Previous cross-sectional studies evaluating the relationship between diabetes prevalence and migraine status have found conflicting results. We examined the relationship between migraine and incident type 2 diabetes (T2D) in a cohort of adult women.
Prospective cohort study conducted among participants in the Women’s Health Study who provided information on migraine and did not have diabetes at baseline. Our four exposure groups were migraine with aura, migraine without aura, past history of migraine and no history of migraine. Cox proportional hazards models were used to determine the hazard ratio for incident T2D.
Among the 38,620 women included in this study, 5062 (13.1%) women had migraine, of whom 2014 (39.8%) reported migraine with aura, and 2,087 (5.4%) women had a past history of migraine. During a mean of 14.6 years of follow-up, there were 3,032 cases of incident T2D. After adjustment for confounders, the hazard ratio (95% confidence interval) for developing diabetes was 1.06 (0.91–1.24) for women with migraine with aura, 1.01 (0.89–1.16) for women with migraine without aura, 1.13 (0.98–1.30) for women with a past history of migraine compared to women with no history of migraine.
Results of this prospective study in women do not support an association between migraine and incident T2D.
migraine; diabetes; epidemiology
Some cross-sectional studies have suggested an association between migraine and increased body weight. However, prospective data on the association are lacking.
We conducted a prospective cohort study among 19,162 participants in the Women’s Health Study who had a body mass index (BMI) of 18.5–<25kg/m2 at baseline. Migraine was self-reported by standardized questionnaires. Main outcome measures were: incident overweight (BMI ≥25kg/m2), incident obesity (BMI ≥30kg/m2), and mean weight change. Age- and multivariable-adjusted hazard ratios were calculated for the association between migraine and incident overweight and obesity. Differences in weight change were evaluated by ANCOVA.
3,483 (18.2%) women reported any migraine history. After 12.9 years of follow-up, 7,916 incident overweight and 730 incident obesity cases occurred. Migraineurs had multivariable-adjusted HRs (95%CI) of 1.11 (1.05–1.17) for becoming overweight and 1.00 (0.83–1.19) for becoming obese. These associations remained stable after censoring for chronic diseases and were similar according to migraine aura status. Multivariable-adjusted mean weight change from baseline to the end of study was +4.7kg for migraineurs and +4.4kg for women without migraine (P=0.02).
Results of this large prospective study of middle-aged women do not indicate a consistent association between migraine and incident overweight, obesity, or relevant weight gain.
Migraine; body mass index; overweight; obesity; prospective study
To test whether supplementation with alternate-day vitamin E or daily vitamin C affects the incidence of the diagnosis of age-related macular degeneration (AMD) in a large-scale randomized trial of male physicians.
Randomized, double-masked, placebo-controlled trial.
We included 14 236 apparently healthy United States male physicians aged ≥50 years who did not report a diagnosis of AMD at baseline.
Participants were randomly assigned to receive 400 international units (IU) of vitamin E or placebo on alternate days, and 500 mg of vitamin C or placebo daily. Participants reported new diagnoses of AMD on annual questionnaires and medical record data were collected to confirm the reports.
Main Outcome Measures
Incident diagnosis of AMD responsible for a reduction in best-corrected visual acuity to ≤20/30.
After 8 years of treatment and follow-up, a total of 193 incident cases of visually significant AMD were documented. There were 96 cases in the vitamin E group and 97 in the placebo group (hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.78–1.37). For vitamin C, there were 97 cases in the active group and 96 in the placebo group (HR, 0.99; 95% CI, 0.75–1.31).
In a large-scale, randomized trial of United States male physicians, alternate-day use of 400 IU of vitamin E and/or daily use of 500 mg of vitamin C for 8 years had no appreciable beneficial or harmful effect on risk of incident diagnosis of AMD.
Few clinic-based studies report an association between migraine and restless legs syndrome (RLS); however, population-based data are unavailable.
Cohort study among 31,370 women participating in the Women’s Health Study. We had detailed self-reported information on migraine, including aura status, and RLS. RLS was ascertained at the 9-year follow-up. We calculated odds ratios (OR) and 95% confidence intervals (CI) for the association between migraine and RLS. We investigated any indication of migraine until RLS ascertainment as well as migraine with and without aura at baseline, prior migraine before baseline, and new reports of migraine during follow-up.
At baseline or during follow-up 6,857 (21.9%) women reported any migraine. These women had an increased risk for RLS (multivariable-adjusted OR=1.22; 95%CI 1.13–1.32). Further analyses indicated a similar association for migraine with aura (multivariable-adjusted OR=1.27; 95%CI 1.10–1.48) and migraine without aura (multivariable-adjusted OR=1.24; 95%CI 1.09–1.40) as well as for new reports of migraine during follow-up (multivariable-adjusted OR=1.30; 95%CI 1.10–1.54). Prior migraine did not appear to be associated with RLS.
Our data suggest an association between migraine and RLS at the population level. The association is similar for migraine with and without aura and for new reports of migraine during follow-up.
migraine; restless legs syndrome; cohort study; association
Atropine has is currently recommended to facilitate haemodynamic stability during critical care intubation. Our objective was to determine whether atropine use at induction influences ICU mortality.
A 2-year prospective, observational study of all first non-planned intubations, September 2007–9 in PICU and Intensive Care Transport team of Hôpital Robert Debré, Paris, 4 other PICUs and 5 NICUs in the Paris Region, France. Follow-up was from intubation to ICU discharge. A propensity score was used to adjust for patient specific characteristics influencing atropine prescription. 264/333 (79%) intubations were included. The unadjusted ICU mortality was 7.2% (9/124) for those who received atropine compared to 15.7% (22/140) for those who did not (OR 0.42, 95%CI 0.19–0.95, p = 0.04). One child died during intubation (1/264, 0.4%). Two age sub-groups of neonates (≤28 days) and older children (>28 days, <8 years) were examined. This difference in mortality arose from the higher mortality in children aged over one month when atropine was not used (propensity score adjusted OR 0.22, 95%CI 0.06–0.85, p = 0.028). No effect was seen in neonates (propensity score adjusted OR 1.3, 95%CI 0.31–5.1 p = 0.74). Using the propensity score, atropine maintained the mean heart rate 45.9 bpm above that observed when no atropine was used in neonates (95%CI 34.3–57.5, p<0.001) and 43.5 bpm for older children (95%CI 25.5–61.5 bpm, p<0.001).
Atropine use during induction was associated with a reduction in ICU mortality in children over one month. This effect is independent of atropine’s capacity to attenuate bradycardia during intubation which occurred similarly in neonates and older children. This result needs to be confirmed in a study using randomised methodology.
Few prospective studies have explored the association between renal function and risk of incident atrial fibrillation (AF) in apparently healthy populations. A total of 24,746 women participating in the Women’s Health Study who were free of cardiovascular disease (CVD), AF and provided a blood sample at baseline were prospectively followed for incident AF from 1993 to 2010. AF events were confirmed by medical chart review. Estimated glomerular filtration rate (eGFR) was calculated from baseline creatinine using the Chronic Kidney Disease – Epidemiology equation. Cox models were used to estimate hazard ratios (HR) and 95% CI for incident AF across eGFR categories controlling for AF risk factors. During 15.4 years (median) of follow-up, 786 incident AF events occurred. The multivariable-adjusted HR for incident AF across eGFR categories (<60, 60–74.9, 75–89, and ≥ 90 ml/min/1.73 m2) were:1.36 (1.00–1.84), 0.90 (0.71–1.14), 0.99 (0.84–1.18) and 1.00, respectively, without evidence of a linear association (P for trend, 0.48). Similarly, there was no significant curvilinear association (P quadratic, 0.10) in multivariable analysis across categories. As compared to women with an eGFR ≥ 60 ml/min/1.73 m2, the 1008 women with an eGFR < 60 ml/min/1.73 m2 had a multivariable adjusted HR for AF of 1.39 (1.04–1.86, p value 0.03). In conclusion, no significant linear or curvilinear relationship was observed between incident AF and less severe impairment of renal function in this large prospective cohort of women. However, a significant elevation in AF risk was observed at a threshold eGFR of < 60 ml/min/1.73 m2.
atrial fibrillation; renal function
α-Methylacyl-CoA racemase (AMACR) is an enzyme that serves as a diagnostic biomarker of prostate cancer in clinical practice. Recent studies suggest that low AMACR expression is associated with biochemical recurrence and the development of fatal disease.
We conducted a prospective cohort study among 920 men aged 47–84 years, who were diagnosed with prostate cancer in the Physicians’ Health Study and the Health Professionals Follow-up Study cohorts, and whose resected tissue specimens were available for immunohistochemical analysis. We used Cox proportional hazards regression to evaluate the association of AMACR expression with lethal prostate cancer over a 20-year follow-up period.
In total, 68 men died from prostate cancer, and an additional 18 developed bony metastases during follow-up. We found that lower AMACR intensity was associated with higher prostate-specific antigen levels (p=0.003) and more advanced clinical stage (p=0.06) at diagnosis, and a non-significant trend for higher risk of lethal outcomes. The hazard ratio comparing the lowest to the highest quartile of AMACR expression intensity was 1.53 ((95% CI: 0.86, 2.73), p-for-trend across quartiles=0.07); this trend was further attenuated after adjustment for age, Gleason score, stage and cohort with a hazard ratio of 1.24 (95% CI 0.69, 2.22), p-for-trend=0.23.
Low AMACR expression in primary tumor specimens was not independently associated with the development of metastatic and lethal prostate cancer after treatment over a 20-year follow-up period, after adjustment for important clinical covariates at diagnosis.
Migraine is an independent risk factor for stroke. Mechanisms underlying this association are unclear. Familial hemiplegic migraine (FHM), a migraine subtype that also carries an increased stroke risk, is a useful model for common migraine phenotypes because of shared aura and headache features, trigger factors, and underlying glutamatergic mechanisms.
Methods and Results
Here, we show that FHM type 1 (FHM1) mutations in CaV2.1 voltage-gated Ca2+ channels render the brain more vulnerable to ischemic stroke. Compared to wild-type, two FHM1 mutant mouse strains developed earlier onset of anoxic depolarization and more frequent peri-infarct depolarizations, associated with rapid expansion of infarct core on diffusion-weighted MRI and larger perfusion deficits on laser speckle flowmetry. Cerebral blood flow required for tissue survival was higher in the mutants, leading to infarction with milder ischemia. As a result, mutants developed larger infarcts and worse neurological outcomes after stroke, which were selectively attenuated by a glutamate receptor antagonist.
We propose that enhanced susceptibility to ischemic depolarizations akin to spreading depression predisposes migraineurs to infarction during mild ischemic events, thereby increasing the stroke risk.
stroke; spreading depression; migraine; calcium channels
Migraine has been linked with several measures of socioeconomic status (SES). However, results are inconsistent and data on the association between SES and non-migraine headache, migraine subtypes and migraine frequency are sparse.
We conducted a cross-sectional study among 36,858 participants in the Women’s Health Study. As proxy for SES, we calculated an SES index using annual household income and education. Migraine, migraine aura, and non-migraine headache were self-reported with good validation rates. Multinomial logistic regression models were used to evaluate the association between SES index and the various headache forms.
12,140 (32.9%) women reported any history of headache, 6,801 women (18.4%) reported any history of migraine and 5,339 (14.5%) reported non-migraine headache. Women with low SES had an increased risk for all headache forms. The multivariable-adjusted OR (95% CI) were 1.22 (1.10–1.36) for non-migraine headache, 1.40 (1.28–1.54) for any migraine, 1.44 (1.23–1.69) for migraine with aura, and 1.38 (1.21–1.58) for migraine without aura. Among active migraineurs, low SES was associated with an increased OR for ≥weekly attack frequency (1.77, 1.26–2.49).
In this large cohort of female health professionals, low SES was associated with an increased prevalence for all headache forms and an increased migraine attack frequency.
Migraine; non-migraine headache; migraine frequency; socioeconomic status
Numerous studies have indicated an increased risk of vascular disease among migraineurs. Alterations in endothelial and arterial function, which predispose to atherosclerosis and cardiovascular diseases, have been suggested as an important link between migraine and vascular disease. However, the available evidence is inconsistent. We aimed to review and summarize the published evidence about the peripheral vascular dysfunction of migraineurs.
We systematically searched in BIOSIS, the Cochrane database, Embase, Google scholar, ISI Web of Science, and Medline to identify articles, published up to April 2013, evaluating the endothelial and arterial function of migraineurs.
Several lines of evidence for vascular dysfunction were reported in migraineurs. Findings regarding endothelial function are particularly controversial since studies variously indicated the presence of endothelial dysfunction in migraineurs, the absence of any difference in endothelial function between migraineurs and non-migraineurs, and even an enhanced endothelial function in migraineurs. Reports on arterial function are more consistent and suggest that functional properties of large arteries are altered in migraineurs.
Peripheral vascular function, particularly arterial function, is a promising non-invasive indicator of the vascular health of subjects with migraine. However, further targeted research is needed to understand whether altered arterial function explains the increased risk of vascular disease among patients with migraine.
Migraine; Migraine with aura; Arterial stiffness; Endothelial function; Flow mediated dilation; Pulse wave velocity; Augmentation index; Stroke; Coronary artery disease; Cardiovascular disease; Risk factors
To validate a rapid questionnaire as a screening tool, because application of the diagnostic revised criteria of the ICHD-II for medication overuse headache (MOH) requires experience for the physician and is time-consuming.
ICHD-II criteria for probable MOH (pMOH) were transformed in questions formulated in such a way that they could be self-administered, easily understood, and quickly filled out. We compared this questionnaire to the gold standard: the diagnosis made by headache specialists, based on the the ICHD-II criteria. Patients who were consulting for pMOH or migraine for the first time were consecutively included. As validity indicators, we calculated sensitivity, specificity, positive and negative predictive values of the items.
Seventy-nine patients were screened, 77 included, 2 female patients excluded. Forty-two patients have been considered as suffering from pMOH, 35 patients suffered from migraine without medication overuse. The association of the question “do you take a treatment for attacks more than 10 days per month” and the question “is this intake on a regular basis?” had a sensitivity of 95.2% and a specificity of 80%.
This screening tool can detect pMOH with a sensitivity that could be of interest to screen patients in clinical practice and to pre-include patients for research as epidemiological studies.
Medications overuse headaches; Screening tool; Validation; Questionnaire; Sensitivity; Specificity
In studies enrolling stroke patients, higher levels of pre-stroke physical activity are associated with better functional outcomes. However, prospective studies evaluating this association are sparse. Using a cohort of initially healthy men, we aimed to prospectively assess the association between physical activity and functional outcomes from cerebral vascular events.
Prospective cohort study among 21,794 men enrolled in the Physician's Health Study who provided information on physical activity at baseline and who did not have a history of stroke or transient ischemic attack (TIA). Baseline levels of physical activity were categorized as: vigorous exercise <1, 1, 2–4 and ≥5 times/week. Possible functional outcomes included TIA and stroke with mRS score of 0–1, 2–3 or 5–6. Multinomial logistic regression was used to determine the association between physical activity and functional outcomes from cerebral vascular events.
After a mean of 20.2 years of follow-up, 761 TIAs, 1146 ischemic strokes, 221 hemorrhagic strokes and 11 strokes of unknown type occurred. Compared with men who did not experience a stroke or TIA and who exercise vigorously <1 time/week, men who exercise vigorously ≥5 times/week had adjusted relative risk (95% CIs) of 0.67 (0.53–0.86) for TIA, 0.84 (0.61–1.14) for stroke with mRS 0–1, 0.85 (0.67–1.08) for mRS 2–3, and 1.12 (0.78–1.60) for mRS 5–6 after total stroke. Other levels of physical activity did not have a significant impact on the risk of our outcomes.
Physical activity prior to TIA or stroke does not appear to influence functional outcomes after cerebral vascular events.
We examined patient-reported outcomes among prostate cancer patients managed by watchful waiting (WW) in a nationwide cohort.
Materials and Methods
We collected treatment information and patient-reported outcomes from 1230 prostate cancer patients diagnosed with T1-T2 prostate cancer in the Physicians’ Health Study; 125 were initially managed by WW. Cox proportional-hazards regression was used to identify predictors of treatment initiation among WW patients. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) to assess disease-targeted quality of life by initial treatment or WW.
At 7.3 years’ mean follow-up, 41% of WW patients remained free of treatment while 34% underwent radiotherapy or brachytherapy, 16% underwent primary hormonal therapy, and 10% underwent prostatectomy. Younger age, higher clinical stage, higher Gleason score, and higher PSA at diagnosis predicted progression to treatment. Watchful waiting compared to immediate treatment was associated with less urinary incontinence (3.5% vs 10%) and impotence (68% vs 78%) but more common obstructive urinary symptoms (22% vs 13%) in univariate analyses (p< 0.05 for each), with incontinence and impotence differences remaining significant after adjustment for age, comorbidity, and time after cancer diagnosis. Quality of life outcomes among men who underwent delayed treatment after initially waiting were not worse than among men who underwent immediate treatment.
Our findings suggest quality of life benefits subsequent to WW among select patients with early-stage prostate cancer compared to men treated immediately following diagnosis. Younger age and greater cancer severity at diagnosis predicted progression to treatment.
watchful waiting; prostate cancer; prospective study; quality of life; outcomes
To evaluate the association between restless legs syndrome (RLS) and all-cause mortality.
Four prospective cohort studies.
The Dortmund Health Study (DHS) and the Study of Health in Pomerania (SHIP) from Germany. The Women's Health Study (WHS) and the Physicians’ Health Study (PHS) from the USA.
In DHS: a random sample (n=1 299) from the population of Dortmund; in SHIP: a sample (n=4 291) from residents living in West Pomerania were drawn by multistage random sampling design; in WHS: female healthcare professionals (n=31 370); in PHS: male physicians (n=22 926)
Main outcome measures
The prevalence of RLS ranged between 7.4% and 11.9% at baseline. During follow-up (ranging between 6 and 11 years) RLS was not associated with increased risk of all-cause mortality in any of the four cohorts. The multivariable-adjusted HRs (95% CI) for all-cause mortality ranged from 0.21 (0.03 to 1.53) to 1.07 (0.93 to 1.23) across the four studies. The HRs for all-cause mortality did not differ according to gender.
In these four independently conducted large prospective cohort studies from Germany and the USA, RLS did not increase the risk of all-cause mortality. These findings do not support the hypothesis that RLS is a risk factor for mortality of any cause.
restless legs sydrome; prospective cohort study; mortality
Migraine with aura has been associated with increased prevalence of cardiovascular risk factors, including elevated levels of some vascular biomarkers. However, little research has been done on this association among the elderly. We examined the associations of lipid levels with headache and migraine in a cohort of elderly individuals.
Cross-sectional study among 1155 participants enrolled in the Epidemiology of Vascular Aging Study with available information on headache and blood biomarkers. We used multinomial logistic regression to evaluate the association between biomarker tertiles and headache categories.
925 people had no severe headache, 64 people had non-migraine headache, and 166 people had migraine of whom 23 had aura. Compared to participants without headache, we observed strong associations between increasing tertiles of total cholesterol and migraine with aura. The OR (95% CI) was 4.67 (0.99–21.97) for the 2nd tertile and 5.97 (1.29–27.61) for the 3rd tertile. We also found strong associations between triglycerides and migraine with aura (OR for 3rd tertile:4.42 (1.32–14.77).) We did not see significant associations between increased biomarkers levels and any other headache group.
Elevated levels of total cholesterol and triglycerides are associated with migraine with aura but not other headache forms in the elderly.
migraine; cholesterol; epidemiology
Data on the association between TNF-alpha and TNF-beta gene polymorphisms and migraine are conflicting.
We performed a systematic review and meta-analysis of studies published until January 2011. We used data from published papers and as provided after contact with the authors. We calculated study specific odds ratios (OR) and 95% confidence intervals (CI) assuming additive, dominant, and recessive genetic models as well as pooled effect estimates.
Among the ten studies identified the best evidence is available for the TNF-alpha -308G>A and TNF-beta 252A>G polymorphisms indicating no overall association with migraine. Subgroup analyses suggested that the A allele of the TNF-alpha -308G>A variant more than doubles the risk for migraine among populations with a heterogeneous ethnic background, which was driven by associations for MO (additive model: pooled OR=2.87; 95% CI 1.86–4.43). Further, the risk for MA was increased among Asian populations (additive model: pooled OR=1.71; 95% CI 1.07–2.71). Both observed effects were stronger among females than males.
Our results indicate no overall association between TNF-alpha and TNF-beta gene variants. However, associations differed among specific populations. Our findings need to be treated with caution and further targeted research is warranted to evaluate population-specific effects including population stratification.
migraine; tumor necrosis factor; lymphotoxin; polymorphism; meta-analysis
To evaluate the evidence on the association between migraine and mortality.
Systematic review and meta-analysis of studies investigating the association between any migraine (all forms of migraine collectively) or migraine subtypes (e.g. migraine with aura) and mortality published until March 2011.
We identified ten cohort studies. Studies differed regarding the types of mortality investigated and only four presented aura-stratified results, limiting pooled analyses for migraine subtypes and cause-specific mortality. For any migraine pooled analysis does not suggest an association with all-cause (five studies; pooled relative risk [RR]=0.90, 95%CI 0.71–1.16), cardiovascular (CVD; six studies; pooled RR=1.09, 95%CI 0.89–1.32), or coronary heart disease mortality (CHD; three studies; pooled RR=0.95, 95%CI 0.57–1.60). Heterogeneity among studies is moderate to high. Two studies each suggest that migraine with aura increases risk for CVD and CHD mortality.
This meta-analysis does not suggest that any migraine is associated with mortality from all-causes, CVD, or CHD. However, there is heterogeneity among studies and suggestion that migraine with aura increases CVD and CHD mortality. Given the high migraine prevalence a definitive answer to the question if migraine or a subtype alters risk for mortality is of high public health importance; hence, further studies are needed.
migraine; migraine aura; mortality; cardiovascular disease; meta-analysis
Previous studies on migraine and cognition have shown mixed results. However, many could not assess the relationship between migraine and change in cognitive function or only used a limited number of cognitive tests.
Prospective cohort study among 1170 participants of the Epidemiology of Vascular Aging Study who provided information about migraine status and completed cognitive testing. Participants were classified as having no severe headache, non-migraine headache and migraine. Cognitive functioning was measured at up to four time points using nine different cognitive functioning tests. Linear mixed effects models were used to evaluate the relationship between migraine status and change in cognitive function.
Of the 1170 participants, 938 had no severe headache, 167 had migraine, and 65 had non-migraine headache. After adjusting for age, gender, education, and smoking status, people with migraine or non-migraine headache did not experience a greater rate of cognitive decline than those without headache or migraine in any domain (for the MMSE, p-values were 0.68 for the non-migraine headache and time interaction and 0.85 for the migraine and time interaction) during 4-5 years of follow-up. For the Wechsler, those with migraine declined less over time (p-value=.02).
Migraine was not associated with faster cognitive decline over time.
Migraine; cognitive function; epidemiology
In a population-based genome-wide analysis including 5122 migraineurs and 18,108 non-migraineurs, rs2651899 (PRDM16), rs10166942 (TRMP8), and rs11172113 (LRP1) were among the top associations (p<5×10−6) with migraine. All three SNPs were significant in meta-analysis among replication cohorts and met genome-wide significance (p<4.3×10−9) in meta-analysis combining discovery and replication cohorts. Rs2651899 and rs10166942 associated with migraine compared to non-migraine headache; none of the three SNPs specifically associated with migraine subtypes or features.
Migraine with aura (MA) has been associated with increased risk of cardiovascular disease (CVD). The role of aspirin on this association remains unclear.
Post-hoc subgroup analyses of the Women’s Health Study, a randomized trial testing 100mg aspirin on alternate days in primary prevention of CVD among 39,876 women aged ≥45.
During 10 years, 998 major CVD events were confirmed in 39,757 women with complete migraine information. Aspirin reduced risk of ischemic stroke (RR=0.76; 95%CI=0.63–0.93) but not other CVD. Migraine or MA did not modify the effect of aspirin on CVD except for myocardial infarction (MI) (p-interaction=0.01). Women with MA on aspirin had increased risk of MI (RR=3.72, 95%CI=1.39–9.95). Further exploratory analyses indicate this is only apparent among women with MA on aspirin who ever smoked or had history of hypertension (p-interaction<0.01).
In post-hoc subgroup analyses, aspirin had similar protective effects on ischemic stroke for women with or without migraine. By contrast, our data suggest that women with MA on aspirin had increased risk of MI. The small number of outcome events in subgroups, the exploratory nature of our analyses, and lack of plausible mechanisms raise the possibility of a chance finding, which must caution the interpretation.
The detrimental effects of smoking on risk of myocardial infarction and stroke are well documented, but less information is available regarding peripheral artery disease (PAD), particularly among women.
To prospectively assess the association of current smoking status, cumulative smoking exposure and smoking cessation with incident symptomatic PAD in women
Prospective cohort study
U.S. female health care professionals in the Women's Health Study
39825 women free of cardiovascular disease were prospectively followed for a median of 12.7 years.
Incident symptomatic PAD (n=178). Cox proportional hazards models were used to compare PAD risk among never (n=20336) and former smoking (n=14263) women, women who smoked <15 cigarettes/day (n=1967) and women who smoked ≥15 cigarettes/day (n=3259).
Age-adjusted incidences across smoking categories were 0.12, 0.34, 0.95 and 1.63 per 1000 person-years of follow-up. Multivariable adjustment had little impact on this risk gradient; adjusted hazard ratios (HRs) (95% confidence intervals (CIs)) were 3.14 (2.01–4.90), 8.93 (5.02–15.89) and 16.95 (10.77–26.67) compared with never-smokers. Additional adjustment for high sensitivity C-reactive protein and soluble intercellular adhesion molecule 1 among women with available blood samples (n=28314, 117 events) attenuated risk estimates with HRs of 5.58 (2.61–11.93) and 9.52 (5.17–7.53) for women smoking <15 and ≥15 cigarettes/day, respectively. We found a strong dose-response relationship for lifetime exposure such that the fully adjusted HR’s for 0 (reference), <10, 10–30 and ≥30 pack years were 2.52 (1.49–4.25), 6.75 (4.33–10.52) and 11.09 (6.94–17.72). Compared to current smokers, the adjusted HRs (95% CIs) for smoking abstinence of <10 years, 10–20 years, >20 years and lifelong abstinence were 0.39 (0.24–0.66), 0.28 (0.17–0.46), 0.16 (0.10–0.26) and 0.08 (0.05–0.12).
The use of symptomatic PAD as the primary a priori end point excludes asymptomatic disease.
Among initially healthy women, smoking is a potent risk factor for symptomatic PAD, an effect partially explained by subclinical inflammation. Smoking cessation substantially reduces PAD risk, but an increased occurrence of PAD persists even among former smokers who maintain abstinence.
Primary Funding Source
National Heart, Lung, and Blood Institute and National Cancer Institute
Peripheral artery disease; cardiovascular disease; smoking; inflammation; women
We evaluated the current evidence on the association between migraine including aura status and cervical artery dissection.
We performed a systematic review and meta-analysis of studies investigating the association between migraine or migraine subtypes (e.g. migraine with aura) and cervical artery dissection published until October 2010.
We identified five case-control studies investigating the association between migraine and cervical artery dissection. In pooled analysis, migraine doubled the risk of cervical artery dissection (pooled odds ratio [OR]=2.06, 95% CI 1.33–3.19). All studies allowed evaluation of migraine aura status. While the effect estimate for migraine without aura (pooled OR=1.94, 95% CI 1.21–3.10) was similar to overall migraine, the association was weaker for migraine with aura (pooled OR=1.50, 95% CI 0.76–2.96) However, there is no evidence that aura status significantly modifies the association between migraine and cervical artery dissection (meta-regression on aura status p=0.58). The risk does not appear to differ between women and men; however, only few studies presented gender-specific data. Heterogeneity among studies was low to moderate.
In this meta-analysis migraine is associated with a two-fold increased risk of cervical artery dissection. This risk does not appear to significantly differ by migraine aura status or gender.
migraine; migraine aura; cervical artery dissection; carotid artery dissection; vertebral artery dissection; meta-analysis
Migraine is a common and debilitating neurovascular disorder with a complex envirogenomic aetiology. Numerous studies have demonstrated a preponderance of women affected with migraine and previous pedigree linkage studies in our laboratory have identified susceptibility loci on chromosome Xq24-Xq28. In this study we have used the genetic isolate of Norfolk Island to further analyse the X chromosome for migraine susceptibility loci.
An association approach was employed to analyse 14,124 SNPs spanning the entire X chromosome. Genotype data from 288 individuals comprising a large core-pedigree, of which 76 were affected with migraine, were analysed. Although no SNP reached chromosome-wide significance (empirical α = 1×10−5) ranking by P-value revealed two primary clusters of SNPs in the top 25. A 10 SNP cluster represents a novel migraine susceptibility locus at Xq12 whilst a 11 SNP cluster represents a previously identified migraine susceptibility locus at Xq27. The strongest association at Xq12 was seen for rs599958 (OR = 1.75, P = 8.92×10−4), whilst at Xq27 the strongest association was for rs6525667 (OR = 1.53, P = 1.65×10−4). Further analysis of SNPs at these loci was performed in 5,122 migraineurs from the Women’s Genome Health Study and provided additional evidence for association at the novel Xq12 locus (P<0.05).
Overall, this study provides evidence for a novel migraine susceptibility locus on Xq12. The strongest effect SNP (rs102834, joint P = 1.63×10−5) is located within the 5′UTR of the HEPH gene, which is involved in iron homeostasis in the brain and may represent a novel pathway for involvement in migraine pathogenesis.
Migraine has a wide clinical spectrum. Our aim was to group information on migraine characteristics into meaningful components and to identify key components of the migraine phenotype.
We performed two principal component analyses, one among participants in the Women's Health Study enrolment cohort and one in a sub-cohort with additional migraine-specific information.
Among the 9,427 women with migraine attack-related information at enrolment, the three most important components pertained to central nervous system (CNS) sensitization, attack frequency/pain location, and aura/visual phenomena. In the sub-group of 1,675 women with more detailed information, food triggers and unspecific symptoms constituted two principal components that explain more of the variance of the migraine phenotype than the three attack-related components.
Our results indicate that information on migraine-associated features, symptoms, and triggers is highly correlated allowing the extraction of principal components. Migraine attack-related symptoms are best summarized by symptoms related to CNS sensitization, attack frequency/pain location, and aura/visual phenomena. Taking a more general view, unspecific symptoms and food triggers appear to carry stronger importance in characterizing the migraine phenotype. These components are useful for future research on the pathophysiology and genetics of migraine and may have implications for diagnosing and treating patients.
migraine; features; triggers; sensitization; principal component analysis