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1.
J Vasc Surg ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32882349

RESUMO

OBJECTIVE: Few studies have prospectively examined the associations of lipoprotein(a) [Lp(a)] levels with the risk of abdominal aortic aneurysm (AAA), especially in women. Accounting for commonly recognized risk factors, we investigated the baseline Lp(a) levels and the risk of AAA among postmenopausal women participating in the ongoing national Women's Health Initiative. METHODS: Women's Health Initiative participants with baseline Lp(a) levels available who were beneficiaries of Medicare parts A and B fee-for-service at study enrollment or who had aged into Medicare at any point were included. Participants with missing covariate data or known AAA at baseline were excluded. Thoracic aneurysms were excluded owing to the different pathophysiology. The AAA cases and interventions were identified using the International Classification of Diseases, 9th and 10th revision, codes and Current Procedural Terminology codes from claims data. Hazard ratios were computed using Cox proportional hazard models according to the quintiles of Lp(a). RESULTS: The mean age of the 6615 participants included in the analysis was 65.3 years. Of the 6615 participants, 66.6% were non-Hispanic white, 18.9% were black, 7% were Hispanic and 4.7% were Asian/Pacific Islander. Compared with the participants in the lowest Lp(a) quintile, those in higher quintiles were more likely to be overweight, black, and former or current smokers, to have hypertension, hyperlipidemia, and a history of cardiovascular disease, and to use menopausal hormone therapy and statins. During 65,476 person-years of follow-up, with a median of 10.4 years, 415 women had been diagnosed with an AAA and 36 had required intervention. More than one half had required intervention for a ruptured AAA. We failed to find a statistically significant association between Lp(a) levels and incident AAA. Additional sensitivity analyses stratified by race, with exclusion of statin users and alternative categorizations of Lp(a) using log-transformed levels, tertiles, and a cutoff of >50 mg/dL, were conducted, which did not reveal any significant associations. CONCLUSIONS: We found no statistically significant association between Lp(a) levels and the risk of AAA in a large and well-phenotyped sample of postmenopausal women. Women with high Lp(a) levels were more likely to be overweight, black, and former or current smokers, and to have hypertension, hyperlipidemia, and a history of cardiovascular disease, or to use hormone therapy and statins compared with those with lower Lp(a) levels. These findings differ from previous prospective, case-control, and meta-analysis studies that had supported a significant relationship between higher Lp(a) levels and an increased risk of AAA. Differences in the association could have resulted from study limitations or sex differences.

2.
Am J Clin Nutr ; 112(1): 168-179, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32133498

RESUMO

BACKGROUND: We recently presented associations between serum-based biomarkers of carotenoid and tocopherol intake and chronic disease risk in a Women's Health Initiative (WHI) Measurement Precision subcohort (n = 5488). Questions remain as to whether self-reported dietary data can usefully augment such biomarkers or can be calibrated using biomarkers for reliable disease association estimation in larger WHI cohorts. OBJECTIVES: The aims were to examine the potential of FFQ data to explain intake variation in a WHI Feeding Study and to compare association parameter estimates and their precision from studies based on biomarker-calibrated FFQ intake in larger WHI cohorts, with those previously presented. METHODS: Serum-based intake measures were augmented by using FFQ data in a WHI Feeding Study (n = 153). Corresponding calibration equations were generated, both in a companion Nutritional Biomarker Study (n = 436) and in the previously mentioned subcohort (n = 5488), by regressing these intake measures on dietary data and participant characteristics, for α- and ß-carotene, lutein plus zeaxanthin, and α-tocopherol. The supplemental value of FFQ data was considered by examining the fraction of feeding study intake variation explained by these regression models. Calibrated intake and disease association analyses were evaluated by comparisons with previously reported subcohort results. RESULTS: The inclusion of FFQ data led to some increases in feeding study intake variation explained (total R2 of ∼50%). Calibrated intake estimates explained 25-75% of serum-based intake variation, whether developed using either of the 2 cohort subsamples. Related disease associations for micronutrients were precisely estimated in larger WHI cohorts (n = 76,691) but were often closer to the null compared with previously reported associations. CONCLUSIONS: FFQ data may usefully augment blood concentrations in estimating the intake of carotenoids and tocopherols. Calibrated intake estimates using FFQ, dietary supplement, and participant characteristics only may require further justification to ensure reliable estimation of related disease associations.


Assuntos
Micronutrientes/sangue , Idoso , Biomarcadores/sangue , Carotenoides/sangue , Doença Crônica , Estudos de Coortes , Feminino , Humanos , Micronutrientes/metabolismo , Pessoa de Meia-Idade , Estado Nutricional , Saúde da Mulher , alfa-Tocoferol/sangue , beta Caroteno/sangue
3.
Int J Cancer ; 146(9): 2394-2405, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276202

RESUMO

Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.

4.
Medicine (Baltimore) ; 98(24): e15869, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192918

RESUMO

Higher trait optimism and/or lower cynical hostility are associated with healthier behaviors and lower risk of morbidity and mortality, yet their association with health care utilization has been understudied. Whether these psychological attitudes are associated with breast cancer screening behavior is unknown. To assess the association of optimism and cynical hostility with screening mammography in older women and whether sociodemographic factors acted as mediators of these relationships, we used Women's Health Initiative (WHI) observational cohort survey data linked to Medicare claims. The sample includes WHI participants without history of breast cancer who were enrolled in Medicare Parts A and B for ≥2 years from 2005-2010, and who completed WHI baseline attitudinal questionnaires (n = 48,291). We used survival modeling to examine whether screening frequency varied by psychological attitudes (measured at study baseline) after adjusting for sociodemographic characteristics, health conditions, and healthcare-related variables. Psychological attitudes included trait optimism (Life Orientation Test-Revised) and cynical hostility (Cook Medley subscale), which were self-reported at study baseline. Sociodemographic, health conditions, and healthcare variables were self-reported at baseline and updated through 2005 as available. Contrary to our hypotheses, repeated events survival models showed that women with the lowest optimism scores (i.e., more pessimistic tendencies) received 5% more frequent screenings after complete covariate adjustment (p < .01) compared to the most optimistic group, and showed no association between cynical hostility and frequency of screening mammograms. Sociodemographic factors did not appear to mediate the relationship between optimism and screenings. However, higher levels of education and higher levels of income were associated with more frequent screenings (both p < .01). We also found that results for optimism were primarily driven by women who were aged 75 or older after January 2009, when changes to clinical guidelines lead to uncertainty about risks and benefits of screening in this age group. The study demonstrated that lower optimism, higher education, and higher income were all associated with more frequent screening mammograms in this sample after repeated events survival modeling and covariate adjustment.


Assuntos
Mamografia/estatística & dados numéricos , Otimismo/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Idoso , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Revisão da Utilização de Seguros , Estudos Longitudinais , Medicare , Fatores Socioeconômicos , Estados Unidos , Saúde da Mulher
5.
Am J Clin Nutr ; 109(4): 1189-1196, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30915444

RESUMO

BACKGROUND: Biomarkers provide potential to objectively measure the intake of nutrients and foods, and thereby to strengthen nutritional epidemiology association studies. However, there are only a few established intake biomarkers, mostly based on recovery of nutrients or their metabolites in urine. Blood concentration measures provide a potential biomarker source for many additional nutritional variables, but their use in disease-association studies requires further development. OBJECTIVE: The aim of this study was to apply recently proposed serum-based carotenoid and tocopherol intake biomarkers and to examine their association with the incidence of major cardiovascular diseases, cancers, and diabetes in a subset of Women's Health Initiative (WHI) cohorts. METHODS: Serum concentrations of α- and ß-carotene, lutein plus zeaxanthin (L + Z), and α-tocopherol were routinely measured at baseline in a subset of 5488 enrollees in WHI cohorts. Intake biomarkers for these 4 micronutrients, obtained by combining serum concentrations with participant characteristics, were recently proposed using a 153-woman feeding study within WHI. These biomarker equations are augmented here to include pertinent disease risk factors and are associated with subsequent chronic disease incidence in this WHI subset. RESULTS: HRs for a doubling of micronutrient intake differed only moderately from the null for the outcomes considered. However, somewhat lower risks of specific cardiovascular outcomes, breast cancer, and diabetes were associated with a higher intake of α- and ß-carotene, lower risk of diabetes was associated with higher L + Z intake, and elevated risks of certain cardiovascular outcomes were associated with a higher intake of α-tocopherol. These patterns remained following the exclusion of baseline users of dietary supplements. CONCLUSIONS: Concentration biomarkers can be calculated from blood specimens obtained in large epidemiologic cohorts and applied directly in disease-association analyses, without relying on self-reported dietary data. Observed associations between carotenoid and tocopherol biomarkers and chronic disease risk could be usefully evaluated further using stored serum specimens on the entire WHI cohort. This study was registered at www.clinicaltrials.gov as NCT00000611.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Carotenoides/sangue , Diabetes Mellitus/prevenção & controle , Neoplasias/prevenção & controle , Tocoferóis/sangue , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doença Crônica/prevenção & controle , Estudos de Coortes , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Suplementos Nutricionais/análise , Feminino , Humanos , Luteína/sangue , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/epidemiologia , Estado Nutricional , Fatores de Risco , Estados Unidos/epidemiologia , Zeaxantinas/sangue
6.
BMJ ; 364: k4981, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606716

RESUMO

OBJECTIVES: To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. DESIGN: Nested case-control study. SETTING: 20 population based cohort studies in Asia, Europe, Australia, and the United States. PARTICIPANTS: 5299 patients with incident lung cancer, with individually incidence density matched controls. EXPOSURE: Circulating hsCRP concentrations in prediagnostic serum or plasma samples. MAIN OUTCOME MEASURE: Incident lung cancer diagnosis. RESULTS: A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up. CONCLUSIONS: Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.


Assuntos
Proteína C-Reativa/metabolismo , Carcinoma de Células Grandes/sangue , Carcinoma de Células Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Pulmonares/sangue , Fumar/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Grandes/epidemiologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Ex-Fumantes/estatística & dados numéricos , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , não Fumantes/estatística & dados numéricos , Razão de Chances , Estudos Prospectivos , Medição de Risco , Sensibilidade e Especificidade , Fumantes/estatística & dados numéricos , Fumar/epidemiologia , Adulto Jovem
7.
Int J Cancer ; 145(6): 1499-1503, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-30499135

RESUMO

Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer etiology via direct measurements of pre-diagnostic circulating vitamin B12 concentrations in a nested case-control study, complemented with a Mendelian randomization (MR) approach in an independent case-control sample. We used pre-diagnostic biomarker data from 5183 case-control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre-diagnostic blood samples from the nested case-control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [ORlog2B12 ] = 1.15, 95% confidence interval (95%CI) = 1.06-1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [ORSD ] = 1.08, 95%CI = 1.00-1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer.


Assuntos
Neoplasias Pulmonares/etiologia , Vitamina B 12/sangue , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fumar
8.
J Clin Rheumatol ; 25(3): 127-132, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29794514

RESUMO

OBJECTIVE: The aim of this study was to evaluate whether tea or coffee consumption is associated with an increased risk of older-onset rheumatoid arthritis (RA) using the Women's Health Initiative Observational Study. METHODS: The Women's Health Initiative Observational Study is a longitudinal prospective cohort study conducted from 1993 to 1998. There were 76,853 women who completed a self-administered questionnaire about their daily consumption of tea and coffee. One hundred eighty-five women self-reported and validated incident cases of RA were observed after 3 years of observation. Multivariable Cox proportional hazards models were performed to assess the relationship between consumption habits and disease incidence. Trend tests were calculated using categorical variables modeled as a continuous variable without collapsing. RESULTS: There was no increase in the hazard ratio for incident RA in those participants who drank coffee compared with those who did not. The amount of coffee consumed and the method of preparation (caffeinated/decaffeinated; filtered/unfiltered) also did not alter the risk of incident RA. There was a positive association of incident RA and caffeinated tea consumption in the trend test (p = 0.03). When assessing any caffeinated tea consumption versus no tea consumption, the hazard ratio for incident RA was 1.40 (confidence interval, 1.01-1.93; p = 0.04). CONCLUSIONS: In a large prospective cohort of older women, there was no association between coffee consumption and incident RA. A small association between daily caffeinated, nonherbal tea consumption and incident RA was found.


Assuntos
Artrite Reumatoide , Café , Comportamento de Ingestão de Líquido , Chá , Idoso , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/psicologia , Estudos de Coortes , Correlação de Dados , Feminino , Humanos , Incidência , Estudos Longitudinais , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologia , Saúde da Mulher
9.
PLoS One ; 13(12): e0207509, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30513095

RESUMO

IMPORTANCE: Carpal tunnel syndrome (CTS) is a common and debilitating condition that commonly affects postmenopausal women. OBJECTIVE: To determine the effect of menopausal hormone therapy (HT) in healthy postmenopausal women on CTS risk. DESIGN: We conducted a secondary analysis of the Women's Health Initiative's (WHI) HT trials linked to Medicare claims data. Separate intention-to-treat analyses were performed for the two trials; the conjugated equine estrogens alone (CEE alone) and the trial of CEE plus medroxyprogesterone acetate (MPA) trial. (ClinicalTrials.gov, NCT number): NCT00000611. SETTING: Two randomized, double-blind, placebo-controlled trials conducted at 40 US clinical centers. PARTICIPANTS: The sample size included in the analysis was 16,053 community-dwelling women aged ≥65 years at study entry or those who later aged into Medicare eligibility, and who were enrolled in Medicare (including Part A and/or Part B coverage). INTERVENTION: Women with hysterectomy were randomized to 0.625 mg/d of conjugated equine estrogens (CEE) or placebo (n = 8376). Women without hysterectomy were randomized to estrogen plus progestin (E+P), given as CEE plus 2.5 mg/d of medroxyprogesterone acetate (n = 14203). MAIN OUTCOME(S): The primary outcome was incident CTS and the secondary outcome was therapeutic CTS procedure occurring during the intervention phases of the trials. RESULTS: A total of 16,053 women were randomized in both trials. During mean follow up of 4.5 ± 2.8 years in the CEE trial (n = 6,833), there were 203 incident CTS cases in the intervention and 262 incident CTS cases in the placebo group (HR, 0.78; 95% CI, 0.65-0.94; P = 0.009). The CEE+MPA trial (n = 9,220) followed participants for a mean of 3.7 ± 2.3 years. There were 173 incident CTS cases in the intervention compared to 203 cases in the placebo group (HR, 0.80, 95% CI, 0.65-0.97; P = 0.027). CONCLUSIONS: These findings suggest a protective effect of menopausal HT on the incidence of CTS among postmenopausal women. A potential therapeutic role for other forms of estrogen therapy in the management of CTS warrants future research.


Assuntos
Síndrome do Túnel Carpal/epidemiologia , Terapia de Reposição Hormonal/estatística & dados numéricos , Pós-Menopausa/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Síndrome do Túnel Carpal/terapia , Método Duplo-Cego , Feminino , Humanos , Incidência , Pessoa de Meia-Idade
10.
Menopause ; 25(11): 1313-1320, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30358728

RESUMO

OBJECTIVE: Although joint symptoms are commonly reported after menopause, observational studies examining exogenous estrogen's influence on joint symptoms provide mixed results. Against this background, estrogen-alone effects on joint symptoms were examined in post hoc analyses in the Women's Health Initiative randomized, placebo-controlled, clinical trial. METHODS: A total of 10,739 postmenopausal women who have had a hysterectomy were randomized to receive daily oral conjugated equine estrogens (0.625 mg/d) or a matching placebo. The frequency and severity of joint pain and joint swelling were assessed by questionnaire in all participants at entry and on year 1, and in a 9.9% random subsample (n = 1,062) after years 3 and 6. Logistic regression models were used to compare the frequency and severity of symptoms by randomization group. Sensitivity analyses evaluated adherence influence on symptoms. RESULTS: At baseline, joint pain and joint swelling were closely comparable in the randomization groups (about 77% with joint pain and 40% with joint swelling). After 1 year, joint pain frequency was significantly lower in the estrogen-alone group compared with the placebo group (76.3% vs 79.2%, P = 0.001), as was joint pain severity, and the difference in pain between randomization groups persisted through year 3. However, joint swelling frequency was higher in the estrogen-alone group (42.1% vs 39.7%, P = 0.02). Adherence-adjusted analyses strengthen estrogen's association with reduced joint pain but attenuate estrogen's association with increased joint swelling. CONCLUSIONS: The current findings suggest that estrogen-alone use in postmenopausal women results in a modest but sustained reduction in the frequency of joint pain.


Assuntos
Artralgia/tratamento farmacológico , Terapia de Reposição de Estrogênios , Estrogênios Conjugados (USP)/administração & dosagem , Estrogênios/administração & dosagem , Pós-Menopausa/fisiologia , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Histerectomia/efeitos adversos , Modelos Logísticos , Pessoa de Meia-Idade , Inquéritos e Questionários , Resultado do Tratamento , Saúde da Mulher
11.
Am J Epidemiol ; 187(10): 2126-2135, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29868784

RESUMO

The inconsistent findings from epidemiologic studies relating total sugars (TS) consumption to cardiovascular disease (CVD) or type 2 diabetes (T2D) risk may be partly due to measurement error in self-reported intake. Using regression calibration equations developed based on the predictive biomarker for TS and recovery biomarker for energy, we examined the association of TS with T2D and CVD risk, before and after dietary calibration, in 82,254 postmenopausal women participating in the Women's Health Initiative Observational Study. After up to 16 years of follow-up (1993-2010), 6,621 T2D and 5,802 CVD incident cases were identified. The hazard ratio for T2D per 20% increase in calibrated TS was 0.94 (95% confidence interval (CI): 0.77, 1.15) in multivariable energy substitution, and 1.00 (95% CI: 0.85, 1.18) in energy partition models. Multivariable hazard ratios for total CVD were 0.97 (95% CI: 0.87, 1.09) from energy substitution, and 0.91 (95% CI: 0.80, 1.04) from energy partition models. Uncalibrated TS generated a statistically significant inverse association with T2D and total CVD risk in multivariable energy substitution and energy partition models. The lack of conclusive findings from our calibrated analyses may be due to the low explanatory power of the calibration equations for TS, which could have led to incomplete deattenuation of the risk estimates.


Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Inquéritos sobre Dietas/estatística & dados numéricos , Dieta/efeitos adversos , Açúcares da Dieta/análise , Idoso , Biomarcadores/análise , Calibragem , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/etiologia , Inquéritos sobre Dietas/métodos , Ingestão de Energia , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Análise Multivariada , Pós-Menopausa , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Regressão , Medição de Risco , Estados Unidos/epidemiologia , Saúde da Mulher
12.
Int J Epidemiol ; 47(6): 1760-1771, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29901778

RESUMO

Background: Self-reported smoking is the principal measure used to assess lung cancer risk in epidemiological studies. We evaluated if circulating cotinine-a nicotine metabolite and biomarker of recent tobacco exposure-provides additional information on lung cancer risk. Methods: The study was conducted in the Lung Cancer Cohort Consortium (LC3) involving 20 prospective cohort studies. Pre-diagnostic serum cotinine concentrations were measured in one laboratory on 5364 lung cancer cases and 5364 individually matched controls. We used conditional logistic regression to evaluate the association between circulating cotinine and lung cancer, and assessed if cotinine provided additional risk-discriminative information compared with self-reported smoking (smoking status, smoking intensity, smoking duration), using receiver-operating characteristic (ROC) curve analysis. Results: We observed a strong positive association between cotinine and lung cancer risk for current smokers [odds ratio (OR ) per 500 nmol/L increase in cotinine (OR500): 1.39, 95% confidence interval (CI): 1.32-1.47]. Cotinine concentrations consistent with active smoking (≥115 nmol/L) were common in former smokers (cases: 14.6%; controls: 9.2%) and rare in never smokers (cases: 2.7%; controls: 0.8%). Former and never smokers with cotinine concentrations indicative of active smoking (≥115 nmol/L) also showed increased lung cancer risk. For current smokers, the risk-discriminative performance of cotinine combined with self-reported smoking (AUCintegrated: 0.69, 95% CI: 0.68-0.71) yielded a small improvement over self-reported smoking alone (AUCsmoke: 0.66, 95% CI: 0.64-0.68) (P = 1.5x10-9). Conclusions: Circulating cotinine concentrations are consistently associated with lung cancer risk for current smokers and provide additional risk-discriminative information compared with self-report smoking alone.


Assuntos
Cotinina/sangue , Neoplasias Pulmonares/sangue , Fumar Tabaco/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Autorrelato
13.
Menopause ; 25(9): 985-991, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29738414

RESUMO

OBJECTIVE: Research on the relationships between different hormone therapy doses, formulation and routes of delivery, and subsequent breast cancer incidence has been limited. This study directly compared different estrogen doses, formulations, and route of delivery of estrogen alone among women with a hysterectomy in relation to invasive breast cancer incidence. METHODS: The Women's Health Initiative Observational Study is a large multicenter prospective cohort study conducted at 40 US sites. Analyses included 26,525 postmenopausal women with a hysterectomy, aged 50 to 79 years, at study entry, recruited between September, 1993 and December, 1998, with annual follow-up through September 12, 2005. RESULTS: Average follow-up was 8.2 years. For conjugated equine estrogen (CEE) users, no difference was observed between low-dose CEE (<0.625 mg) compared with conventional-dose CEE (0.625 mg) for breast cancer (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.65, 1.48)]. Compared with conventional-dose CEE, transdermal estrogen was associated with a nonsignificant lower risk of invasive breast cancer (HR 0.75, 95% CI 0.47, 1.19). The low prevalence of transdermal use likely limited power for this comparison, and for a comparison of oral estradiol to conventional-dose CEE (HR 1.20, 95% CI 0.84, 1.39). CONCLUSION: Our results indicate that invasive breast cancer risk did not differ appreciably in women with a hysterectomy using estrogen-alone when directly comparing different doses, formulations, and routes of delivery to the conventional oral CEE. These findings suggest that the lower breast cancer risk found in the WHI estrogen-alone trial may extend to lower doses of CEE. Additional research is needed to confirm these hypotheses.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Terapia de Reposição de Estrogênios/efeitos adversos , Estrogênios Conjugados (USP)/administração & dosagem , Estrogênios Conjugados (USP)/uso terapêutico , Estrogênios/administração & dosagem , Estrogênios/uso terapêutico , Administração Cutânea , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Histerectomia/efeitos adversos , Incidência , Pessoa de Meia-Idade , Invasividade Neoplásica , Pós-Menopausa , Modelos de Riscos Proporcionais , Estudos Prospectivos , Inquéritos e Questionários , Estados Unidos/epidemiologia
14.
J Natl Cancer Inst ; 110(1)2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28922778

RESUMO

Background: Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown. Methods: Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models. Results: Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1 ) being 0.88 (95% confidence interval [CI] = 0.78 to 1.00) and 0.86 (95% CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95% CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95% CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95% CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95% CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups. Conclusions: Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who avoid low concentrations of circulating folate and vitamin B6.


Assuntos
Ácido Fólico/sangue , Neoplasias Pulmonares/epidemiologia , Metionina/sangue , Vitamina B 6/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Ásia/epidemiologia , Austrália/epidemiologia , Estudos de Casos e Controles , Cotinina/sangue , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Proteção , Fatores de Risco , Fatores Sexuais , Fumar/sangue , Fumar/epidemiologia , Estados Unidos/epidemiologia
15.
Int J Cancer ; 142(12): 2425-2434, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29238985

RESUMO

Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5'-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer. We prospectively evaluated the association of the functional marker of vitamin B6 status, the 3-hydroxykynurenine:xanthurenic acid (HK:XA) ratio, with risk of lung cancer in a nested case-control study consisting of 5,364 matched case-control pairs from the Lung Cancer Cohort Consortium (LC3). We used conditional logistic regression to evaluate the association between HK:XA and lung cancer, and random effect models to combine results from different cohorts and regions. High levels of HK:XA, indicating impaired functional B6 status, were associated with an increased risk of lung cancer, the odds ratio comparing the fourth and the first quartiles (OR4thvs.1st ) was 1.25 (95% confidence interval, 1.10-1.41). Stratified analyses indicated that this association was primarily driven by cases diagnosed with squamous cell carcinoma. Notably, the risk associated with HK:XA was approximately 50% higher in groups with a high relative frequency of squamous cell carcinoma, i.e., men, former and current smokers. This risk of squamous cell carcinoma was present in both men and women regardless of smoking status.


Assuntos
Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Vitamina B 6/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco
16.
Am J Clin Nutr ; 105(6): 1314-1326, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28424186

RESUMO

Background: Circulating concentrations of biomarkers that are related to vitamin status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also been influenced by the variation across laboratories, which complicates a comparison of results from different studies.Objective: We robustly and comprehensively assessed differences in biomarkers that are related to vitamin status across geographic regions.Design: The trial was a cross-sectional study in which we investigated 38 biomarkers that are related to vitamin status and one-carbon and tryptophan metabolism in serum and plasma from 5314 healthy control subjects representing 20 cohorts recruited from the United States, Nordic countries, Asia, and Australia, participating in the Lung Cancer Cohort Consortium. All samples were analyzed in a centralized laboratory.Results: Circulating concentrations of riboflavin, pyridoxal 5'-phosphate, folate, vitamin B-12, all-trans retinol, 25-hydroxyvitamin D, and α-tocopherol as well as combined vitamin scores that were based on these nutrients showed that the general B-vitamin concentration was highest in the United States and that the B vitamins and lipid soluble vitamins were low in Asians. Conversely, circulating concentrations of metabolites that are inversely related to B vitamins involved in the one-carbon and kynurenine pathways were high in Asians. The high B-vitamin concentration in the United States appears to be driven mainly by multivitamin-supplement users.Conclusions: The observed differences likely reflect the variation in intake of vitamins and, in particular, the widespread multivitamin-supplement use in the United States. The results provide valuable information about the differences in biomarker concentrations in populations across continents.


Assuntos
Carbono/sangue , Cinurenina/sangue , Vitamina A/sangue , Complexo Vitamínico B/sangue , Vitamina D/sangue , alfa-Tocoferol/sangue , Idoso , Ásia , Austrália , Biomarcadores/sangue , Estudos Transversais , Suplementos Nutricionais , Feminino , Humanos , Laboratórios , Masculino , Pessoa de Meia-Idade , Países Escandinavos e Nórdicos , Triptofano/sangue , Estados Unidos
17.
Circ Heart Fail ; 9(10)2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27682440

RESUMO

BACKGROUND: Heart failure is an important and growing public health problem in women. Risk factors for incident hospitalized heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF) in women and differences by race/ethnicity are not well characterized. METHODS AND RESULTS: We prospectively evaluated the risk factors for incident hospitalized HFpEF and HFrEF in a multiracial cohort of 42 170 postmenopausal women followed up for a mean of 13.2 years. Cox regression models with time-dependent covariate adjustment were used to define risk factors for HFpEF and HFrEF. Differences by race/ethnicity about incidence rates, baseline risk factors, and their population-attributable risk percentage were analyzed. Risk factors for both HFpEF and HFrEF were as follows: older age, white race, diabetes mellitus, cigarette smoking, and hypertension. Obesity, history of coronary heart disease (other than myocardial infarction), anemia, atrial fibrillation, and more than one comorbidity were associated with HFpEF but not with HFrEF. History of myocardial infarction was associated with HFrEF but not with HFpEF. Obesity was found to be a more potent risk factor for African American women compared with white women for HFpEF (P for interaction=0.007). For HFpEF, the population-attributable risk percentage was greatest for hypertension (40.9%) followed by obesity (25.8%), with the highest population-attributable risk percentage found in African Americans for these risk factors. CONCLUSIONS: In this multiracial cohort of postmenopausal women, obesity stands out as a significant risk factor for HFpEF, with the strongest association in African American women. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.

18.
BMC Geriatr ; 16: 76, 2016 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-27038789

RESUMO

BACKGROUND: Results from studies assessing the association between anticholinergic use and falls are mixed, and prior studies are limited in their ability to control for important potential confounders. Thus, we sought to examine the association between anticholinergic medication use, including over-the-counter medications, and recurrent falls in community-dwelling older women. METHODS: We analyzed data from a prospective cohort study of women aged 65 to 79 years from the Women's Health Initiative Observational Study and Clinical Trials. Women were recruited between 1993 and 1998, and analyses included 61,451 women with complete information. Medications with moderate or strong anticholinergic effects were ascertained directly from drug containers during face-to-face interviews. The main outcome measure was recurrent falls (≥2 falls in previous year), which was determined from self-report within 1.5 years subsequent to the medication assessment. RESULTS: At baseline, 11.3 % were using an anticholinergic medication, of which antihistamines (commonly available over-the-counter) were the most common medication class (received by 45.2 % of individuals on anticholinergic medication). Using multivariable GEE models and controlling for potential confounders, the adjusted odds ratio for anticholinergic medication use was 1.51 (95 % CI, 1.43-1.60) for recurrent falls. Participants using multiple anticholinergic medications had a 100 % increase in likelihood of recurrent falls (adjusted odds ratio 2.00, 95 % CI 1.73-2.32). Results were robust to sensitivity analysis. CONCLUSIONS: Anticholinergic medication use was associated with increased risk for recurrent falls. Our findings reinforce judicious use of anticholinergic medications in older women. Public health efforts should emphasize educating older women regarding the risk of using over-the-counter anticholinergics, such as first-generation antihistamines.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Antagonistas Colinérgicos/efeitos adversos , Pós-Menopausa , Idoso , Antagonistas Colinérgicos/administração & dosagem , Estudos de Coortes , Feminino , Antagonistas dos Receptores Histamínicos/administração & dosagem , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Recidiva , Fatores de Risco , Estados Unidos
20.
J Gerontol A Biol Sci Med Sci ; 71 Suppl 1: S13-22, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25922347

RESUMO

BACKGROUND: The Women's Health Initiative has collected data on the aging process of postmenopausal women for over two decades, including data on many women who have achieved age 80 years and older. However, there has not been any previous effort to characterize the 80+ cohort and to identify associated retention factors. METHODS: We include all women at baseline of the Women's Health Initiative who would be at least 80 years of age as of September 17, 2012. We summarize retention rates during the study and across two re-enrollment campaigns as well as the demographic and health-related characteristics that predicted retention. Further, we describe the longitudinal change from baseline in the women identified as members of the 80+ cohort. RESULTS: Retention rates were lower during each of two re-enrollment periods (74% and 83% retained during re-enrollment periods 1 and 2, respectively) than during the first and second data collection periods (90% each). Women who were retained were more likely to be white, educated, and healthier at baseline. Women age 80 and older saw modest changes in body mass index and depression burden, despite lower physical activity and increased cardiovascular disease. CONCLUSIONS: The characteristics of women who were retained in the 80+ cohort differ in significant ways compared with their peers at baseline. Identifying the characteristics associated with attrition in older cohorts is important because aging and worsening health has a negative impact on study attrition. Strategies should be implemented to improve retention rates among less healthy older adults.


Assuntos
Envelhecimento/fisiologia , Envelhecimento/psicologia , Cooperação do Paciente/estatística & dados numéricos , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Saúde da Mulher , Idoso de 80 Anos ou mais , Estudos de Coortes , Demografia , Feminino , Indicadores Básicos de Saúde , Inquéritos Epidemiológicos , Humanos , Qualidade de Vida , Estados Unidos
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