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1.
BMJ ; 368: l6669, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915124

RESUMO

OBJECTIVE: To examine how a healthy lifestyle is related to life expectancy that is free from major chronic diseases. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: The Nurses' Health Study (1980-2014; n=73 196) and the Health Professionals Follow-Up Study (1986-2014; n=38 366). MAIN EXPOSURES: Five low risk lifestyle factors: never smoking, body mass index 18.5-24.9, moderate to vigorous physical activity (≥30 minutes/day), moderate alcohol intake (women: 5-15 g/day; men 5-30 g/day), and a higher diet quality score (upper 40%). MAIN OUTCOME: Life expectancy free of diabetes, cardiovascular diseases, and cancer. RESULTS: The life expectancy free of diabetes, cardiovascular diseases, and cancer at age 50 was 23.7 years (95% confidence interval 22.6 to 24.7) for women who adopted no low risk lifestyle factors, in contrast to 34.4 years (33.1 to 35.5) for women who adopted four or five low risk factors. At age 50, the life expectancy free of any of these chronic diseases was 23.5 (22.3 to 24.7) years among men who adopted no low risk lifestyle factors and 31.1 (29.5 to 32.5) years in men who adopted four or five low risk lifestyle factors. For current male smokers who smoked heavily (≥15 cigarettes/day) or obese men and women (body mass index ≥30), their disease-free life expectancies accounted for the lowest proportion (≤75%) of total life expectancy at age 50. CONCLUSION: Adherence to a healthy lifestyle at mid-life is associated with a longer life expectancy free of major chronic diseases.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Estilo de Vida Saudável/fisiologia , Expectativa de Vida , Neoplasias , Comportamento de Redução do Risco , Adulto , Consumo de Bebidas Alcoólicas , Índice de Massa Corporal , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/psicologia , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Mellitus Tipo 2/psicologia , Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/prevenção & controle , Neoplasias/psicologia , Pesquisa em Enfermagem , Estudos Prospectivos , Fumar
2.
Heart ; 105(18): 1414-1422, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30936410

RESUMO

OBJECTIVE: To evaluate changes in left ventricular diastolic function (LVDF) parameters and their associated risk factors over a period of 11 years among community-dwelling women and men. METHODS: Echocardiography was performed three times among 870 women and 630 men (age 67±3 years) from the prospective population-based Rotterdam Study during a period of 11-year follow-up. Changes in six continuous LVDF parameters were correlated with cardiovascular risk factors using a linear-mixed effect model (LMM). RESULTS: In women, smoking was associated with deleterious longitudinal changes in deceleration time (DT) (Beta (ß): 7.73; 95% CI 2.56 to 12.9) and high-density lipoprotein cholesterol was associated with improvement of septal e' (ß: 0.37; 95% CI 0.13 to 0.62) and E/e' ratio (ß: -0.46; 95% CI -0.84 to -0.08) trajectories. Among men, diabetes was associated with deleterious longitudinal changes in A wave (ß: 3.83; 95% CI 0.06 to 7.60), septal e' (ß: -0.40; 95% CI -0.70 to -0.09) and E/e' ratio (ß: 0.60; 95% CI 0.14 to 1.06) and body mass index was associated with deleterious longitudinal changes in A wave (ß: 1.25; 95% CI 0.84 to 1.66), E/A ratio (ß: -0.007; 95% CI -0.01 to -0.003), DT (ß: 0.86; 95% CI 0.017 to 1.71) and E/e' ratio (ß: 0.12; 95% CI 0.06 to 0.19). CONCLUSIONS: Smoking among women and metabolic factors (diabetes mellitus and body mass index) among men showed larger deleterious associations with longitudinal changes in LVDF parameters. The favourable association of HDL was mainly observed among women. This study, for the first time, evaluates risk factors associated with changes over time in continuous LVDF parameters among women and men and generates new hypothesis for further medical research.

3.
Am J Epidemiol ; 188(2): 372-381, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30299452

RESUMO

Reliable population estimates of life expectancy with dementia are required for shaping health-care policy. From the Dutch, population-based Rotterdam Study, 10,348 persons were followed during 1990-2015 for dementia and death. We created multistate lifetables, and assessed the effect of postponing disease onset. During 120,673 person-years, 1,666 persons developed dementia, and 6,150 died. Overall life expectancy of women ranged from 18.0 years (95% confidence interval (CI): 17.8, 18.2) at age 65 to 2.3 years (95% CI: 2.2, 2.3) at age 95. Of total life expectancy at age 65, 5.7% (1.0 year (95% CI: 1.0, 1.1)) was lived with dementia, increasing with age to 42.1% (1.0 year, 95% CI: 0.9, 1.0) at age 95. For men, life expectancy ranged from 15.6 years (95% CI: 15.4, 15.9) at age 65 to 1.8 years (95% CI: 1.7, 1.8) at age 95, of which 3.7% (95% CI: 0.6 year, 0.5, 0.6) and 35.3% (95% CI: 0.6 year, 0.5, 0.7), respectively, was lived with dementia. Postponing dementia onset by 1-3 years resulted in 25%-57% reductions in years lived with dementia. Survival after diagnosis ranged from 6.7 years (95% CI: 5.3, 8.1) before age 70, to 2.6 years (95% CI: 2.3, 2.9) after age 90. The burden of dementia on individuals and society in terms of healthy life-years lost is large but could potentially be mitigated by preventive interventions at the population level.


Assuntos
Demência/epidemiologia , Expectativa de Vida/tendências , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas E , Glicemia , Pressão Sanguínea , Índice de Massa Corporal , Demência/genética , Demência/mortalidade , Escolaridade , Feminino , Genótipo , Humanos , Masculino , Países Baixos , Fatores de Risco , Fatores Sexuais , Fatores Socioeconômicos
5.
BMJ ; 362: k2486, 2018 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-29973352

RESUMO

OBJECTIVE: To examine the association between an overall maternal healthy lifestyle (characterized by a healthy body mass index, high quality diet, regular exercise, no smoking, and light to moderate alcohol intake) and the risk of developing obesity in offspring. DESIGN: Prospective cohort studies of mother-child pairs. SETTING: Nurses' Health Study II (NHSII) and Growing Up Today Study (GUTS) in the United States. PARTICIPANTS: 24 289 GUTS participants aged 9-14 years at baseline who were free of obesity and born to 16 945 NHSII women. MAIN OUTCOME MEASURE: Obesity in childhood and adolescence, defined by age and sex specific cutoff points from the International Obesity Task Force. Risk of offspring obesity was evaluated by multivariable log-binomial regression models with generalized estimating equations and an exchangeable correlation structure. RESULTS: 1282 (5.3%) offspring became obese during a median of five years of follow-up. Risk of incident obesity was lower among offspring whose mothers maintained a healthy body mass index of 18.5-24.9 (relative risk 0.44, 95% confidence interval 0.39 to 0.50), engaged in at least 150 min/week of moderate/vigorous physical activities (0.79, 0.69 to 0.91), did not smoke (0.69, 0.56 to 0.86), and consumed alcohol in moderation (1.0-14.9 g/day; 0.88, 0.79 to 0.99), compared with the rest. Maternal high quality diet (top 40% of the Alternate Healthy Eating Index 2010 diet score) was not significantly associated with the risk of obesity in offspring (0.97, 0.83 to 1.12). When all healthy lifestyle factors were considered simultaneously, offspring of women who adhered to all five low risk lifestyle factors had a 75% lower risk of obesity than offspring of mothers who did not adhere to any low risk factor (0.25, 0.14 to 0.47). This association was similar across sex and age groups and persisted in subgroups of children with various risk profiles defined by factors such as pregnancy complications, birth weight, gestational age, and gestational weight gain. Children's lifestyle did not significantly account for the association between maternal lifestyle and offspring obesity risk, but when both mothers and offspring adhered to a healthy lifestyle, the risk of developing obesity fell further (0.18, 0.09 to 0.37). CONCLUSION: Our study indicates that adherence to a healthy lifestyle in mothers during their offspring's childhood and adolescence is associated with a substantially reduced risk of obesity in the children. These findings highlight the potential benefits of implementing family or parental based multifactorial interventions to curb the risk of childhood obesity.


Assuntos
Estilo de Vida Saudável , Mães , Cooperação do Paciente , Obesidade Pediátrica/epidemiologia , Adolescente , Adulto , Criança , Comportamento Infantil , Feminino , Seguimentos , Humanos , Incidência , Masculino , Relações Mãe-Filho , Enfermeiras e Enfermeiros , Obesidade Pediátrica/prevenção & controle , Estudos Prospectivos , Fatores de Risco , Comportamento Sedentário
6.
Circulation ; 138(4): 345-355, 2018 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-29712712

RESUMO

BACKGROUND: Americans have a shorter life expectancy compared with residents of almost all other high-income countries. We aim to estimate the impact of lifestyle factors on premature mortality and life expectancy in the US population. METHODS: Using data from the Nurses' Health Study (1980-2014; n=78 865) and the Health Professionals Follow-up Study (1986-2014, n=44 354), we defined 5 low-risk lifestyle factors as never smoking, body mass index of 18.5 to 24.9 kg/m2, ≥30 min/d of moderate to vigorous physical activity, moderate alcohol intake, and a high diet quality score (upper 40%), and estimated hazard ratios for the association of total lifestyle score (0-5 scale) with mortality. We used data from the NHANES (National Health and Nutrition Examination Surveys; 2013-2014) to estimate the distribution of the lifestyle score and the US Centers for Disease Control and Prevention WONDER database to derive the age-specific death rates of Americans. We applied the life table method to estimate life expectancy by levels of the lifestyle score. RESULTS: During up to 34 years of follow-up, we documented 42 167 deaths. The multivariable-adjusted hazard ratios for mortality in adults with 5 compared with zero low-risk factors were 0.26 (95% confidence interval [CI], 0.22-0.31) for all-cause mortality, 0.35 (95% CI, 0.27-0.45) for cancer mortality, and 0.18 (95% CI, 0.12-0.26) for cardiovascular disease mortality. The population-attributable risk of nonadherence to 5 low-risk factors was 60.7% (95% CI, 53.6-66.7) for all-cause mortality, 51.7% (95% CI, 37.1-62.9) for cancer mortality, and 71.7% (95% CI, 58.1-81.0) for cardiovascular disease mortality. We estimated that the life expectancy at age 50 years was 29.0 years (95% CI, 28.3-29.8) for women and 25.5 years (95% CI, 24.7-26.2) for men who adopted zero low-risk lifestyle factors. In contrast, for those who adopted all 5 low-risk factors, we projected a life expectancy at age 50 years of 43.1 years (95% CI, 41.3-44.9) for women and 37.6 years (95% CI, 35.8-39.4) for men. The projected life expectancy at age 50 years was on average 14.0 years (95% CI, 11.8-16.2) longer among female Americans with 5 low-risk factors compared with those with zero low-risk factors; for men, the difference was 12.2 years (95% CI, 10.1-14.2). CONCLUSIONS: Adopting a healthy lifestyle could substantially reduce premature mortality and prolong life expectancy in US adults.


Assuntos
Pessoal de Saúde , Estilo de Vida Saudável , Expectativa de Vida , Comportamento de Redução do Risco , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Índice de Massa Corporal , Causas de Morte , Bases de Dados Factuais , Exercício , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , não Fumantes , Enfermeiras e Enfermeiros , Inquéritos Nutricionais , Fatores de Proteção , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
7.
Am J Epidemiol ; 187(8): 1662-1669, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29762635

RESUMO

We conducted an epigenome-wide association study on obesity-related traits. We used data from 2 prospective, population-based cohort studies: the Rotterdam Study (RS) (2006-2013) and the Atherosclerosis Risk in Communities (ARIC) Study (1990-1992). We used the RS (n = 1,450) as the discovery panel and the ARIC Study (n = 2,097) as the replication panel. Linear mixed-effect models were used to assess the cross-sectional associations between genome-wide DNA methylation in leukocytes and body mass index (BMI) and waist circumference (WC), adjusting for sex, age, smoking, leukocyte proportions, array number, and position on array. The latter 2 variables were modeled as random effects. Fourteen 5'-C-phosphate-G-3' (CpG) sites were associated with BMI and 26 CpG sites with WC in the RS after Bonferroni correction (P < 1.07 × 10-7), of which 12 and 13 CpGs were replicated in the ARIC Study, respectively. The most significant novel CpGs were located on the Musashi RNA binding protein 2 gene (MSI2; cg21139312) and the leucyl-tRNA synthetase 2, mitochondrial gene (LARS2; cg18030453) and were associated with both BMI and WC. CpGs at BRDT, PSMD1, IFI44L, MAP1A, and MAP3K5 were associated with BMI. CpGs at LGALS3BP, MAP2K3, DHCR24, CPSF4L, and TMEM49 were associated with WC. We report novel associations between methylation at MSI2 and LARS2 and obesity-related traits. These results provide further insight into mechanisms underlying obesity-related traits, which can enable identification of new biomarkers in obesity-related chronic diseases.


Assuntos
Aminoacil-tRNA Sintetases/genética , Epigenômica/métodos , Obesidade/genética , Proteínas de Ligação a RNA/genética , Biomarcadores/análise , Ilhas de CpG/genética , Metilação de DNA , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Fenótipo , Estudos Prospectivos , Estados Unidos/epidemiologia
8.
Int J Epidemiol ; 47(5): 1705-1713, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29672692

RESUMO

Background: Physical activity (PA) is associated with lower risk for all-cause mortality. However, in elderly people, it remains unknown which types of PA are associated with mortality and whether the association between PA and mortality differs by cause of death. Methods: We assessed the association of total PA, walking, cycling, domestic work, sports and gardening with all-cause mortality, and the association of total PA with cause-specific mortality, using Cox proportional hazard models among 7225 older adults (mean age: 70 years) from the prospective population-based Rotterdam Study. Deaths were classified as due to cardiovascular diseases (CVDs), cancer, infections, external causes, dementia, chronic lung diseases or other causes. Activities were categorized into tertiles (lowest tertile as reference). To account for the possibility of reverse causation, we excluded the first 5 and 10 years of follow-up. Results: Over a median of 13.1 years of follow-up (interquartile range: 8.4-14.6 years), 3261 participants died. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) associated with high total PA compared with low were 0.69 (0.63, 0.75), 0.69 (0.58, 0.81), 0.44 (0.27, 0.71), 0.47 (0.32, 0.71) and 0.56 (0.46, 0.69) for mortality from all causes, CVDs, chronic lung diseases, infections and other causes, respectively. With longer exclusion times, the strength of these associations was attenuated. All PA types were associated with lower all-cause mortality risk. Conclusions: Engagement in higher PA levels was associated with lower risk of mortality from CVDs, chronic lung diseases, infections and other causes. Participating in any PA might reduce mortality risk in older adults.


Assuntos
Doenças Cardiovasculares/mortalidade , Exercício , Pneumopatias/mortalidade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/mortalidade , Países Baixos/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo
9.
Eur J Epidemiol ; 33(9): 831-845, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29524110

RESUMO

Cardiovascular disease (CVD) risk factors, incidence and death increases from around the time of menopause comparing to women in reproductive age. A healthy lifestyle can prevent CVD, but it is unclear which lifestyle factors may help maintain and improve cardiovascular health for women after menopausal transition. We conducted a systematic review and meta-analysis of prospective cohort studies to evaluate the association between modifiable lifestyle factors (specifically smoking, physical activity, alcohol intake, and obesity), with CVD and mortality in middle-aged and elderly women. Pubmed, Embase, among other databases and reference lists were searched until February 29th, 2016. Study specific relative risks (RR) were meta-analyzed using random effect models. We included 59 studies involving 5,358,902 women. Comparing current versus never smokers, pooled RR were 3.12 (95% CI 2.15-4.52) for CHD incidence, 2.09 (95% CI 1.51-2.89) for stroke incidence, 2.76 (95% CI 1.62-4.71) for CVD mortality and 2.22 (95% CI 1.92-2.57) for all-cause mortality. Physical activity was associated with a decreased risk of 0.74 (95% CI 0.67-0.80) for overall CVD, 0.71 (95% CI 0.67-0.75) for CHD, 0.77 (95% CI 0.70-0.85) for stroke, 0.70 (95% CI 0.58-0.84) for CVD mortality and 0.71 (95% CI 0.65-0.78) for all-cause mortality. Comparing moderate drinkers versus non-drinkers, the RR was 0.72 (95% CI 0.56-0.91) for CHD, 0.63 (95% CI 0.57-0.71) for CVD mortality and 0.80 (95% CI 0.76-0.84) for all-cause mortality. For women with BMI 30-35 kg/m2 the risk was 1.67 (95% CI 1.24-2.25) for CHD and 2.3 (95% CI 1.56-3.40) for CVD mortality, compared to normal weight. Each 5 kg/m2 increase in BMI was associated with 24% (95% CI 16-33%) higher risk for all-cause mortality. This meta-analysis suggests that physical activity and moderate alcohol intake were associated with a reduced risk for CVD and mortality. Smoking and higher BMI were associated with an increased risk of these endpoints. Adherence to a healthy lifestyle may substantially lower the burden of CVD and reduce the risk of mortality among middle-aged and elderly women. However, this review highlights important gaps, as lack of standardized methods in assessing lifestyle factors and lack of accurate information on menopause status, which should be addressed by future studies in order to understand the role of menopause on the association between lifestyle factors and cardiovascular events.


Assuntos
Doenças Cardiovasculares/mortalidade , Exercício , Estilo de Vida , Menopausa , Idoso , Causas de Morte , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade , Comportamento de Redução do Risco , Acidente Vascular Cerebral/mortalidade
10.
Int J Obes (Lond) ; 42(7): 1275-1284, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29568108

RESUMO

BACKGROUND: In women, adhering to an overall healthy lifestyle is associated with a dramatically reduced risk of cardio-metabolic disorders. Whether such a healthy lifestyle exerts an intergenerational effects on child health deserves examination. METHODS: We included 5701 children (9-14 years old at baseline) of the Growing Up Today Study 2, and their mothers, who are participants in the Nurses' Health Study II. Pre-pregnancy healthy lifestyle was defined as a normal body mass index, no smoking, physical activity ≥150 min/week, and diet in the top 40% of the Alternative Healthy Eating Index-2010. Obesity during childhood and adolescence was defined using the International Obesity Task Force age- and sex-specific cutoffs. Multivariable log-binominal regression models with generalized estimating equations were used to evaluate the association of pre-pregnancy healthy lifestyle and offspring obesity. RESULTS: We identified 520 (9.1%) offspring who became obese during follow-up. A healthy body weight of mothers and no smoking before pregnancy was significantly associated with a lower risk of obesity among offspring: the relative risks [RRs; 95% confidence intervals (CIs)] were 0.37 (0.31-0.43) and 0.64 (0.49-0.84), respectively. Eating a healthy diet and regular moderate-to-vigorous physical activities were inversely related to offspring obesity risk, but these relations were not statistically significant. Compared to children of mothers who did not meet any low-risk lifestyle factors, offspring of women who adhered to all four healthy lifestyle factors had 75% lower risk of obesity (RR: 0.25, 95% CI: 0.14-0.43). CONCLUSION: Adherence to an overall healthy lifestyle before pregnancy is strongly associated with a low risk of offspring obesity in childhood, adolescence, and early adulthood. These findings highlight the importance of an overall healthy lifestyle before pregnancy as a potential strategy to prevent obesity in future generations.


Assuntos
Estilo de Vida Saudável , Mães/estatística & dados numéricos , Obesidade Pediátrica/epidemiologia , Cuidado Pré-Concepcional , Adolescente , Adulto , Índice de Massa Corporal , Peso Corporal , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Mães/psicologia , Gravidez , Estudos Prospectivos , Inquéritos e Questionários
11.
J Clin Endocrinol Metab ; 103(4): 1622-1630, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29408955

RESUMO

Context: Polycystic ovary syndrome (PCOS) is closely linked to hyperandrogenism (HA). In PCOS, HA has been associated with metabolic disturbances that increase the risk for cardiovascular disease (CVD). Objective: To assess the association of high serum androgen levels, as a postmenopausal remnant of PCOS, with the prevalence of atherosclerosis and incidence of CVD in postmenopausal women. Design: The Rotterdam Study, a prospective population-based cohort study. Median follow-up was 11.36 years. Setting: General community. Participants: A total of 2578 women aged >55 years. Exclusion criteria were missing informed consent or follow-up data, perimenopausal status, and menopause by surgical intervention or at an unnatural age (age <40 or >62). Intervention: None. Main Outcomes and Measures: Linear, logistic, and Cox regression models assessed the association of top quartiles (P75) of serum testosterone, free androgen index (FAI), dehydroepiandrosterone, and androstenedione and sex hormone-binding globulin with coronary artery calcium, carotid intima-media thickness (IMT), pulse wave velocity, peripheral artery disease, and incidence of coronary heart disease (CHD), stroke, and CVD. Results: Mean age (standard deviation) was 70.19 (8.71) years, and average time since menopause was 19.85 (9.94) years. Highest quartile FAI was associated with higher pulse wave velocity (ß [95% confidence interval (CI)], 0.009 [0.000 to 0.018]). Highest quartile dehydroepiandrosterone [ß (95% CI), -0.008 (-0.015 to -0.001)] and androstenedione [ß (95% CI), -0.010 (-0.017 to -0.003)] levels were associated with a lower IMT. We found no association between high androgen levels and incident stroke, CHD, or CVD. Conclusion: Postmenopausal high androgen levels were not associated with an elevated risk for CVD. Cardiovascular health in women with PCOS might be better than was anticipated.


Assuntos
Androgênios/sangue , Aterosclerose/epidemiologia , Doenças Cardiovasculares/epidemiologia , Pós-Menopausa/sangue , Testosterona/sangue , Idoso , Idoso de 80 Anos ou mais , Androstenodiona/sangue , Aterosclerose/sangue , Cálcio/metabolismo , Doenças Cardiovasculares/sangue , Espessura Intima-Media Carotídea , Desidroepiandrosterona/sangue , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Globulina de Ligação a Hormônio Sexual/metabolismo
12.
PLoS Med ; 15(2): e1002502, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29438414

RESUMO

BACKGROUND: The potential endocrine-disrupting effects of perfluoroalkyl substances (PFASs) have been demonstrated in animal studies, but whether PFASs may interfere with body weight regulation in humans is largely unknown. This study aimed to examine the associations of PFAS exposure with changes in body weight and resting metabolic rate (RMR) in a diet-induced weight-loss setting. METHODS AND FINDINGS: In the 2-year POUNDS Lost randomized clinical trial based in Boston, Massachusetts, and Baton Rouge, Louisiana, that examined the effects of energy-restricted diets on weight changes, baseline plasma concentrations of major PFASs were measured among 621 overweight and obese participants aged 30-70 years. Body weight was measured at baseline and 6, 12, 18, and 24 months. RMR and other metabolic parameters, including glucose, lipids, thyroid hormones, and leptin, were measured at baseline and 6 and 24 months. Participants lost an average of 6.4 kg of body weight during the first 6 months (weight-loss period) and subsequently regained an average of 2.7 kg of body weight during the period of 6-24 months (weight regain period). After multivariate adjustment, baseline PFAS concentrations were not significantly associated with concurrent body weight or weight loss during the first 6 months. In contrast, higher baseline levels of PFASs were significantly associated with a greater weight regain, primarily in women. In women, comparing the highest to the lowest tertiles of PFAS concentrations, the multivariate-adjusted mean weight regain (SE) was 4.0 (0.8) versus 2.1 (0.9) kg for perfluorooctanesulfonic acid (PFOS) (Ptrend = 0.01); 4.3 (0.9) versus 2.2 (0.8) kg for perfluorooctanoic acid (PFOA) (Ptrend = 0.007); 4.7 (0.9) versus 2.5 (0.9) kg for perfluorononanoic acid (PFNA) (Ptrend = 0.006); 4.9 (0.9) versus 2.7 (0.8) kg for perfluorohexanesulfonic acid (PFHxS) (Ptrend = 0.009); and 4.2 (0.8) versus 2.5 (0.9) kg for perfluorodecanoic acid (PFDA) (Ptrend = 0.03). When further adjusted for changes in body weight or thyroid hormones during the first 6 months, results remained similar. Moreover, higher baseline plasma PFAS concentrations, especially for PFOS and PFNA, were significantly associated with greater decline in RMR during the weight-loss period and less increase in RMR during the weight regain period in both men and women. Limitations of the study include the possibility of unmeasured or residual confounding by socioeconomic and psychosocial factors, as well as possible relapse to the usual diet prior to randomization, which could have been rich in foods contaminated by PFASs through food packaging and also dense in energy. CONCLUSIONS: In this diet-induced weight-loss trial, higher baseline plasma PFAS concentrations were associated with a greater weight regain, especially in women, possibly explained by a slower regression of RMR levels. These data illustrate a potential novel pathway through which PFASs interfere with human body weight regulation and metabolism. The possible impact of environmental chemicals on the obesity epidemic therefore deserves attention. TRIAL REGISTRATION: ClinicalTrials.gov NCT00072995.


Assuntos
Metabolismo Basal/efeitos dos fármacos , Dieta Redutora , Disruptores Endócrinos/sangue , Fluorcarbonetos/sangue , Obesidade/dietoterapia , Sobrepeso/dietoterapia , Perda de Peso/efeitos dos fármacos , Adulto , Idoso , Peso Corporal/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Sobrepeso/sangue , Descanso
13.
Lancet Public Health ; 2(1): e23-e34, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-29249477

RESUMO

BACKGROUND: Controversy exists about the differences in air pollution exposure and inhalation dose between mode of transport. We aimed to review air pollution exposure and inhaled dose according to mode of transport and pollutant and their effect in terms of years of life expectancy (YLE). METHODS: In this systematic review, we searched ten online databases from inception to April 13, 2016, without language or temporal restrictions, for cohort, cross-sectional, and experimental studies that compared exposure to carbon monoxide, black carbon, nitrogen dioxide, and fine and coarse particles in active commuters (pedestrian or cyclist) and commuters using motorised transport (car, motorcycle, bus, or massive motorised transport [MMT-ie, train, subway, or metro]). We excluded studies that measured air pollution exposure exclusively with biomarkers or on the basis of simulated data, reviews, comments, consensuses, editorials, guidelines, in-vitro studies, meta-analyses, ecological studies, and protocols. We extracted average exposure and commuting time per mode of transport and pollutant to calculate inhaled doses. We calculated exposure and inhaled dose ratios using active commuters as the reference and summarised them with medians and IQRs. We also calculated differences in YLE due to fine particle inhaled dose and physical activity. FINDINGS: We identified 4037 studies, of which 39 were included in the systematic review. Overall, car commuters had higher exposure to all pollutants than did active commuters in 30 (71%) of 42 comparisons (median ratio 1·22 [IQR 0·90-1·76]), followed by those who commuted by bus in 57 (52%) of 109 (1·0 [0·79-1·41]), by motorcycle in 16 (50%) of 32 (0·99 [0·86-1·38]), by a car with controlled ventilation settings in 39 (45%) of 86 (0·95 [0·66-1·54]), and by MMT in 21 (38%) of 55 (0·67 [0·49-1·13]). Overall, active commuters had higher inhalation doses than did commuters using motorised transport (median ratio car with controlled ventilation settings 0·16 [0·10-0·28]; car 0·22 [0·15-0·30]; motorcycle 0·38 [0·26-0·78]; MMT 0·49 [0·34-0·81]; bus 0·72 [IQR 0·50-0·99]). Commuters using motorised transport lost up to 1 year in YLE more than did cyclists. INTERPRETATION: Proximity to traffic and high air interchange increased the exposure to air pollution of commuters using motorised transport. Larger inhalation rates and commuting time increased inhaled dose among active commuters. Benefits of active commuting from physical activity are larger than the risk from an increased inhaled dose of fine particles. FUNDING: Departamento Administrativo de Ciencia, Tecnología e Innovación (COLCIENCIAS), National Health and Medical Research Council, Nestlé Nutrition (Nestec), Metagenics, and AXA.


Assuntos
Poluição do Ar/análise , Exposição por Inalação/análise , Transportes/métodos , Humanos , Expectativa de Vida
14.
Int J Epidemiol ; 46(6): 1913-1923, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29025080

RESUMO

Background: It is known that perchlorate, nitrate and thiocyanate have the property of inhibiting sodium iodide symporter. Animal studies have suggested that these compounds, especially perchlorate, might also interfere with insulin secretion. However, the association between their exposure and diabetes risk is largely unknown in humans. Methods: Among 11 443 participants (mean age 42.3 years) from the National Health and Nutritional Examination Survey 2001-14, urinary perchlorate, nitrate and thiocyanate were measured by using ion chromatography coupled with electrospray tandem mass spectrometry. Diabetes was defined as self-reported doctor diagnosis, use of oral hypoglycaemic medication or insulin, fasting plasma glucose ≥ 126 mg/dl or glycated haemoglobin A1c (HbA1c) ≥ 6.5%. Results: The median (interquartile range) levels of urinary perchlorate, nitrate and thiocyanate were 3.32 (1.84, 5.70) µg/l, 46.4 (27.9, 72.0) mg/l and 1.23 (0.59, 2.78) mg/l, respectively. Higher levels of urinary perchlorate were associated with elevated levels of fasting glucose, HbA1c, insulin and homeostatic model assessment of insulin resistance (all Ptrend < 0.001). After multivariate adjustment including urinary creatinine, smoking status and body mass index (BMI), higher urinary perchlorate, but not nitrate or thiocyanate, was associated with an increased prevalence of diabetes mellitus. Comparing extreme quintiles, the odds ratio (95% confidence interval) of diabetes was 1.53 (1.21, 1.93; Ptrend < 0.001) for perchlorate, 1.01 (0.77, 1.32; Ptrend = 0.44) for nitrate and 0.98 (0.73, 1.31; Ptrend = 0.64) for thiocyanate. When urinary perchlorate, nitrate and thiocyanate were further mutually adjusted, the results did not materially change. Similar results were observed when analyses were stratified by smoking status, as well as by age, gender, kidney function and BMI. Conclusions: Higher urinary perchlorate levels are associated with an increased prevalence of diabetes mellitus, independent of traditional risk factors. Future prospective studies are needed to confirm these findings.


Assuntos
Diabetes Mellitus/epidemiologia , Exposição Ambiental , Nitratos/urina , Percloratos/urina , Tiocianatos/urina , Adulto , Feminino , Humanos , Resistência à Insulina , Modelos Logísticos , Masculino , Análise Multivariada , Inquéritos Nutricionais , Simportadores/antagonistas & inibidores , Estados Unidos/epidemiologia
15.
JAMA Intern Med ; 177(11): 1650-1657, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28975207

RESUMO

Importance: Variations in thyroid function within reference ranges are associated with an increased risk of cardiovascular disease (CVD) and mortality. However, the impact of thyroid function on life expectancy (LE) and the number of years lived with and without CVD remains unknown. Objective: To investigate the association of thyroid function with total LE and LE with and without CVD among euthyroid individuals. Design, Setting, and Participants: The Rotterdam Study, a population-based, prospective cohort study. We included participants without known thyroid disease and with thyrotropin and free thyroxine (FT4) levels within the reference ranges. Main Outcomes and Measures: Multistate life tables were used to calculate total LE and LE with and without CVD among thyrotropin and FT4 tertiles. Life expectancy estimates in men and women aged 50 years and older were obtained using prevalence, incidence rates, and hazard ratios for 3 transitions (healthy to CVD, healthy to death, and CVD to death), adjusting for sociodemographic and cardiovascular risk factors. Results: The mean (SD) age of the 7785 participants was 64.7 (9.8) years, and 52.5% were women. Over a median follow-up of 8.1 (interquartile range, 2.7-9.9) years, we observed 789 incident CVD events and 1357 deaths. Compared with those in the lowest tertile, men and women in the highest thyrotropin tertile lived 2.0 (95% CI, 1.0 to 2.8) and 1.4 (95% CI, 0.2 to 2.4) years longer, respectively, of which, 1.5 (95% CI, 0.2 to 2.6) and 0.9 (95% CI, -0.2 to 2.0) years longer without CVD. Compared with those in the lowest tertile, the difference in life expectancy for men and women in the highest FT4 tertile was -3.2 (95% CI, -5.0 to -1.4) and -3.5 (95% CI, -5.6 to -1.5) years, respectively, of which, -3.1 (95% CI, -4.9 to -1.4) and -2.5 (95% CI, -4.4 to -0.7) years without CVD. Conclusions and Relevance: At the age of 50 years, participants with low-normal thyroid function live up to 3.5 years longer overall and up to 3.1 years longer without CVD than participants with high-normal thyroid function. These findings provide supporting evidence for a reevaluation of the current reference ranges of thyroid function and can help inform preventive and clinical care.


Assuntos
Doenças Cardiovasculares/mortalidade , Expectativa de Vida , Testes de Função Tireóidea , Idoso , Feminino , Humanos , Incidência , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prevalência , Estudos Prospectivos , Fatores de Risco
16.
JAMA Cardiol ; 2(9): 986-994, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28746709

RESUMO

Importance: Besides age, other discriminators of atherosclerotic cardiovascular disease (ASCVD) risk are needed in older adults. Objectives: To examine the predictive ability of coronary artery calcium (CAC) score vs age for incident ASCVD and how risk prediction changes by adding CAC score and removing only age from prediction models. Design, Setting, and Participants: We conducted an analysis of pooled US population-based studies, including the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study. Results were compared with 2 European cohorts, the Rotterdam Study and the Heinz Nixdorf Recall Study. Participants underwent CAC scoring between 1998 and 2006 using cardiac computed tomography. The participants included adults older than 60 years without known ASCVD at baseline. Exposures: Coronary artery calcium scores. Main Outcomes and Measures: Incident ASCVD events including coronary heart disease (CHD) and stroke. Results: The study included 4778 participants from 3 US cohorts, with a mean age of 70.1 years; 2582 (54.0%) were women, and 2431 (50.9%) were nonwhite. Over 11 years of follow-up (44 152 person-years), 405 CHD and 228 stroke events occurred. Coronary artery calcium score (vs age) had a greater association with incident CHD (C statistic, 0.733 vs 0.690; C statistics difference, 0.043; 95% CI of difference, 0.009-0.075) and modestly improved prediction of incident stroke (C statistic, 0.695 vs 0.670; C statistics difference, 0.025; 95% CI of difference, -0.015 to 0.064). Adding CAC score to models including traditional cardiovascular risk factors, with only age being removed, provided improved discrimination for incident CHD (C statistic, 0.735 vs 0.703; C statistics difference, 0.032; 95% CI of difference, 0.002-0.062) but not for stroke. Coronary artery calcium score was more likely than age to provide higher category-free net reclassification improvement among participants who experienced an ASCVD event (0.390; 95% CI, 0.312-0.467 vs 0.08; 95% CI -0.001 to 0.181) and to result in more accurate reclassification of risk for ASCVD events among these individuals. The findings were similar in the 2 European cohorts (n = 4990). Conclusions and Relevance: Coronary artery calcium may be an alternative marker besides age to better discriminate between lower and higher CHD risk in older adults. Whether CAC score can assist in guiding the decision to initiate statin treatment for primary prevention in older adults requires further investigation.


Assuntos
Doença da Artéria Coronariana/epidemiologia , Doença das Coronárias/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Calcificação Vascular/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/epidemiologia , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Risco , Medição de Risco , Tomografia Computadorizada por Raios X , Estados Unidos/epidemiologia , Calcificação Vascular/diagnóstico por imagem
17.
Gastroenterology ; 153(4): 1096-1106.e2, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28624579

RESUMO

BACKGROUND & AIMS: Epigenetic mechanisms might be involved in the regulation of liver enzyme level. We aimed to identify CpG sites at which DNA methylation levels are associated with blood levels of liver enzymes and hepatic steatosis. METHODS: We conducted an epigenome-wide association study in whole blood for liver enzyme levels, including gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), among a discovery set of 731 participants of the Rotterdam Study and sought replication in a non-overlapping sample of 719 individuals. Significant DNA methylation changes were further analyzed to evaluate their relation with hepatic steatosis. Expression levels of the top identified gene were measured in 9 human liver cell lines and compared with expression profiles of its potential targets associated with lipid traits. The candidate gene was subsequently knocked down in human hepatoma cells using lentiviral vectors expressing small hairpin RNAs. RESULTS: Eight probes annotated to SLC7A11, SLC1A5, SLC43A1, PHGDH, PSORS1C1, SREBF1, ANKS3 were associated with GGT and 1 probe annotated to SLC7A11 was associated with ALT after Bonferroni correction (1.0 × 10-7). No probe was identified for AST levels. Four probes for GGT levels including cg06690548 (SLC7A11), cg11376147 (SLC43A1), cg22304262 (SLC1A5), and cg14476101 (PHGDH), and 1 for ALT cg06690548 (SLC7A11) were replicated. DNA methylation at SLC7A11 was associated with reduced risk of hepatic steatosis in participants (odds ratio, 0.69; 95% CI= 0.55-0.93; P value: 2.7 × 10-3). In functional experiments, SLC7A11 was highly expressed in human liver cells; its expression is positively correlated with expression of a panel of lipid-associated genes, indicating a role of SLC7A11 in lipid metabolism. CONCLUSIONS: Our results provide new insights into epigenetic mechanisms associated with markers of liver function and hepatic steatosis, laying the groundwork for future diagnostic and therapeutic applications.


Assuntos
Alanina Transaminase/sangue , Sistema y+ de Transporte de Aminoácidos/genética , Aspartato Aminotransferases/sangue , Metilação de DNA , Epigênese Genética , Fígado Gorduroso/genética , Metabolismo dos Lipídeos/genética , gama-Glutamiltransferase/sangue , Idoso , Idoso de 80 Anos ou mais , Sistema ASC de Transporte de Aminoácidos/genética , Sistema ASC de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+L de Transporte de Aminoácidos/genética , Sistema y+L de Transporte de Aminoácidos/metabolismo , Biomarcadores/sangue , Linhagem Celular Tumoral , Ilhas de CpG , Fígado Gorduroso/sangue , Fígado Gorduroso/enzimologia , Fígado Gorduroso/prevenção & controle , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Menor/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Países Baixos , Razão de Chances , Fenótipo , Fosfoglicerato Desidrogenase/genética , Fosfoglicerato Desidrogenase/metabolismo , Fatores de Proteção , Interferência de RNA , Medição de Risco , Fatores de Risco , Transfecção
18.
Eur J Prev Cardiol ; 24(9): 934-941, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28436726

RESUMO

Background Being overweight or obese is associated with an increased risk of cardiovascular disease (CVD). Physical activity might reduce the risk associated with overweight and obesity. We examined the association between overweight and obesity and CVD risk as a function of physical activity levels in a middle-aged and elderly population. Design The study was a prospective cohort study. Methods The study included 5344 participants aged 55 years or older from the population-based Rotterdam Study. Participants were classified as having high or low physical activity based on the median of the population. Normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2) and obese participants (≥30 kg/m2) were categorized as having high or low physical activity to form six categories. We assessed the association of the six categories with CVD risk using Cox proportional hazard models adjusted for confounders. High physical activity and normal weight was used as the reference group. Results During 15 years of follow-up (median 10.3 years, interquartile range 8.2-11.7 years), 866 (16.2%) participants experienced a CVD event. Overweight and obese participants with low physical activity had a higher CVD risk than normal weight participants with high physical activity. The HRs and 95% confidence intervals (CIs) were 1.33 (1.07-1.66) and 1.35 (1.04-1.75), respectively. Overweight and obese participants with high physical activity did not show a higher CVD risk (HRs (95%CIs) 1.03 (0.82-1.29) and 1.12 (0.83-1.52), respectively). Conclusions Our findings suggest that the beneficial impact of physical activity on CVD might outweigh the negative impact of body mass index among middle-aged and elderly people. This emphasizes the importance of physical activity for everyone across all body mass index strata, while highlighting the risk associated with inactivity even among normal weight people.


Assuntos
Doenças Cardiovasculares/fisiopatologia , Exercício , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Comportamento Sedentário , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Obesidade/diagnóstico , Obesidade/epidemiologia , Sobrepeso/diagnóstico , Sobrepeso/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Proteção , Medição de Risco , Fatores de Risco , Comportamento de Redução do Risco , Fatores de Tempo
19.
Clin Epigenetics ; 9: 15, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28194238

RESUMO

BACKGROUND: DNA methylation is a key epigenetic mechanism that is suggested to be associated with blood lipid levels. We aimed to identify CpG sites at which DNA methylation levels are associated with blood levels of triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol in 725 participants of the Rotterdam Study, a population-based cohort study. Subsequently, we sought replication in a non-overlapping set of 760 participants. RESULTS: Genome-wide methylation levels were measured in whole blood using the Illumina Methylation 450 array. Associations between lipid levels and DNA methylation beta values were examined using linear mixed-effect models. All models were adjusted for sex, age, smoking, white blood cell proportions, array number, and position on array. A Bonferroni-corrected p value lower than 1.08 × 10-7 was considered statistically significant. Five CpG sites annotated to genes including DHCR24, CPT1A, ABCG1, and SREBF1 were identified and replicated. Four CpG sites were associated with triglycerides, including CpG sites annotated to CPT1A (cg00574958 and cg17058475), ABCG1 (cg06500161), and SREBF1 (cg11024682). Two CpG sites were associated with HDL-C, including ABCG1 (cg06500161) and DHCR24 (cg17901584). No significant associations were observed with LDL-C or total cholesterol. CONCLUSIONS: We report an association of HDL-C levels with methylation of a CpG site near DHCR24, a protein-coding gene involved in cholesterol biosynthesis, which has previously been reported to be associated with other metabolic traits. Furthermore, we confirmed previously reported associations of methylation of CpG sites within CPT1A, ABCG1, and SREBF1 and lipids. These results provide insight in the mechanisms that are involved in lipid metabolism.


Assuntos
Ilhas de CpG , Metilação de DNA , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Idoso , Carnitina O-Palmitoiltransferase/genética , Estudos de Coortes , Epigênese Genética , Epigenômica/métodos , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genética
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