One-year prevalence of cluster headache, hemicrania continua, paroxysmal hemicrania and SUNCT in Norway: a population-based nationwide registry study.

BACKGROUND: There is lack of population-based studies evaluating the prevalence of paroxysmal hemicrania, hemicrania continua and short-lasting unilateral neuralgiform headache attacks. OBJECTIVES: The aim of this study was to investigate the gender-specific 1-year prevalence of cluster headache, paroxysmal hemicrania, hemicrania continua, and short-lasting unilateral neuralgiform headache attacks. METHODS: A nationwide study was conducted from January 1 2022 and December 31 2022 by linking diagnostic codes from Norwegian Patient Registry and prescription of relevant drugs from Norwegian Prescription Database on an individual basis. The 1-year prevalence with 95% confidence intervals (CI) of cluster headache, paroxysmal hemicrania, hemicrania continua and short-lasting unilateral neuralgiform headache attacks are estimated based on the combination of diagnostic codes, prescription of drugs and corresponding reimbursement codes. RESULTS: Among 4,316,747 individuals aged ≥ 18 years, the 1-year prevalence per 100,000 was 14.6 (95% CI 13.5-15.8) for cluster headache, 2.2 (95% CI 1.8-2.7) for hemicrania continua, 1.4 (95% CI 1.0-1.8) for paroxysmal hemicrania, and 1.2 (95% CI 0.8-1.4) for short-lasting unilateral neuralgiform headache attacks. For all the trigeminal autonomic cephalalgies, cluster headache included, the prevalence was higher for women than men. CONCLUSIONS: In this nationwide register-based study, we found a 1-year prevalence per 100,100 of 14.6 for cluster headache, 2.2 for hemicranias continua, 1.4 for paroxysmal hemicranias, and 1.2 for short-lasting unilateral neuralgiform headache attacks. This is the first study reporting higher prevalence of cluster headache for women than men.

Randomized controlled studies evaluating Topiramate, Botulinum toxin type A, and mABs targeting CGRP in patients with chronic migraine and medication overuse headache: A systematic review and meta-analysis.

BACKGROUND: This systematic review focuses on chronic migraine patients with medication overuse headache using, respectively, topiramate, botulinum toxin type A, and human monoclonal antibodies targeting calcitonin gene-related peptide or its receptor. METHODS: A systematic search was conducted in the databases CENTRAL, MEDLINE, Embase and Web of Science until May 2022. We included randomized controlled trials reporting the outcomes of change in monthly headache/migraine days, ≥50% response rates and change in medication overuse status. Studies were excluded if response rates were not reported. Risk of bias assessment was performed using the Cochrane RoB2 tool. The quality of evidence for outcomes across included studies was evaluated according to the five factors outlined in Cochrane GRADE approach. FINDINGS: The initial search resulted in 1599 records. Following screening, 10 studies met our inclusion criteria, while seven studies with sufficient data were included in the meta-analysis. Studies assessing Botulinum toxin type A included 1139 patients and showed a mean reduction in headache frequency by 1.92 days per month compared to placebo (-1.92; 95% CI -2.68 to -1.16). Studies assessing human monoclonal antibodies included 1982 patients, and showed significant positive effect compared to placebo for all measured outcomes. The overall odds ratio for the ≥50% response rate was 2.90 (95% CI, 2.23 to 3.78). No significant difference was observed in the frequency of adverse effect for both Botulinum toxin type A and low dose of human monoclonal antibodies compared to placebo. There is currently insufficient evidence to determine the impact of topiramate in chronic migraine patients with medication overuse headache. INTERPRETATION: Botulinum toxin type A and human monoclonal antibodies targeting calcitonin gene-related peptide receptor were beneficial in reducing monthly migraine days and ≥50% response rate, but uncertainties remained for Botulinum toxin type A regarding response rate. The effect size for human monoclonal antibodies was greater with relatively lower drop-out rate. High-quality randomized trials are required to evaluate the effect of topiramate in chronic migraine patients with medication overuse headache.

Menopausal hormone therapy, oral contraceptives and risk of chronic low back pain: the HUNT Study.

BACKGROUND: There are indications that use of menopausal hormone therapy (MHT) and oral contraceptives (OC) increases the risk of low back pain (LBP), with higher oestrogen levels involved in the underlying mechanisms. The purpose of the present study was to investigate associations between use of systemic MHT or OC and risk of chronic LBP in a large population-based data set. METHODS: Data were obtained from two surveys in the Trøndelag Health Study in Norway, HUNT2 (1995-1997) and HUNT3 (2006-2008). A cross-sectional study of association between use of systemic MHT and prevalence of chronic LBP comprised 12,974 women aged 40-69 years in HUNT2, with 4007 women reporting chronic LBP. A cohort study involving MHT comprised 6007 women without chronic LBP at baseline in HUNT2, and after 11 years 1245 women reported chronic LBP at follow-up in HUNT3. The cross-sectional study of association with use of OC included 23,593 women aged 20-69 years in HUNT2, with 6085 women reporting chronic LBP. The corresponding cohort study included 10,586 women without chronic LBP at baseline in HUNT2, of whom 2084 women reported chronic LBP in HUNT3. Risk of chronic LBP was examined in both study designs in generalised linear models with adjustment for potential confounders. RESULTS: In the cohort study, current users of systemic MHT at baseline showed a greater risk of chronic LBP (relative risk (RR) 1.30; 95% CI: 1.14-1.49; compared with never users). The risk increased according to duration of MHT use (P for linear trend = 0.003). Known users of systemic MHT based exclusively on oestrogen experienced the highest risk (RR 1.49; 95% CI: 1.16-1.91), but an increased risk was also seen among known users of oestrogen-progestin combination MHT (RR 1.35; 95% CI: 1.16-1.57). A slight increase in risk of chronic LBP was found in the cohort study among former users of OC (RR 1.17; 95% CI: 1.06-1.30; compared with never users). CONCLUSIONS: Long-lasting use of systemic MHT, in particular therapy based on oestrogen only, is associated with greater risk of chronic LBP. Having been a user of OC most likely entails a minor increase in risk.

The global prevalence of headache: an update, with analysis of the influences of methodological factors on prevalence estimates.

BACKGROUND: According to the Global Burden of Disease (GBD) study, headache disorders are among the most prevalent and disabling conditions worldwide. GBD builds on epidemiological studies (published and unpublished) which are notable for wide variations in both their methodologies and their prevalence estimates. Our first aim was to update the documentation of headache epidemiological studies, summarizing global prevalence estimates for all headache, migraine, tension-type headache (TTH) and headache on ≥15 days/month (H15+), comparing these with GBD estimates and exploring time trends and geographical variations. Our second aim was to analyse how methodological factors influenced prevalence estimates. METHODS: In a narrative review, all prevalence studies published until 2020, excluding those of clinic populations, were identified through a literature search. Prevalence data were extracted, along with those related to methodology, world region and publication year. Bivariate analyses (correlations or comparisons of means) and multiple linear regression (MLR) analyses were performed. RESULTS: From 357 publications, the vast majority from high-income countries, the estimated global prevalence of active headache disorder was 52.0% (95%CI 48.9-55.4), of migraine 14.0% (12.9-15.2), of TTH 26.0% (22.7-29.5) and of H15+ 4.6% (3.9-5.5). These estimates were comparable with those of migraine and TTH in GBD2019, the most recent iteration, but higher for headache overall. Each day, 15.8% of the world's population had headache. MLR analyses explained less than 30% of the variation. Methodological factors contributing to variation, were publication year, sample size, inclusion of probable diagnoses, sub-population sampling (e.g., of health-care personnel), sampling method (random or not), screening question (neutral, or qualified in severity or presumed cause) and scope of enquiry (headache disorders only or multiple other conditions). With these taken into account, migraine prevalence estimates increased over the years, while estimates for all headache types varied between world regions. CONCLUSION: The review confirms GBD in finding that headache disorders remain highly prevalent worldwide, and it identifies methodological factors explaining some of the large variation between study findings. These variations render uncertain both the increase in migraine prevalence estimates over time, and the geographical differences. More and better studies are needed in low- and middle-income countries.

Validation of questionnaires for restless legs syndrome in the general population: the Trøndelag Health Study (HUNT).

Questionnaires for restless legs syndrome have rarely been validated against face-to-face interviews in the general population. We aimed to validate the modified Norwegian, seven-item Cambridge-Hopkins restless legs syndrome questionnaire and a single diagnostic question for restless legs syndrome. We also aimed to stratify validity at 65 years of age. Among a random sample of 1,201 participants from the fourth wave of the Trøndelag Health Study, 232 (19%) agreed to participate, out of whom 221 had complete data for analyses. Participants completed the questionnaires for restless legs syndrome immediately before attending a face-to-face interview using the latest diagnostic criteria. We calculated sensitivity, specificity, and Cohen's kappa statistic (κ) of questionnaire- versus interview-based diagnoses. We found acceptable validity of the seven-item modified Cambridge-Hopkins diagnostic questionnaire for restless legs syndrome (κ = 0.37, 95% confidence interval [CI] 0.23-0.51) and good validity of the single diagnostic question (κ = 0.47, 95% CI 0.35-0.58). We also found good validity through the combination of modified Cambridge-Hopkins diagnostic questionnaire for restless legs syndrome items 2 and 5, while item 1 or 2 alone showed only acceptable validity. The single diagnostic question was significantly more valid among those aged <65 years (κ = 0.60 versus κ = 0.26). Both single- and two-item questionnaire-based diagnoses overestimated interview-based restless legs syndrome prevalence. The seven-item modified Cambridge-Hopkins diagnostic questionnaire for restless legs syndrome will be useful for epidemiological studies although low sensitivity may cause underestimation of true restless legs syndrome prevalence in the general population, especially among elderly. Brief questionnaire-based diagnoses of up to three items seem best utilised as an initial screen. Future studies should identify brief and even more valid questionnaire-based diagnoses for restless legs syndrome in order to estimate prevalence accurately in large epidemiological studies.

Does the risk of chronic low back pain depend on age at menarche or menopause? A population-based cross-sectional and cohort study: the Trøndelag Health Study.

OBJECTIVE: In most population-based studies of low back pain (LBP), women have a higher risk than men, possibly reflecting hormonal influences. The aim of this study was to explore associations between age at menarche and menopause and risk of chronic LBP. DESIGN: Population-based cross-sectional and cohort study designs. SETTING: The HUNT2 and HUNT3 medical surveys of the entire population of Nord-Trøndelag County in Norway. MAIN OUTCOME MEASURE: Prevalence or risk of chronic LBP, defined as LBP persisting at least 3 months continuously during last year. PARTICIPANTS: Associations between age at menarche and prevalence of chronic LBP were examined in cross-sectional data from HUNT2, comprising 27 697 women aged 20-69 years, with 7300 women reporting LBP. The corresponding cohort data included 11 659 women without LBP at baseline in HUNT2, with 2353 women reporting LBP at follow-up 11 years later in HUNT3. Cross-sectional data on age at menopause or premenopausal status included 11 332 women aged 40-69 years, with 3439 women reporting chronic LBP. Corresponding cohort data included 7893 women without LBP at baseline, of whom 1100 developed LBP. METHODS: Associations between age at menarche or menopause and risk of chronic LBP were examined by generalised linear modelling. RESULTS: A U-shaped association was indicated between age at menarche and risk of chronic LBP, both in the cross-sectional and cohort studies. Age at menarche ≤11 years was associated with an increased risk of chronic LBP, with a relative risk of 1.32 (95% CI 1.15 to 1.52), compared with age 14 years at menarche, after relevant adjustments. Corresponding cross-sectional crude absolute risks were 32% and 25%, respectively. No association was established between age at menopause and risk of LBP. Being premenopausal had no influence on risk. CONCLUSIONS: In contrast to results for age at menopause, the association with age at menarche suggests that hormonal factors affect the risk of LBP.

Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles.

Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.

FollowTheSutures: Piloting a new way to administer onabotulinumtoxinA for chronic migraine.

BACKGROUND: Anatomical and experimental data indicate that onabotulinimtoxin A could be more efficient and cost-effective for treating chronic migraine with injections targeting the cranial sutures, where collaterals from the meninges penetrate the skull. METHODS: A new injection paradigm (FollowTheSutures) was tested for safety, tolerability and feasibility in a Phase II, open-label, non-controlled, single-center pilot study. Ninety units of onabotulinimtoxin A (Botox®), were injected in 18 sites over the area of the cranial sutures. Adverse events and potential beneficial effects were recorded in a headache diary at least 4 weeks before, and for 12 weeks after the injections. A higher dilution than normal of onabotulinimtoxin A was used to get better diffusion. RESULTS: Nineteen (of 20 included) women with chronic migraine received the injections and were evaluable. There was only one treatment-related adverse event (reduced power of chewing for some weeks). Otherwise, the procedure was overall well tolerated. Patients improved on most efficacy parameters after the injections. There was little or no effect on glabellar or forehead lines. CONCLUSIONS: The protocol was safe and well tolerated. Lower risk of unblinding due to the absence of cosmetic effects should make the injection procedure well suited for a large, randomized, placebo-controlled study. If efficacy is confirmed, it will be markedly less costly than the standard procedure.Trial registration: EUDRACT (2017-002516-13), ClinicalTrials.gov (NCT03543254).

The bidirectional temporal relationship between headache and affective disorders: longitudinal data from the HUNT studies.

BACKGROUND: Few prospective population-based studies have evaluated the bidirectional relationship between headache and affective disorder. The aim of this large-scale population-based follow-up study was to investigate whether tension-type headache (TTH) and migraine had increased risk of developing anxiety and depression after 11 years, and vice-versa. METHODS: Data from the Trøndelag Health Study (HUNT) conducted in 2006-2008 (baseline) and 2017-2019 (follow-up) were used to evaluate the bidirectional relationship between migraine and TTH and anxiety and depression measured by Hospital Anxiety and depression Scale (HADS). The population at risk at baseline consisted of respectively 18,380 persons with HADS score ≤ 7 and 13,893 without headache, and the prospective data was analyzed by Poisson regression. RESULTS: In the multi-adjusted model, individuals with HADS anxiety (HADS-A) and depression scores (HADS-D) of ≥8 at baseline nearly doubled the risk of migraine (Risk rations (RR) between 1.8 and 2.2) at follow-up whereas a 40% increased risk (RR 1.4) was found for TTH. Vice versa, the risk of having HADS-A and HADS-D scores of ≥8 at follow-up were increased for TTH (RR 1.3) and migraine (RR 1.3-1.6) at baseline. Migraine with aura was associated with 81% (RR 1.81, 95% 1.52-2.14) increased risk of HADS-A score of ≥8. CONCLUSIONS: In this large-scale population-based follow-up study we found a bidirectional relationship between anxiety and depression and migraine and TTH. For anxiety, this bidirectional association was slightly more evident for migraine than TTH.

Reliability of a self-administrated musculoskeletal questionnaire: The fourth Trøndelag health study.

BACKGROUND: The reliability of the Nordic Musculoskeletal Questionnaire (NMQ) has not been evaluated in an unselected general population. The aim of this population-based follow-up study was to estimate the reliability between a self-administered NMQ-based questionnaire and a face-to-face interview performed approximately two months later. To interpret the results, we assessed the 1-year prevalence of various pain musculoskeletal pain locations. METHODS: A random sample of 1201 participants in the fourth wave of the Trøndelag Health Survey were invited to a follow-up interview focusing on sleep and pain. A total of 232 (19%) participated a semi-structured interview, and the agreement with the corresponding answers in the musculoskeletal questionnaire in HUNT4 were evaluated by Cohen's kappa statistics with 95% confidence interval (CI). The 1-year prevalence of the various pain sites was stratified by age and gender. RESULTS: The reliability was good for chronic musculoskeletal pain (CMSP), chronic widespread musculoskeletal pain (CWMSP) and pain in hip and knee (kappa values between 0.63 and 0.68). Moderate kappa values between 0.51 and 0.60 were found for pain in the neck, shoulder, elbow, wrist/hand, upper back, lower back, calf, ankle/feet, and ≥7 pain sites. The 1-year prevalence was 54.3% for CMSP and 17.2 for CWMSP, substantially higher for women and among those aged 50 years or more. CONCLUSION: In this population-based study the reliability between interview and questionnaire was good to moderate for most pain locations. In particular, the self-administered musculoskeletal questionnaire seems to be a useful tool in identifying individuals with CMSP, CWMSP, and pain in hip and knee.

Pragmatic trials - what are they? / Pragmatiske studier ­ hva er det?

Pragmatic clinical trials are based on data from unselected patients recruited from common clinical practice. These trials therefore bridge the gap between evidence-based medicine and clinical practice.

Long-term changes in self-reported sleep quality and risk of chronic musculoskeletal pain: The HUNT Study.

We examined the association between long-term (~10 years) changes in self-reported sleep quality and risk of any chronic musculoskeletal pain and chronic widespread pain. The study comprised data on 6,033 people who participated in three consecutive surveys in the Norwegian HUNT Study (1995-1997, 2006-2008 and 2017-2019) and who were without chronic musculoskeletal pain at the first two surveys. We used a modified Poisson regression model to calculate adjusted risk ratios for chronic pain at follow-up (2017-2019) associated with categories of poor and good sleep quality reported in 1995-1997 and 2006-2008. Compared with people who reported good sleep at both surveys (crude absolute risk: 32.4%), the risk ratios of any chronic pain were 1.20 (95% confidence interval: 1.02-1.41) for those who changed from poor to good sleep; 1.25 (95% confidence interval: 1.12-1.39) for those who changed from good to poor sleep; and 1.41 (95% confidence interval: 1.21-1.63) for those who reported long-term poor sleep. The corresponding risk ratios for chronic widespread pain were 1.35 (95% confidence interval: 0.82-2.23), 1.55 (95% confidence interval: 1.14-2.12) and 2.09 (95% confidence interval: 1.38-3.17), respectively. In conclusion, these findings indicate that people with long-term poor sleep quality have a markedly higher risk of chronic musculoskeletal pain and chronic widespread pain, compared with people who remain good sleep quality.

Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain.

BACKGROUND AND OBJECTIVES: Chronic widespread musculoskeletal pain (CWP) is a symptom of fibromyalgia and a complex trait with poorly understood pathogenesis. CWP is heritable (48%-54%), but its genetic architecture is unknown and candidate gene studies have produced inconsistent results. We conducted a genome-wide association study to get insight into the genetic background of CWP. METHODS: Northern Europeans from UK Biobank comprising 6914 cases reporting pain all over the body lasting >3 months and 242 929 controls were studied. Replication of three independent genome-wide significant single nucleotide polymorphisms was attempted in six independent European cohorts (n=43 080; cases=14 177). Genetic correlations with risk factors, tissue specificity and colocalisation were examined. RESULTS: Three genome-wide significant loci were identified (rs1491985, rs10490825, rs165599) residing within the genes Ring Finger Protein 123 (RNF123), ATPase secretory pathway Ca2+transporting 1 (ATP2C1) and catechol-O-methyltransferase (COMT). The RNF123 locus was replicated (meta-analysis p=0.0002), the ATP2C1 locus showed suggestive association (p=0.0227) and the COMT locus was not replicated. Partial genetic correlation between CWP and depressive symptoms, body mass index, age of first birth and years of schooling were identified. Tissue specificity and colocalisation analysis highlight the relevance of skeletal muscle in CWP. CONCLUSIONS: We report a novel association of RNF123 locus and a suggestive association of ATP2C1 locus with CWP. Both loci are consistent with a role of calcium regulation in CWP. The association with COMT, one of the most studied genes in chronic pain field, was not confirmed in the replication analysis.

Validation of insomnia questionnaires in the general population: The Nord-Trøndelag Health Study (HUNT).

The primary aim was to validate questionnaire-based insomnia diagnoses from a modified Karolinska Sleep Questionnaire (KSQ) and the Insomnia Severity Index (ISI), by age category (< or >65 years), against a semi-structured face-to-face interview. Secondary aims were to split validity by diagnostic certainty of the interview and to compare prevalence estimates of questionnaire- and interview-based diagnoses. A total of 232 out of 1,200 invited (19.3%) from the fourth Nord-Trøndelag Health Study (HUNT4) completed questionnaires, including the KSQ and ISI, shortly before attending a face-to-face diagnostic interview for insomnia based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Both a tentative (DSM-5 criteria A-E) and a definite (criteria A-H) interview diagnosis was evaluated. Cohen's kappa statistic quantified questionnaire validity. In all, 33% (95% confidence interval 27-39%) of participants had definite insomnia: 40% of women and 21% of men. The ISI (cut-off 12) and several KSQ-based diagnoses showed very good validity (κ ≤0.74) against the tentative, versus good validity (κ ≤0.61) against the definite interview diagnosis. Short questionnaires, requiring a daytime symptom at least three times a week, may underestimate insomnia prevalence. Validity was consistently higher for persons aged below versus above 65 years (definite insomnia: κ ≤0.64 vs. κ ≤0.56). Our results have implications for epidemiological population-based studies utilising insomnia questionnaires.

Caesarean section and the association with migraine: a retrospective register-linked HUNT population cohort study.

OBJECTIVES: To evaluate the association between caesarean section and migraine in a population-based register-linked cohort study. SETTING: Data from the population-based Nord-Trøndelag Health Studies (HUNT2 and HUNT3) were linked to information from the Norwegian Medical Birth Registry. PARTICIPANTS: 65 343 participants responded to the headache questions in any of the two HUNT studies. Only those answering the headache questions in HUNT2 or 3 and had information about mode of delivery in the Norwegian Medical Birth Registry (born after 1967) were included. Our final sample consisted of 6592 women and 4602 men, aged 19-41 years. OUTCOMES: ORs for migraine given caesarean section. Analyses were performed in multivariate logistic regression models. RESULTS: After adjusting for sex, age and fetal growth restriction, delivery by caesarean section was not associated with migraine later in life (OR 0.86, 95% CI 0.64 to 1.15). Delivery by caesarean section was associated with a reduced OR of non-migrainous headache (OR 0.77, 95% CI 0.60 to 0.99). CONCLUSION: No association was found between caesarean section and migraine in this population-based register-linked study.

Associations between the number of children, age at childbirths and prevalence of chronic low back pain: the Nord-Trøndelag Health Study.

BACKGROUND: Associations between childbirths and subsequent risk of low back pain (LBP) have not been clarified. Changes in sex hormone levels or lumbar posture during pregnancy may have an impact on LBP later in life. The purpose of this study was to explore associations between the number of childbirths, age at childbirths and prevalence of chronic LBP in a general population of women. METHODS: Data were obtained from the Norwegian community-based Nord-Trøndelag Health Study, HUNT2 (1995-1997). Women aged 20-69 years indicated whether they suffered from chronic LBP, defined as LBP persisting at least 3 months continuously during last year. Information about LBP was collected from 3936 women who had experienced no childbirths, 3143 women who had delivered one child only and 20,584 women who had delivered 2 or more children. Of these, 7339 women reported chronic LBP. The 595 women who were pregnant when information was collected were considered separately, regardless of previous births, with 80 women reporting chronic LBP. Associations with prevalence of chronic LBP were examined by generalised linear modelling with adjustment for potential confounders in a cross-sectional design. RESULTS: Women who had delivered one child only showed a higher prevalence of chronic LBP than women with no childbirths (prevalence ratio (PR) 1.11; 95% CI: 1.01-1.22). Among women with one or more childbirths, no overall change in prevalence could be demonstrated with an increasing number of children in analyses adjusted for age at first delivery. In women with at least two childbirths, an age less than 20 years at first childbirth was associated with an increased prevalence of chronic LBP (PR 1.36; 95% CI: 1.25-1.49; compared with age 25-29 years). No association was observed between age at last delivery and chronic LBP. The lowest prevalence of chronic LBP was found among women who were currently pregnant (PR 0.80; 95% CI: 0.63-1.00; compared with women with no childbirths). CONCLUSIONS: Having experienced at least one childbirth seems to be associated with a higher prevalence of chronic LBP later in life. A young age at first childbirth is also associated with a long-lasting increased prevalence.

Migraine, obesity and body fat distribution - a population-based study.

BACKGROUND: Obesity has been linked to an increased prevalence of migraine, and to increased migraine attack frequency, but several questions are left unanswered by previous studies. We examined the relationship between obesity and headache in a large, population-based study where we could take into account body fat distribution, migraine subtypes and tension-type headache. METHODS: The third population-based Nord-Trøndelag Health Study (HUNT3) included validated headache questionnaires and objective anthropometric measurements. Using a cross-sectional design, our sample consisted of 18,191 women and 14,985 men, aged 19 to 96 years. Of these 4290 (12.9%) had migraine, 4447 (13.4%) had frequent tension-type headache (TTH), and 24,439 were headache-free controls. A total of 5049 individuals with unclassified headache were excluded from the analyses. Using logistic regression, we modeled the association between obesity and headache prevalence, adjusting for relevant confounders. RESULTS: Both total body obesity (TBO) and abdominal obesity (AO) were associated with a higher prevalence of migraine when compared to headache-free controls (OR 1.45 95% CI 1.32-1.59 and OR 1.29 95% CI 1.18-1.41, respectively), in particular for individuals < 50 years of age (OR 1.74 95% CI 1.54-1.98 and OR 1.89 95% CI 1.69-2.11). Similar results were seen for migraine with and without aura. Similar Overall, a weaker associations were as observed between obesity and TTH. There was a dose-response relationship between obesity categories and increased headache frequency in subjects with migraine. TBO was associated with migraine prevalence and attack frequency independent of AO. CONCLUSION: Both TBO and AO were associated with migraine prevalence and attack frequency. This association was largely limited to individuals < 50 years of age. TBO, rather than AO, may be a better measure of obesity in relation to migraine.

High sensitivity C-reactive protein and risk of migraine in a 11-year follow-up with data from the Nord-Trøndelag health surveys 2006-2008 and 2017-2019.

BACKGROUND: Several previous studies have reported a cross-sectional association between elevated high sensitivity C-reactive protein (hs-CRP) and migraine. The aim of this population-based follow-up study was to investigate the influence of hs-CRP at baseline on the risk of developing migraine 11 years later. METHODS: Data from the Nord-Trøndelag Health Study performed in 2006-2008 (baseline) and 2017-2019 were used. A total of 19,574 participants without migraine at baseline were divided into three groups based on hs-CRP levels (< 3 mg/L, 3-9.99 mg/L and 10.00-20 mg/L). Poisson regression was used to evaluate the associations between hs-CRP levels and risk ratios (RRs) of migraine, and precision of the estimates was assessed by 95% confidence interval (CIs). RESULTS: In the multi-adjusted model, increased risk of migraine (RR 1.46, 95% CI 1.05-2.04) was found in the highest hs-CRP levels group compared to the lowest group. In the group with the highest hs-CRP levels, a nearly three times higher risk of chronic migraine (RR 2.81, 95% CI 1.12-7.06) was found, whereas no evident relationship was found between high hs-CRP level and risk of developing episodic migraine. CONCLUSIONS: The main finding in this 11-year follow-up was that hs-CRP levels between 10.00-20.00 mg/L at baseline was associated with increased risk of chronic migraine.

Time trends of major headache diagnoses and predictive factors. Data from three Nord-Trøndelag health surveys.

AIMS: The primary aim of this study was to investigate time trends of major headache diagnoses using cross-sectional data from two population-based health surveys. In addition, we aimed to perform a longitudinal assessment of baseline characteristics and subsequent risk for having headache at 22-years' follow-up among those participating in three health surveys. METHODS: Data from the Nord-Trøndelag Health Study (HUNT) performed in 1995-1997 (HUNT2), 2006-2008 (HUNT3) and 2017-2019 (HUNT4) were used. The 1-year prevalence time trends of major headache diagnoses were estimated among 41,460 participants in HUNT4 and among 39,697 participants in HUNT3, two surveys with identical headache questions. 16,118 persons participated in all three surveys, and among these, a Poisson regression was used to evaluate health-related baseline information in HUNT2 and the risk ratios (RRs) with 95% confidence interval (CIs) of consistently reporting headache during follow-up. RESULTS: Compared with the 1-year prevalence in HUNT3, a higher proportion of participants in HUNT4 had tension-type headache (20.7% vs. 15.9%, p < 0.001), whereas a lower 1-year prevalence was found for migraine (11.1% vs. 12.0%, p < 0.001) and medication overuse headache (MOH) (0.3% vs. 1.0%, p < 0.001). Participants in the age group 20-39 years at baseline nearly three times increased risk (RR = 2.8, 95% CI 2.5-3.1) of reporting headache in HUNT2, HUNT3 and HUNT4 than persons aged 50 years or more. Female sex, occurrence of chronic musculoskeletal complaints and high score of depression or anxiety at baseline doubled the risk of having headache in all three surveys. CONCLUSIONS: The 1-year prevalence of migraine and MOH was lower in HUNT4 than in HUNT3. Young age, female sex, and occurrence of musculoskeletal complaints and high score of anxiety and/or depression were all associated with substantially increased risk of reporting headache in all three surveys.

Mitochondrial genome-wide association study of migraine - the HUNT Study.

BACKGROUND: Variation in mitochondrial DNA (mtDNA) has been indicated in migraine pathogenesis, but genetic studies to date have focused on candidate variants, with sparse findings. We aimed to perform the first mitochondrial genome-wide association study of migraine, examining both single variants and mitochondrial haplogroups. METHODS: In total, 71,860 participants from the population-based Nord-Trøndelag Health Study were genotyped. We excluded samples not passing quality control for nuclear genotypes, in addition to samples with low call rate and closely maternally related. We analysed 775 mitochondrial DNA variants in 4021 migraine cases and 14,288 headache-free controls, using logistic regression. In addition, we analysed 3831 cases and 13,584 controls who could be reliably assigned to a mitochondrial haplogroup. Lastly, we attempted to replicate previously reported mitochondrial DNA candidate variants. RESULTS: Neither of the mitochondrial variants or haplogroups were associated with migraine. In addition, none of the previously reported mtDNA candidate variants replicated in our data. CONCLUSIONS: Our findings do not support a major role of mitochondrial genetic variation in migraine pathophysiology, but a larger sample is needed to detect rare variants and future studies should also examine heteroplasmic variation, epigenetic changes and copy-number variation.