Blood pressure as a risk factor for headache and migraine: a prospective population-based study.

BACKGROUND AND PURPOSE: During the past decade, several population-based studies have found an inverse association between blood pressure (BP) and headache. However, most of them have a cross-sectional design or lack a validated definition of a headache-free population at baseline. Therefore, additional population-based studies using a clearly defined headache-free population and a prospective design are warranted. METHODS: Data from two large epidemiological studies, the Nord-Trondelag Health Survey 1995-1997 (HUNT 2) and 2006-2008 (HUNT 3), were used to evaluate the association between BP (systolic, diastolic and pulse pressure) at baseline and headache (migraine and tension type headache) at follow-up. RESULTS: An inverse relationship was found between all three BP measures at baseline in HUNT 2 and any headache in HUNT 3, more evident for systolic BP [odds ratio (OR) 0.90 per 10 mmHg increase in systolic BP, 95% confidence interval (CI) 0.87-0.93, P < 0.001] and pulse pressure (OR 0.84 per 10 mmHg increase in pulse pressure, 95% CI 0.80-0.89, P < 0.001) than for diastolic BP (OR 0.92 per 10 mmHg increase in diastolic BP, 95% CI 0.87-1.00, P = 0.036). The most robust finding, evident for both sexes, was that increased pulse pressure was linked to decreased prevalence of both migraine and tension type headache. CONCLUSION: An inverse relationship between BP and subsequent development of headache was confirmed in this large-scale population-based cohort study. Nevertheless, further research is needed to investigate the underlying mechanisms explaining these findings.

Does high blood pressure reduce the risk of chronic low back pain? The Nord-Trøndelag Health Study.

BACKGROUND: Epidemiological studies have suggested inverse relationships between blood pressure and prevalence of conditions such as migraine and headache. It is not yet clear whether similar relationships can be established for back pain in particular in prospective studies. METHODS: Associations between blood pressure and chronic low back pain were explored in the cross-sectional HUNT 2 survey of a Norwegian county in 1995-1997, including 39,872 individuals who never used antihypertensive medication. A prospective study, comprising 17,209 initially back pain-free individuals and 5740 individuals reporting low back pain, was established by re-examinations in the HUNT 3 survey in 2006-2008. Associations were assessed by logistic regression with respect to systolic, diastolic and pulse pressure, with adjustment for education, work status, physical activity, smoking, body mass and lipid levels. RESULTS: In the cross-sectional study, all three blood pressure measures showed inverse relationships with prevalence of low back pain in both sexes. In the prospective study of disease-free women, baseline pulse pressure and systolic pressure were inversely associated with risk of low back pain [odds ratio (OR) 0.93 per 10 mm Hg increase in pulse pressure, 95% confidence interval (CI) 0.89-0.98, p = 0.007; OR 0.95 per 10 mm Hg increase in systolic pressure, 95% CI 0.92-0.99, p = 0.005]. Results among men were equivocal. No associations were indicated with the occurrence of pain in individuals with low back pain at baseline. CONCLUSIONS: Results for low back pain are consistent with the theory of hypertension-associated hypalgesia, predicting diminished pain sensitivity with increasing blood pressure, possibly with modified reactions in people suffering from long-lasting pain.

Birth and parental characteristics and risk of neuroblastoma in a population-based Norwegian cohort study.

In this population-based Norwegian cohort study (2.1 million children), the impact of birth and parental characteristics on the risk of neuroblastoma (178 cases) was evaluated. In children below the age of 18 months, there was an increased neuroblastoma risk among those with congenital malformations and suggestion of increased risk when the mother had pre-eclampsia.

The combined effect of albuminuria and inflammation on all-cause and cardiovascular mortality in nondiabetic persons.

OBJECTIVES AND DESIGN: Recent studies have shown that albuminuria accompanied by evidence of subclinical inflammation is more strongly associated with metabolic abnormalities and the development of atherosclerosis than albuminuria alone. The aim of this population-based prospective study was to examine the combined effect of albuminuria and inflammatory markers on all-cause and cardiovascular-mortality in nondiabetic individuals without macroalbuminuria. SUBJECTS AND METHODS: Urinary albumin and creatinine, some inflammatory markers (fibrinogen, white blood cell and monocyte count) and cardiovascular risk factors were measured in 5702 persons in Tromsø, Norway. Baseline data were collected in 1994-1995 and follow-up was through 2005. RESULTS: For a one standard deviation higher value of the log-transformed ratio between albumin and creatinine (ACR), the mortality rate ratio for all-cause mortality was 1.21 when adjusted for age, gender, established cardiovascular risk factors as well as fibrinogen and white blood cell count (P < 0.001). The corresponding mortality rate ratio for cardiovascular mortality was 1.24 (P < 0.001). Persons in the upper quartile of both ACR and either of the inflammatory markers had an age- and gender-adjusted all-cause and cardiovascular mortality rate that was four times that of subjects in the lowest quartiles (P < 0.001). CONCLUSION: ACR predicts all-cause and cardiovascular mortality in persons without known diabetes and macroalbuminuria. The mortality is especially high amongst individuals with elevated levels of both ACR and inflammatory markers.

Reproductive factors and pancreatic cancer risk: a Norwegian cohort study.

A cohort of 63,090 Norwegian women born 1886-1928 was followed more than 38 years, and relations between reproductive factors and risk of pancreatic cancer were explored; 449 cases were recorded at ages 50-89 years. Age at menopause showed a moderately positive association with risk (rate ratio (RR)=1.08 per 2 years delay in menopause; 95% confidence interval (CI)=1.00-1.17). Neither parity nor duration of breastfeeding showed significant associations with risk after adjusting only for demographic factors. With mutual adjustment, however, parity became positively associated (RR=1.13 per delivery; 95% CI=1.05-1.22) while duration of breastfeeding was inversely associated (RR=0.87 per 12 months; 95% CI=0.78-0.97). These associations lessened in magnitude with increasing age, and were essentially absent above age 80 years. Risk was raised among women reporting at least one abortion, but no trend was seen with number of abortions. Together with previous studies, the findings raise questions about the role of chance, but do not exclude hormonal factors related to breastfeeding and pregnancy from affecting pancreatic cancer risk.

Twin births, sex of children and maternal risk of ovarian cancer: a cohort study in Norway.

In a follow-up of 1,208,001 women aged 20-74 years, no significant association was found between twin births (112 cases) and risk, though those with twin girls had a non-significantly higher risk than those with singleton births; among the latter, those with girls only had a higher risk of endometrioid tumours (incidence rate ratio 1.35; 95% confidence interval 1.03-1.76, based on 475 cases) than women with boys only.

Effect of recall on estimation of non-fatal injury rates: a community based study in Tanzania.

STUDY OBJECTIVE: To investigate the effect of recall on estimation of non-fatal injury rates in Tanzania. DESIGN: Retrospective population based survey. SETTING: Eight branches in an urban area and six villages in a relatively prosperous rural area in Tanzania. SUBJECTS: Individuals of all ages living in households selected by cluster sampling. MAIN OUTCOME MEASURES: Estimated non-fatal injury rates calculated at each of the 12 recall periods (one to 12 months before the interview). RESULTS: Out of a population of 15 223 persons, 509 individuals reported 516 injuries during the preceding year. Of these 313 (61.5%) were males and 196 (38.5%) females. The data showed notable declining incidence rates from 72 per 1000 person-years when based on a one month recall period to 32.7 per 1000 person-years for a 12 month recall period (55% decline). The decline was found for injuries resulting in fewer than 30 days of disability whereas rates for severe injuries (disability of 30 days or more) did not show a consistent variation with recall period. Decline in injury rates by recall period was higher in rural than in urban areas. Age, sex, and education did not notably affect recall. CONCLUSIONS: Longer recall periods underestimate injury rates compared with shorter recall periods. For severe injuries, a recall period of up to 12 months does not affect the rate estimates. It is essential that a recall period of less than three months be used to calculate injury rates for less severe injuries.

Breast cancer risk by age at birth, time since birth and time intervals between births: exploring interaction effects.

In a Norwegian, prospective study we investigated breast cancer risk in relation to age at, and time since, childbirth, and whether the timing of births modified the risk pattern after delivery. A total of 23,890 women of parity 5 or less were diagnosed with breast cancer during follow-up of 1.7 million women at ages 20-74 years. Results, based on Poisson regression analyses of person-years at risk, showed long-term protective effects of the first, as well as subsequent, pregnancies and that these were preceded by a short-term increase in risk. The magnitude and timing of this adverse effect differed somewhat by birth order, maternal age at delivery and birth spacing. No transient increase in risk was seen shortly after a first birth below age 25 years, but an early first birth did not prevent a transient increase in risk after subsequent births. In general, the magnitude of the adverse effect was strongest after pregnancies at age 30 years or older. A wide birth interval was also related to a more pronounced adverse effect. Increasing maternal age at the first and second childbirth was associated with an increase in risk in the long run, whereas no such long-term effect was seen with age at higher order births.

Attributable fractions: fundamental concepts and their visualization.

A general methodology for visualizing attributable fractions in epidemiology is described. The methodology applies to the multifactorial exposure situation and embraces various types of attributable fractions including adjusted, sequential and average attributable fractions. The concept of the scaled Venn diagram plays a central role, illustrating total disease risk and excess disease risk attributable to the exposures as areas in a unit square. This forms the ground for making simple pie charts of attributable fractions summing to 1 (or 100%). The potential applications extend from cohort and cross-sectional data to data from case-control studies. The methodology is illustrated by theoretical as well as empirical examples including the risk of motor fatalities attributable to driver's blood alcohol concentration and age, and the prevalence of chronic cough attributable to smoking habits, occupational exposure to dust or gas, and residence. A total of 40 figures illustrate the methodology.

Menstrual and reproductive factors and risk of gastric cancer: a Norwegian cohort study.

OBJECTIVE: To explore relations between menstrual and reproductive factors and incidence of gastric cancer in a cohort study of 63,090 Norwegian women, followed over a period of 29 years. METHODS: Associations with potential risk factors were evaluated by Poisson regression analysis, considering 572 cases of gastric cancer diagnosed in women aged less than 80 years. RESULTS: Age at menarche showed a moderate inverse association with overall risk of gastric cancer (incidence rate ratio 0.93 per year; 95% confidence interval 0.88-1.00). No association could be established with age at menopause. Among women aged less than 50 years, an old age at first delivery was related to an increased risk, mainly of cancer of the distal part of the stomach. In multiparous women aged 50 years or more, relations with childbearing history differed significantly between subsites. Women with many pregnancies over a short period of time had an increased risk of cancer of the proximal part of the stomach. In the distal part, pregnancies over a long period seemed to confer a higher risk. CONCLUSIONS: Relations between reproductive factors and risk of gastric cancer should be assessed separately for pre- and postmenopausal women and for subsites.

Modeling effects of age at and time since delivery on subsequent risk of cancer.

We describe a simple model for examining the temporal effects of childbirth on cancer risk, considering data on uniparous and nulliparous women, from either a cohort or case-control study design. For uniparous women, the expression for risk includes terms for age at delivery and time since delivery. With a suitable definition of the effect of uniparity, no terms relating to delivery are needed for nulliparous women. If the pure age effect is assumed to be the same in all women, the effects of age at delivery and time since delivery are both estimable, despite the linear dependence involving attained age in uniparous women. Omitting terms for time since delivery and considering the heterogeneity of age-specific effects of uniparity provides a valid test for the effect of time since delivery, although risk estimates are biased. Tests based on linear interaction terms for age at delivery and attained age, as applied in recent case-control studies, are not appropriate for investigating the effect of time since delivery. We show how our basic model may be applied to the analysis of case-control data from a Norwegian study of breast cancer. We then compare these results with those from other models.

Joint effects on cancer risk of age at childbirth, time since birth and attained age: circumventing the problem of collinearity.

In previous studies of female cancer risk, we introduced a new method for circumventing the problem of collinearity in age-adjusted analysis of the joint effects of age at birth and time since birth. The basic idea was to estimate the pure age effect considering nulliparous women, assuming that the age effect is common to all women. However, risk estimates for attained age obtained in this manner may suffer from bias, in particular in small data sets, which may in turn influence risk estimates for reproductive factors among parous women. Certain factors possibly affecting cancer risk among nulliparous women only, for instance biological infertility, might also introduce bias. The purpose of this paper is to investigate the accuracy of risk estimates obtained by the joint approach, and to reveal the extent of bias in traditional separate age-adjusted analyses of age at birth or time since birth among parous women. Results are based on analyses of simulated data sets reflecting reproductive and demographic characteristics of a cohort of 1.1 million Norwegian women. Incidence rate ratios are calculated in Poisson regression analyses of person-years at risk. Our simulations show that the joint analysis in general yields unbiased risk estimates, but the number of cases must be rather high to achieve reliable results. Risk estimates from separate analyses can be seriously biased, although the amount of bias depends on the strength and direction of associations with cancer risk. With a total of 5500 cancer cases, the estimators for age at last birth and time since last birth were 13-78 per cent and 5-66 per cent more efficient in the joint than in the separate analysis, respectively. Significance levels were close to the nominal 5 per cent in the joint analysis, but about twice as high in the separate analysis. Adding an effect of biological infertility on cancer risk among nulliparous women, without taking it into account in the analyses, did not seriously affect risk estimates in the joint model.

Risk of primary childhood brain tumors related to birth characteristics: a Norwegian prospective study.

Relations between birth characteristics and risk of primary brain tumor were explored in a prospective study of the 1,489,297 children born in Norway between 1967 and 1992. A total of 459 primary brain tumors, including 78 medulloblastomas and 168 astrocytomas, were diagnosed in the age interval 0-15 years. The overall risk of brain tumor depended on the season of birth (p = 0.01), with a higher risk for children born in winter than those born in spring [incidence rate ratio (IRR) = 1.52; 95% confidence interval (CI) 1.18-1.97]. An inverse association was observed with father's age at birth of child. The risk of medulloblastoma was positively associated with birth weight (IRR = 1.27/500 g; p = 0.05). Inverse relationships with length at birth were found for astrocytoma in the 0-1 and 5-10 year age intervals. Among 5-10-year-old children, birth weight was also inversely related to risk of astrocytoma. Our results suggest that risk factors may differ over age intervals and histological subgroups.

Reproductive factors and fatal hip fractures. A Norwegian prospective study of 63,000 women.

STUDY OBJECTIVE: The aim of the study was to investigate the impact of reproductive variables (age at menarche, menopause, first and last birth as well as parity, lactation, and abortions) on hip fracture mortality. DESIGN AND SETTING: A prospective study in Norway with more than 60,000 women followed up for 29 years. A total of 465 deaths as a result of hip fracture were recorded. MAIN RESULTS: Statistically significant linear relations (p < or = 0.02) were found between both age at menarche and length of reproductive period (defined as age at menopause to age at menarche) and the mortality of hip fractures in women aged less than 80. The death rate for women with a late menarche (> or = 17 years) was twice that of the women with relatively early menarche (< or = 13 years). Compared with women with less than 30 years between menopause and menarche, the mortality rate ratio in women with more than 38 reproductive years was 0.5. We also found an inverse relation with age at first birth. CONCLUSIONS: This study supports by hypothesis that an early menarche and a long reproductive period protect against hip fracture mortality. High age at first birth may also be protective.

Does age at natural menopause affect mortality from ischemic heart disease?

We examined the relationship between age at natural menopause and mortality of ischemic heart disease in 19,309 Norwegian postmenopausal women. A total of 2767 fatal infarctions occurred during 29 years of follow up. Overall, a relatively weak inverse relationship was seen with approximately 10% lower ischemic heart disease mortality in women aged > or = 47 years at the menopause compared to women with an early menopause (< 44 years). Risk estimates were similar for women aged 47 and more at menopause. However, the inverse relationship was stronger and statistically significant (p = 0.01) in women aged less than 70 years. In this group of women, we observed a nearly 60% reduction in the ischemic heart disease mortality in women with a late menopause (> or = 53 years) compared to women aged < 44 years at menopause (mortality rate ratio = 0.42; 95% confidence interval 0.25-0.72). This protective effect of a late menopause is reduced with advancing age, however, and is of minor significance in the age groups where the great proportion of the ischemic heart disease deaths occur.