brain magnetic resonance imaging (MRI) and cognitive tests can identify heritable endophenotypes associated with an increased risk of developing stroke, dementia and Alzheimer's disease (AD). We conducted a genome-wide association (GWA) and linkage analysis exploring the genetic basis of these endophenotypes in a community-based sample.

Methods: A total of 705 stroke- and dementia-free Framingham participants (age 62 +9 yrs, 50% male) who underwent volumetric brain MRI and cognitive testing (1999-2002) were genotyped.

Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study.

Background: Family studies and heritability estimates provide evidence for a genetic contribution to variation in the human life span.

Methods: We conducted a genome wide association study (Affymetrix 100K SNP GeneChip) for longevity-related traits in a community-based sample. We report on 5 longevity and aging traits in up to 1345 Framingham Study participants from 330 families.

Antecedent blood pressure, body mass index, and the risk of incident heart failure in later life.

Higher blood pressure and body mass index (BMI) are risk factors for heart failure. It is unknown whether the presence of these risk factors in midadulthood affect the future development of heart failure. In the community-based Framingham Heart Study, we examined the associations of antecedent blood pressure and BMI with heart failure incidence in later life.

Parental occurrence of premature cardiovascular disease predicts increased coronary artery and abdominal aortic calcification in the Framingham Offspring and Third Generation cohorts.

Background: Parental premature cardiovascular disease (CVD) is a risk factor for coronary heart disease (CHD). We related validated parental premature CVD with the subclinical measures of coronary artery (CAC) and abdominal aortic (AAC) calcification in the community.

Methods And Results: We studied 2 generations of Framingham Heart Study subjects who underwent multidetector computed tomography measurements of CAC and AAC and who had 2 parents in the study.

Visceral and subcutaneous adipose tissue volumes are cross-sectionally related to markers of inflammation and oxidative stress: the Framingham Heart Study.

Background: Excess adiposity is associated with greater systemic inflammation. Whether visceral adiposity is more proinflammatory than subcutaneous abdominal adiposity is unclear.

Methods And Results: We examined the relations of abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), assessed by multidetector computerized tomography, to circulating inflammatory and oxidative stress biomarkers in 1250 Framingham Heart Study participants (52% women; age 60+/-9 years).

Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study.

Background: Visceral adipose tissue (VAT) compartments may confer increased metabolic risk. The incremental utility of measuring both visceral and subcutaneous abdominal adipose tissue (SAT) in association with metabolic risk factors and underlying heritability has not been well described in a population-based setting.

Methods And Results: Participants (n=3001) were drawn from the Framingham Heart Study (48% women; mean age, 50 years), were free of clinical cardiovascular disease, and underwent multidetector computed tomography assessment of SAT and VAT volumes between 2002 and 2005.

Stent thrombosis in randomized clinical trials of drug-eluting stents.

Background: Definitions of stent thrombosis that have been used in clinical trials of drug-eluting stents have been restrictive and have not been used in a uniform manner.

Methods: We applied a hierarchical classification of stent thrombosis set by the Academic Research Consortium (ARC) across randomized trials involving 878 patients treated with sirolimus-eluting stents, 1400 treated with paclitaxel-eluting stents, and 2267 treated with bare-metal stents. We then pooled 4 years of follow-up data.

Association of white matter hyperintensity volume with decreased cognitive functioning: the Framingham Heart Study.

Objective: To examine the relationship between white matter hyperintensity (WMH) volume on magnetic resonance images and cognitive tests in a large, population-based sample.

Methods: Quantitative magnetic resonance imaging and neuropsychological evaluations were performed in 1820 dementia- and stroke-free participants from the Framingham Offspring Cohort. The WMH volume relative to total cranial volume was computed; WMH volumes more than 1 SD above the age-predicted mean were defined as large.

Evidence for lower variability of coronary artery calcium mineral mass measurements by multi-detector computed tomography in a community-based cohort--consequences for progression studies.

Purpose: To compare the measurement variability for coronary artery calcium (CAC) measurements using mineral mass compared with a modified Agatston score (AS) or volume score (VS) with multi-detector CT (MDCT) scanning, and to estimate the potential impact of these methods on the design of CAC progression studies.

Materials And Methods: We studied 162 consecutive subjects (83 women, 79 men, mean age 51 +/- 11 years) from a general Caucasian community-based cohort (Framingham Heart Study) with duplicate runs of prospective electrocardiographically-triggered MDCT scanning. Each scan was independently evaluated for the presence of CAC by four experienced observers who determined a "modified" AS, VS and mineral mass.

Genome-wide scan for white matter hyperintensity: the Framingham Heart Study.

Background And Purpose: White matter hyperintensity (WMH) volume is associated with aging and cerebrovascular disease and has been demonstrated to have a high heritability in the Framingham Heart Study as well as in other studies. We performed a genome-wide linkage analysis to identify chromosomal regions that may harbor genes influencing WMH in a family-based sample of the Framingham Heart Study.

Methods: Brain magnetic resonance scans were performed, and WMH and total cranial volume (TCV) were quantified as previously described on 2259 cohort and offspring participants.

Alcohol consumption and platelet activation and aggregation among women and men: the Framingham Offspring Study.

Background: Alcohol intake has been associated with lower platelet activity; however, few large-scale studies have included women, and to our knowledge, the relationship of alcohol intake with measures of platelet activation has not been studied.

Methods: We performed a cross-sectional analysis of adults free of cardiovascular disease enrolled in the Framingham Offspring Study. Study physicians assessed alcohol consumption with a standardized questionnaire.

Genome scan of systemic biomarkers of vascular inflammation in the Framingham Heart Study: evidence for susceptibility loci on 1q.

Vascular inflammation plays a central role in atherosclerosis and inflammatory biomarkers predict risk of cardiovascular disease (CVD). Thus, finding genes that influence systemic levels of inflammatory biomarkers may provide insights into genetic determinants of vascular inflammation and CVD. We conducted variance-component linkage analyses of blood levels of four biomarkers of vascular inflammation [C-reactive protein (CRP), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1)] in 304 extended families from the Framingham Heart Study, using data from a 10cM genome scan.

CCL2 polymorphisms are associated with serum monocyte chemoattractant protein-1 levels and myocardial infarction in the Framingham Heart Study.

Background: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine strongly implicated in promoting atherosclerosis in animal models, but human genetic evidence is contradictory.

Methods And Results: We analyzed the association of genetic variation in the MCP-1 gene (CCL2) with prevalent myocardial infarction and serum MCP-1 levels in the community-based Framingham Heart Study Offspring Cohort (50% women; mean age, 62 years). MCP-1 levels and CCL2 genotypes were determined in 3236 and 1797 individuals, respectively.

Brachial artery vasodilator function and systemic inflammation in the Framingham Offspring Study.

Background: In experimental studies, traditional risk factors and proinflammatory processes alter the regulatory functions of the vascular endothelium to promote atherosclerosis. These alterations include expression of leukocyte adhesion molecules and decreased bioavailability of endothelium-derived nitric oxide, an important regulator of vascular homeostasis and tone. The precise relations among risk factors, inflammation, and nitric oxide bioavailability remain uncertain.

Warfarin and aspirin use and the predictors of major bleeding complications in atrial fibrillation (the Framingham Heart Study).

The Framingham Heart Study records of participants with atrial fibrillation (AF) during 1980 and 1994 were retrospectively reviewed to determine the prevalence of warfarin and aspirin use in AF. Anticoagulant use increased significantly in the 393 men and women (mean ages 72.5 and 79.

Utility of the Safe-Cross-guided radiofrequency total occlusion crossing system in chronic coronary total occlusions (results from the Guided Radio Frequency Energy Ablation of Total Occlusions Registry Study).

The Safe-Cross radiofrequency guidewire (IntraLuminal Therapeutics, Carlsbad, California) combines 3 capabilities: (1) steerability of a conventional 0.014-in intermediate-stiffness guidewire, (2) optical coherence reflectometry to warn the operator when the wire tip approaches within 1 mm of the vessel wall, and (3) delivery of radiofrequency energy pulses to the wire tip to facilitate passage through an occluded segment. The Guided Radio Frequency Energy Ablation of Total Occlusions Registry was a prospective, nonrandomized, multicenter registry that enrolled 116 patients who had long-term coronary total occlusions and in whom a >10-minute good-faith attempt to cross the occlusion using conventional guidewires had failed.

Lifetime risk for development of atrial fibrillation: the Framingham Heart Study.

Background: Atrial fibrillation (AF) is the most common cardiac dysrhythmia and a source of considerable morbidity and mortality, but lifetime risk for AF has not been estimated.

Methods And Results: We included all participants in the Framingham Heart Study who were free of AF at index ages of 40 years and older. We estimated lifetime risks for AF (including atrial flutter) to age 95 years, with death free of AF as a competing event.

Heritability and correlates of intercellular adhesion molecule-1 in the Framingham Offspring Study.

Objectives: We sought to determine the clinical factors and heritability associated with inflammation measured as circulating levels of soluble-intercellular adhesion molecule-1 (sICAM-1) in a community-based cohort.

Background: Several prospective studies indicate that circulating sICAM-1 is predictive of future cardiovascular events. However, in some studies this predictive value is lost after multivariable adjustment for traditional cardiovascular disease (CVD) risk factors.

Cerebral microbleeds: prevalence and associations with cardiovascular risk factors in the Framingham Study.

Background And Purpose: Cerebral microbleeds (CMBs) are areas of low signal intensity on gradient echo T2*-weighted magnetic resonance imaging (T2*MRI) corresponding to hemosiderin deposits in the perivascular space. Microangiopathy from atherosclerosis or amyloid angiopathy might lead to the formation of these lesions; therefore, there may be associations between CMBs and cardiovascular risk factors, APOE allele status, and brain morphology. We examined these relationships in the Framingham Study (FHS).

Genetic variation in white matter hyperintensity volume in the Framingham Study.

Background And Purpose: In a previous study of normal elderly male twins, the heritability of quantitative white matter hyperintensity (WMH) volume has been estimated to be high (0.73). We investigated heritability of WMH in a family-based sample of the Framingham Heart Study for sex differences and the impact of age.

Presentation of multivariate data for clinical use: The Framingham Study risk score functions.

The Framingham Heart Study has been a leader in the development and dissemination of multivariable statistical models to estimate the risk of coronary heart disease. These models quantify the impact of measurable and modifiable risk factors on the development of coronary heart disease and can be used to generate estimates of risk of coronary heart disease over a predetermined period, for example the next 10 years. We developed a system, which we call a points system, for making these complex statistical models useful to practitioners.

Long-term alcohol consumption and the risk of atrial fibrillation in the Framingham Study.

Atrial fibrillation (AF) is a major risk factor for stroke. Although acute alcohol intake has been associated with AF, it is not known whether long-term alcohol consumption in moderation is associated with an increased risk of AF. We used a risk set method to assess the relation of long-term alcohol consumption to the risk of AF among participants in the Framingham Study.

Anticardiolipin antibodies and risk of ischemic stroke and transient ischemic attack: the Framingham cohort and offspring study.

Background And Purpose: The role of anticardiolipin antibodies (aCLs) as novel risk factors for ischemic stroke and transient ischemic attacks (TIAs) has been a matter of debate. Prior cohort studies included only selected subjects, mostly men. We related serum concentrations of aCLs to incident first ischemic stroke/TIA among men and women in the Framingham Heart Study cohort and offspring.