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Background: Self-rated health is a commonly used global indicator of health status. Few studies have examined the association of self-rated health and mobility with estrone and estradiol in men. Accordingly, we determined the cross-sectional, incident, and mediating relations between circulating estrone and estradiol levels with self-rated health, mobility limitation, and physical performance in community-dwelling men.Methods: The cross-sectional sample included 1,148 men, who attended Framingham Offspring Study Examinations 7 and 8. Estrone and estradiol levels were measured using liquid chromatography tandem mass spectrometry at Examination 7. Self-reported mobility limitation and self-rated health were assessed at Examinations 7 and 8. Additionally, short physical performance battery, usual walking speed, and grip strength were assessed at Examination 7.Results: In incident analysis, estradiol levels at Examination 7 were associated with increased odds of fair or poor self-rated health at Examination 8, after adjusting for age, body mass index, comorbidities, and testosterone levels; in an individual with 50% greater estradiol than other, the odds of reporting "fair or poor" self-rated health increased by 1.78 (95% confidence interval: 1.25-2.55; p = .001). Neither estrone nor estradiol levels were associated with any physical performance measure at baseline.Conclusions: Higher circulating levels of estradiol are associated with increased risk of incident fair/poor self-rated health in community-dwelling men. The mechanisms by which circulating levels of estradiol are related to self-rated health in men need further investigation. [ABSTRACT FROM AUTHOR]

Background: The healthy aging index (HAI) was developed as a marker of health in multiple systems that can identify individuals who age most successfully.Methods: We calculated an HAI in 934 Framingham Offspring Study participants aged 60 or older at baseline. Heart rate and C-reactive protein (CRP) were added in modified versions of the HAI. Cox proportional hazard models were used to quantify the association of the HAI with mortality, cardiovascular disease (CVD), and cancer. We used fully conditional specification to multiply impute missing values for HAI components, increasing the sample size by 44%.Results: Over 10 years of follow-up, there were 138 deaths, 103 incident cases of CVD, and 138 incident cases of cancer. In models adjusted for age, sex, and behavioral risk factors, the HAI was associated with mortality (hazard ratio [HR] per unit of HAI 1.24, 95% confidence interval [CI] 1.13-1.36) and with CVD (HR 1.27, 95% CI 1.13-1.42), but not with cancer (HR 1.01, 95% CI 0.91-1.11) in observed (non-missing) data. In multivariable models further adjusting for prevalent diseases, results were slightly attenuated. When including heart rate and CRP, a modified HAI gave stronger associations. Results with imputed data are similar to results from complete case analyses.Conclusions: In our large community-based sample, the HAI is a strong predictor of mortality and CVD. Other factors that are strongly associated with mortality, such as heart rate and CRP can improve the ability of the HAI to identify the healthiest older adults. [ABSTRACT FROM AUTHOR]

Background: Alcohol consumption has important health-related consequences and numerous biological and social determinants. Objective: To explore quantitatively whether alcohol consumption behavior spreads from person to person in a large social network of friends, coworkers, siblings, spouses, and neighbors, followed for 32 years. Design: Longitudinal network cohort study. Setting: The Framingham Heart Study. Participants: 12 067 persons assessed at several time points between 1971 and 2003. Measurements: Self-reported alcohol consumption (number of drinks per week on average over the past year and number of days drinking within the past week) and social network ties, measured at each time point. Results: Clusters of drinkers and abstainers were present in the network at all time points, and the clusters extended to 3 degrees of separation. These clusters were not only due to selective formation of social ties among drinkers but also seem to reflect interpersonal influence. Changes in the alcohol consumption behavior of a person's social network had a statistically significant effect on that person's subsequent alcohol consumption behavior. The behaviors of immediate neighbors and coworkers were not significantly associated with a person's drinking behavior, but the behavior of relatives and friends was. Limitations: A nonclinical measure of alcohol consumption was used. Also, it is unclear whether the effects on long-term health are positive or negative, because alcohol has been shown to be both harmful and protective. Finally, not all network ties were observed. Conclusion: Network phenomena seem to influence alcohol consumption behavior. This has implications for clinical and public health interventions and further supports group-level interventions to reduce problematic drinking. Primary Funding Source: National Institutes of Health and the Robert Wood Johnson Foundation. The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute. [ABSTRACT FROM AUTHOR]

Background: Breast and prostate cancer are two commonly diagnosed cancers in the United States. Prior work suggests that cancer causing genes and cancer susceptibility genes can be identified. Methods: We conducted a genome-wide association study (Affymetrix 100K SNP GeneChip) of cancer in the community-based Framingham Heart Study. We report on 2 cancer traits - prostate cancer and breast cancer - in up to 1335 participants from 330 families (54% women, mean entry age 33 years). Multivariable-adjusted residuals, computed using Cox proportional hazards models, were tested for association with qualifying SNPs (70, 987 autosomal SNPs with genotypic call rate ≥80%, minor allele frequency ≥10%, Hardy-Weinberg test p ≥ 0.001) using generalized estimating equations (GEE) models and family based association tests (FBAT). Results: There were 58 women with breast cancer and 59 men with prostate cancer. No SNP associations attained genome-wide significance. The top SNP associations in GEE models for each trait were as follows: breast cancer, rs2075555, p = 8.0 × 10-8 in COL1A1; and prostate cancer, rs9311171, p = 1.75 × 10-6 in CTDSPL. In analysis of selected candidate cancer susceptibility genes, two MSR1 SNPs (rs9325782, GEE p = 0.008 and rs2410373, FBAT p = 0.021) were associated with prostate cancer and three ERBB4 SNPs (rs905883 GEE p = 0.0002, rs7564590 GEE p = 0.003, rs7558615 GEE p = 0.0078) were associated with breast cancer. The previously reported risk SNP for prostate cancer, rs1447295, was not included on the 100K chip. Results of cancer phenotype-genotype associations for all autosomal SNPs are web posted at http://www.ncbi.nlm.nih.gov/projects/ gap/cgi-bin/study.cgi?id=phs000007. Conclusion: Although no association attained genome-wide significance, several interesting associations emerged for breast and prostate cancer. These findings can serve as a resource for replication in other populations to identify novel biologic pathways contributing to cancer susceptibility. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) and its most common manifestations - including coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF) - are major causes of morbidity and mortality. In many industrialized countries, cardiovascular disease (CVD) claims more lives each year than any other disease. Heart disease and stroke are the first and third leading causes of death in the United States. Prior investigations have reported several single gene variants associated with CHD, stroke, HF, and AF. We report a community-based genome-wide association study of major CVD outcomes. Methods: In 1345 Framingham Heart Study participants from the largest 310 pedigrees (54% women, mean age 33 years at entry), we analyzed associations of 70,987 qualifying SNPs (Affymetrix 100K GeneChip) to four major CVD outcomes: major atherosclerotic CVD (n = 142; myocardial infarction, stroke, CHD death), major CHD (n = 118; myocardial infarction, CHD death), AF (n = 151), and HF (n = 73). Participants free of the condition at entry were included in proportional hazards models. We analyzed model-based deviance residuals using generalized estimating equations to test associations between SNP genotypes and traits in additive genetic models restricted to autosomal SNPs with minor allele frequency ≥0.10, genotype call rate ≥0.80, and Hardy-Weinberg equilibrium p-value ≥ 0.001. Results: Six associations yielded p < 10-5. The lowest p-values for each CVD trait were as follows: major CVD, rs499818, p = 6.6 × 10-6; major CHD, rs2549513, p = 9.7 × 10-6; AF, rs958546, p = 4.8 × 10-6; HF: rs740363, p = 8.8 × 10-6. Of note, we found associations of a 13 Kb region on chromosome 9p21 with major CVD (p 1.7 - 1.9 × 10-5) and major CHD (p 2.5 - 3.5 × 10-4) that confirm associations with CHD in two recently reported genome-wide association studies. Also, rs10501920 in CNTN5 was associated with AF (p = 9.4 × 10-6) and HF (p = 1.2 × 10-4). Complete results for these phenotypes can be found at the dbgap website http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. Conclusion: No association attained genome-wide significance, but several intriguing findings emerged. Notably, we replicated associations of chromosome 9p21 with major CVD. Additional studies are needed to validate these results. Finding genetic variants associated with CVD may point to novel disease pathways and identify potential targeted preventive therapies. [ABSTRACT FROM AUTHOR]

Objective: To identify chromosomal regions linked to age at natural menopause. Design: Two-generation families studied with a 10-centimorgan (cM) genome-wide scan. Setting: The Framingham Study, a community-based epidemiologic study. Patient(s): A total of 861 women in 291 families reporting a natural menopause (mean age at menopause, 49 years). Intervention(s): None. Main Outcome Measure(s): Multipoint variance components linkage analysis was performed with Genehunter software (Whitehead Institute, Massachusetts Institute of Technology, Boston, MA) for age at natural menopause. Result(s): In the crude variance components analysis, 11 chromosomes had a log odds ratio (LOD) score of ≥1.0. Two chromosomal regions revealed suggestive linkage: chromosome 8 at 26 cM (LOD 2.6; nearest marker GATA23D06) and chromosome 16 at 11 cM (LOD 2.4; nearest marker ATA41E04). In the analysis adjusted for generation, smoking, and body mass index, chromosome 11 revealed suggestive linkage at 113 cM (LOD 2.1; nearest marker GATA23E06). Conclusion(s): We have identified novel loci suggestive for linkage to age at natural menopause. Further research is needed to identify genes involved in the onset of menopause, which might provide insights into loss of fertility. [Copyright &y& Elsevier]

Cumulative exposure to socioeconomic disadvantage across the life course may be inversely associated with coronary heart disease (CHD); the mechanisms are not fully clear. An objective of this study was to determine whether cumulative life-course socioeconomic position (SEP) is associated with CHD incidence in a well-characterized US cohort that had directly assessed childhood and adulthood measures of SEP and prospectively measured CHD incidence. Furthermore, analyses aimed to evaluate whether adjustment for CHD risk factors reduces the association between cumulative life-course SEP and CHD. The authors examined 1,835 subjects who participated in the Framingham Heart Study Offspring Cohort from 1971 through 2003 (mean age, 35.0 years; 52.4% women). Childhood SEP was measured as fathers education; adulthood SEP was assessed as own education and occupation. CHD incidence included myocardial infarction, coronary insufficiency, and coronary death. Cox proportional hazards analyses indicated that cumulative SEP was associated with incident CHD after adjustment for age and sex (hazard ratio = 1.82, 95% confidence interval: 1.17, 2.85 for low vs. high cumulative SEP score). Adjustment for CHD risk factors reduced that magnitude of association (hazard ratio = 1.29, 95% confidence interval: 0.78, 2.13). These findings underscore the potential importance of CHD prevention and treatment efforts for those whose backgrounds include low SEP throughout life. [ABSTRACT FROM AUTHOR]

Abstract: Associations between life course socioeconomic position (SEP) and novel biological risk markers for coronary heart disease such as inflammatory markers are not well understood. Most studies demonstrate inverse associations of life course SEP with C-reactive protein (CRP), interleukin-6 (IL-6) and fibrinogen, however little is known about associations between life course SEP and other inflammatory markers including intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor II (TNFR2), lipoprotein phospholipase A2 (Lp-PLA2) activity, monocyte chemoattractant protein-1 (MCP-1) or P-selectin. The objectives of this analysis were to determine whether three life course SEP frameworks (“accumulation of risk”, “social mobility” and “sensitive periods”) are associated with the aforementioned inflammatory markers. We examined 1413 Framingham Offspring Study participants (mean age 61.2 ± 8.6 years, 54% women), using multivariable regression analyses. In age- and sex-adjusted regression analyses, cumulative SEP (“accumulation of risk” SEP framework), for low vs. high SEP, was inversely associated with CRP, IL-6, ICAM-1, TNFR2, Lp-PLA2 activity, MCP-1 and fibrinogen. We found that there were few consistent trends between social mobility trajectories and most inflammatory markers. Own educational attainment was inversely associated with 7 of 8 studied inflammatory markers, while father’s education, father’s occupation and own occupation were inversely associated with 4, 5 and 4 inflammatory markers, respectively, in age- and sex-adjusted analyses. The strengths of association between SEP and inflammatory markers were typically substantially accounted for by CHD risk markers (smoking, body mass index, systolic blood pressure, total:HDL cholesterol ratio, fasting glucose, medications, depressive symptomatology) suggesting these may be important mechanisms that explain associations between SEP and the studied inflammatory markers. [Copyright &y& Elsevier]