Association of the multi-biomarker disease activity score with arterial 18-fluorodeoxyglucose uptake in rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) and atherosclerosis share many common inflammatory pathways. We studied whether a multi-biomarker panel for RA disease activity (MBDA) would associate with changes in arterial inflammation in an interventional trial. METHODS: In the TARGET Trial, RA patients with active disease despite methotrexate were randomly assigned to the addition of either a TNF inhibitor or sulfasalazine+hydroxychloroquine (triple therapy). Baseline and 24-week follow-up 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography scans were assessed for change in arterial inflammation measured as the maximal arterial target-to-blood background ratio of FDG uptake in the most diseased segment of the carotid arteries or aorta (MDS-TBRmax). The MBDA test, measured at baseline and weeks 6, 18, and 24, was assessed for its association with the change in MDS-TBRmax. RESULTS: Interpretable scans were available at baseline and week 24 for n = 112 patients. The MBDA score at week 24 was significantly correlated with the change in MDR-TBRmax (Spearman's rho = 0.239; p= 0.011) and remained significantly associated after adjustment for relevant confounders. Those with low MBDA at week 24 had a statistically significant adjusted reduction in arterial inflammation of 0.35 units vs no significant reduction in those who did not achieve low MBDA. Neither DAS28-CRP nor CRP predicted change in arterial inflammation. The MBDA component with the strongest association with change in arterial inflammation was serum amyloid A (SAA). CONCLUSIONS: Among treated RA patients, achieved MBDA predicts of changes in arterial inflammation. Achieving low MBDA at 24 weeks was associated with clinically meaningful reductions in arterial inflammation, regardless of treatment.

Reducing cardiovascular risk with immunomodulators: a randomised active comparator trial among patients with rheumatoid arthritis.

OBJECTIVE: Recent large-scale randomised trials demonstrate that immunomodulators reduce cardiovascular (CV) events among the general population. However, it is uncertain whether these effects apply to rheumatoid arthritis (RA) and if certain treatment strategies in RA reduce CV risk to a greater extent. METHODS: Patients with active RA despite use of methotrexate were randomly assigned to addition of a tumour necrosis factor (TNF) inhibitor (TNFi) or addition of sulfasalazine and hydroxychloroquine (triple therapy) for 24 weeks. Baseline and follow-up 18F-fluorodeoxyglucose-positron emission tomography/CT scans were assessed for change in arterial inflammation, an index of CV risk, measured as an arterial target-to-background ratio (TBR) in the carotid arteries and aorta. RESULTS: 115 patients completed the protocol. The two treatment groups were well balanced with a median age of 58 years, 71% women, 57% seropositive and a baseline disease activity score in 28 joints of 4.8 (IQR 4.0, 5.6). Baseline TBR was similar across the two groups. Significant TBR reductions were observed in both groups-ΔTNFi: -0.24 (SD=0.51), Δtriple therapy: -0.19 (SD=0.51)-without difference between groups (difference in Δs: -0.02, 95% CI -0.19 to 0.15, p=0.79). While disease activity was significantly reduced across both treatment groups, there was no association with change in TBR (ß=0.04, 95% CI -0.03 to 0.10). CONCLUSION: We found that addition of either a TNFi or triple therapy resulted in clinically important improvements in vascular inflammation. However, the addition of a TNFi did not reduce arterial inflammation more than triple therapy. TRIAL REGISTRATION NUMBER: NCT02374021.

Association between white matter hyperintensity volume and social functioning limitations among stroke survivors.

OBJECTIVE: Existing literature on white matter hyperintensity volume (WMHV) in stroke patients has rarely focused on post-stroke outcomes related to social functioning limitations, such as transportation, social interaction, food preparation, grocery shopping, and housekeeping. Using prospective data from the VITamin D and OmegA-3 TriaL (VITAL) study, we evaluated the association between WMHV and social functioning limitations among 151 ischemic stroke patients. MATERIALS AND METHODS: WMHV was ascertained from magnetic resonance imaging (MRI) collected at the time of the stroke event using a validated semiautomated method, and social functioning limitations were assessed using a stroke outcomes questionnaire administered a median of 1.25 years after the date of the MRI scan. Logistic regression was used to explore the association between WMHV and social functioning limitations. RESULTS: After adjusting for age and sex, a statistically significant association was found between WMHV and limitations in social interaction (OR=2.82; 95% CI: 1.21-7.55). Increased risks were seen for limitations related to food preparation (OR=2.06; 95% CI: 0.99-4.54), transportation (OR=1.39; 95% CI: 0.85-2.27), and housekeeping (OR=1.37; 95% CI: 0.91-2.11); however, the associations did not reach statistical significance. We observed no association between WMHV and limitations in grocery shopping (OR=1.08; 95% CI: 0.61-1.89). CONCLUSIONS: Future studies are needed to further explore the biological mechanisms underlying the relationship with limitations in social interaction and to replicate our findings using a larger and more diverse study sample.

Multimodal chiropractic care for migraine: A pilot randomized controlled trial.

BACKGROUND: Spinal manipulation may reduce migraine frequency, but effects of multimodal chiropractic care on migraine frequency have not been evaluated. METHODS: We conducted a pilot randomized controlled trial comparing multimodal chiropractic care + enhanced usual care (MCC+) versus enhanced usual care alone (EUC) among adult women with episodic migraine. EUC was comprised of usual medical care and migraine education literature. MCC+ participants received 10 sessions of chiropractic care over 14 weeks. Primary aims evaluated feasibility of recruitment, retention, protocol adherence, and safety. Change in migraine days was a secondary aim. RESULTS: Of 422 patients screened, 61 were randomized over 20 months. Fifty-seven (93%) completed daily migraine logs during the intervention, 51 (84%) completed final follow-up, and 45 (74%) completed all assessments. Twenty-four of 29 MCC+ participants (83%) attended > 75% of the chiropractic sessions. Ninety-eight non-serious adverse events were reported by 26 participants (43%) with 39 events among 11 EUC participants and 59 events among 15 MCC+ participants. MCC+ participants experienced greater reductions in migraine days (-2.9 days for MCC+ vs. -1.0 days for EUC, difference = -1.9; 95% confidence interval: -3.5, -0.4). CONCLUSIONS: Pre-specified feasibility criteria were not met, but deficits were remediable. Preliminary data support a definitive trial of MCC+ for migraine. TRIAL REGISTRATION: This study is registered at Clinicaltrials.gov (NCT03177616).

Effect of vitamin D and/or omega-3 fatty acid supplementation on stroke outcomes: A randomized trial.

BACKGROUND AND PURPOSE: Among stroke patients, low serum 25-hydroxyvitamin D predicts poor outcomes. In mice, higher omega-3 (n-3) fatty acid intake diminishes brain damage after stroke. In this study, we tested whether vitamin D or n-3 fatty acids supplementation prior to stroke reduces the risk of functional limitations and physical disability after stroke. METHODS: We used data from VITAL (the VITamin D and OmegA-3 TriaL) which randomized middle-aged and older men and women without cardiovascular disease to vitamin D3 (2000 IU/day) and/or marine n-3 fatty acids (1 g/day) and followed them for incident stroke events. Individuals experiencing a non-fatal stroke were mailed questionnaires assessing functional limitations (the physical performance scale adapted from Nagi) and physical disability (the modified Katz Activities of Daily Living and Rosow-Breslau Functional Health scales). We used logistic regression to analyze associations between randomized treatment and limitations on each scale. RESULTS: A total of 290 individuals experienced their first stroke during the trial, of whom 197 stroke survivors completed the stroke outcomes questionnaire a median of 1.4 years after diagnosis. We observed no associations between randomized treatment to vitamin D and functional limitations (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.52, 1.97) or physical disability (Rosow-Breslau scale: OR 0.92, 95% CI 0.50, 1.67; Katz scale: OR 1.03, 95% CI 0.31, 3.42). Those randomized to n-3 fatty acids had a non-significantly lower risk of functional limitations (OR 0.55, 95% CI 0.28, 1.09) and physical disability (Rosow-Breslau scale: OR 0.56, 95% CI 0.31, 1.02; Katz sclae: OR 0.32, 95% CI 0.50, 1.67). CONCLUSION: Vitamin D or omega-3 fatty acid supplementation prior to stroke did not result in significantly improved post-stroke outcomes.

Perceptions of Chiropractic Care Among Women With Migraine: A Qualitative Substudy Using a Grounded-Theory Framework.

OBJECTIVE: The purpose of this study was to characterize expectations, attitudes, and experiences of individuals with migraine who were randomly assigned to receive chiropractic care delivered within a randomized controlled trial in a hospital-based integrative care center. METHODS: This qualitative substudy was conducted as a part of a 2-arm pilot pragmatic randomized controlled trial investigating a multimodal model of chiropractic care for women with episodic migraine (4-13 migraines per month). Women were randomly assigned to chiropractic care (10 sessions over 14 weeks) plus enhanced usual care vs enhanced usual care alone. Semistructured interviews were conducted at baseline and 14-week follow-up with 15 randomly selected participants from the 29 participants randomized to the chiropractic group. Qualitative analysis was performed by 2 independent reviewers using a constant comparative method of analysis for generating grounded theory. RESULTS: Integrating baseline and follow-up interviews, 3 themes emerged: over the course of treatment with chiropractic care, participants became more aware of the role of musculoskeletal tension, pain, and posture in triggering migraine; participants revised their prior conceptions of chiropractic care beyond spinal manipulation; and participants viewed the chiropractor-patient relationship as an essential and valuable component to effectively managing their migraines. CONCLUSION: In this qualitative study, women with episodic migraine after receiving comprehensive chiropractic care described chiropractic as a multimodal intervention where they learned about musculoskeletal contributions to migraine, discovered new ways to affect their symptoms, and developed a collaborative patient-practitioner relationship. The results of this study provide insights into perceptions of chiropractic care among women with migraine and suggestions for future trials.

Effect of genetic liability to migraine on cognition and brain volume: A Mendelian randomization study.

OBJECTIVE: To investigate potential causality between genetic liability to migraine and Alzheimer's disease, intelligence, and brain volume using two-sample Mendelian randomization. METHODS: The exposure consisted of independent genetic variants associated with migraine in the largest (59,674 cases/316,078 controls) published genome-wide association study. Outcomes included Alzheimer's disease (71,880 cases/383,378 controls), a measure of general intelligence (n = 269,867), intracranial volume (n = 11,373), and seven subcortical brain volumes (n ∼ 13,000), all with available genome-wide association study summary statistics. Mendelian randomization effects were estimated using inverse-variance weighted analysis. RESULTS: Genetic liability to migraine did not associate with Alzheimer's disease (odds ratio [95% confidence interval] 1.01 [1.00-1.02], p = 0.07), intelligence (standardized beta [95% confidence interval] 0.01 [0.00-0.02], p = 0.13), or any brain volume measures (all p > 0.05). No individual migraine variant associated with any of the outcomes at genome-wide significance. CONCLUSIONS: These data do not support a causal effect of migraine liability on Alzheimer's disease, intelligence, or brain volume.

Development and Implementation of the Integrative Toolbox for Headache Management.

Patients with migraine are interested in integrative therapies and overall wellness. They also suffer from social isolation as they try to manage a chronic medical condition. We implemented a three-part workshop structured as a group visit that teaches multiple integrative therapies from specialists and offers a chance for shared support and learning.

Association of Migraine With Aura and Other Risk Factors With Incident Cardiovascular Disease in Women.

Importance: Migraine with aura is known to increase the risk of cardiovascular disease (CVD). The absolute contribution of migraine with aura to CVD incidence in relation to other CVD risk factors remains unclear. Objective: To estimate the CVD incidence rate for women with migraine with aura relative to women with other major vascular risk factors. Design, Setting, and Participants: Female health professionals in the US (the Women's Health Study cohort) with lipid measurements and no CVD at baseline (1992-1995) were followed up through December 31, 2018. Exposures: Self-reported migraine with aura compared with migraine without aura or no migraine at baseline. Main Outcomes and Measures: The primary outcome was major CVD (first myocardial infarction, stroke, or CVD death). Generalized modeling procedures were used to calculate multivariable-adjusted incidence rates for major CVD events by risk factor status that included all women in the cohort. Results: The study population included 27 858 women (mean [SD] age at baseline, 54.7 [7.1] years), among whom 1435 (5.2%) had migraine with aura and 26 423 (94.8%) did not (2177 [7.8%] had migraine without aura and 24 246 [87.0%] had no migraine in the year prior to baseline). During a mean follow-up of 22.6 years (629 353 person-years), 1666 major CVD events occurred. The adjusted incidence rate of major CVD per 1000 person-years was 3.36 (95% CI, 2.72-3.99) for women with migraine with aura vs 2.11 (95% CI, 1.98-2.24) for women with migraine without aura or no migraine (P < .001). The incidence rate for women with migraine with aura was significantly higher than the adjusted incidence rate among women with obesity (2.29 [95% CI, 2.02-2.56]), high triglycerides (2.67 [95% CI, 2.38-2.95]), or low high-density lipoprotein cholesterol (2.63 [95% CI, 2.33-2.94]), but was not significantly different from the rates among those with elevated systolic blood pressure (3.78 [95% CI, 2.76-4.81]), high total cholesterol (2.85 [95% CI, 2.38-3.32]), or family history of myocardial infarction (2.71 [95% CI, 2.38-3.05]). Incidence rates among women with diabetes (5.76 [95% CI, 4.68-6.84]) or who currently smoked (4.29 [95% CI, 3.79-4.79]) were significantly higher than those with migraine with aura. The incremental increase in the incidence rate for migraine with aura ranged from 1.01 additional cases per 1000 person-years when added to obesity to 2.57 additional cases per 1000 person-years when added to diabetes. Conclusions and Relevance: In this study of female health professionals aged at least 45 years, women with migraine with aura had a higher adjusted incidence rate of CVD compared with women with migraine without aura or no migraine. The clinical importance of these findings, and whether they are generalizable beyond this study population, require further research.

Prospectively Collected Cardiovascular Biomarkers and White Matter Hyperintensity Volume in Ischemic Stroke Patients.

BACKGROUND: Few prospective cohort studies collect detailed information on stroke characteristics among individuals who experience ischemic stroke, including white matter hyperintensity volume, and thus cannot explore how prospectively collected biomarkers prior to the stroke influence white matter hyperintensity volume. We explored the association between a large panel of prospectively collected lipid and inflammatory biomarkers and white matter hyperintensity volume among participants in the Women's Health Study with incident ischemic stroke. METHODS: Among Women's Health Study participants with first ischemic stroke who had baseline serum biomarkers and available magnetic resonance imaging, we measured white matter hyperintensity volume using a validated semi-automated method. Linear regression was used to explore the associations between biomarkers and log-transformed white matter hyperintensity volume. RESULTS: After multivariate adjustment, a 1% increment in HbA1c% was associated with an increase in white matter hyperintensity volume (P value = .05). Evidence of a nonlinear association between high density lipoprotein cholesterol levels and ApoA1 levels with white matter hyperintensity volume was noted (P values for nonlinearity = .01 and .001, respectively). No other biomarkers were significantly associated with white matter hyperintensity volume. CONCLUSIONS: Chronic hyperglycemia as evidenced by HbA1c levels measured years prior to stroke is associated with white matter hyperintensity volume at the time of stroke. Additional research is needed to explain why low levels of high density lipoprotein cholesterol levels and ApoA1 may be associated with similar white matter hyperintensity volume as high levels.

Migraine, headache, and mortality in women: a cohort study.

BACKGROUND: Migraine carries a high global burden, disproportionately affects women, and has been implicated as a risk factor for cardiovascular disease. Migraine with aura has been consistently associated with increased risk of cardiovascular mortality. However, published evidence on relationships between migraine or non-migraine headache and all-cause mortality is inconclusive. Therefore, we aimed to estimate the effect of non-migraine headache and migraine as well as migraine subtypes on all-cause and cause-specific mortality in women. METHODS: In total, 27,844 Women's Health Study participants, aged 45 years or older at baseline, were followed up for a median of 22.7 years. We included participants who provided information on migraine (past history, migraine without aura, or migraine with aura) or headache status and a blood sample at study start. An endpoints committee of physicians evaluated reports of incident deaths and used medical records to confirm deaths due to cardiovascular, cancer, or female-specific cancer causes. We used multivariable Cox proportional hazards models to estimate the effect of migraine or headache status on both all-cause and cause-specific mortality. RESULTS: Compared to individuals without any headache, no differences in all-cause mortality for individuals suffering from non-migraine headache or any migraine were observed after adjustment for confounding (HR = 1.01, 95%CI, 0.93-1.10 and HR = 0.96, 95% CI: 0.89-1.04). No differences were observed for the migraine subtypes and all-cause death. Women having the migraine with aura subtype had  a higher mortality due to cardiovascular disease (adjusted HR = 1.64, 95%CI: 1.06-2.54). As an explanation for the lack of overall association with all-cause mortality, we observed slightly protective signals for any cancer and female-specific cancers in this group. CONCLUSIONS: In this large prospective study of women, we found no association between non-migraine headache or migraine and all-cause mortality. Women suffering from migraine with aura had an increased risk of cardiovascular death. Future studies should investigate the reasons for the increased risk of cardiovascular mortality and evaluate whether changes in migraine patterns across the life course have differential effects on mortality.

The Impact of Spinal Manipulation on Migraine Pain and Disability: A Systematic Review and Meta-Analysis.

BACKGROUND: Several small studies have suggested that spinal manipulation may be an effective treatment for reducing migraine pain and disability. We performed a systematic review and meta-analysis of published randomized clinical trials (RCTs) to evaluate the evidence regarding spinal manipulation as an alternative or integrative therapy in reducing migraine pain and disability. METHODS: PubMed and the Cochrane Library databases were searched for clinical trials that evaluated spinal manipulation and migraine-related outcomes through April 2017. Search terms included: migraine, spinal manipulation, manual therapy, chiropractic, and osteopathic. Meta-analytic methods were employed to estimate the effect sizes (Hedges' g) and heterogeneity (I2 ) for migraine days, pain, and disability. The methodological quality of retrieved studies was examined following the Cochrane Risk of Bias Tool. RESULTS: Our search identified 6 RCTs (pooled n = 677; range of n = 42-218) eligible for meta-analysis. Intervention duration ranged from 2 to 6 months; outcomes included measures of migraine days (primary outcome), migraine pain/intensity, and migraine disability. Methodological quality varied across the studies. For example, some studies received high or unclear bias scores for methodological features such as compliance, blinding, and completeness of outcome data. Due to high levels of heterogeneity when all 6 studies were included in the meta-analysis, the 1 RCT performed only among chronic migraineurs was excluded. Heterogeneity across the remaining studies was low. We observed that spinal manipulation reduced migraine days with an overall small effect size (Hedges' g = -0.35, 95% CI: -0.53, -0.16, P < .001) as well as migraine pain/intensity. CONCLUSIONS: Spinal manipulation may be an effective therapeutic technique to reduce migraine days and pain/intensity. However, given the limitations to studies included in this meta-analysis, we consider these results to be preliminary. Methodologically rigorous, large-scale RCTs are warranted to better inform the evidence base for spinal manipulation as a treatment for migraine.

Prospectively collected lifestyle and health information as risk factors for white matter hyperintensity volume in stroke patients.

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.

Migraine and invasive epithelial ovarian cancer risk in the Nurses' Health Study II and the Women's Health Study.

Migraine is a common primary headache disorder, which predominantly impacts women. Recently, migraine has been hypothesized to be associated with hormonally related cancers; however, the potential association between migraine and ovarian cancer has not been studied. Therefore, we evaluated the association between migraine and invasive epithelial ovarian cancer risk in two prospective cohorts, the Nurses' Health Study II (NHSII) and the Women's Health Study (WHS). Our prospective analysis included 113,124 NHSII participants aged 25-42 at study baseline as well as 33,490 participants in the WHS who were 45 years or older at study entry. We used Cox proportional hazards models to estimate the hazard ratios (HR) and 95% confidence intervals (CIs) for the association between migraine and ovarian cancer risk in each cohort. In secondary analyses, we stratified by age and menopausal status. After adjusting for potential covariates, there was no statistically significant association between migraine and ovarian cancer risk in either the NHSII (HR = 1.29, 95%CI: 0.96, 1.74) or the WHS (HR = 0.60, 95%CI: 0.34, 1.06). In stratified analysis in the NHSII, there was a statistically significant positive association between migraine and ovarian cancer risk among women <45 years of age (HR = 1.76, 95%CI: 1.01, 3.07). We did not observe a clear association between migraine and ovarian cancer risk in two large prospective cohort studies.

Migraine and the risk of incident hypertension among women.

Background Few studies have examined whether migraine is associated with an increased risk of incident hypertension. Methods We performed a prospective cohort study among 29,040 women without hypertension at baseline. Women were classified as having active migraine with aura, active migraine without aura, a past history of migraine, or no history of migraine. Incident hypertension was defined as new physician diagnosis or newly self-reported systolic or diastolic blood pressure ≥140 mmHg or ≥90 mmHg respectively. Cox proportional hazards models were used to evaluate the association between migraine and incident hypertension. Results During a mean follow-up of 12.2 years, 15,176 incident hypertension cases occurred. Compared to those with no history of migraine, women who experience migraine with aura had a 9% increase in their risk of developing hypertension (95% CI: 1.02, 1.18); women who experience migraine without aura had a 21% increase in their risk of developing hypertension (95% CI: 1.14, 1.28); and women with a past history of migraine had a 15% increase in their risk of developing hypertension (95% CI: 1.07, 1.23). Conclusions Women with migraine have a higher relative risk of developing hypertension compared to women without migraine.

Plasma Retinol-Binding Protein 4 Levels and the Risk of Ischemic Stroke among Women.

BACKGROUND: Plasma retinol-binding protein 4 (RBP4) levels have been associated with cardiovascular risk factors and risk of coronary heart disease, but little is known about the association between RBP4 and the risk of ischemic stroke. We hypothesized that elevated RBP4 levels would be associated with an increased risk of ischemic stroke among women. METHODS: We performed a nested case-control study among women enrolled in the Nurses' Health Study who provided blood samples between 1989 and 1990 and were free of prior stroke and cancer. We measured prediagnostic RBP4 levels in 471 ischemic stroke cases who were confirmed by medical record review and in 471 controls who were matched 1:1 to the cases on age, race, blood collection date, menopausal status, postmenopausal hormone use, and smoking status. We analyzed the association between RBP4 levels and ischemic stroke using multivariable conditional logistic regression conditional on the matching factors and adjusted for physical activity, body mass index, aspirin use, alcohol consumption, diet, history of diabetes, high cholesterol, high blood pressure, or heart disease, and cholesterol and hemoglobin A1C levels. RESULTS: Median levels of RBP4 were similar in cases (31.1 µg/mL) and controls (31.0 µg/mL; P value from the Wilcoxon rank-sum test = .82). Quartiles of RBP4 were not associated with an increased risk of ischemic stroke (highest quartile compared to lowest quartile: multivariate-adjusted odds ratio, .75; 95% confidence interval, .48, 1.17). We also did not observe associations between RBP4 and ischemic stroke of thrombotic or embolic origin. CONCLUSIONS: Elevated levels of RBP4 were not associated with an increased risk of ischemic stroke.

Multivitamin Use and the Risk of Cardiovascular Disease in Men.

BACKGROUND: Although multivitamins are widely used by US adults, few prospective studies have investigated their association with the long- and short-term risks of cardiovascular disease (CVD). OBJECTIVE: The aim of this study was to investigate how multivitamin use is associated with the risk of CVD in initially healthy men at baseline. METHODS: We studied 18,530 male physicians aged ≥40 y from the Physicians' Health Study I cohort who were free of CVD and cancer at baseline (1982). All men provided a wide range of self-reported lifestyle and clinical factors plus intake of selected foods and dietary supplements. Cox proportional hazards models were used to calculate multivariable-adjusted HRs (95% CIs). RESULTS: During a mean follow-up of 12.2 y (total of 225,287 person-years), there were 1697 incident cases of major CVD (defined as nonfatal myocardial infarction, nonfatal stroke, and CVD death). In multivariable-adjusted analyses, no significant associations were observed among baseline multivitamin users compared with nonusers for the risk of major CVD events (HR: 0.94; 95% CI: 0.84, 1.05), whereas a self-reported duration of ≥20 y at baseline was associated with lower risk (HR: 0.56; 95% CI: 0.35, 0.90; P-trend = 0.05). Baseline multivitamin use was also significantly inversely associated with the risk of cardiac revascularization (HR: 0.86; 95% CI: 0.75, 0.98). Baseline use of multivitamins was not significantly associated with other CVD endpoints. CONCLUSION: In this long-term prospective study in initially healthy men, multivitamin use for ≥20 y was associated with a lower risk of major CVD events.

Families and Disability Onset: Are Spousal Resources Less Important for Individuals at High Risk of Dementia?

OBJECTIVE: To determine whether social contacts and spousal characteristics predict incident instrumental or basic activities of daily living (I/ADL) limitations and whether effects differ for individuals with high risk of dementia. DESIGN: Cohort study. SETTING: Biennial interviews of Health and Retirement Study participants over up to 12 years. PARTICIPANTS: 4,125 participants aged 65 years and older without baseline I/ADL limitations. MEASUREMENTS: Participants' family characteristics (living arrangements, proximity to children, contacts with friends, marital status, and spouse's depression, employment, and education) and dementia probability (high versus low risk of dementia based on direct and proxy cognitive assessments) were characterized at baseline. Family characteristics and their interactions with dementia probability were used to predict incident I/ADL limitations in pooled logistic regressions. RESULTS: ADL limitation incidence was higher among the unmarried (odds ratio [OR] versus married: 1.14; 95% CI: 1.01-1.30); those married to a depressed spouse (OR versus nondepressed spouse: 1.56, 95% CI: 1.21-2.00); or whose spouse had less than high school education (OR versus spouse with high school or more: 1.29, 95% CI: 1.06-1.57). Living with someone other than a spouse compared with living with a spouse predicted higher risk of both incident ADL (OR: 1.35; 95% CI: 1.11-1.65), and IADL (OR: 1.30; 95% CI: 1.06-1.61) limitations. Effects were similar for respondents with high and low dementia probability. CONCLUSIONS: Regardless of dementia risk, older adults may receive important marriage benefits, which help delay disability. The salience of spouse's education and depression status implicate modifiable mechanisms, such as information and instrumental support, which may be amenable to interventions.

Dietary patterns according to headache and migraine status: a cross-sectional study.

BACKGROUND: Several potential dietary trigger factors for migraine have been proposed. However, few studies have examined the intake pattern of these dietary items compared to adequate control populations and whether intake levels may vary by migraine aura status or attack frequency. METHODS: We conducted a cross-sectional study among participants in the Women's Health Study. We used logistic regression to evaluate the association between migraine and headache status and low intake of foods commonly reported to affect migraine. RESULTS: A total of 25,755 women reported no history of migraine or headache, 5573 reported non-migraine headache and 7042 reported any migraine. Those with non-migraine headache or any migraine were more likely to have low intake of total alcohol (OR = 1.22, 95% CI:1.14-1.29 and OR = 1.17, 95% CI:1.11-1.24, respectively). Migraineurs with aura were more likely to have low intake of chocolate, ice cream, hot dogs, and processed meats. Those who experience migraine at least once per week were more likely to have low intake of skim/low-fat milk and white and red wine. CONCLUSION: Intake of most suggested migraine dietary triggers differs by migraine aura status and attack frequency, a pattern not found for non-migraine headache.

Does the "widowhood effect" precede spousal bereavement? Results from a nationally representative sample of older adults.

OBJECTIVE: Increased mortality risk following spousal bereavement (often called the "widowhood effect") is well documented, but little prior research has evaluated health deteriorations preceding spousal loss. DESIGN: Data are from the Health and Retirement Study, a nationally representative sample of Americans over 50 years old. METHOD: Individuals who were married in 2004 were considered for inclusion. Outcome data from 2006 on mobility (walking, climbing stairs), number of depressive symptoms, and instrumental activities of daily living (IADLs) were used. Exposure was characterized based on marital status at the time of outcome measurement: "recent widows" (N=396) were bereaved between 2004 and 2006, before outcomes were assessed; "near widows" (N=380) were bereaved between 2006 and 2008, after outcomes were assessed; "married" individuals (N=7,330) remained married from 2004 to 2010, the follow-up period for this analysis. Linear regression models predicting standardized mobility, depressive symptoms, and IADLs, were adjusted for age, race, gender, birthplace, socio-economic status, and health at baseline. RESULTS: Compared to married individuals, recent widows had worse depressive symptoms (ß=0.71, 95% confidence interval (CI): [0.57, 0.85]). Near widows had worse depressive symptoms (ß=0.21, 95% CI: [0.08, 0.34]), mobility (ß=0.14, 95%CI: [0.01, 0.26]), and word recall (ß=-0.13, 95%CI: [-0.23, -0.02]) compared to married individuals. CONCLUSIONS: Health declines before spousal death suggests some portion of the "widowhood effect" may be attributable to experiences that precede widowhood and interventions prior to bereavement might help preserve the health of the surviving spouse.