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2.
Eur J Epidemiol ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399938

RESUMO

Most studies of white matter hyperintensity volume (WMHV) in stroke patients lack reliable information on antecedent exposure to vascular risk factors. By leveraging prospective cohort data, we explored associations between lifestyle and health factors assessed 1 year prior to stroke and WMHV in individuals who experienced an ischemic stroke. This analysis was nested within two large prospective studies of initially healthy individuals. Information on lifestyle factors and health conditions was collected prior to the stroke event through annual or biannual questionnaires. For individuals who experienced their first confirmed ischemic stroke and had available magnetic resonance imaging, we measured WMHV using a validated semiautomated method. Linear regression was used to explore associations between lifestyle factors and health conditions and log-transformed WMHV. We measured WMHV in 345 participants with a first ischemic stroke event (mean age = 74.4 years; 24.9% male). After multivariate adjustment, history of diabetes was associated with decreased WMHV (p value = 0.06) while history of transient ischemic attack (p value = 0.09) and hypertension (p value = 0.07) were associated with increased WMHV. Most lifestyle factors and health conditions measured 1 year prior to stroke were not associated with WMHV measured at the time of ischemic stroke. Future studies could examine whether long term exposure to these factors impacts diffuse microvascular ischemic brain injury among stroke patients.

3.
Nat Rev Dis Primers ; 5(1): 56, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420554

RESUMO

Atherosclerosis, the formation of fibrofatty lesions in the artery wall, causes much morbidity and mortality worldwide, including most myocardial infarctions and many strokes, as well as disabling peripheral artery disease. Development of atherosclerotic lesions probably requires low-density lipoprotein, a particle that carries cholesterol through the blood. Other risk factors for atherosclerosis and its thrombotic complications include hypertension, cigarette smoking and diabetes mellitus. Increasing evidence also points to a role of the immune system, as emerging risk factors include inflammation and clonal haematopoiesis. Studies of the cell and molecular biology of atherogenesis have provided considerable insight into the mechanisms that link all these risk factors to atheroma development and the clinical manifestations of this disease. An array of diagnostic techniques, both invasive (such as selective coronary arteriography) and noninvasive (such as blood biomarkers, stress testing, CT and nuclear scanning), permit assessment of cardiovascular disease risk and targeting of therapies. An expanding armamentarium of therapies that can modify risk factors and confer clinical benefit is available; however, we face considerable challenge in providing equitable access to these treatments and in maximizing adherence. Yet, the clinical application of the fruits of research has advanced preventive strategies, enhanced clinical outcomes in affected individuals, and improved their quality of life. Rapidly accelerating knowledge and continued research promise to provide further progress in combating this common chronic disease.

4.
Int J Cancer ; 2019 Jul 05.
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.

5.
Sleep ; 42(10)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31361895

RESUMO

STUDY OBJECTIVES: Short sleep duration is associated with increased cardiovascular disease (CVD) risk. However, it is uncertain whether sleep debt, a measure of sleep deficiency during the week compared to the weekend, confers increased cardiovascular risk. Because sleep disturbances increase with age particularly in women, we examined the relationship between sleep debt and ideal cardiovascular health (ICH) in older women. METHODS: Sleep debt is defined as the difference between self-reported total weekday and weekend sleep hours of at least 2 hours among women without apparent CVD and cancer participating in the Women's Health Stress Study follow-up cohort of female health professionals (N = 22 082). The ICH consisted of seven health factors and behaviors as defined by the American Heart Association Strategic 2020 goals including body mass index, smoking, physical activity, diet, blood pressure, total cholesterol, and glucose. RESULTS: Mean age was 72.1 ± 6.0 years. Compared to women with no sleep debt, women with sleep debt were more likely to be obese and have hypertension (pall < .05). Linear regression models adjusted for age and race/ethnicity revealed that sleep debt was significantly associated with poorer ICH (B = -0.13 [95% CI = -0.18 to -0.08]). The relationship was attenuated but remained significant after adjustment for education, income, depression/anxiety, cumulative stress, and snoring. CONCLUSION: Sleep debt was associated with poorer ICH, despite taking into account socioeconomic status and psychosocial factors. These results suggest that weekly sleep duration variation, possibly leading to circadian misalignment, may be associated with cardiovascular risk in older women.

6.
J Am Heart Assoc ; 8(15): e012790, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31322059

RESUMO

Background Pathologic angiogenesis is a hallmark of type 2 diabetes mellitus (T2DM) microvascular complications and may modulate adipogenesis and precede the onset of clinical diabetes mellitus; however, longitudinal data are unavailable. Placental growth factor is a potent proangiogenic factor that stimulates the formation of mature and durable vessels but is understudied in human diseases. Methods and Results We conducted a prospective case-cohort study of baseline placental growth factor and incident T2DM within the WHS (Women's Health Study). A random sample of incident T2DM cases (n=491) occurring over a 15-year follow-up period was selected and compared with a reference subcohort (n=561). Case subjects were matched to the reference risk set on 5-year age groups and race. All subjects in this analysis were required to have a hemoglobin A1c <6.5% at WHS enrollment. Median baseline levels of placental growth factor were higher in case subjects compare to the reference subcohort (18.0 pg/mL versus 17.2 pg/mL) but were only weakly correlated with glycemic measures and not associated with obesity. The risk of diabetes mellitus increased across placental growth factor quartile in the base model (hazard ratios, 1.00, 1.14, 1.46, and 2.14; P-trend<0.001) and in multivariable-adjusted models accounting for clinical T2DM risk factors (hazard ratios, 1.00, 1.17, 1.45, and 2.61; P-trend<0.001). These findings were not substantially altered by further adjustment for high-sensitivity C-reactive protein, hemoglobin A1c, or fasting insulin and remained robust in sensitivity analyses excluding those diagnosed within 2 years of enrollment and those with baseline hemoglobin A1c ≥6.0%. Conclusions Elevated placental growth factor levels are associated with future T2DM independent of traditional risk factors, measures of glycemia, insulin resistance, and high-sensitivity C-reactive protein. These prospective data suggest that pathologic angiogenesis may occur well before the clinical onset of T2DM and thus may have relevance to vascular complications of this disease. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.

7.
Eur Heart J ; 2019 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-31228190

RESUMO

AIMS: Efficacy of aspirin in primary prevention of cardiovascular disease (CVD) may be influenced by a common allele in guanylate cyclase GUCY1A3, which has been shown to modify platelet function and increase CVD risk. METHODS AND RESULTS: We investigated whether homozygotes of the GUCY1A3 rs7692387 risk (G) allele benefited from aspirin in two long-term, randomized placebo-controlled trials of aspirin in primary CVD prevention: the Women's Genome Health Study (WGHS, N = 23 294) and a myocardial infarction (MI, N = 550) and stroke (N = 382) case-control set from the Physician's Health Study (PHS, N = 22 071). Bleeding risk was evaluated in the WGHS. In the placebo group of the WGHS, the GUCY1A3 risk (G) allele was confirmed to increase CVD risk [hazard ratio 1.38; 95% confidence interval (CI) 1.08-1.78; P = 0.01]. Random-effects meta-analysis of the WGHS and PHS revealed that aspirin reduced CVD events among risk allele homozygotes [G/G: odds ratio (OR) 0.79; 95% CI 0.65-0.97; P = 0.03] but increased CVD events among non-risk allele carriers (e.g. G/A: OR 1.39; 95% CI 1.03-1.87; P = 0.03) thus implying an interaction between genotype stratum and aspirin intake (Pinteraction = 0.01). Bleeding associated with aspirin increased in all genotype groups, with higher risks in heterozygotes. CONCLUSION: In two randomized placebo-controlled trials in the setting of primary prevention, aspirin reduced the incidence of CVD events in individuals homozygous for the GUCY1A3 risk (G) allele, whereas heterozygote individuals had more events when taking aspirin.

8.
JAMA Intern Med ; 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31141585

RESUMO

Importance: A goal of 10 000 steps/d is commonly believed by the public to be necessary for health, but this number has limited scientific basis. Additionally, it is unknown whether greater stepping intensity is associated with health benefits, independent of steps taken per day. Objective: To examine associations of number of steps per day and stepping intensity with all-cause mortality. Design, Setting, and Participants: This prospective cohort study included 18 289 US women from the Women's Health Study who agreed to participate by wearing an accelerometer during waking hours for 7 days between 2011 and 2015. A total of 17 708 women wore and returned their devices; data were downloaded successfully from 17 466 devices. Of these women, 16 741 were compliant wearers (≥10 h/d of wear on ≥4 days) and included in the analyses, which took place between 2018 and 2019. Exposures: Steps per day and several measures of stepping intensity (ie, peak 1-minute cadence; peak 30-minute cadence; maximum 5-minute cadence; time spent at a stepping rate of ≥40 steps/min, reflecting purposeful steps). Main Outcomes and Measures: All-cause mortality. Results: Of the 16 741 women who met inclusion criteria, the mean (SD) age was 72.0 (5.7) years. Mean step count was 5499 per day, with 51.4%, 45.5%, and 3.1% of time spent at 0, 1 to 39 (incidental steps), and 40 steps/min or greater (purposeful steps), respectively. During a mean follow-up of 4.3 years, 504 women died. Median steps per day across low-to-high quartiles of distribution were 2718, 4363, 5905, and 8442, respectively. The corresponding quartile hazard ratios (HRs) associated with mortality and adjusted for potential confounders were 1.00 (reference), 0.59 (95% CI, 0.47-0.75), 0.54 (95% CI, 0.41-0.72), and 0.42 (95% CI, 0.30-0.60), respectively (P < .01). In spline analysis, HRs were observed to decline progressively with higher mean steps per day until approximately 7500 steps/d, after which they leveled. For measures of stepping intensity, higher intensities were associated with significantly lower mortality rates; however, after adjusting for steps per day, all associations were attenuated, and most were no longer significant (highest vs lowest quartile for peak 1-minute cadence, HR = 0.87 [95% CI, 0.68-1.11]; peak 30-minute cadence, HR = 0.86 [95% CI, 0.65-1.13]; maximum 5-minute cadence, HR = 0.80 [95% CI, 0.62-1.05]; and time spent at a stepping rate of ≥40 steps/min, HR = 1.27 [95% CI, 0.96-1.68]; P > .05). Conclusions and Relevance: Among older women, as few as approximately 4400 steps/d was significantly related to lower mortality rates compared with approximately 2700 steps/d. With more steps per day, mortality rates progressively decreased before leveling at approximately 7500 steps/d. Stepping intensity was not clearly related to lower mortality rates after accounting for total steps per day.

9.
J Natl Cancer Inst ; 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31127946

RESUMO

BACKGROUND: Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear. METHODS: We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with smoking and alcohol consumption were calculated. Random effects meta-analysis produced summary estimates. All statistical tests were two-sided. RESULTS: Over a period of 38,369,156 person-years of follow-up, 1,391 gallbladder, 758 intrahepatic bile duct, 1,208 extrahepatic bile duct, and 623 ampulla of Vater cancer cases were identified. Ever, former, and current smoking were associated with increased extrahepatic bile duct and ampulla of Vater cancers risk (e.g., current versus never smokers hazard ratio [HR] = 1.69, 95% confidence interval [CI] = 1.34 to 2.13 and 2.22, 95%CI = 1.69 to 2.92, respectively), with dose-response effects for smoking pack-years, duration, and intensity (all P-trend<0.01). Current smoking and smoking intensity were also associated with intrahepatic bile duct cancer (e.g., >40 cigarettes/day versus never smokers HR = 2.15, 95%CI: 1.15 to 4.00; P-trend=0.001). No convincing association was observed between smoking and gallbladder cancer. Alcohol consumption was only associated with intrahepatic bile duct cancer, with increased risk for individuals consuming ≥5 versus 0 drinks/day (HR = 2.35, 95%CI = 1.46 to 3.78; P-trend=0.04). There was evidence of statistical heterogeneity between several cancer sites, particularly between gallbladder cancer and the other biliary tract cancers. CONCLUSIONS: Smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer. Alcohol may increase the risk of intrahepatic bile duct cancer. Findings highlight etiologic heterogeneity across the biliary tract.

10.
Cancer Res ; 79(15): 3973-3982, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31113819

RESUMO

Biliary tract cancers are rare but highly fatal with poorly understood etiology. Identifying potentially modifiable risk factors for these cancers is essential for prevention. Here we estimated the relationship between adiposity and cancer across the biliary tract, including cancers of the gallbladder (GBC), intrahepatic bile ducts (IHBDC), extrahepatic bile ducts (EHBDC), and the ampulla of Vater (AVC). We pooled data from 27 prospective cohorts with over 2.7 million adults. Adiposity was measured using baseline body mass index (BMI), waist circumference, hip circumference, waist-to-hip, and waist-to-height ratios. HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models adjusted for sex, education, race, smoking, and alcohol consumption with age as the time metric and the baseline hazard stratified by study. During 37,883,648 person-years of follow-up, 1,343 GBC cases, 1,194 EHBDC cases, 784 IHBDC cases, and 623 AVC cases occurred. For each 5 kg/m2 increase in BMI, there were risk increases for GBC (HR = 1.27; 95% CI, 1.19-1.36), IHBDC (HR = 1.32; 95% CI, 1.21-1.45), and EHBDC (HR = 1.13; 95% CI, 1.03-1.23), but not AVC (HR = 0.99; 95% CI, 0.88-1.11). Increasing waist circumference, hip circumference, waist-to-hip ratio, and waist-to-height ratio were associated with GBC and IHBDC but not EHBDC or AVC. These results indicate that adult adiposity is associated with an increased risk of biliary tract cancer, particularly GBC and IHBDC. Moreover, they provide evidence for recommending weight maintenance programs to reduce the risk of developing these cancers. SIGNIFICANCE: These findings identify a correlation between adiposity and biliary tract cancers, indicating that weight management programs may help minimize the risk of these diseases.

11.
Neurology ; 92(19): e2286-e2294, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-30971484

RESUMO

OBJECTIVE: To examine the association between lipid levels and hemorrhagic stroke risk among women. METHODS: We performed a prospective cohort study among 27,937 women enrolled in the Women's Health Study with measured total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), as well as triglycerides. Strokes were confirmed by medical record review. We used Cox proportional hazards models to analyze associations between lipid categories and hemorrhagic stroke risk. RESULTS: During a mean of 19.3 years of follow-up, 137 hemorrhagic strokes occurred. Compared to those with LDL-C levels 100-129.9 mg/dL, after multivariable adjustment, those with LDL-C levels <70 mg/dL had 2.17 times the risk (95% confidence interval [CI] 1.05, 4.48) of experiencing a hemorrhagic stroke. No significant increase in risk was seen for those with LDL-C levels 130-159.9 mg/dL (relative risk [RR] 1.14; 95% CI 0.72, 1.80) or 70-99.9 mg/dL (RR 1.25; 95% CI 0.76, 2.04). There was a suggestion, although not significant, of increased risk for those with LDL-C levels ≥160 mg/dL (RR 1.53; 95% CI 0.92, 2.52). Women in the lowest quartile of triglycerides had a significantly increased risk of hemorrhagic stroke compared to women in the top quartile after multivariable adjustment (RR 2.00; 95% CI 1.18, 3.39). We observed no significant associations between total cholesterol or HDL-C levels and hemorrhagic stroke risk. CONCLUSION: LDL-C levels <70 mg/dL and low triglyceride levels were associated with increased risk of hemorrhagic stroke among women.

12.
Circulation ; 139(17): 2012-2021, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30813768

RESUMO

BACKGROUND: Research implicates acute and chronic stressors in racial/ethnic health disparities, but the joint impact of multiple stressors on racial/ethnic disparities in cardiovascular health is unknown. METHODS: In 25 062 women (24 053 white; 256 Hispanic; 440 black; 313 Asian) articipating in the Women's Health Study follow-up cohort, we examined the relationship between cumulative psychosocial stress (CPS) and ideal cardiovascular health (ICH), as defined by the American Heart Association's 2020 strategic Impact Goals. This health metric includes smoking, body mass index, physical activity, diet, blood pressure, total cholesterol, and glucose, with higher levels indicating more ICH and less cardiovascular risk (score range, 0-7). We created a CPS score that summarized acute stressors (eg, negative life events) and chronic stressors (eg, work, work-family spillover, financial, discrimination, relationship, and neighborhood) and traumatic life event stress reported on a stress questionnaire administered in 2012 to 2013 (score range, 16-385, with higher scores indicating higher levels of stress). RESULTS: White women had the lowest mean CPS scores (white: 161.7±50.4; Hispanic: 171.2±51.7; black: 172.5±54.9; Asian: 170.8±50.6; Poverall<0.01). Mean CPS scores remained higher in Hispanic, black, and Asian women than in white women after adjustment for age, socioeconomic status (income and education), and psychological status (depression and anxiety) ( P<0.01 for each). Mean ICH scores varied by race/ethnicity ( P<0.01) and were significantly lower in black women and higher in Asian women compared with white women (ß-coefficient [95% CI]: Hispanics, -0.02 [-0.13 to -0.09]; blacks, -0.34 [-0.43 to -0.25]; Asians, 0.34 [0.24 to 0.45]); control for socioeconomic status and CPS did not change these results. Interactions between CPS and race/ethnicity in ICH models were not significant. CONCLUSIONS: Both CPS and ICH varied by race/ethnicity. ICH remained worse in blacks and better in Asians compared with whites, despite taking into account socioeconomic factors and CPS.

13.
J Altern Complement Med ; 25(S1): S138-S146, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30870015

RESUMO

OBJECTIVES: To report the results of health economic analyses comparing two treatment approaches for chronic low back pain (CLBP). DESIGN: Observational prospective cohort study comparing effectiveness and cost-effectiveness of CLBP care provided at an integrative care clinic with that provided in other clinics within the same hospital. CLBP-related medical utilization, function, quality of life, and days of work incapacity were self-reported at baseline, 3, 6, and 12 months. SETTINGS/LOCATION: Osher Clinical Center (OCC) based at a tertiary academic hospital (Brigham and Women's Hospital [BWH]) and other clinics at BWH. SUBJECTS: CLBP patients seeking care at OCC or non-OCC BWH clinics. INTERVENTIONS: Integrative or conventional care for CLBP as prescribed by the treating clinician(s). OUTCOME MEASURES: Quality-adjusted life years (QALYs) were estimated per treatment approach based on the SF-12. Cost per QALY gained was evaluated using an incremental cost-effectiveness ratio (ICER). ICERs based on CLBP-specific effectiveness measures (Roland Disability Questionnaire [RDQ] and bothersomeness of pain [BOP]) were exploratory outcomes. RESULTS: Total adjusted annual CLBP-related costs per patient were greater in the OCC versus non-OCC group ($11,526.73 vs. $6,810.63). Between group differences in QALYs were small and ICER estimate of cost per QALY gained was high ($436,676). However, unadjusted mean direct costs per patient decreased over time in the OCC group. Savings in direct costs of $391 (95% confidence interval: -1,078 to 1,861) were observed in the OCC group for the 6- to 12-month period, driven primarily by reduced medication usage. ICERs based on adjusted RDQ and BOP group differences showed cost of $2,073 and $4,203 for a one-point reduction per respective scale. CONCLUSIONS: When adjusted for baseline differences, self-reported costs were higher in the OCC group with only small effects on QALYs. However, trends toward decreased direct expenditures and medication usage over time warrant further investigation. Future studies evaluating potential benefits of integrative care models for the management of CLBP should employ randomized designs, longer observational periods, and explore multiple metrics of cost-effectiveness.


Assuntos
Dor nas Costas/economia , Dor nas Costas/terapia , Dor Crônica/economia , Dor Crônica/terapia , Terapias Complementares/economia , Medicina Integrativa , Adulto , Idoso , Dor nas Costas/epidemiologia , Dor Crônica/epidemiologia , Terapias Complementares/estatística & dados numéricos , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Anos de Vida Ajustados por Qualidade de Vida , Resultado do Tratamento
14.
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
15.
J Natl Cancer Inst ; 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30624689

RESUMO

Background: Vitamins are among the most frequently used supplements (48% of US adults). However, little is known about contributions of genetic variation to their efficacy and safety. Multiple pathways link catechol-O-methyltransferase (COMT) to the vitamin E supplement, alpha-tocopherol, and cancer. Methods: Here we determined if COMT exerted pharmacogenetic effects on cancer prevention in two randomized trials of alpha-tocopherol supplementation. Pharmacogenetic effects of common COMT rs4680 (val158met), which encodes a nonsynonymous valine-to-methionine substitution, were examined in the trial plus a 10-year post-trial follow-up (overall) period of The Women's Genome Health Study (WGHS, N = 23 294), a 10-year alpha-tocopherol and aspirin trial with 10 years post-trial follow-up. Results were validated in a case/control (N = 2396/2235) subset of the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC, N = 29 133). The primary outcome was total cancers. Rates of cancer types prevalent in women (colorectal, breast, lung, uterine, and lymphoma/leukemia) were also examined. All statistical tests were two-sided. Results: Random-effects meta-analysis of rs4680 genotype strata, in WGHS and ATBC overall periods, revealed differential alpha-tocopherol effects compared with placebo: met/met (hazard ratio [HR] = 0.88; 95% confidence interval [CI] = 0.80 to 0.97; P = .01), val/met (HR = 0.99; 95% CI = 0.92 to 1.06; P = .74), and val/val (HR = 1.18; 95% CI = 1.06 to 1.31; P = .002) with a statistically significant COMT by alpha-tocopherol interaction (Pinteraction <.001). Timing of effects differed, with stronger effects in WGHS trial and ATBC post-trial. Conclusion: Pharmacogenetic analysis of COMT and cancer prevention in two large randomized trials revealed statistically significant COMT by alpha-tocopherol interaction, such that alpha-tocopherol was beneficial among rs4680 met-allele (28.0%), but not val-allele (22.8%) homozygotes. These effects indicate the need for additional studies of genetic variation as a determinant of the benefits and possible harms of over-the-counter supplements, like alpha-tocopherol, used for health promotion.

16.
Int J Cancer ; 2018 Nov 29.
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 aetiology 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 5,183 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. This article is protected by copyright. All rights reserved.

17.
N Engl J Med ; 2018 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-30415629

RESUMO

BACKGROUND: It is unclear whether supplementation with vitamin D reduces the risk of cancer or cardiovascular disease, and data from randomized trials are limited. METHODS: We conducted a nationwide, randomized, placebo-controlled trial, with a two-by-two factorial design, of vitamin D3 (cholecalciferol) at a dose of 2000 IU per day and marine n-3 (also called omega-3) fatty acids at a dose of 1 g per day for the prevention of cancer and cardiovascular disease among men 50 years of age or older and women 55 years of age or older in the United States. Primary end points were invasive cancer of any type and major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes). Secondary end points included site-specific cancers, death from cancer, and additional cardiovascular events. This article reports the results of the comparison of vitamin D with placebo. RESULTS: A total of 25,871 participants, including 5106 black participants, underwent randomization. Supplementation with vitamin D was not associated with a lower risk of either of the primary end points. During a median follow-up of 5.3 years, cancer was diagnosed in 1617 participants (793 in the vitamin D group and 824 in the placebo group; hazard ratio, 0.96; 95% confidence interval [CI], 0.88 to 1.06; P=0.47). A major cardiovascular event occurred in 805 participants (396 in the vitamin D group and 409 in the placebo group; hazard ratio, 0.97; 95% CI, 0.85 to 1.12; P=0.69). In the analyses of secondary end points, the hazard ratios were as follows: for death from cancer (341 deaths), 0.83 (95% CI, 0.67 to 1.02); for breast cancer, 1.02 (95% CI, 0.79 to 1.31); for prostate cancer, 0.88 (95% CI, 0.72 to 1.07); for colorectal cancer, 1.09 (95% CI, 0.73 to 1.62); for the expanded composite end point of major cardiovascular events plus coronary revascularization, 0.96 (95% CI, 0.86 to 1.08); for myocardial infarction, 0.96 (95% CI, 0.78 to 1.19); for stroke, 0.95 (95% CI, 0.76 to 1.20); and for death from cardiovascular causes, 1.11 (95% CI, 0.88 to 1.40). In the analysis of death from any cause (978 deaths), the hazard ratio was 0.99 (95% CI, 0.87 to 1.12). No excess risks of hypercalcemia or other adverse events were identified. CONCLUSIONS: Supplementation with vitamin D did not result in a lower incidence of invasive cancer or cardiovascular events than placebo. (Funded by the National Institutes of Health and others; VITAL ClinicalTrials.gov number, NCT01169259 .).

18.
N Engl J Med ; 2018 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-30415637

RESUMO

BACKGROUND: Higher intake of marine n-3 (also called omega-3) fatty acids has been associated with reduced risks of cardiovascular disease and cancer in several observational studies. Whether supplementation with n-3 fatty acids has such effects in general populations at usual risk for these end points is unclear. METHODS: We conducted a randomized, placebo-controlled trial, with a two-by-two factorial design, of vitamin D3 (at a dose of 2000 IU per day) and marine n-3 fatty acids (at a dose of 1 g per day) in the primary prevention of cardiovascular disease and cancer among men 50 years of age or older and women 55 years of age or older in the United States. Primary end points were major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes) and invasive cancer of any type. Secondary end points included individual components of the composite cardiovascular end point, the composite end point plus coronary revascularization (expanded composite of cardiovascular events), site-specific cancers, and death from cancer. Safety was also assessed. This article reports the results of the comparison of n-3 fatty acids with placebo. RESULTS: A total of 25,871 participants, including 5106 black participants, underwent randomization. During a median follow-up of 5.3 years, a major cardiovascular event occurred in 386 participants in the n-3 group and in 419 in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P=0.24). Invasive cancer was diagnosed in 820 participants in the n-3 group and in 797 in the placebo group (hazard ratio, 1.03; 95% CI, 0.93 to 1.13; P=0.56). In the analyses of key secondary end points, the hazard ratios were as follows: for the expanded composite end point of cardiovascular events, 0.93 (95% CI, 0.82 to 1.04); for total myocardial infarction, 0.72 (95% CI, 0.59 to 0.90); for total stroke, 1.04 (95% CI, 0.83 to 1.31); for death from cardiovascular causes, 0.96 (95% CI, 0.76 to 1.21); and for death from cancer (341 deaths from cancer), 0.97 (95% CI, 0.79 to 1.20). In the analysis of death from any cause (978 deaths overall), the hazard ratio was 1.02 (95% CI, 0.90 to 1.15). No excess risks of bleeding or other serious adverse events were observed. CONCLUSIONS: Supplementation with n-3 fatty acids did not result in a lower incidence of major cardiovascular events or cancer than placebo. (Funded by the National Institutes of Health and others; VITAL ClinicalTrials.gov number, NCT01169259 .).

19.
Contemp Clin Trials ; 74: 11-17, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30282055

RESUMO

Diabetic kidney disease (DKD), defined as reduced glomerular filtration rate (GFR), elevated urine albumin excretion, or both that is clinically attributable to diabetes, is a common and morbid diabetes complication. Animal-experimental data, observational human studies, and short-term clinical trials suggest that vitamin D and omega-3 fatty acid supplements may be safe and inexpensive interventions to reduce the incidence and progression of DKD. The Vitamin D and Omega-3 Trial to Prevent and Treat DKD (VITAL-DKD) was designed as an ancillary study to the VITAL trial of 25,871 US adults. In a 2 × 2 factorial design, VITAL participants were randomly assigned to vitamin D3 (cholecalciferol, 2000 IU daily) or placebo and to marine omega-3 fatty acids (eicospentaenoic acid and docosahexaenoic acid, 1 g/d) or placebo. VITAL-DKD enrolled a subset of 1326 VITAL participants with type 2 diabetes at baseline to test the effects of vitamin D and omega-3 fatty acids on changes in estimated GFR and urine albumin excretion. Over five years of follow-up, VITAL-DKD collected blood and urine samples to quantify changes in estimated GFR (the primary study outcome) and urine albumin excretion. At baseline, mean age of VITAL-DKD participants was 67.6 years, 46% were women, 30% were of racial or ethnic minority, and the prevalence of DKD (estimated GFR <60 mL/min/1.73m2 or urine albumin-creatinine ratio ≥ 30 mg/g) was 17%. In this type 2 diabetes population, VITAL-DKD will test the hypotheses that vitamin D and omega-3 fatty acids help prevent the development and progression of DKD.

20.
Am J Gastroenterol ; 113(10): 1494-1505, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30177781

RESUMO

OBJECTIVE: Obesity and diabetes are associated with an increased liver cancer risk. However, most studies have examined all primary liver cancers or hepatocellular carcinoma, with few studies evaluating intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. Thus, we examined the association between obesity and diabetes and ICC risk in a pooled analysis and conducted a systematic review/meta-analysis of the literature. DESIGN: For the pooled analysis, we utilized the Liver Cancer Pooling Project, a consortium of 13 US-based, prospective cohort studies with data from 1,541,143 individuals (ICC cases n = 414). In our systematic review, we identified 14 additional studies. We then conducted a meta-analysis, combining the results from LCPP with results from the 5 prospective studies identified through September 2017. RESULTS: In the LCPP, obesity and diabetes were associated with a 62% [Hazard Ratio (HR) = 1.62, 95% Confidence Interval (CI): 1.24-2.12] and an 81% (HR = 1.81, 95% CI: 1.33-2.46) increased ICC risk, respectively. In the meta-analysis of prospectively ascertained cohorts and nested case-control studies, obesity was associated with a 49% increased ICC risk [Relative Risk (RR) = 1.49, 95% CI: 1.32-1.70; n = 4 studies; I2 = 0%]. Diabetes was associated with a 53% increased ICC risk (RR = 1.53, 95% CI: 1.31-1.78; n = 6 studies). While we noted heterogeneity between studies (I2 = 67%) for diabetes, results were consistent in subgroup analyses. Results from hospital-based case-control studies (n = 9) were mostly consistent, but these studies are potentially subject to reverse causation. CONCLUSIONS: These findings suggest that obesity and diabetes are associated with increased ICC risk, highlighting similar etiologies of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. However, additional prospective studies are needed to verify these associations.

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