Journal Club Week 1 Doctor, I have migraine with aura, am I more likely to die of cardiovascular disease?!!!!!!!!!!!!!! Samantha Warhurst! Med3000 Student!
! Article in Review Gudmundsson, L. S., Scher, A. I., Aspelund, T., Eliasson, J. H., Johannsson, M., Thorgeirsson, G.,... & Gudnason, V. (2010). Migraine with aura and risk of cardiovascular and all cause mortality in men and women: prospective cohort study. BMJ, 341.! Citations to date: 67!
Summary of article Section 1!
The British Medical Journal The BMJ s average weekly print circulation is 121,762 (ABC multi-platform certificate January-June 2013). In the same six month period total monthly unique browsers of bmj.com peaked in May at 1,365,786.!! The BMJ s Impact Factor is 16.3 (ISI Web of Science, 2014).! From: http://www.bmj.com/about-bmj!
NHMRC Level II Study - Prospective Cohort Study
What is a Prospective Cohort Study? Prospective cohort study where groups of people (cohorts) are observed at a point in time to be exposed to an intervention/factor under study. They are then followed prospectively with further outcomes recorded as they happen.! es for recommendations for developers of guidelines. Available at: http://www.nhmrc.gov.au/_files_nhmrc/file/gu
Aim of study To estimate whether migraine in mid-life is associated with mortality from cardiovascular disease, other causes and all causes.!
What is Migraine with Aura? Recurrent disorder manifesting in attacks of reversible focal neurological symptoms that usually develop gradually over 5-20 minutes and last for less than 60 minutes. Headache with the features of migraine without aura usually follows the aura symptoms. Less commonly, headache lacks migrainous features or is completely absent!!! From: http://ihs-classification.org/en/02_klassifikation/ 02_teil1/01.02.00_migraine.html!
What is Migraine with Aura? Criteria from Gudmundsson et al, 2010 (similar to International Headache Society, 2004)! Migraine with aura = Headache with a visual and/or sensory aura.! Migraine without aura = headache with at least two of the three non-aura symptoms (nausea, unilateral location, photophobia).!
Is there a link between Migraine and Cardiovascular Disease? Conflicting evidence between studies - some indicate migraine is a risk factor, some indicate it s a protective factor and some are inconclusive (Gudmusson et al., 2010).! Preceding meta-analysis (Schurks et al., 2009) found migraine with aura is associated with two-fold increase in risk of ischaemic stroke. Meta-analysis did not have enough data to examine link between migraine with aura and cardiovascular causes of mortality.!
Method Participants were taken from the Reykjavik study (Iceland), a population based study to prospectively study cardiovascular disease in Iceland.! Initial examination of each person conducted between 1965-1991, average year of initial examination was 1975.! Migraine assessment was via symptomatic questionnaire/interview (not specified).!
Methods At same time as migraine assessment, assessment of cardiovascular risk was performed by nurses:! Questionnaires! Physical measurements! Spirometry! ECG! Venous blood sampling!
Method Participants were followed for up to 40 years (until end 2007).! Information re cause of death was obtained from Statistics Iceland and given and ICD code.! Main endpoints:! Death from cardiovascular disease (also separated into fatal CHD, fatal stroke, other fatal CVD)! Death from non-cardiovascular disease! Death from all causes.! Statistical analysis was using Cox proportional hazards to estimate relative risk of death (hazard ratio) after adjusting for demographic and baseline risk factors for cardiovascular disease!
Participants Sample of 18725 at start of study and by 2007, 10 358 participants had died.! 4323 died from cardiovascular disease (mostly coronary heart disease)! 6035 from non cardiovascular disease.! 11% (n = 2023) were classified as having migraine, 3% without aura and 8% with aura.!
Results/Conclusions People with migraine with aura were at increased risk of:! All cause mortality! Mortality from cardiovascular disease! Mortality from coronary heart disease and stroke**! when compared with people with migraine without aura or non-migraine headache.! Women with migraine with aura were also at an increased risk of mortality from non-cardiovascular disease compared to women with migraine without aura/non-migraine headache.! Increases in risk were moderate (hazard ratio = 1.19-1.40).!
Over to you. What does this mean in terms of clinical care?!
Clinical Implications Migraine with aura is an independent risk factor for cardiovascular and all cause mortality but it is weaker than major established risk factors such as smoking, diabetes and high blood pressure. (Gudmundsson et al., 2010, p8)!
Critical appraisal Based on protocol detailed in: Young JM, Solomon MJ (2009). How to critically appraise an article! Nature Clinical Practice: Gastroenterology & Hepatology, 6(2); 82-91!
Is the study question relevant? The study addressed a pertinent issue in primary care, risk factors for cardiovascular mortality, and mortality from other causes. It has concrete clinical implications which may, over time, influence clinical practice. Is this study relevant to medical students? Definitely. Implications for patient care as above but also makes us think about the link between migraine with aura and cardiovascular disease and why this might be the case.
Does the study add anything new? Enhances understanding of relationship between migraine with aura, cardiovascular mortality, in particular from coronary heart disease and stroke. This was identified as a gap by a previous systematic review/ meta-analysis (Schurks et al, 2009). It adds to the existing literature base on cardiovascular risk factors.
What type of research question is being asked? Population: People born between 1907-1935 from Reykjavik! Intervention: migraine with aura! Comparison: no migraine, migraine without aura! Outcomes: Cardiovascular mortality, noncardiovascular mortality, all causes of death!
Was the study design appropriate for the question? Yes, the prospective cohort study allowed researchers to gather specific exposure data (i.e. re migraine with aura and cardiac risk factors) and follow the patients over time to link this exposure with an outcome (various types of mortality).!
From: http://www.ncbi.nlm.nih.gov/pmc/articles/pmc2998589/!
Did the study methods address the most important sources of bias? Most important sources of bias in cohort studies are selection bias and attrition bias.! Prospective cohort studies may be susceptible to attrition bias. Due to use of Statistics Iceland for endpoint data this was minimised in current study and it only had 1% attrition.! Participants all selected from same population so minimal selection bias.!
Did the study methods address the most important sources of bias? Other potentially confounding factors:! Study statistics accounted potentially-confounding cardiac risk factors at the time of initial assessment (i.e., BMI, smoking, hypertension ) but not risk factors developed during the course of the study.! No information on any treatments received for migraine which may have altered cardiovascular mortality.! Venous measurement techniques for cholesterol may have changed in course of long initial data collection period (1967-1991)??!
Was the study performed according to the original protocol? Yes, few changes were possible as original data collected between 1967-1991 and protocol appears to have remained the same during this period.!
Does the study test a stated hypothesis Hypothesis was not stated as previous studies on the topic were inconclusive. Only a statement of aim was included: We estimated the risk of mortality from cardiovascular disease, non-cardiovascular disease, and all causes associated with having migraine with or without aura at mid-life during up to 40 years of follow-up in a population based cohort.
Were the statistical analyses performed correctly? Utilised Cox proportional hazards model to estimate the relative risk of death (hazard ratio) after adjusting for demographic and baseline risk factors for cardiovascular disease (e.g., BMI, smoking, diabetes, pref history of coronary event, use of anti-hypertensive drugs etc).! A Cox model is a statistical technique for exploring the relationship between the survival of a patient and several explanatory variables.! Provides an estimate of a variable s effect on survival (time to death) after adjustment for other explanatory variables.! Regression model i.e. it can account for several variables at once! Tested for violations and these were reported.! Info on Cox model from: http://www.medicine.ox.ac.uk/bandolier/painres/download/whatis/cox_model.pdf!
Are there any conflicts of interest? None stated!
Can the results be applied to the local population? Maybe. Study undertaken in Iceland on a population who were born a long time ago. So results may differ from those that might be obtained in Australia with a much newer/younger population.! Statistics performed on large subject numbers >10000.!
OVERALL study critique Strengths:! Good study design! Large sample size! Data is statistically significant with moderate effect sizes.! Minimal bias or confounding factors! Weaknesses:! Population differs from local Australian population in terms of locality and generationality.! Hypothesis was not stated (but it could not be determined from previous literature).! Long initial data collection period - may impact on measurement!