Oxylipin Dynamics Following A Single Bout of Yoga Exercise: A Pilot Randomized Controlled Trial Secondary Analysis.

Background: Yoga may promote health via a complex modulation of inflammation. Little is known about oxylipins, a class of circulating mediators involved in inflammation resolution. Objective: To explore the acute effects of yoga exercise on systemic levels of oxylipins. Methods: This is a secondary analysis of a three-arm (high-intensity-yoga: HY, n = 10); moderate-intensity-yoga: MY, n = 10; and no-intervention-control: CON, n = 10) pilot randomized controlled trial employing a single bout of yoga exercise. Blood samples (baseline and 4-timepoint post-intervention) were used for an unbiased metabolipidomic profiling analysis. Net Areas Under the Curve per oxylipin were evaluated for each group. Results: Lipoxin(LX)B4, prostaglandin(PG)D2, and resolvin(Rv)D3 exhibited a greater magnitude of change in HY compared with MY and CON. Conclusion: Findings inform the design of future trials exploring the acute effects of yoga exercise on oxylipins' systemic levels.

Omega-3 Fatty Acids and Risk of Ischemic Stroke in REGARDS.

We examined associations between lipidomic profiles and incident ischemic stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Plasma lipids (n = 195) were measured from baseline blood samples, and lipids were consolidated into underlying factors using exploratory factor analysis. Cox proportional hazards models were used to test associations between lipid factors and incident stroke, linear regressions to determine associations between dietary intake and lipid factors, and the inverse odds ratio weighting (IORW) approach to test mediation. The study followed participants over a median (IQR) of 7 (3.4-11) years, and the case-cohort substudy included 1075 incident ischemic stroke and 968 non-stroke participants. One lipid factor, enriched for docosahexaenoic acid (DHA, an omega-3 fatty acid), was inversely associated with stroke risk in a base model (HR = 0.84; 95%CI 0.79-0.90; P = 8.33 × 10-8) and fully adjusted model (HR = 0.88; 95%CI 0.83-0.94; P = 2.79 × 10-4). This factor was associated with a healthy diet pattern (ß = 0.21; 95%CI 0.12-0.30; P = 2.06 × 10-6), specifically with fish intake (ß = 1.96; 95%CI 0.95-2.96; P = 1.36 × 10-4). DHA was a mediator between fish intake and incident ischemic stroke (30% P = 5.78 × 10-3). Taken together, DHA-containing plasma lipids were inversely associated with incident ischemic stroke and mediated the relationship between fish intake and stroke risk.

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.

Biomarkers of Cardiovascular Risk in Patients With Rheumatoid Arthritis: Results From the TARGET Trial.

Cardiovascular disease remains an important comorbidity in patients with rheumatoid arthritis (RA), but traditional models do not accurately predict cardiovascular risk in patients with RA. The addition of biomarkers could improve prediction. METHODS AND RESULTS: The TARGET (Treatments Against RA and Effect on FDG PET/CT) trial assessed whether different treatment strategies in RA differentially impact cardiovascular risk as measured by the change in arterial inflammation on arterial target to background ratio on fluorodeoxyglucose positron emission tomography/computed tomography scans conducted 24 weeks apart. A group of 24 candidate biomarkers supported by prior literature was assessed at baseline and 24 weeks later. Longitudinal analyses examined the association between baseline biomarker values, measured in plasma EDTA, and the change in arterial inflammation target to background ratio. Model fit was assessed for the candidate biomarkers only, clinical variables only, and models combining both. One hundred nine patients with median (interquartile range) age 58 years (53-65 years), RA duration 1.4 years (0.5-6.6 years), and 82% women had biomarkers assessed at baseline and follow-up. Because the main trial analyses demonstrated significant target to background ratio decreases with both treatment strategies but no difference across treatment groups, we analyzed all patients together. Baseline values of serum amyloid A, C-reactive protein, soluble tumor necrosis factor receptor 1, adiponectin, YKL-40, and osteoprotegerin were associated with significant change in target to background ratio. When selected candidate biomarkers were added to the clinical variables, the adjusted R2 improved from 0.20 to 0.33 (likelihood ratio P=0.0005). CONCLUSIONS: A candidate biomarker approach identified several promising biomarkers that associate with baseline and treatment-associated changes in arterial inflammation in patients with RA. These will now be tested in an external validation cohort.

Effect of multivitamin-mineral supplementation versus placebo on cognitive function: results from the clinic subcohort of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial and meta-analysis of 3 cognitive studies within COSMOS.

BACKGROUND: Longer effects of multivitamin-mineral (MVM) supplementation on late-life cognitive function remain untested using in-person, detailed neuropsychological assessments. Furthermore, insufficient evidence exists for healthcare providers to recommend daily MVM supplements to prevent cognitive decline. OBJECTIVES: This study aimed to test MVM effects on cognitive change using in-person, detailed neuropsychological assessments and conduct a meta-analysis within COSMOS (COcoa Supplement and Multivitamin Outcomes Study) cognitive substudies for a robust evaluation of MVM effects on cognition. METHODS: COSMOS is a 2 × 2 factorial trial of cocoa extract (500 mg flavanols/d) and/or a daily MVM supplement for cardiovascular disease and cancer prevention among 21,442 United States adults aged ≥60 y. There were 573 participants in the clinic subcohort of COSMOS (that is, COSMOS-Clinic) who completed all cognitive tests administered at baseline. For the meta-analysis, we included nonoverlapping participants across 3 COSMOS cognitive substudies: COSMOS-Clinic (n = 573); COSMOS-Mind (n = 2158); COSMOS-Web (n = 2472). RESULTS: In COSMOS-Clinic, we observed a modest benefit of MVM compared with placebo on global cognition over 2 y {mean difference [95% confidence interval (CI)] = 0.06 SD units (SU) (-0.003, 0.13)}, with a significantly more favorable change in episodic memory [mean difference (95% CI) = 0.12 SU (0.002, 0.23)] but not in executive function or attention [mean difference (95% CI) = 0.04 SU (-0.04, 0.11)]. The meta-analysis of COSMOS substudies showed clear evidence of MVM benefits on global cognition [mean difference (95% CI) = 0.07 SU (0.03, 0.11); P = 0.0009] and episodic memory [mean difference (95% CI) = 0.06 SU (0.03, 0.10); P = 0.0007]; the magnitude of effect on global cognition was equivalent to reducing cognitive aging by 2 y. CONCLUSIONS: In COSMOS-Clinic, daily MVM supplementation leads to a significantly more favorable 2-y change in episodic memory. The meta-analysis within COSMOS cognitive substudies indicates that daily MVM significantly benefits both global cognition and episodic memory. These findings within the COSMOS trial support the benefits of a daily MVM in preventing cognitive decline among older adults. This trial was registered at COSMOS-clinicaltrials.gov as NCT02422745, at COSMOS-Mind-clinicaltrials.gov as NCT03035201, and at COSMOS-Web-clinicaltrials.gov as NCT04582617.

Effect of cocoa extract supplementation on cognitive function: results from the clinic subcohort of the COSMOS trial.

BACKGROUND: Some prior randomized clinical trials (RCTs) that tested the effects of cocoa extract (CE), a source of flavanols, on late-life cognition have yielded promising findings. A long-term RCT using in-person neuropsychological tests covering multiple cognitive domains may clarify the cognitive effects of CE. OBJECTIVES: To test whether daily supplementation with CE, compared with placebo, produces better cognitive change over 2 y. METHODS: The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a 2 × 2 factorial RCT of CE [500 mg flavanols/d, including 80 mg (-)-epicatechin] and/or a daily multivitamin-mineral supplement for cardiovascular disease and cancer prevention among 21,442 United States adults aged ≥60 y. There were 573 participants in the clinic subcohort of COSMOS (that is, COSMOS-Clinic) who completed all cognitive tests at baseline; of these, 492 completed 2-y follow-up assessments. The primary outcome was global cognition (averaging z-scores across 11 tests). Secondary outcomes were episodic memory and executive function/attention. Repeated measures models were used to compare randomized groups. RESULTS: Participants' mean age (standard deviation) was 69.6 (5.3); 49.2% were females. Daily supplementation with CE, compared with placebo, had no significant effect on 2-y change in global cognition {mean difference [95% confidence interval (CI)]: -0.01 (-0.08, 0.05) standard deviation units (SU)}. CE, compared with placebo, had no significant effects on 2-y change in episodic memory [mean difference (95% CI): -0.01 (-0.13, 0.10) SU] or executive function/attention [mean difference (95% CI): 0.003 (-0.07, 0.08) SU]. Subgroup analyses uncorrected for multiple-testing suggested cognitive benefits of CE supplementation, compared with placebo among those with poorer baseline diet quality. CONCLUSIONS: Among 573 older adults who underwent repeat in-person, detailed neuropsychological assessments over 2 y, daily CE supplementation, compared with placebo, showed no overall benefits for global or domain-specific cognitive function. Possible cognitive benefits of CE among those with poorer diet quality warrant further study. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov with identifier - NCT02422745.

Long-term Tai Chi practice in older adults is associated with "younger" functional abilities.

Age-related alterations in physiology lead to declines in physical function that are associated with numerous adverse outcomes among older adults. Utilizing a hybrid design, we aimed to understand whether both long-term and short-term Tai Chi (TC) training are associated with age-related decline in physical function in healthy older adults. We first conducted cross-sectional comparisons among TC-naïve older adults (n = 60, 64.2 ± 7.7 years), TC-expert older adults (n = 27, 62.8 ± 7.6 years, 24.5 ± 12 years experience), and TC-naïve younger adults (n = 15, 28.7 ± 3.2 years) to inform long-term effects of TC training on physical function, including single leg stance time with eyes closed, grip strength, Timed Up and Go, maximum walking speed, functional reach, and vertical jump for lower-extremity power. There were significant differences among the three groups on all the six tests. For most functional tests, TC-experts performed better than age-matched TC-naïve controls and were statistically indistinguishable from young healthy adult controls. Long-term TC training was associated with higher levels of physical function in older adults, suggesting a potential preventative healthy aging effect. In the randomized longitudinal trial, TC-naïve subjects were randomized (n = 31 to Tai Chi group, n = 29 to usual care control group) to evaluate the short-term effects of TC over 6 months on all outcomes. TC's short-term impacts on physical function were small and not statistically significant. The impact of short-term training in healthy adults is less clear. Both potential longer-term preventive effects and shorter-term restorative effects warrant further research with rigorous, adequately powered controlled clinical trials.

Acceptance-Commitment Therapy for Women with Episodic Migraine: A Pilot Randomized Trial.

Objective: The aim of this study was to conduct a pilot, randomized controlled trial (RCT) of acceptance-commitment therapy (ACT) among women with episodic migraine, aged 18-65 years, and living in the United States. Background: Biobehavioral treatments have recently been proposed as possible preventive therapies for migraine management. ACT is a third wave biobehavioral therapy focused on acceptance and development of psychological flexibility and is evidence based for use in other chronic pain conditions. However, its use for reducing migraine frequency and disability has been understudied to date. Methods: The authors performed a pilot RCT evaluating ACT versus enhanced usual care (EUC) among adult women with episodic migraine. ACT consisted of eight virtual weekly sessions (for 8 weeks). Primary aims evaluated feasibility, retention, and protocol adherence. Secondary clinical outcomes included changes in migraine days and Migraine Disability Assessment (MIDAS). Results: We were able to successfully recruit 54 women in 15 months, which surpassed our recruitment goal. However, the completion rates of migraine logs and questionnaires at both outcome assessments were lower than anticipated. Among the 17 individuals randomized to EUC, 12 (71%) completed migraine logs and 12 (71%) completed questionnaires at the end of the intervention. In the postintervention follow-up, 11 (65%) individuals completed logs and 11 (65%) completed questionnaires. We observed slightly larger decreases in migraine days for those assigned to ACT from baseline to the end of the intervention, but these differences did not persist during postintervention follow-up. Both groups reported similar decreases in MIDAS over time. Conclusions: Recruitment for a large-scale trial of ACT is feasible. Challenges with remote data collection as well as participant burden during the COVID-19 pandemic resulted in lower than anticipated completion rates. Future studies should focus on decreasing participant burden and streamlining study procedures. Clinical Trials Registration: NCT05003362.

History of Migraine and Risk of COVID-19: A Cohort Study.

BACKGROUND: Although studies have reported migraine and headache as common symptoms of COVID-19, little is known about the association between migraine and the risk of developing COVID-19. METHODS: This is a prospective cohort study among 16,492 women enrolled in the Women's Health Study who completed a series of questionnaires in 2020 and 2021 concerning the COVID-19 pandemic. We defined history of migraine as reporting a physician diagnosis of migraine on any of the annual questionnaires from enrollment into the study (1992-1995) through the end of 2019. Individuals were classified as having had COVID-19 if they reported a positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or its antibodies, were told by a health care provider that they were probably or definitely diagnosed with COVID-19, or were hospitalized for COVID-19. We used logistic regression with inverse probability weighting to adjust for differences in the probability of being tested for SARS-CoV-2 and potential confounding. RESULTS: There were 4759 women (28.9%) that reported any history of migraine through the end of 2019; 1271 women were classified as having COVID-19, including 394 cases among those with a history of migraine. We did not observe evidence of a strong or moderate association between history of migraine and the risk of having had COVID-19 (odds ratio 1.08; 95% confidence interval, 0.95-1.22). Similar results were observed for migraine subtypes as well as for hospitalizations for COVID-19. CONCLUSIONS: Older women with a history of migraine do not have an appreciable increase in the risk of developing COVID-19.

Migraine and the risk of cervical artery dissection: A systematic review and meta-analysis.

INTRODUCTION: Migraine is a common, disabling chronic pain condition possibly related to changes in endothelial and vascular structure and function. Several observational studies have suggested an elevated risk of cervical artery dissection (CeAD) in patients with a history of migraine. We aimed to investigate this potential association using systematic review and meta-analytic methods. PATIENTS AND METHODS: We utilized a pre-defined search protocol to identify and screen studies related to migraine and CeAD in PubMed, Embase, and the Web of Science Core Collection. We assessed the risk of bias and performed a meta-analysis of selected studies to assess the association between migraine and CeAD. We also performed subgroup analyses by migraine subtype, biological sex, and the use of stroke versus non-stroke controls. RESULTS: We identified 11 studies (N = 9857 patients) for inclusion in the meta-analysis. Meta-analysis showed an association between migraine and CeAD with an odds ratio of 1.74 (95%CI 1.38-2.19). There was high heterogeneity among the included studies (I2 = 61%). Publication bias was present but the Trim-Fill imputation suggested that the impact on results was likely minimal. Subgroup analyses revealed an association between migraine without aura and CeAD (OR 1.86, 95%CI 1.55-2.24) but not migraine with aura and CeAD (OR 1.15, 95%CI 0.71-1.88). There was no difference in the association between migraine and CeAD in men compared to women. DISCUSSION AND CONCLUSION: A history of migraine is associated with an increased risk of CeAD. Further studies are needed to elucidate the potential pathophysiologic mechanisms underlying this association.

Contribution of Migraine to Cardiovascular Disease Risk Prediction.

BACKGROUND: Migraine with aura (MA) is associated with cardiovascular disease (CVD) independently from traditional vascular risk factors. However, the importance of MA on CVD occurrence relative to existing cardiovascular prediction tools remains unclear. OBJECTIVES: In this study, we sought to determine if adding MA status to 2 CVD risk prediction models improves risk prediction. METHODS: Participants enrolled in the Women's Health Study self-reported MA status and were followed for incident CVD events. We included MA status as a covariable in the Reynolds Risk Score and the American Heart Association (AHA)/American College of Cardiology (ACC) pooled cohort equation and assessed discrimination (Harrell c-index), continuous and categorical net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: MA status was significantly associated with CVD after including covariables in the Reynolds Risk Score (HR: 2.09; 95% CI: 1.54-2.84) and the AHA/ACC score (HR: 2.10; 95% CI: 1.55-2.85). Adding information on MA status improved discrimination of the Reynolds Risk Score model (from 0.792 to 0.797; P = 0.02) and the AHA/ACC score model (from 0.793 to 0.798; P = 0.01). We observed a small but statistically significant improvement in the IDI and continuous NRI after adding MA status to both models. We did not, however, observe significant improvements in the categorical NRI. CONCLUSIONS: Adding information on MA status to commonly used CVD risk prediction algorithms enhanced model fit but did not substantially improve risk stratification among women. Despite the strong association of migraine with CVD risk, the relatively low prevalence of MA compared with other CV risk factors limits its usefulness in improving risk classification at the population level.

Rationale and design of an ancillary study evaluating the effects of the cocoa flavanol and/or multivitamin interventions on falls and physical performance outcomes in the COcoa Supplement and Multivitamin Outcomes Study (COSMOS).

BACKGROUND: Falls and decreased physical function increase markedly with age and result in injury, hospitalization, and premature death. Emerging studies show potential benefits of supplemental cocoa extract on physical performance, including grip strength and walking speed in older adults. However, there are no large, long-term randomized controlled trials of effects of supplemental cocoa extract on falls, muscle performance, and/or fall-related injuries. METHODS: The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a double-blind, placebo-controlled, 2 × 2 factorial trial investigating effects of supplementation with cocoa extract (500 mg/d, including 80 mg (-)-epicatechin) and/or a multivitamin on prevention of cardiovascular disease and cancer in 21,442 women (≥65 years) and men (≥60 years). COSMOS: Effects on Falls and Physical Performance is an ancillary study to COSMOS that will clarify effects of cocoa extract and/or multivitamin supplementation on falls, physical performance, and incident fracture outcomes in older adults. Injurious fall(s) resulting in healthcare utilization and recurrent falls were regularly assessed by follow-up questionnaires in the overall cohort. Incident fractures were also assessed by annual questionnaires. Circumstances surrounding falls and any fall-related injuries will be confirmed by medical record review. Effects of the interventions on 2-year changes in physical performance measures (grip strength, walking speed, and the Short Physical Performance Battery) will be tested in a clinic sub-cohort (n = 603). CONCLUSION: Results from this ancillary study will determine whether supplemental cocoa extract slows age-related declines in physical performance and decrease injurious and recurrent falls and fall-related injuries and fractures that are major public health problems in older adults.

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.

Radiomics-Derived Brain Age Predicts Functional Outcome After Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: While chronological age is one of the most influential determinants of poststroke outcomes, little is known of the impact of neuroimaging-derived biological "brain age." We hypothesized that radiomics analyses of T2-FLAIR images texture would provide brain age estimates and that advanced brain age of patients with stroke will be associated with cardiovascular risk factors and worse functional outcomes. METHODS: We extracted radiomics from T2-FLAIR images acquired during acute stroke clinical evaluation. Brain age was determined from brain parenchyma radiomics using an ElasticNet linear regression model. Subsequently, relative brain age (RBA), which expresses brain age in comparison with chronological age-matched peers, was estimated. Finally, we built a linear regression model of RBA using clinical cardiovascular characteristics as inputs and a logistic regression model of favorable functional outcomes taking RBA as input. RESULTS: We reviewed 4,163 patients from a large multisite ischemic stroke cohort (mean age = 62.8 years, 42.0% female patients). T2-FLAIR radiomics predicted chronological ages (mean absolute error = 6.9 years, r = 0.81). After adjustment for covariates, RBA was higher and therefore described older-appearing brains in patients with hypertension, diabetes mellitus, a history of smoking, and a history of a prior stroke. In multivariate analyses, age, RBA, NIHSS, and a history of prior stroke were all significantly associated with functional outcome (respective adjusted odds ratios: 0.58, 0.76, 0.48, 0.55; all p-values < 0.001). Moreover, the negative effect of RBA on outcome was especially pronounced in minor strokes. DISCUSSION: T2-FLAIR radiomics can be used to predict brain age and derive RBA. Older-appearing brains, characterized by a higher RBA, reflect cardiovascular risk factor accumulation and are linked to worse outcomes after stroke.

Acceptance and commitment therapy for episodic migraine: Rationale and design of a pilot randomized controlled trial.

Migraine is a debilitating disorder with limited pharmacological options. Many migraine medications can have intolerable side effects leading patients to seek complementary and integrative health (CIM) approaches for treatment. One option that is growing in popularity and evidence is Acceptance and Commitment Therapy (ACT), a mindfulness-based therapy. The purpose of this paper is to describe how ACT may be an effective modality integrated into the treatment of migraine and to describe the design of a pilot study of ACT for migraine. First, we review the research and the promise of mindfulness therapies for the treatment of migraine. Then, we describe how ACT differs from other mindfulness therapies for migraine and why it can be a promising option for these patients. Finally, we summarize the design of a pilot study designed to determine the feasibility of performing a future fully powered study to determine the effectiveness of ACT on migraine frequency and disability. This pilot study includes unique features, including a remotely-delivered ACT intervention and the measurement of cortisol levels before and after the intervention.

Vascular Risk Score and Associations With Past, Current, or Future Migraine in Women: Cohort Study.

BACKGROUND AND OBJECTIVES-: Migraine has consistently been associated with an increased risk of cardiovascular disease (CVD) events. It remains, however, unclear to what extent cardiovascular risk profiles might be linked with migraine activity status, and how these profiles relate to the development of migraine. METHODS-: We used data from a cohort study of female health professionals (Women's Health Study, n=27,539, age ≥45 years at baseline) without a history of CVD or other major diseases and who provided a blood sample at baseline. Framingham risk scores (FRS) estimating the ten-year risk of coronary heart disease calculated at baseline were used to create vascular risk categories. The presence or development of self-reported migraine was assessed by questionnaires. Women were classified as having 'no migraine', 'history of migraine' (experienced migraine in the past but did not experience any migraine attacks in the year before enrollment), 'migraine at baseline' (active), or 'incident migraine' (first report of migraine during follow-up but not at baseline). We used multinomial logistic regression models to calculate odds ratios (ORs) for the association between FRS categories and migraine status. RESULTS-: Of the 27,539 participants, a total of 21,927 women did not report migraine, 1,500 women reported a history of migraine, 3,579 had migraine at baseline, and 533 reported migraine for the first time during follow-up. The odds of the probability of having a history of migraine at baseline (versus never migraine) was 76% higher among those with FRS ≥10% compared with FRS ≤1% after adjustment (OR=1.76, 95%CI: 1.39-2.23). In contrast, having FRS ≥10% was inversely associated with migraine at baseline (OR=0.64, 95%CI: 0.52-0.80), and with newly reported migraine during follow-up (OR=0.42, 95%CI: 0.22-0.81) when compared with women with FRS category ≤1% and those not reporting migraine. A similar inverse association pattern was observed for FRS categories 5-9% and 2-4%. DISCUSSION-: High FRS categories were only observed among women with a history of migraine but not with active migraine at baseline or incident migraine after baseline. Our results suggest that the life course of migraine should be considered when studying associations with the vascular system. Our data further suggest that a relatively healthy vascular system, as assessed by the FRS, is associated with active migraine status or developing migraine in the future.

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.

Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial.

BACKGROUND: Cocoa extract is a source of flavanols that favorably influence vascular risk factors in small and short-term trials, yet effects on clinical cardiovascular events are untested. OBJECTIVES: We examined whether cocoa extract supplementation decreases total cardiovascular disease (CVD) among older adults. METHODS: We conducted a randomized, double-blind, placebo-controlled, 2-by-2 factorial trial of cocoa extract supplementation and multivitamins for prevention of CVD and cancer among 21,442 US adults (12,666 women aged ≥65 y and 8776 men aged ≥60 y), free of major CVD and recently diagnosed cancer. The intervention phase was June 2015 through December 2020. This article reports on the cocoa extract intervention. Participants were randomly assigned to a cocoa extract supplement [500 mg flavanols/d, including 80 mg (-)-epicatechin] or placebo. The primary outcome was a composite of confirmed incident total cardiovascular events, including myocardial infarction (MI), stroke, coronary revascularization, cardiovascular death, carotid artery disease, peripheral artery surgery, and unstable angina. RESULTS: During a median follow-up of 3.6 y, 410 participants taking cocoa extract and 456 taking placebo had confirmed total cardiovascular events (HR: 0.90; 95% CI: 0.78, 1.02; P = 0.11). For secondary endpoints, HRs were 0.73 (95% CI: 0.54, 0.98) for CVD death, 0.87 (95% CI: 0.66, 1.16) for MI, 0.91 (95% CI: 0.70, 1.17) for stroke, 0.95 (95% CI: 0.77, 1.17) for coronary revascularization, neutral for other individual cardiovascular endpoints, and 0.89 (95% CI: 0.77, 1.03) for all-cause mortality. Per-protocol analyses censoring follow-up at nonadherence supported a lower risk of total cardiovascular events (HR: 0.85; 95% CI: 0.72, 0.99). There were no safety concerns. CONCLUSIONS: Cocoa extract supplementation did not significantly reduce total cardiovascular events among older adults but reduced CVD death by 27%. Potential reductions in total cardiovascular events were supported in per-protocol analyses. Additional research is warranted to clarify whether cocoa extract may reduce clinical cardiovascular events. This trial is registered at www.clinicaltrials.gov as NCT02422745.

Multivitamins in the prevention of cancer and cardiovascular disease: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial.

BACKGROUND: Although older adults commonly take multivitamin-multimineral (MVM) supplements to promote health, evidence on the use of daily MVMs on invasive cancer is limited. OBJECTIVES: The study objective was to determine if a daily MVM decreases total invasive cancer among older adults. METHODS: We performed a randomized, double-blind, placebo-controlled, 2-by-2 factorial trial of a daily MVM and cocoa extract for prevention of cancer and cardiovascular disease (CVD) among 21,442 US adults (12,666 women aged ≥65 y and 8776 men aged ≥60 y) free of major CVD and recently diagnosed cancer. The intervention phase was from June 2015 through December 2020. This article reports on the MVM intervention. Participants were randomly assigned to daily MVM or placebo. The primary outcome was total invasive cancer, excluding nonmelanoma skin cancer. Secondary outcomes included major site-specific cancers, total CVD, all-cause mortality, and total cancer risk among those with a baseline history of cancer. RESULTS: During a median follow-up of 3.6 y, invasive cancer occurred in 518 participants in the MVM group and 535 participants in the placebo group (HR: 0.97; 95% CI: 0.86, 1.09; P = 0.57). We observed no significant effect of a daily MVM on breast cancer (HR: 1.06; 95% CI: 0.79, 1.42) or colorectal cancer (HR: 1.30; 95% CI: 0.80, 2.12). We observed a protective effect of a daily MVM on lung cancer (HR: 0.62; 95% CI: 0.42, 0.92). The composite CVD outcome occurred in 429 participants in the MVM group and 437 participants in the placebo group (HR: 0.98; 95% CI: 0.86, 1.12). MVM use did not significantly affect all-cause mortality (HR: 0.93; 95% CI: 0.81, 1.08). There were no safety concerns. CONCLUSIONS: A daily MVM supplement, compared with placebo, did not significantly reduce the incidence of total cancer among older men and women. Future studies are needed to determine the effects of MVMs on other aging-related outcomes among older adults. This trial is registered at www.clinicaltrials.gov as NCT02422745.