Vitamin B6 catabolism and lung cancer risk: results from the Lung Cancer Cohort Consortium (LC3).

BACKGROUND: Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known. MATERIALS AND METHODS: For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models. RESULTS: PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3 years of blood draw (OR: 1.73, 95% CI: 1.34-2.23). CONCLUSION: Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.

Aspirin has potential benefits for primary prevention of cardiovascular outcomes in diabetes: updated literature-based and individual participant data meta-analyses of randomized controlled trials.

BACKGROUND: The clinical benefit of aspirin for the primary prevention of cardiovascular disease (CVD) in diabetes remains uncertain. To evaluate the efficacy and safety of aspirin for the primary prevention of cardiovascular outcomes and all-cause mortality events in people with diabetes, we conducted an updated meta-analysis of published randomised controlled trials (RCTs) and a pooled analysis of individual participant data (IPD) from three trials. METHODS: Randomised controlled trials of aspirin compared with placebo (or no treatment) in participants with diabetes with no known CVD were identified from MEDLINE, Embase, Cochrane Library, and manual search of bibliographies to January 2019. Relative risks with 95% confidence intervals were used as the summary measures of associations. RESULTS: We included 12 RCTs based on 34,227 participants with a median treatment duration of 5.0 years. Comparing aspirin use with no aspirin, there was a significant reduction in risk of major adverse cardiovascular events (MACE)0.89 (0.83-0.95), with a number needed to treat (NNT)of 95 (95% CI 61 to 208) to prevent one MACE over 5 years average follow-up. Evidence was lacking of heterogeneity and publication bias among contributing trials for MACE. Aspirin use had no effect on other endpoints including all-cause mortality; however, there was a significant reduction in stroke for aspirin dosage ≤ 100 mg/day 0.75 (0.59-0.95). There were no significant effects of aspirin use on major bleeding and other bleeding events, though some of the estimates were imprecise. Pooled IPD from the three trials (2306 participants) showed no significant evidence of an effect of aspirin on any of the outcomes evaluated; however, aspirin reduced the risk of MACE in non-smokers 0.70 (0.51-0.96) with a NNT of 33 (95% CI 20 to 246) to prevent one MACE. CONCLUSIONS: Aspirin has potential benefits in cardiovascular primary prevention in diabetes. The use of low dose aspirin may need to be individualised and based on each individual's baseline CVD and bleeding risk. Systematic review registration PROSPERO: CRD42019122326.

Coffee, tea, and caffeine intake and amyotrophic lateral sclerosis mortality in a pooled analysis of eight prospective cohort studies.

BACKGROUND AND PURPOSE: Caffeine is associated with a lower risk of some neurological diseases, but few prospective studies have investigated caffeine intake and risk of amyotrophic lateral sclerosis (ALS) mortality. We therefore determined associations between coffee, tea and caffeine intake, and risk of ALS mortality. METHODS: We conducted pooled analyses of eight international, prospective cohort studies, including 351 565 individuals (120 688 men and 230 877 women). We assessed coffee, tea and caffeine intake using validated food-frequency questionnaires administered at baseline. We used Cox regression to estimate study- and sex-specific risk ratios and 95% confidence intervals (CI) for ALS mortality, which were then pooled using a random-effects model. We conducted analyses using cohort-specific tertiles, absolute common cut-points and continuous measures of all exposures. RESULTS: During follow-up, 545 ALS deaths were documented. We did not observe statistically significant associations between coffee, tea or caffeine intake and risk of ALS mortality. The pooled multivariable risk ratio (MVRR) for ≥3 cups per day vs. >0 to <1 cup per day was 1.04 (95% CI, 0.74-1.47) for coffee and 1.17 (95% CI, 0.77-1.79) for tea. The pooled MVRR comparing the highest with the lowest tertile of caffeine intake (mg/day) was 0.99 (95% CI, 0.80-1.23). No statistically significant results were observed when exposures were modeled as tertiles or continuously. CONCLUSIONS: Our results do not support associations between coffee, tea or total caffeine intake and risk of ALS mortality.

VITamin D and OmegA-3 TriaL (VITAL) bone health ancillary study: clinical factors associated with trabecular bone score in women and men.

We investigated the association of clinical variables with TBS at baseline in the bone health sub-cohort of the VITamin D and OmegA-3 TriaL (VITAL). Lower TBS was associated with female sex, aging, BMI ≥ 25 kg/m2, SSRI use, high alcohol intake, and presence of diabetes; there was a trend towards significance between lower TBS and history of fragility fractures. INTRODUCTION: We investigated whether TBS differs by sex, race, body mass index (BMI), and other clinical variables. METHODS: The VITamin D and OmegA-3 TriaL (VITAL) is determining effects of vitamin D3 and/or omega-3 fatty acid (FA) supplements in reducing risks of cancer and cardiovascular disease. In the VITAL: Effects on Bone Structure/Architecture ancillary study, effects of these interventions on bone will be investigated. Here, we examine the associations of clinical risk factors with TBS assessments at baseline in the bone health sub-cohort, comprised of 672 participants (369 men and 303 women), mean (± SD) age 63.5 ± 6.0 years; BMI ≤ 37 kg/m2, no bisphosphonates within 2 years or other bone active medications within 1 year. RESULTS: TBS was greater in men than women (1.311 vs. 1.278, P < 0.001) and lower with elevated BMIs (P < 0.001), higher age (P = 0.004), diabetes (P = 0.008), SSRI use (P = 0.044), and high alcohol intake (P = 0.009). There was a trend for history of fragility fractures (P = 0.072), and lower TBS. TBS did not vary when analyzed by race, smoking, history of falls, and multivitamin or caffeine use. CONCLUSIONS: Lower TBS was associated with female sex, aging, BMI ≥ 25 kg/m2, SSRI use, alcohol use, and presence of diabetes; there was a trend between lower TBS and history of fragility fractures. TBS may be useful clinically to assess structural changes that may be associated with fractures among patients who are overweight or obese, those on SSRIs, or with diabetes. Ongoing follow-up studies will clarify the effects of supplemental vitamin D3 and/or FA's on TBS and other bone health measures. TRIAL REGISTRATION: NCT01747447.

Reproductive factors, exogenous hormone use and risk of hepatocellular carcinoma among US women: results from the Liver Cancer Pooling Project.

BACKGROUND: Hepatocellular carcinoma (HCC) occurs less commonly among women than men in almost all regions of the world. The disparity in risk is particularly notable prior to menopause suggesting that hormonal exposures during reproductive life may be protective. Exogenous oestrogenic exposures such as oral contraceptives (OCs), however, have been reported to increase risk, suggesting that estrogens may be hepatocarcinogenic. To examine the effects of reproductive factors and exogenous hormones on risk, we conducted a prospective analysis among a large group of US women. METHODS: In the Liver Cancer Pooling Project, a consortium of US-based cohort studies, data from 799,500 women in 11 cohorts were pooled and harmonised. Cox proportional hazards regression models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of reproductive factors and exogenous hormones with HCC (n=248). RESULTS: Bilateral oophorectomy was associated with a significantly increased risk of HCC (HR=2.67, 95% CI=1.22-5.85), which did not appear to be related to a shorter duration of exposure to endogenous hormones or to menopausal hormone therapy use. There was no association between OC use and HCC (HR=1.12, 95% CI=0.82-1.55). Nor were there associations with parity, age at first birth, age at natural menopause, or duration of fertility. CONCLUSIONS: The current study suggests that bilateral oophorectomy increases the risk of HCC but the explanation for the association is unclear. There was no association between OC use and HCC risk. Examination of endogenous hormone levels in relation to HCC may help to clarify the findings of the current study.

Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies.

BACKGROUND: Body mass index (BMI), a measure of obesity typically assessed in middle age or later, is known to be positively associated with pancreatic cancer. However, little evidence exists regarding the influence of central adiposity, a high BMI during early adulthood, and weight gain after early adulthood on pancreatic cancer risk. DESIGN: We conducted a pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium to examine the association of pancreatic cancer mortality with measures of central adiposity (e.g. waist circumference; n = 647 478; 1947 pancreatic cancer deaths), BMI during early adulthood (ages 18-21 years) and BMI change between early adulthood and cohort enrollment, mostly in middle age or later (n = 1 096 492; 3223 pancreatic cancer deaths). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. RESULTS: Higher waist-to-hip ratio (HR = 1.09, 95% CI 1.02-1.17 per 0.1 increment) and waist circumference (HR = 1.07, 95% CI 1.00-1.14 per 10 cm) were associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. BMI during early adulthood was associated with increased pancreatic cancer mortality (HR = 1.18, 95% CI 1.11-1.25 per 5 kg/m(2)), with increased risk observed in both overweight and obese individuals (compared with BMI of 21.0 to <23 kg/m(2), HR = 1.36, 95% CI 1.20-1.55 for BMI 25.0 < 27.5 kg/m(2), HR = 1.48, 95% CI 1.20-1.84 for BMI 27.5 to <30 kg/m(2), HR = 1.43, 95% CI 1.11-1.85 for BMI ≥30 kg/m(2)). BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality (HR = 1.05, 95% CI 1.01-1.10 per 5 kg/m(2)). CONCLUSIONS: Our results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese during early adulthood may be important in influencing pancreatic cancer mortality risk later in life.

Telomere length and Parkinson's disease in men: a nested case-control study.

BACKGROUND AND PURPOSE: Telomere shortening has been implicated in neurodegenerative disorders. However, available data on the association between telomere length and Parkinson's disease (PD) are inconclusive. METHODS: A nested case-control design was used amongst men participating in the prospective Physicians' Health Study. A large proportion of participants provided blood samples in 1997 and they were followed through 2010. Men with self-reported PD were age-matched to controls in a 1:2 ratio. Quantitative PCR was used to determine the telomere repeat copy number to single gene copy number ratio (TSR) in genomic DNA extracted from peripheral blood leukocytes. TSR was used as a measure for relative telomere length (RTL) in our analyses. Conditional logistic regression was used to determine the risk of PD associated with RTL. RESULTS: Data on RTL were available from 408 cases and 809 controls. Median TSR was shorter in controls than in cases (47.7 vs. 50.2; P = 0.02). The age-adjusted odds ratio (OR) for PD was 0.66 [95% confidence interval (CI) 0.46-0.95; Ptrend over quartiles 0.02] comparing the lowest to the highest quartile. The pattern of association was unchanged when comparing RTL below versus above the median (age-adjusted OR 0.75; 95% CI 0.59-0.96). Associations were similar after additional adjustment for many covariates. CONCLUSION: Contrary to what was expected, in this large nested case-control study amongst men shorter telomeres were associated with reduced PD risk. Future research on the nature of this counterintuitive association is warranted.

A candidate gene approach to searching for low-penetrance breast and prostate cancer genes.

Most cases of breast and prostate cancer are not associated with mutations in known high-penetrance genes, indicating the involvement of multiple low-penetrance risk alleles. Studies that have attempted to identify these genes have met with limited success. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium--a pooled analysis of multiple large cohort studies with a total of more than 5,000 cases of breast cancer and 8,000 cases of prostate cancer--was therefore initiated. The goal of this consortium is to characterize variations in approximately 50 genes that mediate two pathways that are associated with these cancers--the steroid-hormone metabolism pathway and the insulin-like growth factor signalling pathway--and to associate these variations with cancer risk.

Biomarkers and functional outcomes from ischaemic cerebral events in women: a prospective cohort study.

BACKGROUND AND PURPOSE: Several biomarkers have been associated with an increased risk of ischaemic stroke. However, the association between these biomarkers and functional outcome from cerebral ischaemic events is unclear. We aimed to assess the patterns of association between cardiovascular disease biomarkers and functional outcomes after incident ischaemic cerebral events in women. METHODS: Prospective cohort study of 27,728 women enrolled in the Women's Health Study who provided information on blood samples and were free of stroke or transient ischaemic attack (TIA) at baseline. Multinomial logistic regression was used to determine the association between elevated biomarker levels and functional outcomes from ischaemic cerebral events. Possible functional outcomes included TIA and ischaemic stroke with modified Rankin Scale (mRS) score of 0-1, 2-3, or 4-6. RESULTS: After a mean follow-up of 15.1 years, 461 TIAs and 380 ischaemic strokes occurred. Elevated levels of total cholesterol were associated with the highest risk of poor functional outcome (mRS 4-6) after incident cerebral ischaemic events (relative risk = 2.02, 95% CI = 1.18-3.46). We observed significant associations between elevated levels of total cholesterol, Lp(a), C-reactive protein, and triglycerides, and mild or moderate functional outcomes after ischaemic cerebral events. Elevations in all other biomarkers were not significantly associated with functional outcomes. CONCLUSIONS: Whilst total cholesterol level was associated with highest risks of poor functional outcome after stroke, we overall observed an inconsistent pattern of association between biomarkers linked with an increased risk of vascular events and more impaired functional outcomes from stroke.

Association between modifiable lifestyle factors and residual lifetime risk of diabetes.

BACKGROUND AND AIMS: While clinical trials have reported beneficial effects of diet, exercise, and weight loss on incident diabetes in subjects with obesity or impaired glucose tolerance, little is known about the incremental benefit of not smoking and moderate drinking on diabetes risk. We sought to examine the association between modifiable lifestyle factors and residual lifetime risk of diabetes. METHODS AND RESULTS: Prospective cohorts involving 20,915 men (1982-2008) and 36,594 women (1992-2008). Modifiable lifestyle factors and adiposity were ascertained at baseline in each cohort and incident diabetes was ascertained during follow up. The mean age at baseline was 53.5 y in men and 54.6 y in women. During an average follow up of 22.6 y in men and 13.0 y in women, 2096 men and 2390 women developed diabetes. At age 45 y, the residual lifetime risk of diabetes (95% CI) for men with 0, 1, 2, 3, and 4 + healthy lifestyle factors was 30.5 (27.3-33.7); 21.5 (19.9-23.0); 15.1 (13.9-16.3); 10.3 (9.1-11.5); and 7.3 (5.7-8.9) percent; respectively. Corresponding values for women were 31.4 (28.3-34.5); 24.1 (21.8-26.5); 14.2 (12.7-15.7); 11.6 (9.7-13.5); and 6.4 (4.2-8.6) percent, respectively. CONCLUSIONS: These data show an inverse and graded relation between desirable lifestyle factors and residual lifetime risk of diabetes in men and women. Not smoking and moderate drinking may have additional benefits when added to exercise, weight control, and diet.

MTHFR 677C->T and ACE D/I polymorphisms and migraine attack frequency in women.

Data on the association of the MTHFR 677C→T and ACE D/I polymorphisms with migraine severity, measured by attack frequency, are scarce. We performed an association study among 24 961 women participating in the Women's Health Study. Migraine, aura status and attack frequency were self-reported. Multinomial logistic regression was used to investigate the genotype-migraine association. Among the 3186 migraineurs with complete genotype and attack frequency data, 1270 reported migraine with aura (MA) (attack frequency 76 ≥ weekly; 219 monthly; 123 every other month; 852 fewer than six times/year) and 1916 migraine without aura (MoA) (attack frequency: 85 ≥ weekly; 414 monthly; 208 every other month; 1209 fewer than six times/year). The MTHFR 677TT genotype was associated with a reduced risk for MA, which only appeared for attacks fewer than six times/year (age-adjusted odds ratio 0.78; 95% confidence interval 0.61, 0.99). We did not find a specific pattern of association of the ACE D/I polymorphism with attack frequency for MA or MoA.

Agreement of self-reported migraine with ICHD-II criteria in the Women's Health Study.

Migraine is a common headache disorder that is increasingly being evaluated in population-based studies. The American Migraine Study II and the Women's Health Study (WHS) have successfully used 'modified' International Classification of Headache Disorders, 1st edition (ICHD-I) criteria to classify patients. Investigating agreement of self-reported migraine in large epidemiological studies with the criteria of the revised version [International Classification of Headache Disorders, 2nd edition (ICHD-II)] is sparse. We have investigated 1675 women with self-reported migraine participating in the WHS, who provided additional information on a detailed migraine questionnaire that allowed us to apply all ICHD-II criteria. In this sub-cohort, we confirmed self-reported migraine in > 87% of women when applying the ICHD-II criteria for migraine (71.5%) and probable migraine without aura (16.2%). In conclusion, there is excellent agreement between self-reported migraine and ICHD-II-based migraine classification in the WHS. In addition, questionnaire-based migraine assessment according to full ICHD-II criteria in large population-based studies is feasible.

Body mass index, migraine, migraine frequency and migraine features in women.

We evaluated the association of body mass index (BMI) with migraine and migraine specifics in a cross-sectional study of 63 467 women aged > or = 45 years, of whom 12,613 (19.9%) reported any history of migraine and 9195 had active migraine. Compared with women without migraine and a BMI < 23 kg/m(2), women with a BMI > or = 35 kg/m(2) had adjusted odds ratios (ORs) (95% confidence intervals) of 1.03 (0.95, 1.12) for any history of migraine. Findings were similar for active migraineurs. Women with a BMI of > or = 35 kg/m(2) had increased risk for low and high migraine frequency, with the highest estimate for women who reported daily migraine. Compared with women with the lowest associated risk (migraine frequency < 6 times/year; BMI between 27.0 and 29.9 kg/m(2)), women with a BMI > or = 35 kg/m(2) had an OR of daily migraine of 3.11 (1.12, 8.67). Among the women with active migraine, a BMI > or = 35 kg/m(2) was associated with increased risk of phonophobia and photophobia and decreased risk of a unilateral pain characteristic and migraine aura. Our data confirm previous findings that the association between BMI with migraine is limited to migraine frequency and specific migraine features.

Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis.

Uterine leiomyomata (UL) are the most common neoplasms of the female reproductive tract and primary cause for hysterectomy, leading to considerable morbidity and high economic burden. Here we conduct a GWAS meta-analysis in 35,474 cases and 267,505 female controls of European ancestry, identifying eight novel genome-wide significant (P < 5 × 10-8) loci, in addition to confirming 21 previously reported loci, including multiple independent signals at 10 loci. Phenotypic stratification of UL by heavy menstrual bleeding in 3409 cases and 199,171 female controls reveals genome-wide significant associations at three of the 29 UL loci: 5p15.33 (TERT), 5q35.2 (FGFR4) and 11q22.3 (ATM). Four loci identified in the meta-analysis are also associated with endometriosis risk; an epidemiological meta-analysis across 402,868 women suggests at least a doubling of risk for UL diagnosis among those with a history of endometriosis. These findings increase our understanding of genetic contribution and biology underlying UL development, and suggest overlapping genetic origins with endometriosis.

Randomised aspirin assignment and risk of adult-onset asthma in the Women's Health Study.

BACKGROUND: Randomised data in men show a small but significant reduction in the risk of adult-onset asthma among those given aspirin. The results from an observational study in women suggest that frequent use of aspirin decreases the risk of adult-onset asthma, but randomised data in women are lacking. A study was undertaken to test the effect of 100 mg aspirin or placebo on alternate days on the risk of adult-onset asthma in the Women's Health Study. METHODS: A randomised, double-blind, placebo-controlled clinical trial of aspirin and vitamin E was performed in apparently healthy women with no indication or contraindication to aspirin therapy and no history of asthma at study entry. Female health professionals self-reported an asthma diagnosis on yearly questionnaires. RESULTS: Among 37 270 women with no reported history of asthma prior to randomisation and during 10 years of follow-up, there were 872 new cases diagnosed with asthma in the aspirin group and 963 in the placebo group (hazard ratio 0.90; 95% CI 0.82 to 0.99; p = 0.027). This apparent 10% lower relative risk of incident adult-onset asthma among those assigned to aspirin was significantly modified by body mass index, with no effect in women with a body mass index of >/=30 kg/m2. The effect of aspirin on adult-onset asthma was not significantly modified by age, smoking status, exercise levels, postmenopausal hormone use or randomised vitamin E assignment. CONCLUSIONS: In this large randomised clinical trial of apparently healthy adult women, administration of 100 mg aspirin on alternate days reduced the relative risk of a newly reported diagnosis of asthma.

Renin-angiotensin and endothelial nitric oxide synthase gene polymorphisms are not associated with the risk of incident type 2 diabetes mellitus: a prospective cohort study.

OBJECTIVE: The renin-angiotensin system and endothelial function have both been implicated in the pathogenesis of type 2 diabetes. The aim of this study was to assess the relationship between a set of well-characterized genetic variants of the renin-angiotensin system and the endothelial nitric oxide synthase (NOS3) gene and the incidence of type 2 diabetes. DESIGN: Prospective cohort study. SETTING: Women's Health Study, United States. SUBJECTS: A total of 24,309 Caucasian women free of diabetes at baseline. MAIN OUTCOME MEASURES: Six previously characterized single nucleotide polymorphisms (NOS3 rs1800779, NOS3 rs3918226, NOS3 rs1799983, ACE rs1799752, AGT rs699 and AGTR rs5186) were genotyped. Cox proportional-hazards models were constructed to compare the incidence of type 2 diabetes according to the different genotypes. RESULTS: During a median follow-up of 10.2 years (interquartile range 9.6-10.6 years), 999 women developed type 2 diabetes. The age-adjusted incidence rates across the six genotypes were very similar, and ranged from 3.7 to 4.8 cases/1000 person-years of follow-up. The multivariable adjusted hazard ratios (95% confidence intervals) for rs1800779, rs3918226, rs1799983, rs1799752, rs699, and rs5186 were 1.01 (0.92-1.10), 1.09 (0.93-1.27), 0.95 (0.86-1.05), 1.04 (0.95-1.14), 1.08 (0.98-1.18), 1.01 (0.91-1.11), confirming the lack of association between the genotypes and incident type 2 diabetes. Stratification by body mass index revealed essentially unchanged results. Finally, there was no association between NOS3-haplotypes and incident type 2 diabetes. CONCLUSION: We did not find an association between six well-characterized genetic polymorphisms of the renin-angiotensin system or the NOS3 gene and the occurrence of type 2 diabetes.

Migraine and biomarkers of cardiovascular disease in women.

Migraine has been associated with an unfavourable cardiovascular risk profile and with increased risk of cardiovascular disease. In a cross-sectional analysis of 27,626 women aged >or=45 years, we evaluated the association of migraine and migraine aura status with elevated levels of total cholesterol, low- and high-density lipoprotein cholesterol (HDL-C), non-HDL-C, apolipoprotein (Apo) A-1 and B(100), lipoprotein (a), C-reactive protein (CRP), fibrinogen, intercellular adhesion molecule-1, homocysteine and creatinine. A total of 5087 (18.4%) women reported any history of migraine. Compared with women with no migraine history, women who reported any history of migraine had modestly increased adjusted odds ratios (95% confidence interval) of 1.09 (1.01, 1.18) for elevated total cholesterol, 1.14 (1.05, 1.23) for non-HDL-C, 1.09 (1.01, 1.18) for Apo B(100) and 1.13 (1.05, 1.22) for CRP. The increase did not meaningfully differ according to migraine aura status and migraine frequency. In this large cohort of women, only a modest association was found between migraine and adverse levels of certain cardiovascular biomarkers.

Family History of MI, Smoking, and Risk of Periodontal Disease.

Periodontal disease (PD) shares common risk factors with cardiovascular disease. Our hypothesis was that having a family history of myocardial infarction (FamHxMI) may be a novel risk factor for PD. Risk assessment based on FamHxMI, conditional on smoking status, was examined given the strong influence of smoking on PD. Exploratory analysis with inflammatory biomarkers and genetic determinants was conducted to understand potential mechanistic links. The Women's Genome Health Study (WGHS) is a prospective cohort of US female health care professionals who provided blood samples at baseline in the Women's Health Study, a 2 × 2 factorial clinical trial investigating vitamin E and aspirin in the prevention of cardiovascular disease and cancer. PD was ascertained via self-report over 12 y of follow-up. Prevalence (3,442 cases), incidence (1,365 cases), and survival analysis of PD were investigated for associations of FamHxMI as well as in strata of FamHxMI by smoking. Kruskal-Wallis, chi-square tests, multivariate regression, and Cox proportional hazard models were used for the analyses. In the WGHS, women with FamHxMI showed higher risk of ever having PD. A particularly high-risk group of having both FamHxMI and smoking at baseline was highlighted in the prevalence and risk of developing PD. PD risk increased according to the following strata: no FamHxMI and nonsmokers (reference), FamHxMI and nonsmokers (hazard ratio [HR] = 1.2, 95% CI = 1.0 to 1.5), smokers without FamHxMI (HR = 1.3, 95% CI = 1.2 to 1.5), and smokers with FamHxMI (HR = 1.5, 95% CI = 1.2 to 1.8). An independent analysis by the dental Atherosclerosis Risk in Communities study ( N = 5,552) identified more severe periodontitis cases among participants in the high-risk group (smokers with FamHxMI). Further examination of interactions among inflammatory biomarkers or genetic exploration with FamHxMI did not explain the risk increase of PD associated with FamHxMI in the WGHS. Future efforts based on an integrative-omics approach may facilitate validation of these findings and suggest a mechanistic link between PD and FamHxMI.

Systematic review with meta-analysis: the comparative effectiveness of aspirin vs. screening for colorectal cancer prevention.

BACKGROUND: Both aspirin use and screening with flexible sigmoidoscopy or guaiac faecal occult blood testing (FOBT) may reduce mortality from colorectal cancer, but comparative effectiveness of these interventions is unknown. AIM: To compare aspirin to guaiac FOBT screening with regard to incidence and mortality of colorectal cancer in a network meta-analysis. METHODS: We searched Medline, EMBASE and the COCHRANE central register (CENTRAL) for relevant randomised trials identified until 31 October 2015. Randomised trials in average-risk populations that reported colorectal cancer mortality, colorectal cancer incidence, or both, with a minimum follow-up of 2 years, and more than 100 randomised individuals were included. Three investigators independently extracted data. We calculated relative risks [RR with 95% predictive intervals (PrIs)] for the comparison of the interventions by frequentist network meta-analyses. RESULTS: The effect of aspirin on colorectal cancer mortality was similar to FOBT (RR 1.03; 95% PrI 0.76-1.39) and flexible sigmoidoscopy (RR 1.16; 95% PrI 0.84-1.60). Aspirin was more effective than FOBT (RR 0.36; 95% PrI 0.22-0.59) and flexible sigmoidoscopy (RR 0.37; 95% PrI 0.22-0.62) in preventing death from or cancer in the proximal colon. Aspirin was equally effective as screening in reducing colorectal cancer incidence, while flexible sigmoidoscopy was superior to FOBT (RR 0.84; 95% PrI 0.72-0.97). CONCLUSIONS: Low-dose aspirin seems to be equally effective as flexible sigmoidoscopy or guaiac FOBT screening to reduce colorectal cancer incidence and mortality, and more effective for cancers in the proximal colon. A randomised comparative effectiveness trial of aspirin vs. screening is warranted.