Resting heart rate and the risk of cardiovascular disease, total cancer, and all-cause mortality - A systematic review and dose-response meta-analysis of prospective studies.

BACKGROUND AND AIM: Epidemiological studies have reported increased risk of cardiovascular disease, cancer and all-cause mortality with greater resting heart rate, however, the evidence is not consistent. Differences by gender, adjustment for confounding factors, as well as the potential impact of subclinical disease are not clear. A previous meta-analysis missed a large number of studies, and data for atrial fibrillation have not been summarized before. We therefore aimed to clarify these associations in a systematic review and meta-analysis of prospective studies. METHODS AND RESULTS: PubMed and Embase were searched up to 29 March 2017. Summary RRs and 95% confidence intervals (CIs) were calculated using random effects models. Eighty seven studies were included. The summary RR per 10 beats per minute increase in resting heart rate was 1.07 (95% CI: 1.05-1.10, I2 = 61.9%, n = 31) for coronary heart disease, 1.09 (95% CI: 1.00-1.18, I2 = 62.3%, n = 5) for sudden cardiac death, 1.18 (95% CI: 1.10-1.27, I2 = 74.5%, n = 8) for heart failure, 0.97 (95% CI: 0.92-1.02, I2 = 91.4%, n = 9) for atrial fibrillation, 1.06 (95% CI: 1.02-1.10, I2 = 59.5%, n = 16) for total stroke, 1.15 (95% CI: 1.11-1.18, I2 = 84.3%, n = 35) for cardiovascular disease, 1.14 (95% CI: 1.06-1.23, I2 = 90.2%, n = 12) for total cancer, and 1.17 (95% CI: 1.14-1.19, I2 = 94.0%, n = 48) for all-cause mortality. There was a positive dose-response relationship for all outcomes except for atrial fibrillation for which there was a J-shaped association. CONCLUSION: This meta-analysis found an increased risk of coronary heart disease, sudden cardiac death, heart failure, atrial fibrillation, stroke, cardiovascular disease, total cancer and all-cause mortality with greater resting heart rate.

Tobacco smoking and the risk of diverticular disease - a systematic review and meta-analysis of prospective studies.

AIM: This systematic review and meta-analysis aimed to clarify whether tobacco smoking is associated with an increased risk of diverticular disease. METHOD: The PubMed and Embase databases were searched for studies of smoking and diverticular disease up to 19 February 2016. Prospective studies that reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) of diverticular disease associated with current or previous smoking were included. Summary RRs were estimated using a random effects model. RESULTS: We identified five prospective studies which comprised 6076 cases of incident diverticular disease (diverticulosis and diverticulitis) among 385 291 participants and three studies with 1118 cases of complications related to diverticular disease (abscess or perforation) among 292 965. The summary RR for incident diverticular disease was 1.36 (95% CI 1.15-1.61, I2  = 84%, n = 4) for current smokers, 1.17 (95% CI 1.05-1.31, I2  = 49%, n = 4) for former smokers and 1.29 (95% CI 1.16-1.44, I2  = 62%, n = 5) for ever smokers. The summary RR was 1.11 (95% CI 0.99-1.25, I2  = 82%, n = 4) per 10 cigarettes per day. Although there was some indication of nonlinearity there was a dose-dependent positive association with increasing number of cigarettes smoked per day. There was some evidence that smoking also increases the risk of complications of diverticular disease, but the number of studies was small. CONCLUSION: The current meta-analysis provides evidence that tobacco smoking is associated with an increased incidence of diverticular disease and related complications.

Autoimmune diabetes in adults and risk of myocardial infarction: the HUNT study in Norway.

BACKGROUND: The long-term consequences of autoimmune diabetes in adults (AIDA) are largely unexplored. OBJECTIVE: To investigate the risk of myocardial infarction (MI) in AIDA compared to type 2 diabetes, taking into consideration the effects of socio-economic and lifestyle factors, the metabolic syndrome and glycaemic control. METHODS: A total of 62 995 participants including 207 individuals with AIDA (onset ≥35 years and anti-GAD positive) and 2322 individuals with type 2 diabetes (onset ≥35 years and anti-GAD negative), from the population-based Norwegian HUNT study, were followed for a first MI during the period 1995-2008. We identified 2614 MIs by hospital records or the National Cause of Death Registry. Cox proportional hazard models were used to estimate the risk of MI by diabetes subgroups after adjustment for age and socio-economic and lifestyle factors. RESULTS: AIDA amongst women was associated with a nearly fourfold increased risk of MI [hazard ratio (HR) 3.63, 95% confidence interval (CI) 2.21-5.96) compared to nondiabetic participants, whereas no excess risk was found in men with AIDA (HR 1.30, 95% CI 0.70-2.52). By contrast, type 2 diabetes was associated with an increased MI risk in both men (HR 1.92, 95% CI 1.62-2.26) and women (HR 2.39, 95% CI 1.98-2.89). The metabolic profile was more favourable in patients with AIDA than in those with type 2 diabetes, but glycaemic control was worse. Multivariable models and sensitivity analyses suggest that these results were robust. CONCLUSIONS: Women with AIDA were more likely to develop MI, compared to men with AIDA and both men and women with type 2 diabetes. Further investigations are warranted to confirm this gender difference.

Weight and weight change and risk of acute myocardial infarction and heart failure - the HUNT Study.

OBJECTIVES: To delineate the association of weight with cardiovascular health throughout adulthood. METHODS: We conducted a population-based prospective cohort study of 26 097 community-dwelling individuals who were followed for 11.4 years with measurements of cardiovascular risk factors and common chronic disorders. Body weight and height were directly measured at baseline in 1995-1997 as they had been 10 and 30 years prior to baseline. From these measurements, we estimated average body mass index (BMI) over time and calculated weight change. RESULTS: The association of average BMI with acute myocardial infarction (AMI) became weaker with adjustment for the most recent BMI measurement, whilst this adjustment had a more limited effect on associations with heart failure (HF) risk. For example, the multi-adjusted hazard ratios for AMI in a comparison of individuals with average BMI until baseline ≥35 kg m(-2) and between 18.5 and 22.4 kg m(-2) decreased from 1.75 [95% confidence interval (CI) 1.04-2.95] to 1.32 (0.73-2.40). The corresponding numbers for HF were 3.12 (1.85-5.27) and 2.95 (1.53-5.71), respectively. The associations between weight change and risk of AMI and HF were U-shaped, with stable weight showing the lowest risk. CONCLUSION: Sustained overweight or obesity over time is associated with increased risk of HF, even after adjustment for the most recent BMI. For AMI risk, the most recent BMI appears to be the most important. Weight change also increases risks for both outcomes beyond the effects of BMI. Our results suggest that a global epidemic of obesity is likely to increase the incidence of HF, even if BMI in middle age can be controlled.

Alcohol consumption is associated with a lower incidence of acute myocardial infarction: results from a large prospective population-based study in Norway.

AIMS: Compelling evidence suggests that light-to-moderate alcohol consumption is associated with a reduced risk of acute myocardial infarction (AMI), but several issues from previous studies remain to be addressed. The aim of this study was to investigate some of these key issues related to the association between alcohol consumption and AMI risk, including the strength and shape of the association in a low-drinking setting, the roles of quantity, frequency and beverage type, the importance of confounding by medical and psychiatric conditions, and the lack of prospective data on previous drinking. METHODS: A population-based prospective cohort study of 58 827 community-dwelling individuals followed for 11.6 years was conducted. We assessed the quantity and frequency of consumption of beer, wine and spirits at baseline in 1995-1997 and the frequency of alcohol intake approximately 10 years earlier. RESULTS: A total of 2966 study participants had an AMI during the follow-up period. Light-to-moderate alcohol consumption was inversely and linearly associated with AMI risk. After adjusting for major cardiovascular disease risk factors, the hazard ratio for a one-drink increment in daily consumption was 0.72 (95% confidence interval 0.62-0.86). Accounting for former drinking or comorbidities had almost no effect on the association. Frequency of alcohol consumption was more strongly associated with lower AMI risk than overall quantity consumed. CONCLUSIONS: Light-to-moderate alcohol consumption was linearly associated with a decreased risk of AMI in a population in which abstaining from alcohol is not socially stigmatized. Our results suggest that frequent alcohol consumption is most cardioprotective and that this association is not driven by misclassification of former drinkers.

Resting heart rate and the risk of type 2 diabetes: A systematic review and dose--response meta-analysis of cohort studies.

BACKGROUND: High resting heart rate has been associated with increased risk of type 2 diabetes in several studies, but the available data are not consistent and it is unclear if there is a dose-response relationship between resting heart rate and type 2 diabetes risk. We aimed to clarify this association by conducting a systematic review and meta-analysis of published studies. METHODS AND RESULTS: PubMed, Embase and Ovid Medline databases were searched for prospective studies published up until October 11th, 2013. Summary relative risks were estimated using a random effects model. Ten cohort studies with >5628 cases and 119,915 participants were included. The summary RR for high vs. low resting heart rate was 1.83 (95% CI: 1.28-2.60, I(2) = 88%, n = 7), and in the dose-response analysis the summary RR was 1.20 (95% CI: 1.07-1.34, I(2) = 93%, n = 9) for an increase of 10 beats per minute. The heterogeneity was to a large degree explained by two studies. There was evidence of nonlinear associations between resting heart rate (pnonlinearity < 0.0001) and risk of type 2 diabetes. CONCLUSION: The current meta-analysis indicates a strong positive association between high resting heart rate and the risk of type 2 diabetes. As a non-invasive marker of type 2 diabetes risk, resting heart rate may have potential in the clinical setting, especially for interventions aimed at lowering the risk of type 2 diabetes. Additional studies are needed to clarify the mechanisms that may be responsible for the assoiation between resting heart rate and type 2 diabetes.

A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus.

Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR)=0.81, 95% confidence interval (95% CI) = 0.76-0.86, P(combined) = 3.5 × 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B- and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.

Concentrations of human chorionic gonadotrophin in very early pregnancy and subsequent pre-eclampsia: a cohort study.

STUDY QUESTION: Are low serum concentrations of human chorionic gonadotrophin (hCG) in very early pregnancy associated with pre-eclampsia risk? SUMMARY ANSWER: Low hCG concentrations in very early pregnancy are associated with increased risk of severe pre-eclampsia. WHAT IS KNOWN ALREADY: Low maternal serum concentrations of hCG early in pregnancy may indicate impaired proliferation or invasion of trophoblast cells, and thus low hCG concentrations may serve as a marker for impaired placental development. Impaired placental development is assumed to be a cause of pre-eclampsia, but there is little prospective evidence to support this hypothesis. STUDY DESIGN, SIZE, DURATION: We performed a prospective cohort study of pregnancies after IVF at Oslo University Hospital 1996-2010 with linkage to the Medical Birth Registry of Norway to obtain information on pre-eclampsia development. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included 2405 consecutive singleton pregnancies and examined the association of maternal serum hCG concentrations (measured using Elecsys, Roche) on Day 12 after embryo transfer with the risk of any pre-eclampsia and of mild and severe pre-eclampsia. MAIN RESULTS AND THE ROLE OF CHANCE: HCG concentrations were inversely associated with pre-eclampsia risk in a dose-dependent manner (Ptrend 0.02). Compared with women with hCG ≥150 IU/l, women with hCG <50 IU/l were at 2-fold higher overall risk of pre-eclampsia [absolute risk 6.4 versus 2.8%; odds ratio (OR) 2.3, 95% confidence interval (CI) 1.2-4.7]. The inverse association was restricted to severe pre-eclampsia (Ptrend 0.01), thus, women with hCG <50 IU/l were at 4-fold higher risk of severe pre-eclampsia than women with hCG ≥150 IU/l (absolute risk 3.6 versus 0.9%; OR 4.2, 95% CI 1.4-12.2). For mild pre-eclampsia, there was no corresponding association (Ptrend 0.36). LIMITATIONS, REASONS FOR CAUTION: Results for IVF pregnancies may not be generalizable to spontaneously conceived pregnancies. WIDER IMPLICATIONS OF THE FINDINGS: Plausible causes of low maternal hCG concentrations very early in pregnancy include impaired placental development and delayed implantation. Thus, these results provide prospective evidence to support the hypothesis that impaired placental development may be associated with subsequent development of severe pre-eclampsia. STUDY FUNDING/COMPETING INTEREST: The study was financially supported by the Research Council of Norway. None of the authors has any conflict of interest to declare.

TOP2A gene copy number change in breast cancer.

AIMS: The clinical significance of TOP2A as a prognostic marker has not been clarified. The aims of this study were to investigate the frequency of TOP2A copy number change; to correlate TOP2A with HER2 status, hormone receptor (HR) status and molecular subtype, and further to explore differences in breast cancer-specific survival according to TOP2A and HER2. METHODS: In this study, TOP2A, HER2 and chromosome 17 copy number were assessed in 670 cases of breast cancer using in situ hybridisation techniques. Gene to chromosome ratios ≥2 were classified as amplification. TOP2A deletion (gene to chromosome ratio ≤0.8) or monosomy (only one signal for both gene and chromosome in more than 75% of nuclei) were classified as gene loss. RESULTS: A strong association between TOP2A change and HR and HER2 status was found. During the first 5 years after diagnosis, the risk of death from breast cancer was significantly higher for cases with HER2 amplification irrespective of TOP2A status. CONCLUSIONS: TOP2A copy number change was strongly associated with HR and HER2 status and as a prognostic marker TOP2A is probably of limited value.

Breastfeeding and the maternal risk of type 2 diabetes: a systematic review and dose-response meta-analysis of cohort studies.

BACKGROUND AND AIMS: Breastfeeding has been associated with reduced risk of maternal type 2 diabetes in some cohort studies, but the evidence from published studies have differed with regard to the strength of the association. To clarify this association we conducted a systematic review and dose-response meta-analysis of breastfeeding and maternal risk of type 2 diabetes. METHODS AND RESULTS: We conducted a systematic review and dose-response meta-analysis of prospective studies of breastfeeding and maternal risk of type 2 diabetes. We searched the PubMed, Embase and Ovid databases up to September 19th 2013. Summary relative risks were estimated using a random effects model. Six cohort studies including 10,842 cases among 273,961 participants were included in the meta-analysis. The summary RR for the highest duration of breastfeeding vs. the lowest was 0.68 (95% CI: 0.57-0.82, I(2) = 75%, p heterogeneity = 0.001, n = 6). The summary RR for a three month increase in the duration of breastfeeding per child was 0.89 (95% CI: 0.77-1.04, I(2) = 93%, p heterogeneity < 0.0001, n = 3) and the summary RR for a one year increase in the total duration of breastfeeding was 0.91 (95% CI: 0.86-0.96, I(2) = 81%, p heterogeneity = 0.001, n = 4). There was little difference in the summary estimates whether or not BMI had been adjusted for. The inverse associations appeared to be nonlinear, p nonlinearity < 0.0001 for both analyses, and in both analyses the reduction in risk was steeper when increasing breastfeeding from low levels. CONCLUSION: This meta-analysis suggests that there is a statistically significant inverse association between breastfeeding and maternal risk of type 2 diabetes.

Pregnancy week at delivery and the risk of shoulder dystocia: a population study of 2,014,956 deliveries.

OBJECTIVE: To study whether pregnancy week at delivery is an independent risk factor for shoulder dystocia. DESIGN: Population study. SETTING: Medical Birth Registry of Norway. POPULATION: All vaginal deliveries of singleton offspring in cephalic presentation in Norway during 1967 through 2009 (n = 2,014,956). METHODS: The incidence of shoulder dystocia was calculated according to pregnancy week at delivery. The associations of pregnancy week at delivery with shoulder dystocia were estimated as crude and adjusted odds ratios using logistic regression analyses. We repeated the analyses in pregnancies with and without maternal diabetes. MAIN OUTCOME MEASURES: Shoulder dystocia at delivery. RESULTS: The overall incidence of shoulder dystocia was 0.73% (n = 14,820), and the incidence increased by increasing pregnancy week at delivery. Birthweight was strongly associated with shoulder dystocia. After adjustment for birthweight, induction of labour, use of epidural analgesia at delivery, prolonged labour, forceps-assisted and vacuum-assisted delivery, parity, period of delivery and maternal age in multivariable analyses, the adjusted odds ratios for shoulder dystocia were 1.77 (1.42-2.20) for deliveries at 32-35 weeks of gestation, and 0.84 (0.79-0.88) at 42-43 weeks of gestation, using weeks 40-41 as the reference. In pregnancies affected by diabetes (n = 11,188), the incidence of shoulder dystocia was 3.95%, and after adjustment for birthweight the adjusted odds ratio for shoulder dystocia was 2.92 (95% CI 1.54-5.52) for deliveries at weeks 32-35 of gestation, and 0.91 (95% CI 0.50-1.66) at 42-43 weeks of gestation. CONCLUSION: The risk of shoulder dystocia was associated with increased birthweight, diabetes, induction of labour, use of epidural analgesia at delivery, prolonged labour, forceps-assisted and vacuum-assisted delivery, parity and period of delivery but not with post-term delivery.

Molecular subtypes, histopathological grade and survival in a historic cohort of breast cancer patients.

Molecular subtyping of breast cancer may provide additional prognostic information regarding patient outcome. However, its clinical significance remains to be established. In this study, the main aims were to discover whether reclassification of breast cancer into molecular subtypes provides more precise information regarding outcome compared to conventional histopathological grading and to study breast cancer-specific survival in the different molecular subtypes. Cases of breast cancer occurring in a cohort of women born between 1886 and 1928 with long-term follow-up were included in the study. Tissue microarrays were constructed from archival formalin-fixed, paraffin-embedded tissue from 909 cases. Using immunohistochemistry and in situ hybridisation as surrogates for gene expression analyses, all cases were reclassified into the following molecular subtypes: Luminal A; Luminal B (HER2-); Luminal B (HER2+); HER2 subtype; Basal phenotype; and five negative phenotype. Kaplan-Meier survival curves and Cox proportional hazards models were used in the analyses. During the first 5 years after diagnosis, there were significant differences in prognosis according to molecular subtypes with the best survival for the Luminal A subtype and the worst for HER2 and five negative phenotype. In this historic cohort of women with breast cancer, differences in breast cancer-specific survival according to subtype occur almost exclusively amongst the histopathological grade 2 tumours. From 5 years after time of diagnosis until the end of follow-up, there appears to be no difference in survival according to molecular subtype or histopathological grade.

Weight change in adulthood and risk of postmenopausal breast cancer: the HUNT study of Norway.

BACKGROUND: Adult weight gain is associated with increased risk of postmenopausal breast cancer. Most previous studies are limited by using recalled or self-reported data, and it is not known if age-specific weight changes are important for breast cancer risk. METHODS: In a Norwegian cohort of 28,153 women (and 900 incident breast cancers) with longitudinal anthropometric measurements over up to 30 years, we studied both overall and age-related weight changes in adulthood and risk of postmenopausal breast cancer. RESULTS: Overall, weight gain in adulthood was associated with increased breast cancer risk (hazard ratio (HR) per kg per year 1.31, 95% confidence interval (CI) 1.11-1.54). Weight gain before (HR per kg per year 1.38, 95% CI 1.09-1.75) or around menopause (1.69, 95% CI 1.32-2.16) was associated with increased risk, but there was no clear risk increase associated with later weight gain (HR per kg per year 0.92, 95% CI 0.73-1.18). CONCLUSION: Weight gain in adulthood was associated with increased risk of breast cancer. Our results suggest that weight gain before and around menopausal age may be particularly important for breast cancer risk among postmenopausal women.

Body mass index and the risk of meningioma, glioma and schwannoma in a large prospective cohort study (The HUNT Study).

BACKGROUND: Obesity increases the risk for a number of solid malignant tumours. However, it is not clear whether body mass index (BMI) and height are associated with the risk of primary tumours of the central nervous system (CNS). METHODS: In a large population study (The Nord-Trøndelag Health Study (HUNT Study)) of 74 242 participants in Norway, weight and height were measured. During follow-up, incident CNS tumours were identified by individual linkage to the Norwegian Cancer Registry. Sex- and age-adjusted and multivariable Cox regression analyses were used to evaluate BMI and height in relation to the risk of meningioma, glioma and schwannoma. RESULTS: A total of 138 meningiomas, 148 gliomas and 39 schwannomas occurred during 23.5 years (median, range 0-25) of follow-up. In obese women (BMI ≥ 30 kg m(-2)), meningioma risk was 67% higher (hazard ratio (HR)=1.68, 95% confidence interval (CI): 0.97-2.92, P-trend=0.05) than in the reference group (BMI 20-24.9 kg m(-2)), whereas no association with obesity was observed in males. There was no association of BMI with glioma risk, but there was a negative association of overweight/obesity (BMI ≥ 25 kg m(-2)) with the risk of schwannoma (HR=0.48, 95% CI: 0.23-0.99). However, the schwannoma analysis was based on small numbers. Height was not associated with the risk for any tumour subgroup. CONCLUSION: These results suggest that BMI is positively associated with meningioma risk in women, and possibly, inversely associated with schwannoma risk.

The causal role of smoking in anxiety and depression: a Mendelian randomization analysis of the HUNT study.

BACKGROUND: Cigarette smoking is strongly associated with mental illness but the causal direction of the association is uncertain. We investigated the causal relationship between smoking and symptoms of anxiety and depression in the Norwegian HUNT study using the rs1051730 single nucleotide polymorphism (SNP) variant located in the nicotine acetylcholine receptor gene cluster on chromosome 15 as an instrumental variable for smoking phenotypes. Among smokers, this SNP is robustly associated with smoking quantity and nicotine dependence. Method In total, 53 601 participants were genotyped for the rs1051730 SNP and provided information on smoking habits and symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS). RESULTS: Self-reported smoking was positively associated with the prevalence of both anxiety and depression, and the measured polymorphism was positively associated with being a current smoker and the number of cigarettes smoked in current smokers. In the sample as a whole, risk of anxiety increased with each affected T allele [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.02-1.09, p = 0.002] but there was no association with depression (p = 0.31). However, we found no clear association of the polymorphism with either anxiety (OR 1.03, 95% CI 0.97-1.09, p = 0.34) or depression (OR 1.02, 95% CI 0.95-1.09, p = 0.62) among smokers. CONCLUSIONS: As there was no association of the smoking-related rs1051730 SNP with anxiety and depression among smokers, the results suggest that smoking is not a cause of anxiety and depression.

Mammography screening and breast cancer mortality in Sweden.

BACKGROUND: Swedish women aged 40-69 years were gradually offered regular mammography screening since 1974, and nationwide coverage was achieved in 1997. We hypothesized that this gradual implementation of breast cancer screening would be reflected in county-specific mortality patterns during the last 20 years. METHODS: Using data from the Swedish Board of Health and Welfare from 1960 to 2009, we used joinpoint regression to analyze breast cancer mortality trends in women aged 40 years and older (1,286,000 women in 1995-1996). Poisson regression models were used to compare observed mortality trends with expected trends if screening had resulted in breast cancer mortality reductions of 10%, 20%, or 30% among women screened during 18 years of follow-up after the introduction of screening. All statistical tests were two-sided. RESULTS: From 1972 to 2009, breast cancer mortality rates in Swedish women aged 40 years and older declined by 0.98% annually, from 68.4 to 42.8 per 100,000, and it continuously declined in 14 of the 21 Swedish counties. In three counties, breast cancer mortality declined sharply during or soon after the implementation of screening; in two counties, a steep decline started at least 5 years after screening was introduced; and in two counties, breast cancer mortality increased after screening started. In counties in which screening started in 1974-1978, mortality trends during the next 18 years were similar to those before screening started, and in counties in which screening started in 1986-1987, mortality increased by approximately 12% (P = .007) after the introduction of screening compared with previous trends. In counties in which screening started in 1987-1988 and in 1989-1990, mortality declined by approximately 5% (P = .001) and 8% (P < .001), respectively, after the introduction of screening. Conclusion County-specific mortality statistics in Sweden are consistent with studies that have reported limited or no impact of screening on mortality from breast cancer.

Hypertensive diseases in pregnancy and breast cancer risk.

BACKGROUND: Hypertensive diseases in pregnancy may be associated with a reduced risk of breast cancer. Most previous studies are small and have shown conflicting results. METHODS: In a cohort of 919 712 women who gave their first birth between 1967 and 2008, with linkage of information from two national registries, we assessed whether women with pregnancy hypertensive diseases are at reduced breast cancer risk. We used Cox regression to estimate hazard ratios (HRs) with 95% confidence intervals (CI). RESULTS: Compared with women with a normotensive first pregnancy, women with hypertension or preeclampsia in their first pregnancy had a reduced breast cancer risk (HR 0.83, 95% CI 0.77, 0.90). A reduced risk was consistently observed for hypertensive disease in any pregnancy, for recurrent hypertensive disease in pregnancy, and before and after 50 years of age at breast cancer diagnosis. The association was strongest for women with hypertension in pregnancy, who delivered at term/post-term (HR 0.81, 95% CI 0.75, 0.88) or had a child of average birth weight (HR 0.77, 95% CI 0.69, 0.85). CONCLUSION: Women with pregnancy hypertensive diseases are at reduced breast cancer risk. Whether this association can be attributed to pregnancy-specific events or to underlying biological traits remains unclear.

Risk factors for aneurysmal subarachnoid hemorrhage - BMI and serum lipids: 11-year follow-up of the HUNT and the Tromsø Study in Norway.

OBJECTIVES: Life-style factors have been associated with the risk for aneurysmal subarachnoid hemorrhage (aSAH), but it is not clear whether body mass index (BMI) and serum lipids are associated with risk. We prospectively assessed these associations in two large population studies. METHODS: A total of 65,526 participants in the Nord-Trøndelag Health Study (1995-1997) and 26,882 participants in the Tromsø Study (1994-1995) were included. Studies included measurements of body weight and height, serum lipids, and self-administered questionnaires. Participants who experienced aSAH were identified, and hazard ratios (HRs) were estimated using Cox regression analysis. RESULTS: During 11 years of follow-up, aSAH was diagnosed in 122 participants. Overweight (BMI 25-29.9) was negatively associated with the risk of aSAH (HR 0.7, 95% CI 0.4-1.0). There was no over all association of total serum cholesterol, HDL cholesterol, or triglycerides with the risk of aSAH, but in participants younger than 50 years, HDL cholesterol was inversely associated with the risk (HR per standard deviation increase 0.6, 95% CI 0.4-0.9). CONCLUSIONS: Overweight may be associated with reduced risk of aSAH, but there was no over all association of total serum cholesterol, HDL cholesterol, or triglycerides with the risk of aSAH in this prospective study.

Incidence and mortality of aneurysmal subarachnoid hemorrhage in two Norwegian cohorts, 1984-2007.

OBJECTIVE: The incidence of aneurysmal subarachnoid hemorrhage (aSAH) ranges from 4 to 10 per 100,000 person-years in most countries, and 30-day case fatality is high. The aim of this study was to estimate the incidence and case fatality of aSAH and to assess preictal predictors of survival in 2 large Norwegian population-based cohort studies. METHODS: A total of 94,976 adults (≥20 years) in the Nord-Trøndelag Health Study and 31,753 participants (aged ≥20 years) in the Tromsø Study were included. During follow-up, aSAHs were identified, incidence rates were estimated, and predictors of survival were assessed using Cox and Poisson regression analysis. RESULTS: A total of 214 patients with aSAH were identified during 2,077,927 person-years of follow-up from 1984 to 2007. The incidence rate was 10.3 per 100,000 person-years: 13.3 for women and 7.1 for men. The incidence increased by 2% (95% confidence interval [CI] 0-4) per 5-year time period. Case fatality at 3, 7, and 30 days was 20%, 24%, and 36%. Thirty-day case fatality remained stable during follow-up (odds ratio 1.01, 95% CI 0.97-1.06 per year). Never smokers had poorer survival after aSAH than current and former smokers combined (hazard ratio 1.6, 95% CI 0.9-2.9). CONCLUSIONS: The slight increase in incidence of aSAH over time may be explained by differences in diagnostic procedures. Case fatality remained stable during 23 years of follow-up.

Joint effects of nulliparity and other breast cancer risk factors.

BACKGROUND: Pregnancy may reduce breast cancer risk through induction of persistent changes of the mammary gland that make the breast less susceptible to carcinogenic factors. It is not known to what extent the effects of parity are independent of other breast cancer risk factors. METHODS: In a Norwegian cohort of 58 191 women (2890 breast cancers), we assessed whether the effects of parity on postmenopausal breast cancer risk may be modified by menstrual and anthropometric factors. We calculated attributable proportions due to interaction as a measure of synergism. RESULTS: Parity, height, body mass index (BMI), age at menarche and menopause were all associated with breast cancer risk in the expected directions. For BMI, follow-up was stratified into two age groups because of non-proportional hazards. We found that nulliparity and overweight may amplify each other's effect on breast cancer risk among women after 70 years of age (attributable proportion 0.21, 95% confidence interval 0.04-0.39). There was some indication that parity and age at menopause may antagonise each other's effect. Effects of parity were largely unaffected by age at menarche and height. CONCLUSION: Nulliparity and overweight may have a synergistic effect on breast cancer risk in elderly women. If confirmed by others, the findings may help disentangle the interplay of different causes of breast cancer.