Abstract
Background: To investigate the association between cardiovascular risk-factor profile and migraine in the elderly, we evaluated a population sample of ageing men and women (65 years or more) living in a low-income area in the city of São Paulo, Brazil.
Patients and Methods: We investigated migraine status and cardiovascular profile from a baseline of 1450 participants (65–102 years of age) of the São Paulo Ageing & Health Study (SPAH), a longitudinal population-based study with low-income elderly in Brazil. The following age and sex-adjusted cardiovascular risk factors were analyzed: blood pressure, pulse pressure, serum total and high-density lipoprotein cholesterol, body mass index, smoking, history of hypertension, diabetes and the 10-year risk of myocardial infarction or coronary heart disease death based on the Framingham Risk Score.
Results: The overall prevalence of migraine was 11.4%, and it was 3 times more frequent among women than men (15.3% vs 5.4%; P < 0.0001). Migraineurs were younger than non-migraineurs (mean age 70.6 years vs 72.1 years; P = 0.001, respectively). There was no statistically significant difference regarding the cardiovascular risk-factor profile after adjustment for age and sex among migraineurs and non-migraineurs. Only a decrease in the risk of hypertension among women (OR 0.58; 95% CI 0.38–0.90; P = 0.01) was also observed even after adjustment for age.
Conclusions: Overall, we did not find a worse cardiovascular risk profile among elderly migraineurs. An inverse association between hypertension and migraine in women warrants further investigation.
Introduction
The prevalence of migraine is lower in older people than the young (1,2). However, the increasing number of ageing people makes headache in the elderly a new frontier in clinical practice (1). Many studies support some kind of relationship between cardiovascular disease (CVD) and migraine, especially with aura (3–8). Most related a positive association between major CVD outcomes and migraine, particularly with aura (5,6,9–11). A higher risk of developing coronary heart disease (CHD) and ischaemic stroke in migraineurs compared to non-migraineurs has been described in middle-aged populations (6,9–11). Among young migraineurs, women who are smokers and oral contraceptive users also have an increased risk of early-onset ischaemic stroke (3,4). Conversely, some authors reported no association between migraine and CHD (7,12).
The possible mechanisms explaining the relationship between migraine and CVD are not well known. It has been postulated that migraineurs may have an elevated cardiovascular profile compared to those without migraine (13). Several mechanisms could explain the relationship between migraine and CVD, including a worse profile of cardiovascular and prothrombotic risk factors, vascular dysfunction, and systolic blood pressure (14–16). However, there are few data reporting the actual prevalence of CVD risk factors among migraineurs compared to non-migraineurs (13), particularly among elderly populations (17). Further, information about migraine among elderly populations living in low- and middle-income countries are scarce (18). A recent Brazilian study showed a high prevalence of migraine in a very low-income population sample of elderly people (18). Some studies in Brazil have also showed the high burden of CVD in very-low income populations (19,20). In order to investigate the association between cardiovascular risk-factor profile and migraine in the elderly, we evaluated a population sample of ageing men and women (65 years or more) living in a low-income area in the city of São Paulo, Brazil.
Patients and Methods
The São Paulo Ageing & Health Study (SPAH) is a population-based epidemiological study carried out with residents of an economically deprived area of São Paulo, Brazil. This paper addresses the association between headache and cardiovascular risk factors, using information from the SPAH study. The Institutional Review Board approved the study and all the participants signed an informed consent.
Study design
All people aged 65 years or more resident in 66 pre-determined census sectors (catchment areas) in the area of Butantan, a neighbourhood located in the Western side of the city of São Paulo, were eligible to participate in the SPAH study. The census sectors chosen had predominantly residents of low socio-economic condition, who lived in shanty-towns (favelas) or in households covered by the Family Health Program. A total of 2072 persons (91.4% of those invited) were recruited through systematic door knocking and were included in the SPAH. Details on the case-finding procedures have been published elsewhere (18). Of those 2072 individuals who agreed to participate, 1615 elderly people answered the questionnaire about headache that was first applied when 457 people had already been interviewed. Of these, 1450 participants with no missing data to calculate Framingham Heart Study Risk Score were included for this analysis (21).
Procedures
The study was conducted over a 2-year period, from May 2003 to April 2005. All participants were assessed for sociodemographic characteristics, life-style and cardiovascular risk factors. Participants were interviewed and assessed in their homes, by trained research assistants.
Headache assessment
A headache questionnaire based on the 2004 International Headache Society (IHS) criteria (22) previously validated in Brazil was applied as part of the main questionnaire (23). Headache diagnosis was made according to 2004 IHS criteria (22).
Socio-economic status (SES)
Age was reported as mean ± SD. Race was classified by the interviewer in four categories: White, Afro-Brazilian, Mixed and others (Indian, Asian and undefined race). Education was classified in three categories according to numbers of school years: none, 1–3, and ≥4 years. Monthly personal income (transformed from Brazilian currency to US$) was classified into four categories: none to US$85, US$86 to US$127, US$128 to US$246, and US$247 or more.
Life-style variables
Smoking status was categorised as current, past or never. Alcohol consumption after age 65 years was categorised as ‘yes’ or ‘no’. Participants self-reported their participation in leisure and work activities in four categories as: very, fairly, not very and not at all physically active.
Measures of cardiovascular risk
Three measurements of blood pressure were performed with an OMROM digital sphygmanometer (model HEM-712-C). Measurements were taken at least 1 h without ingestion of caffeine and/or smoking, with participants seated and their arm level with the heart. The first measurement was taken after 5 min rest, and the two remaining measurements were taken at intervals of 5 min. For calculation of the arterial hypertension, the first measurement was discarded, and the arithmetic mean of the second and third measurements was calculated. Data from blood pressure were analysed according to The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) criteria (24). Participants who had diastolic pressure ≥90 mmHg and/or systolic pressure ≥140 mmHg and/or informed a medical diagnosis of hypertension and/or under hypertension treatment were classified as having hypertension. Pulse pressure (PP) was defined as the systolic blood pressure (SBP) minus the diastolic blood pressure (DBP). Baseline body mass index (BMI; weight in kilograms divided by the square of height in metres [kg/m2]) was analyzed as a continuous variable.
Venous blood samples were obtained after an overnight fast. The serum obtained after centrifugation was used for hormone and biochemical measurements. Analyses were carried out using an automated analyzer (ADVIA 1650-Bayer). Fasting blood glucose was determined by the hexoquinase method and determined according to American Diabetes Association criteria (25). Diabetes mellitus was defined as fasting blood glucose ≥126 mg/dl and/or use of hypoglycaemic oral insulin. Total cholesterol was determined using the cholesterol oxidase method. HDL-cholesterol was determined using an enzymatic colorimetric method. LDL-cholesterol was determined according to the Fridewald equation. Cut-off points were defined according to the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report (26).
In addition, The Framingham Risk Score for coronary heart disease (CHD), which estimates the 10-year risk of myocardial infarction or CHD death based on age, sex, smoking status, systolic and/or diastolic blood pressure, total cholesterol, and HDL-cholesterol, was calculated (21). The 10-year CHD risk scores were categorized based on recent clinical guidelines as follows: <10%, 10–19% and >20% risk.
Statistical analysis
Data entry was carried out twice using the program EPIDATA v3.0, and the validity check was carried out to identify and correct data entry errors. Statistical analyses were conducted with the SPSS software (v16.0) and the R software (v11.1). The baseline characteristics and cardiovascular risk factors among migraineurs compared to non-migraineurs were evaluated, using the Cochran–Mantel–Haenszel test for categorical co-variates and General Linear Model (GLM) for continuous co-variates controlling for the effects of sex and age. Adjusted analyses were reported as means ± SD or SE. Logistic regression models were performed to investigate the relationship between migraine status and cardiovascular risk factors using the 10-year risk of CHD based on the Framingham Risk Score, with hypertension and diabetes as dependent variables. It was performed crude and multivariate analyses adjusted by age and sex. Additional adjustments for a number of co-variates, which had a likelihood of <0.20 or that were associated with either migraine or cardiovascular risk (smoking status, BMI, alcohol consumption, use of antihypertensives, monthly personal income) were considered in multivariate analyses. Further, stratified analyses by gender were performed. For each odds ratio, we calculated 95% confidence intervals (95% CIs). For all results, a two-tailed P-value of <0.05 was considered statistically significant.
Results
Baseline characteristics of 1450 elderly according to migraine status
Some proportions might not add up to 100% due rounding or missing values (at most 1.5%).
Yellow or Native Indian.
Defined as presence of hypertension if systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, history of hypertension diagnosed by physician, or current treatment.
Defined as presence of diabetes if fasting blood glucose levels ≥126 mg/dl, or diabetes diagnosed by a physician, or current treatment.
The Framingham Risk Score estimates the 10-year risk of myocardial infarction or coronary heart disease (CHD) death and is based on age, smoking status, systolic blood pressure, HDL cholesterol, and total cholesterol.
All age and sex-adjusted P-values were obtained from Cochran–Mantel–Haenszel test for categorical and General Linear Model for continuous variables.
Relationship between cardiovascular risk factors and migraine in 1450 elderly
Multivariable adjustment by age, sex, body mass index, smoking status, alcohol consumption, monthly income.
<10% of 10-year risk of coronary heart disease on Framingham Risk Score as reference group.
Multivariable adjustment by age, sex, body mass index, alcohol consumption, use of antihypertensives, monthly income. Data are OR, odds ratio with 95%CI values.
Discussion
Overall, migraine status was not associated with a worse profile of cardiovascular risk factors in our study. We did not observe any association between migraine and a Framingham Risk Score greater than 20% of risk of a CHD in 10 years in the multivariate analysis. Hypertension was inversely associated with migraine only among women.
The relationship between migraine and risk of subsequent CVD has long been hypothesized (5,6,9–11). Two cohorts that initially showed a negative association between migraine and coronary heart disease (7), found a positive association between major CVD outcomes such as myocardial infarction and ischaemic stroke in both men and women after longer follow-up periods (5,6). However, a controversy remains about the relationship between migraine and classical cardiovascular risk factors (13,27). In a middle-aged population, Scher et al. (13) found a higher probability of smoking, and parental history of myocardial infarction in migraineurs compared to non-migraineurs. Migraineurs, especially with aura, had an unfavourable cholesterol profile, and an increased risk of having a higher Framingham Risk Score suggesting a worse cardiovascular risk profile compared to non-migraineurs (13). The prospective cohort carried out among 27,519 middle-age women from the Women’s Health Study (WHS) found the strongest association between active migraine with aura and major cardiovascular disease and ischaemic stroke in the lowest Framingham Risk Score group, while the association with myocardial infarction was observed only among women in the highest cardiovascular risk group (28). We found an inverse association between migraine overall and the Framingham Risk Score comparing the lowest with the highest Framingham Risk Score groups. However, this association did not remain significant after considering the adjustment for age and sex. Actually, we observed a decreased risk of hypertension among the subgroup of women with migraine compared to those without migraine. Several studies have explored a possible association between migraine and hypertension, with contradictory results (15,16,29–31). Some studies performed in young and middle-aged populations have found a possible link between migraine and other non-migrainous headache and systolic blood pressure (15,16,29–32). However, there are few data reporting the association between migraine and blood pressure levels or hypertension in the elderly (15). Tzourio et al. (15) evaluated 1373 elderly individuals aged 59–71 years, and found that the mean systolic blood pressure was lower in subjects with migraine than non-migraineurs (128 mmHg vs 137 mmHg). Additionally, Gudmundsson et al. (32) found lower levels of SBP and PP among migraineurs compared to non-migraineurs in subjects aged 19–81 years regardless of gender. However, no significant association was found between hypertension and migraine (32). In our study, a trend of lower levels of systolic blood pressure among migraineurs compared to non-migraineurs was observed (139.9 mmHg vs 145.7 mmHg; P = 0.051, respectively). It has been hypothesized that the stimulation of the baroreflex arch in response to increased systolic blood pressure, which is related to arterial stiffness, could inhibit pain transmission at both spinal and supraspinal levels generating hypo-algesia and may decrease headache (30,33).
Our study has some strengths and limitations that warrant discussion. Beyond the large number of participants, this is a population-based study that investigated the association between cardiovascular risk factors and migraine among low-income subjects aged 65 years or older in a developing country, in which the prevalence of cardiovascular disease and migraine are very high compared to other countries (18–20,34–36). As previously reported by Stewart et al. (37), the prevalence of migraine in the lowest income group (less than $10,000) was reported to be more than 60% higher than in the two highest income groups (greater than or equal to $30,000).
Although this is a prospective cohort, we cannot make assumptions about the directionality of the relationship between migraine and CHD risk factors, because we considered for these analyses information from the baseline. Although our sample size is relatively large, the frequency of migraine was three times higher in women compared to men, which results in less power to detect possible association among men. Furthermore, we did not have information about migraineurs with aura to perform our analyses by aura symptoms, which are much more correlated with CVD (6,9). Although no difference was observed in use of antihypertensives between those with and without migraine, it may be possible that migraineurs seek more medical care for their headaches and hypertension. Consequently, they may also be more likely to be prescribed antihypertensives, and some of them are also used for migraine prophylaxis. Another possibility for our findings is a survival bias: elderly people with high blood pressure presented a higher cardiovascular mortality; consequently people who survived may present lower levels of blood pressure.
Conclusions
These findings did not show a worse cardiovascular risk profile among migraineurs in this elderly population with low income. An inverse association between hypertension and migraine in women warrants further investigation.