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Dutta A.,Epidemiology and Public Health Group | Dutta A.,University of Iowa | Henley W.,Epidemiology and Public Health Group | Henley W.,University of Iowa | And 10 more authors.
Circulation: Cardiovascular Genetics | Year: 2011

Background-Common variation at chromosome 9p21 (marked by rs10757278 or rs1333049) is associated with coronary artery disease (CAD) and peripheral vascular disease. A decreasing effect at older age was suggested, and effects on long-term mortality are unclear. We estimated 9p21 associations with CAD and all-cause mortality in a CAD diagnosis-free older population. We also estimated classification gains on adding the variant to the Framingham Risk Score (FRS) for CAD. Methods and Results-DNA was from an Established Populations for Epidemiological Study of the Elderly-Iowa cohort from 1988 (participants >71 years), with death certificates obtained to 2008 for 92% of participants. Cox regression models were adjusted for confounders and CAD risk factors. Of 1095 CAD diagnosis-free participants, 52% were heterozygous (CG) and 22% were homozygous (CC) for the risk C allele rs1333049. Unadjusted CAD-attributed death rates in the CC group were 30 vs 22 per 1000 person-years for the GG group. The C allele was associated with all-cause (hazard ratio, 1.19; 95% CI, 1.08 -1.30) and CAD (hazard ratio, 1.29; 95% CI, 1.08 -1.56) mortality, independent of CAD risk factors. There was no association with stroke deaths. Variant associations with CAD mortality were attenuated after the age of 80 years (age-interaction term P=0.05). In age group 71 to 80 years, FRS classified as high risk 21% of respondents who died of CAD within 10 years; adding 9p21 identified 27% of respondents. Conclusions-In 71- to 80-year-old subjects free of CAD diagnoses, 9p21 is associated with excess mortality, mainly attributed to CAD mortality. Adding 9p21 to the FRS may improve the targeting of CAD prevention in older people, but validation in independent samples is needed for confirmation. © 2011 American Heart Association, Inc.


Simanek A.M.,University of Michigan | Dowd J.B.,York College - The City University of New York | Pawelec G.,University of Tuebingen Medical School | Melzer D.,Epidemiology and Public Health Group | And 2 more authors.
PLoS ONE | Year: 2011

Background: Studies have suggested that CMV infection may influence cardiovascular disease (CVD) risk and mortality. However, there have been no large-scale examinations of these relationships among demographically diverse populations. The inflammatory marker C-reactive protein (CRP) is also linked with CVD outcomes and mortality and may play an important role in the pathway between CMV and mortality. We utilized a U.S. nationally representative study to examine whether CMV infection is associated with all-cause and CVD-related mortality. We also assessed whether CRP level mediated or modified these relationships. Methodology/Principal Findings: Data come from subjects ≥25 years of age who were tested for CMV and CRP level and were eligible for mortality follow-up on December 31st, 2006 (N = 14153) in the National Health and Nutrition Examination Survey (NHANES) III (1988-1994). Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and CVD-related mortality by CMV serostatus. After adjusting for multiple confounders, CMV seropositivity remained statistically significantly associated with all-cause mortality (HR 1.19, 95% CI: 1.01, 1.41). The association between CMV and CVD-related mortality did not achieve statistical significance after confounder adjustment. CRP did not mediate these associations. However, CMV seropositive individuals with high CRP levels showed a 30.1% higher risk for all-cause mortality and 29.5% higher risk for CVD-related mortality compared to CMV seropositive individuals with low CRP levels. Conclusions/Significance: CMV was associated with a significant increased risk for all-cause mortality and CMV seropositive subjects who also had high CRP levels were at substantially higher risk for both for all-cause and CVD-related mortality than subjects with low CRP levels. Future work should target the mechanisms by which CMV infection and low-level inflammation interact to yield significant impact on mortality. © 2011 Simanek et al.


Dutta A.,Epidemiology and Public Health Group | Henley W.,University of Exeter | Robine J.-M.,French Institute of Health and Medical Research | Langa K.M.,University of Michigan | And 3 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2013

Background. Children of centenarians have lower cardiovascular disease prevalence and live longer. We aimed to estimate associations between the full range of parental attained ages and health status in a middle-aged U.S. representative sample. Methods. Using Health and Retirement Study data, models estimated disease incidence and mortality hazards for respondents aged 51-61 years at baseline, followed up for 18 years. Full adjustment included sex, race, smoking, wealth, education, body mass index, and childhood socioeconomic status. Mother's and father's attained age distributions were used to define short-, intermediate-, and long-lived groups, yielding a ranked parental longevity score (n = 6,055, excluding short-long discordance). Linear models (n = 8,340) tested mother's or father's attained ages, adjusted for each other. Results. With increasing mother's or father's survival (>65 years), all-cause mortality declined 19% (hazard ratio [HR] = 0.81, 95% CI: 0.76-0.86, p <. 001) and 14% per decade (HR = 0.87, 95% CI: 0.81-0.92, p <. 001). Estimates changed only modestly when fully adjusted. Parent-in-law survival was not associated with mortality (n = 1,809, HR = 1.00, 95% CI: 0.90-1.12, p =. 98). Offspring with one or two long-lived parents had lower cancer incidence (938 cases, HR per parental longevity score = 0.76, 95% CI: 0.61-0.94, p =. 01) versus two intermediate parents. Similar HRs for diabetes (HR = 0.89, 95% CI: 0.84-0.96, p =. 001), heart disease (HR = 0.88, 95% CI: 0.82-0.93, p <. 001), and stroke (HR = 0.86, 95% CI: 0.78-0.95, p =. 002) were significant, but there was no trend for arthritis. Conclusions. The results provide the first robust evidence that increasing parental attained age is associated with lower cancer incidence in offspring. Health advantages of having centenarian parents extend to a wider range of parental longevity and may provide a quantitative trait of slower aging. © 2013 The Author.


Zivin K.,Serious Mental Illness Treatment Research and Evaluation Center | Zivin K.,University of Michigan | Llewellyn D.J.,Addenbrookes Hospital | Llewellyn D.J.,University of Cambridge | And 7 more authors.
American Journal of Geriatric Psychiatry | Year: 2010

Context: Depression negatively affects health and well being among older adults, but there have been no nationally representative comparisons of depression prevalence among older adults in England and the United States. Objective: The authors sought to compare depressive symptoms among older adults in these countries and identify sociodemographic and clinical correlates of depression in these countries. Design AND Setting: The authors assessed depressive symptoms in non-Hispanic whites aged 65 years and older in 2002 in two nationally representative, population-based studies: the U.S. Health and Retirement Study and English Longitudinal Study of Ageing. PARTICIPANTS: A total of 8,295 Health and Retirement Study respondents and 5,208 English Longitudinal Study of Ageing respondents. MAIN OUTCOME MEASURES: The authors measured depressive symptoms using the eight-item Center for Epidemiologic Studies Depression Scale. The authors determined whether depressive symptom differences between the United States and England were associated with sociodemographic characteristics, chronic health conditions, and health behaviors. Results: Significant depressive symptoms (Center for Epidemiologic Studies Depression Scale score ≥4) were more prevalent in English than U.S. adults (17.6% versus 14.6%, adjusted Wald test F[1, 1593] = 11.4, p < 0.001). Adjusted rates of depressive symptoms in England were 19% higher compared with the United States (odds ratio: 1.19, 95% confidence interval: 1.01-1.40). U.S. adults had higher levels of education, and net worth, but lower levels of activities of daily living/instrumental activities of daily living impairments, tobacco use, and cognitive impairment, which may have contributed to relatively lower levels of depressive symptoms in the United States. Conclusions: Older adults in the United States had lower rates of depressive symptoms than their English counterparts despite having more chronic health conditions. Future cross-national studies should identify how depression treatment influences outcomes in these populations. © 2010 American Association for Geriatric Psychiatry.


Melzer D.,Epidemiology and Public Health Group | Rice N.,Epidemiology and Public Health Group | Depledge M.H.,Environment and Human Health Group | Henley W.E.,University of Plymouth | Galloway T.S.,University of Exeter
Environmental Health Perspectives | Year: 2010

Background: Perfluorooctanoic acid (PFOA, also known as C8) and perfluorooctane sulfonate (PFOS) are stable compounds with many industrial and consumer uses. Their persistence in the environment plus toxicity in animal models has raised concern over low-level chronic exposure effects on human health. Objectives: We estimated associations between serum PFOA and PFOS concentrations and thyroid disease prevalence in representative samples of the U.S. general population. Methods: Analyses of PFOA/PFOS versus disease status in the National Health and Nutrition Examination Survey (NHANES) for 1999-2000, 2003-2004, and 2005-2006 included 3,974 adults with measured concentrations for perfluorinated chemicals. Regression models were adjusted for age, sex, race/ethnicity, education, smoking status, body mass index, and alcohol intake. Results: The NHANES-weighted prevalence of reporting any thyroid disease was 16.18% (n = 292) in women and 3.06% (n = 69) in men; prevalence of current thyroid disease with related medication was 9.89% (n = 163) in women and 1.88% (n = 46) in men. In fully adjusted logistic models, women with PFOA ≥ 5.7 ng/mL [fourth (highest) population quartile] were more likely to report current treated thyroid disease [odds ratio (OR) = 2.24; 95% confidence interval (CI), 1.38-3.65; p = 0.002] compared with PFOA ≤ 4.0 ng/mL (quartiles 1 and 2); we found a near significant similar trend in men (OR = 2.12; 95% CI, 0.93-4.82; p = 0.073). For PFOS, in men we found a similar association for those with PFOS ≥ 36.8 ng/mL (quartile 4) versus ≤ 25.5 ng/mL (quartiles 1 and 2: OR for treated disease = 2.68; 95% CI, 1.03-6.98; p = 0.043); in women this association was not significant. Conclusions: Higher concentrations of serum PFOA and PFOS are associated with current thyroid disease in the U.S. general adult population. More work is needed to establish the mechanisms involved and to exclude confounding and pharmacokinetic explanations.


Rice N.E.,Epidemiology and Public Health Group | Lang I.A.,Epidemiology and Public Health Group | Henley W.,University of Plymouth | Melzer D.,Epidemiology and Public Health Group
Rejuvenation Research | Year: 2010

Background: The baby-boom generation is entering retirement. Having experienced unprecedented prosperity and improved medical technology, they should be the healthiest generation ever. Methods: We compared prevalence of disease and risk factors at ages 50-61 years in baby boomers with the preceding generation and attributed differences to period or cohort effects. Data were from the Health Survey for England (HSE) from 1994 to 2007 (n=48,563). Logistic regression models compared health status between birth cohorts. Age-period-cohort models identified cohort and period effects separately. Results: Compared to the wartime generation, the baby-boomer group was heavier (3.02 kg; 95% confidence interval [CI], 2.42-3.63; p < 0.001) and reported more diagnoses of hypertension (odds ratio [OR]=1.48; CI, 1.27- 1.72; p < 0.001), diabetes (OR=1.71; CI, 1.37-2.12; p < 0.001), and mental illness (OR=1.90; CI, 1.54-2.53; p < 0.001). Baby boomers reported fewer heart attacks (OR=0.61; CI, 0.47-0.79; p < 0.001) and had lower measured blood pressures (systolic-9.51mmHg; CI,-8.7 to-10.31; p <0.001; diastolic,-2.5mmHg; CI,-1.99 to-3.01; p < 0.001). Higher diagnosed mental disorder prevalence was attributable to a cohort effect (prevalence for 1935-1939 cohort, 2.5%, vs.1950-1954 cohort, 4.7%), whereas changes in diagnoses of diabetes and hypertension and measured body mass index were primarily period effects. Conclusion: English baby boomers are moving toward retirement with improved cardiovascular health. However, the baby-boomer cohort has a higher prevalence of mental illness diagnoses and shows no improvement in self-rated health compared to the wartime birth cohort. There remains substantial scope to reduce health risks and future disability. © Mary Ann Liebert, Inc.


PubMed | Epidemiology and Public Health Group
Type: Comparative Study | Journal: Circulation | Year: 2012

The endocrine-disrupting chemical bisphenol A (BPA) is widely used in food and beverage packaging. Higher urinary BPA concentrations were cross-sectionally associated with heart disease in National Health and Nutrition Examination Survey (NHANES) 2003-2004 and NHANES 2005-2006, independent of traditional risk factors.We included 758 incident coronary artery disease (CAD) cases and 861 controls followed for 10.8 years from the European Prospective Investigation of Cancer-Norfolk UK. Respondents aged 40 to 74 years and free of CAD, stroke, or diabetes mellitus provided baseline spot urine samples. Urinary BPA concentrations (median value, 1.3 ng/mL) were low. Per-SD (4.56 ng/mL) increases in urinary BPA concentration were associated with incident CAD in age-, sex-, and urinary creatinine-adjusted models (n=1919; odds ratio=1.13; 95% confidence interval, 1.02-1.24; P=0.017). With CAD risk factor adjustment (including education, occupational social class, body mass index category, systolic blood pressure, lipid concentrations, and exercise), the estimate was similar but narrowly missed 2-sided significance (n=1744; odds ratio=1.11; 95% confidence interval, 1.00-1.23; P=0.058). Sensitivity analyses with the fully adjusted model, excluding those with early CAD (<3-year follow-up), body mass index >30, or abnormal renal function or with additional adjustment for vitamin C, C-reactive protein, or alcohol consumption, all produced similar estimates, and all showed associations at P0.05.Associations between higher BPA exposure (reflected in higher urinary concentrations) and incident CAD during >10 years of follow-up showed trends similar to previously reported cross-sectional findings in the more highly exposed NHANES respondents. Further work is needed to accurately estimate the prospective exposure-response curve and to establish the underlying mechanisms.


PubMed | Epidemiology and Public Health Group
Type: Journal Article | Journal: Environmental health perspectives | Year: 2010

Perfluorooctanoic acid (PFOA, also known as C8) and perfluorooctane sulfonate (PFOS) are stable compounds with many industrial and consumer uses. Their persistence in the environment plus toxicity in animal models has raised concern over low-level chronic exposure effects on human health.We estimated associations between serum PFOA and PFOS concentrations and thyroid disease prevalence in representative samples of the U.S. general population.Analyses of PFOA/PFOS versus disease status in the National Health and Nutrition Examination Survey (NHANES) for 1999-2000, 2003-2004, and 2005-2006 included 3,974 adults with measured concentrations for perfluorinated chemicals. Regression models were adjusted for age, sex, race/ethnicity, education, smoking status, body mass index, and alcohol intake.The NHANES-weighted prevalence of reporting any thyroid disease was 16.18% (n = 292) in women and 3.06% (n = 69) in men; prevalence of current thyroid disease with related medication was 9.89% (n = 163) in women and 1.88% (n = 46) in men. In fully adjusted logistic models, women with PFOA >or= 5.7 ng/mL [fourth (highest) population quartile] were more likely to report current treated thyroid disease [odds ratio (OR) = 2.24; 95% confidence interval (CI), 1.38-3.65; p = 0.002] compared with PFOA or= 36.8 ng/mL (quartile 4) versus

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