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1.  Segment-specific association between plasma homocysteine and carotid artery intima-media thickness in the Framingham Heart Study 
Higher plasma total homocysteine (tHcy) is an established risk factor for cardiovascular disease. The relation between tHcy and carotid artery intima-media thickness (IMT) at the internal carotid artery (ICA)/bulb-IMT and common carotid artery (CCA)-IMT has not been systematically examined. Since the ICA/bulb segment is more prone to plaque formation than the CCA segment, differential associations with tHcy at these sites might suggest mechanisms of tHcy action.
We examined the cross-sectional segment-specific relations of tHcy to ICA/bulb-IMT and CCA-IMT in 2,499 participants from the Framingham Offspring Study, free of cardiovascular disease.
In multivariable linear regression analysis, ICA/bulb-IMT was significantly higher in the fourth tHcy quartile category compared to the other quartile categories, in both the age- and sex-adjusted and in the multivariable-adjusted model (P for trend <0.0001 and <0.01, respectively). We observed a significant age by tHcy interaction for ICA/bulb-IMT (P=0.03) and therefore stratified the analyses by median age (58 years). There was a significant positive trend between tHcy and ICA/bulb-IMT in individuals 58 years of age or older (P-trend <0.01), but not in the younger individuals (P-trend=0.24). For CCA-IMT, no significant trends were observed in any of the analyses.
The segment-specific association between elevated tHcy levels and ICA/bulb-IMT suggests an association between tHcy and plaque formation.
PMCID: PMC3011043  PMID: 20580253
carotid artery; intima-media thickness; homocysteine; atherosclerosis; Framingham Offspring Study
2.  Epidemiology of Left Ventricular False Tendons: Clinical Correlates in the Framingham Heart Study 
To describe the echocardiographic characteristics and investigate the clinical correlates and prognostic significance of left ventricular false tendons (LVFTs).
Although LVFTs are generally considered as anatomic variants, they have been associated with innocent precordial murmurs and electrocardiographic abnormalities in small case series. The correlates of LVFTs in the community are unknown.
We compared 101 Framingham Study participants with LVFTs (mean age 56 years, 45% women) on routine two-dimensional echocardiograms with 151 referents without LVFTs (mean age 57 years, 44% women). We examined the cross-sectional clinical, electrocardiographic (rest and ambulatory), and echocardiographic correlates of LVFTs using logistic regression models, and evaluated the prospective association between LVFTs and all-cause mortality using Cox proportional hazards regression models.
A total of 107 LVFTs (94 simple with two points of attachment, and 13 complex/branching type with three or more points of attachment) were identified in 101 participants. LVFTs were most commonly visualized in the apical four chamber view (81%) and were predominantly localized to apical-third of the LV cavity (78%). LVFTs were associated with the presence of innocent precordial murmurs (multivariable adjusted odds ratio [OR] 5.55, 95% confidence interval [CI] 1.40-21.94), and electrocardiographic LV hypertrophy (OR 4.43, 95% CI 1.08-18.25). Body mass index (BMI) was inversely related to the presence of LVFTs (per kg/m2 increment, OR 0.94, 95% CI 0.88-0.99). LVFTs were not associated with QRS axis deviation, ventricular premature beats or repolarization abnormalities (all p-values >0.20). During a mean (±SD) follow-up of 7.7 (±1.6) years, 15 participants with and 19 without LVFTs died. In multivariable analyses, presence of LVFTs was not associated with the risk of death (p=0.92).
In our community-based sample of middle-aged to elderly white women and men, LVFTs were more likely to be identified in individuals with lower BMI, were cross-sectionally associated with the presence of innocent precordial murmurs and electrocardiographic LV hypertrophy, but were not associated with the risk of mortality.
PMCID: PMC2722746  PMID: 19423290
Left Ventricular False Tendons; Tendons; Echocardiography; Electrocardiography; Holter; Heart murmurs
3.  Relation of Smoking Status to a Panel of Inflammatory Markers: The Framingham Offspring 
Atherosclerosis  2008;201(1):217-224.
We sought to investigate the hypothesis that smoking is accompanied by systemic inflammation.
Methods and Results
We examined the relation of smoking to 11 systemic inflammatory markers in Framingham Study participants (n=2944, mean age 60 years, 55% women, 12% ethnic minorities) examined from 1998–2001. The cohort was divided into never (n=1149), former (n=1424), and current smokers with last cigarette >6 hours (n=134) or ≤6 hours (n=237) prior to phlebotomy. In multivariable-adjusted models there were significant overall between-smoking group differences (defined as p<0.0045 to account for multiple testing) for every inflammatory marker tested, except for serum CD40 ligand (CD40L), myeloperoxidase (MPO) and tumor necrosis factor receptor-2 (TNFR2). With multivariable-adjustment, pair-wise comparisons with never smokers revealed that former smokers had significantly lower concentrations of plasma CD40L (p<0.0001) and higher concentrations of C-reactive protein (p=0.002).
As opposed to never smokers, those with acute cigarette smoke exposure (≤6 hours) had significantly higher concentrations of all markers (p<0.0001) except serum CD40L, MPO, and TNFR2; plasma CD40L were significantly lower. Compared with never smokers, cigarette smokers have significantly elevated concentrations of most circulating inflammatory markers, consistent with the hypothesis that smoking is associated with a systemic inflammatory state.
PMCID: PMC2783981  PMID: 18289552
smoking; inflammation; cardiovascular disease; epidemiology
4.  Advance Care Planning and Health Care Preferences of Community-Dwelling Elders: The Framingham Heart Study 
To describe self-reported advance care planning, health care preferences, use of advance directives, and health perceptions in a very elderly community-dwelling sample.
Surviving participants of the original cohort of the Framingham Heart Study who were cognitively intact and attended a routine research exam between February 2004 and October 2005. Participants were queried about discussions about end of life care, preferences for care, documentation of advance directives, and health perceptions.
Among 220 community-dwelling respondents, 67% were women with a mean age of 88 years (range 84-100). Overall 69% discussed their wishes for medical care at the end of life with someone, but only 17% discussed their wishes with a physician or health care provider. Two-thirds had a health care proxy, 55% had a living will, and 41% had both. Most (80%) respondents preferred comfort care over life-extending care, and 71% preferred to die at home; however, substantially fewer respondents said they would rather die than receive specific life-prolonging interventions [chronic ventilator (63%) or feeding tube (64%)]. Many were willing to endure distressing health states, with less than half indicating that they would rather die than live out their life in a great deal of pain (46%) or be confused/forgetful (45%) all of the time.
Although the vast majority of very elderly community-dwellers in this sample appear to prefer comfort measures at the end of life, many said they were willing to endure specific life-prolonging interventions and distressing health states to avoid death. Our results highlight the need for physicians better understand patients’ preferences and goals of care to help them make informed decisions at the end of life.
PMCID: PMC2693192  PMID: 18840800
advance directives; geriatrics; end of life care; patient centered care; decision-making

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