Identifying the most appropriate age threshold for TNM stage grouping of well-differentiated thyroid cancer.

OBJECTIVE: Age is integrated in most risk stratification systems for well-differentiated thyroid cancer (WDTC). The most appropriate age threshold for stage grouping of WDTC is debatable. The objective of this study was to evaluate the best age threshold for stage grouping by comparing multivariable models designed to evaluate the independent impact of various prognostic factors, including age based stage grouping, on the disease specific survival (DSS) of our population-based cohort. METHODS: Data from population-based thyroid cancer cohort of 2125 consecutive WDTC, diagnosed during 1970-2010, with a median follow-up of 11.5 years, was used to calculate DSS using the Kaplan Meier method. Multivariable analysis with Cox proportional hazard model was used to assess independent impact of different prognostic factors on DSS. The Akaike information criterion (AIC), a measure of statistical model fit, was used to identify the most appropriate age threshold model. Delta AIC, Akaike weight, and evidence ratios were calculated to compare the relative strength of different models. RESULTS: The mean age of the patients was 47.3 years. DSS of the cohort was 95.6% and 92.8% at 10 and 20 years respectively. A threshold of 55 years, with the lowest AIC, was identified as the best model. Akaike weight indicated an 85% chance that this age threshold is the best among the compared models, and is 16.8 times more likely to be the best model as compared to a threshold of 45 years. CONCLUSION: The age threshold of 55 years was found to be the best for TNM stage grouping.

Risk factors and outcome in ICU-acquired infections.

BACKGROUND: Nosocomial infections are common in intensive care units (ICU). The objectives of this study were to determine risk factors of ICU-acquired infections, and potential mortality attributable to such infections. METHODS: An observational study was performed in a 10-bed multidisciplinary ICU. For a period of 27 months, all patients admitted for >or=48 h were included. Infections were diagnosed according to Centers for Disease Control and Prevention definitions. Airway colonization was explored by molecular typing. Risk factors for infection were determined by multivariable logistic regression. Survival was analyzed with time-varying proportional hazards regression. RESULTS: Of 278 patients, 81 (29%) were infected: urinary tract infections in 39 patients (14%), primary bloodstream infections in 25 (9%), surgical site infections in 22 (8%) and pneumonia in 21 (8%). Of the total of 147 episodes, Gram-negative bacilli were isolated in 90, Gram-positive cocci in 49 and Candida sp. in 25. Risk factors for pneumonia were mechanical ventilation [odds ratio (OR=7.9, CI 1.8-35), lack of enteral nutriment (OR=8.0, CI 1.4-45) and length of time at risk (OR=1.8, CI 1.2-2.8), while gastric acid inhibitors did not affect the risk (OR=0.99, CI 0.32-3.0). Transmission of bacteria from the stomach to the airway was not confirmed. The risk of death was increased as patients were infected with pneumonia [hazard ratio (HR)=3.6; CI: 1.6-8.1], or primary bloodstream infection (HR=2.5; CI: 1.2-5.4), independent of age and disease severity. CONCLUSIONS: Mortality was increased by ICU-acquired pneumonia and primary bloodstream infections. Our findings did not support the gastro-pulmonary hypothesis of ICU-acquired pneumonia. The proposition that blood transfusions increase the risk of ICU-acquired nosocomial infections was not supported.

Migraine patients have lower systolic but higher diastolic blood pressure compared with controls in a population-based study of 21,537 subjects. The Reykjavik Study.

Several studies have explored a possible association between migraine and hypertension, with contradictory results. Because of this uncertainty the relation between blood pressure (BP) and migraine was studied in 10,366 men and 11,171 women in a population-based longitudinal study. A modified version of the 1988 International Headache Society criteria was used for diagnosis of migraine. Logistic regression analysis was used. The crude 1-year prevalence of migraine was 5.2% among men and 14.1% among women. No significant association was found between hypertension and migraine. For a one standard deviation (SD) increase in diastolic BP the probability of having migraine increased 14% (P = 0.11) for men and 30% (P < 0.0001) for women. For a 1-SD increase in systolic BP the probability of having migraine decreased 19% (P = 0.007) for men and 25% (P < 0.0001) for women. It was also found that for a 1-SD increase in pulse pressure the probability of having migraine decreased 13% (P = 0.005) for men and 14% (P < 0.0001) for women. In a population-based study of men and women it was found that subjects with migraine had lower pulse pressure, lower systolic BP and higher diastolic BP compared with controls.

Risk profiles and prognosis of treated and untreated hypertensive men and women in a population-based longitudinal study: the Reykjavik Study.

The aim was to examine the risk profiles and prognosis of treated and untreated hypertensive subjects and examine to what degree confounding by indication was present in a population-based cohort study with up to 30-year follow-up. The study population consisted of 9328 men and 10 062 women, aged 33-87 years at the time of attendance from 1967 to 1996. The main outcome measures were myocardial infarction (MI), cardiovascular disease (CVD) mortality and all-cause mortality. Comparing the risk profiles between treated and untreated subjects entering the study showed significantly higher values for some risk factors for treated subjects. During the first 10 years, hypertensive men without treatment, compared with those treated, had a significantly lower risk of suffering MI, CVD and all-cause mortality, hazard ratio (HR) 0.72 (95% CI; 0.57, 0.90), 0.75 (95% CI; 0.59, 0.95) and 0.81 (95% CI; 0.61, 0.98), respectively. No significant differences in outcome were seen during the following 20 years. In identically defined groups of women, no significant differences in mortality were seen between groups. Subgroup analysis, at two stages of the study 5 years apart, revealed that some cardiovascular risk factors had a higher prevalence in hypertensive men who were treated at the later stage, compared with those who remained untreated (P=0.004). In conclusion, hypertensive treated men had a worse prognosis during the first 10 years of follow-up than untreated ones, which is most likely due to worse baseline risk profile. Hypertensive men that were treated at a later stage had a worse risk profile than those not treated at a later stage.

Survival and trends of occurrence of left ventricular hypertrophy, gender differences, 1967-92: The Reykjavik Study.

OBJECTIVE: We estimated the prevalence, incidence and risk factors of left ventricular hypertrophy (LVH) in a prospective cohort study of 26 489 participants. MATERIAL AND METHODS: The LVH was defined as Minnesota Code 310 on electrocardiogram (ECG). Everyone with this code at first visit was defined as a prevalence case and those who developed it between subsequent visits were incidence cases. The comparison cohort were all other participants in the Reykjavik Study stages I-V. RESULTS: A total of 297 men and 49 women were found to have LVH of 3.2% and 0.5%, respectively. The incidence was 25 per 1000 per year amongst men and six per 1000 per year amongst women. Prevalence in both genders increased with increasing age. Risk factors at the time of diagnosis were systolic blood pressure [odds ratio (OR) per mmHg 1.02; 95% confidence interval (CI): 1.01-1.03], age (OR per year 1.04; 95% CI: 1.02-1.05), silent myocardial infarction (MI) (OR 3.18; 95% CI: 1.39-7.27) and ST-T changes (OR 3.06; 95% CI: 2.14-4.38) amongst men and systolic blood pressure and age for women with similar odds ratio. Predictive factors for acquiring LVH were systolic blood pressure [incidence ratio (IR) 1.01; 95% CI: 1.01-1.02] and angina with ECG changes (IR 2.33; 95% CI: 1.08-5.02) amongst men and systolic blood pressure amongst women (IR 1.03; 95% CI: 1.01-1.04). The risk for coronary mortality was significantly increased amongst women with hypertrophy [hazard ratio (HR) 3.07; 95% CI: 1.5-6.31] and their total survival was poorer with increasing time from diagnosis of LVH (HR 2.17; 95% CI: 1.36-3.48). CONCLUSIONS: We conclude that the presence of LVH and its appearance is associated with age and increased blood pressure amongst both genders. Women with LVH have poorer survival than other women and they are at threefold risk of dying of ischaemic heart disease.

Fifteen percent of myocardial infarctions and coronary revascularizations explained by family history unrelated to conventional risk factors. The Reykjavik Cohort Study.

Aims To examine the relationship between history of myocardial infarction in first-degree relatives and the risk of developing coronary heart disease (myocardial infarction or coronary revascularization). Methods and Results A total of 9328 males and 10062 females, randomly selected residents of the Reykjavik area, aged 33-81 years, were examined in the period from 1967 to 1996 in a prospective cohort study. Cardiovascular risk assessment was based on characteristics at baseline. Information on history of myocardial infarction in first-degree relatives was obtained from a health questionnaire. Mean follow-up was 18 and 19 years for men and women, respectively. During follow-up 2700 men and 1070 women developed coronary heart disease. Compared with subjects without a family history, the hazard ratio of coronary heart disease was 1.75 (95% confidence interval, CI, 1.59-1.92) for men and 1.83 (95% CI, 1.60-2.11) for women, with one or more first-degree relatives with myocardial infarction. The risk factor profile was significantly worse in individuals with a positive family history. After allowance for these risk factors, the hazard ratio was still highly significant, 1.66 (CI, 1.51-1.82) and 1.64 (CI, 1.43-1.89) for men and women, respectively. Family history of myocardial infarction was attributed to 15.1% of all cases of coronary heart disease in men and 16.6% in women, independent of other known risk factors. Conclusion Family history of myocardial infarction increases the risk of developing coronary heart disease in both men and women and is largely independent of other classic risk factors. Approximately 15% of all myocardial infarctions can be attributed to familial factors that have not been measured in the study or remain to be elucidated.

Risk of cancer among relatives of patients with glioma.

We report a population-based, retrospective study of 396 Icelandic people diagnosed with glioma in the years 1940-1995. The purpose of this study was to test whether astrocytomas, other glial tumors, other central nervous system tumors, or other cancers aggregate in families identified through glioma probands who were of Icelandic origin. Pedigrees of the 396 cases were traced by the Genetical Committee of the University of Iceland and linked to the Icelandic Cancer Registry. A total of 25,546 relatives, including 2,080 individuals with cancer were identified within these pedigrees. There was no statistically significant increase of glioma in relatives of glioma patients, nor was there any statistically significant increase in risk for other central nervous system tumors. There was no overall increase in incidence of all cancer combined, nor of specific common cancers (lung, prostate, breast, stomach, and colorectal) and uncommon cancers (melanoma and pancreas) in the relatives of glioma patients. Our results do not support the hypothesis of a familial aggregation of glioma indicative of a glioma susceptibility gene.

The effect of a single BRCA2 mutation on cancer in Iceland.

OBJECTIVE: To estimate the risk of malignant diseases in families of probands with the same mutation in the BRCA2 gene. DESIGN: A cohort study using record linkage of a breast cancer family resource and the Icelandic Cancer Registry. SETTING: Iceland. SUBJECTS: Families of 995 breast cancer patients, from which 887 were tested for a single founder 999del5 mutation; 90 had the mutation and 797 did not. RESULTS: Relatives of probands with the mutation had significantly increased relative risk (RR) of breast cancer. For first degree relatives, the RR was 7.55 (95% CI 6.04 to 9.03) but was 1.72 (95% CI 1.49 to 1.96) in first degree relatives of probands without the mutation. For prostate and ovarian cancer, the first and second degree relatives of probands with the mutation had a significantly increased RR, but in families of probands without the mutation no significant familial risk was found. CONCLUSIONS: The 999del5 mutation in the BRCA2 gene explains a substantial proportion of familial risk of breast cancer in Iceland, but significant familial risk remains in relatives of probands without the mutation. For prostate and ovarian cancer, the mutation accounts for most of the familiality observed in families of breast cancer patients.

The relationship between educational level and mortality. The Reykjavík Study.

OBJECTIVE: Epidemiological studies have indicated an association between socioeconomic factors and health. It has not been clearly established whether this association is wholly or partly independent of classical risk factors. Our objective was to estimate the relationship between educational level and coronary artery disease (CAD), mortality and all-cause mortality. The Reykjavík Study involving 18 912 participants followed-up 4-30 years provides an ideal opportunity to address this question. DESIGN AND SUBJECTS: The participants were aged 33-81 years and living in the Reykjavík area. They were divided into four groups according to education. The standard risk factors were assessed on entry and mortality, and cause of death registered during follow-up. Multiple Cox regression analysis was applied to assess the relationship between age at examination, year of examination, educational level and mortality. RESULTS: The all-cause mortality and CAD mortality was significantly related to education, even after adjustment for classical risk factors. For men, 14% (95% CI: 2-24) reduction was found in CAD mortality for those having high school education relative to elementary school. The figures for junior college and university education were 17% (95% CI: 1-31) and 38% (95% CI: 21-32), respectively. These figures were only slightly lower when major CAD risk factors were controlled for and still significant. Similar figures were found for all-cause mortality. For women 34% (95% CI: 18-48) reduction was found in CAD mortality for high school education and 55% (95% CI: 22-74) for junior college, but too few had university education for reliable results. The figures were lower for all-cause mortality, but significant. The figures were reduced when major CAD risk factors were controlled for, but still significant. CONCLUSION: Education is a strong protective factor both for all-cause and CAD mortality. Only a small part of this effect can be explained through conventional risk factors.

Helicobacter pylori antibodies and gastric cancer in Iceland - The decline in IgG antibody level is a risk factor.

H. pylori infection is considered a causal agent of duodenal ulcer and a significant risk factor for gastric cancer. Retrospective cohort studies have demonstrated a significant association between presence of antibody to H. pylori and gastric cancer when using samples obtained years before the diagnosis but not at the time of diagnosis. The present study investigates, in a population-based cohort, whether a decline occurs in H. pylori antibody levels before the diagnosis of stomach cancer. Repeat samples (2 to 5) were available from 23 persons with gastric cancer taken up to 20 years before the diagnosis and 128 control subjects matched for gender, age, time and number of repeat samples. The odds ratio of developing stomach cancer was 1.16 (95% CI 1.05-1.28) for those showing decline in antibody levels of 1 relative antibody activity unit per year versus those with constant or rising levels. We conclude that this decline in antibody levels in cases, and not in controls, supports an active role of H. pylori in the pathogenesis of gastric cancer by causing atrophic gastritis, and provides a better risk assessment for gastric cancer compared to single measurements.

[Changes in myocardial infarction incidence and mortality in Iceland.].

INTRODUCTION: According to public health reports ischaemic heart disease was an uncommon cause of death in Iceland at the beginning of the last century. This death rate increased steadily until the ninety-eighties whereafter it leveled off and started to decline. The objective of the present study is to assess in detail the changes in myocardial infarction attack, incidence and death rate as well as case fatality. MATERIAL AND METHODS: Crude death rate from ischaemic heart disease is available from the Statistical Bureau of Iceland from 1911 to 1996 and age and sex standardized death rate from 1951. In this paper, however, the material is mainly from the MONICA Project, a multinational study of myocardial infarction under the auspices of the World Health Organization. The study, in which Iceland has participated since 1981, registers all myocardial infarctions in people aged 25-74 years in the whole country. The registration is performed according to standardized criteria and external quality control was applied throughout by WHO designated quality control centers. The registration now covers the period 1981-1998. RESULTS: The crude death rate in ischaemic heart disease in both sexes combined increased steadily until about 1980 when it accounted for about 30% of deaths. Age and sex specific death rate from these diseases increased from 1951 to about 1970, leveled off for the next 10 years and has since decreased. The MONICA data show a decline of death rate from myocardial infarction of 57% in men aged 25-74 during 1981-1998 and a 51% decline in women. Incidence rate has declined by 40% and 34% in men and women respectively and attack rate by 49% and 44%. Incidence, death rate and case fatality in myocardial infarction in Iceland compares favorably with other European countries. CONCLUSIONS: Myocardial infarction incidence and death rates have been declining in Iceland during the last two decades. Case fatality is now among the lowest compared to other countries. Preventive measures are most likely to further reduce incidence and death rates in myocardial infarction in Iceland.

[In search for explanatory factors in the relationship between educational level and mortality.].

OBJECTIVE: The connection between socioeconomic status and mortality is well known in Western countries. Educational level has frequently been used as a socioeconomic indicator. In a recent Icelandic prospective study, an inverse relationship between educational level and mortality was shown. The objective of the present study is to consider possible explanatory factors. MATERIAL AND METHODS: This study was a part of the Reykjavík Study. A stratified sample of 400 people was taken from one of six study groups. The sample was equally divided between the sexes and four educational levels. Mean age of the sample was 72.7 years. Participants completed a questionnaire concerning knowledge of risk factors for coronary heart disease, expected response to symptoms of cardiac infarction, social network and use of health care. Response rate was 78.5%. The relationship between answers and educational level was assessed with logistic regression. RESULTS: People with higher education were more likely to be in personal contact with nurses and doctors and receive advice concerning health and treatment from them. Participants were generally satisfied with the Icelandic health care system and seemed generally to have good access to it. A relationship with educational level was not shown. A larger proportion of those with lower education had regular communication with their general practician. CONCLUSIONS: Our results suggest that certain health care services are integrated into the social network of those with higher education. This may lower their morbidity and mortality. Other hypotheses concerning possible explanatory factors for differences in health were not supported.

[Survival and trends of ocurrence of left ventricular hypertrophy, gender differences during 1967-1992. The Reykjavík Study.].

OBJECTIVE: We estimated the prevalence and incidence of left ventricular hypertrophy (LVH) in this large prospective cohort study of almost 20,000 participants and identified risk factors in them. Predictive factors of its appearance were evaluated along with morbidity and mortality calculations. MATERIAL AND METHODS: LVH was defined as Minnesota Code 310 on ECG. Everyone with this code at first visit was defined as a prevalence case and those who developed it between subsequent visits were incidence cases. Risk factors at the time of the diagnosis of LVH were determined with logistic regression. Predictive factors for acquiring this ECG abnormality were determined by Poisson regression. The comparison cohort were all other participants in the Reykjavík Study stages I-V. RESULTS: Two hundred ninety-seven men and 49 women were found to have LVH or 3.2% and 0.5%, respectively. The incidence was 25/1000/year among men and 6/1000/ year among women. Prevalence in both genders increased with increasing age. Risk factors at the time of diagnosis were systolic blood pressure (odds ratio pr. mmHg (OR) 1.02; 95% confidence interval (CI): 1.01-1.03), age (OR pr. year: 1.04; 95% CI: 1.02-1.05), silent myocardial infarction (MI) (OR: 3.18; 95% CI: 1.39-7.27) and ST-T changes (OR: 3.06; 95% CI: 2.14-4.38) among men and systolic blood pressure and age for women with similar odds ratio. Predictive factors for acquiring LVH were systolic blood pressure (incidence ratio (IR): 1.01; 95% CI: 1.01-1.02) and angina with ECG changes (IR: 2.33; 95% CI: 1.08-5.02) among men and systolic blood pressure among women (IR: 1.03; 95% CI: 1.01-1.04). In men severe smoking seemed to have a protective effect against developing LVH (IR: 0.36; 95% CI: 0.18-0.71). The risk for coronary mortality was significantly increased among women with hypertrophy (hazard ratio (HR): 3.07; 95% CI: 1.5-6.31) and their total survival was poorer with increasing time from diagnosis of LVH (HR: 2.17; 95% CI: 1.36-3.48). CONCLUSIONS: We conclude that the presence of LVH and its appearance is associated with age and increased blood pressure among both genders. Women with LVH have poorer survival than other women and they are at threefold risk of dying of ischemic heart disease. This could indicate that criteria for detecting LVH on ECG detect both mild and severe hypertrophy among men but only the severe hypertrophy cases among women. More sensitive ECG methods may have to be used to detect mild, moderate and severe LVH among both genders in order to differentiate the severity of LVH based on the ECG diagnosis.

The association between parathyroid hormone, vitamin D and bone mineral density in 70-year-old Icelandic women.

Parathyroid hormone (PTH) may be an important determinant of cortical bone remodeling in the elderly. Vitamin D status is one of the determining factors in this relationship. The aim of this study was to quantify the relationship between serum PTH, vitamin D and bone mineral density (BMD) in elderly women in Reykjavik (64 degrees N), where daily intake of cod liver oil is common and mean calcium intake is high. In PTH correlated inversely with 25(OH)D (r = -0.26, p<0.0 1). In multivariate analysis PTH correlated inversely with whole body BMD (mostly cortical bone) (R2 = 2.2%, p = 0.04) but not with the lumbar spine BMD, reflecting more cancellous bone. No association was found between 25(OH)D levels and BMD at any site in univariate or multivariate analysis. Osteocalcin, a measure of bone turnover, was negatively associated with BMD and this association remained significant when corrected for PTH levels. In summary, in this fairly vitamin D replete population with high calcium intake, PTH was negatively associated with total body BMD. We infer that suppression of PTH may reduce cortical bone loss, but other factors are likely to contribute to age-related bone remodeling and osteoporosis.

Serum thyroglobulin as a risk factor for thyroid carcinoma.

Samples from a biological serum bank taken up to 23 years prior to diagnosis of thyroid carcinoma were analysed for human thyroglobulin, thyroid-stimulating hormone and thyroxin. After exclusions, the final study material consisted of 59 cases of papillary and follicular carcinomas. These cases were compared with 164 controls, matched for sex, age and time of sample taking. The most interesting finding was that concentrations of thyroglobulin in serum were abnormally elevated in cases compared with controls, equal to or above 30 microg/L, with odds ratio 7.0 (CI 3.1-15.7). This elevation of serum thyroglobulin occurred in 44% of the carcinoma cases. Sensitivity was around 50 for measurements taken up to 15 years prior to diagnosis, but 21 when the interval was over 15 years. Specificity was 89. No differences were found between cases and controls in values for thyroid-stimulating hormone and thyroxin.

Genetic epidemiology of breast cancer: segregation analysis of 389 Icelandic pedigrees.

A genetic epidemiologic investigation of breast cancer involving 389 breast cancer pedigrees including information on 14,721 individuals from the Icelandic population-based cancer registry is presented. Probands were women born in or after 1920 and reported to have breast cancer in the cancer registry. The average age of the 389 probands was 45.5 years (SD 8.92). Segregation analyses was performed evaluating residual maternal effects, a dichotomous cohort effect, and assuming the age at diagnosis followed a logistic distribution after log-transformation. Familial aggregation could be best explained by the inheritance of a high-risk allele leading to early onset breast cancer among the homozygotes, which represent approximately 2.6% of the population. A Mendelian codominant model was selected as the best fitting model, with an estimated age at diagnosis of 51.8 years among these high-risk homozygotes, 64.0 years for heterozygotes and 76.3 years for the low-risk genotype. The predicted cumulative risk for homozygote carriers of the high-risk allele is 32.2% by age 60, compared to 16.4% for heterozygotes and 5.0% for non-carriers of the same age. These predicted age profiles in the current study complement recent reports from Iceland of a majority of BRCA2 mutation carriers being diagnosed with breast cancer below the age of 50 years, and 60 years being the mean age at diagnosis for non-carriers. This model also predicted a high background risk of breast cancer for women in this population (estimated susceptibility gamma = 0.44 +/- 0.08). This implies that if carriers and non-carriers did not die of competing causes, the estimated risk of being diagnosed with breast cancer by age 80 years irrespective of carrier status is 11.4%.

The prevalence and prognosis of third-degree atrioventricular conduction block: the Reykjavik study.

OBJECTIVES: The objectives of this study were to find the prevalence of third-degree atrioventricular block in representative population sample and to estimate its prognostic significance. Most earlier studies have been performed on hospital patients and some professional groups. SETTING AND SUBJECTS: In the Reykjavik Study, a prospective cardiovascular population study, 9139 men and 9773 women aged 33-79 years were examined in 1967-91. Electrocardiograms were taken and coded according to the Minnesota code. Third-degree atrioventricular block was found in 11 persons, seven male and four female, an overall prevalence of 0.04%. All of these individuals had signs of dysrhythmia on electrocardiograms taken later, and in addition some other heart disease. The heart block was temporary in seven individuals (64%); six (55%) needed a pacemaker. CONCLUSIONS: The prevalence of third-degree atrioventricular block in this general population was low. The block was temporary in the majority of subjects. All had some underlying heart disease, which may affect the prognosis more than the heart block. Fewer subjects than expected were found to need a pacemaker.

Effects of leisure-time physical activity and ventilatory function on risk for stroke in men: the Reykjavík Study.

BACKGROUND: Stroke is a major cause of illness, death, and health expenditures. Leisure-time physical activity may reduce the risk for stroke. OBJECTIVE: To examine the association of leisure-time physical activity and pulmonary function with risk for stroke. DESIGN: Prospective cohort study. SETTING: Reykjavík, Iceland. PARTICIPANTS: 4484 men 45 to 80 years of age followed for a mean (+/-SD) of 10.6 +/- 3.6 years. MEASUREMENTS: Patients underwent physical examination, blood sampling, and spirometry and completed a questionnaire about health and exercise. Computerized hospital records were used to identify strokes, and the Icelandic National Registry was used to identify deaths. RESULTS: New stroke developed in 249 men (5.6%) (hemorrhagic stroke in 44 [18%] and ischemic stroke in 205 [82%]). In a multivariable hazard analysis that controlled for known risk factors for cerebrovascular disease, leisure-time physical activity maintained after 40 years of age was associated with a reduced risk for stroke (relative risk, 0.69 [CI, 0.47 to 1.01] for total stroke and 0.62 [CI, 0.40 to 0.97] for ischemic stroke). Risk for stroke increased with diminished ventilatory function (FVC or FEV1) (relative risk, 1.9 [CI, 1.06 to 3.25] for the lowest compared with the highest quintile). CONCLUSION: Middle-aged men who participate in leisure-time physical activity and have good pulmonary function seem to have a lower risk for stroke than men who are not active or have diminished pulmonary function.

Breast cancer incidence and familiality in Iceland during 75 years from 1921 to 1995.

Information in the Icelandic Cancer Registry on breast cancer and its collection of breast cancer families has been used to elucidate changes in breast cancer incidence by time period and by age, and the effect of degree of relationship and age on the familial risk of breast cancer. Since 1921 the incidence rates have increased, but the increase is significantly greater (2.06% per year) for ages over 44 years than for ages 20-44 (1.20% per year). It has been shown before that when familial risk is computed, the age of the proband influences the risk for the relatives. However, this study shows that the age of the relative is also important and with increasing age the familial risk decreases.