Cervical cancer mortality in Norway according to screening attendance and age.

INTRODUCTION: The association between cervical cancer screening and reduction of cervical cancer has been dealt with in much research. However, little has been published on the association between screening and cervical cancer mortality. We assessed cervical cancer deaths according to screening history, histopathology, and age among women in, under, and above screening age. MATERIAL AND METHODS: In this nationwide, registry-based case-control study from Norway, we included 817 cervical cancer deaths in women diagnosed with cervical cancer in the period 1998-2009. We matched each case with 10 population-based controls free from cervical cancer, obtained by density-based sampling. Odds ratios (ORs) with 95% confidence intervals (CIs) for the association between screening attendance and cervical cancer mortality were estimated using conditional logistic regression models. RESULTS: Of all fatal cervical cancers, 35% were diagnosed among women over screening age and altogether, 83% were either in age groups not covered by the screening program or in non-attenders of screening age. The estimated risk reduction associated with a cytology test in the preceding 3.5 years was 80% in screening age 25-69 years (OR 0.20; 95% CI 0.16-0.24) with the largest reduction in squamous cell carcinomas (84%) but also a substantial estimated risk reduction of 65% for adenocarcinomas. The associated risk reduction was strongest in women aged 45-69 years, with ORs in the range 0.09-0.18, compared with ORs 0.42-1.35 in women aged 25-39 years. CONCLUSIONS: To reduce the mortality of cervical cancer, screening programs should focus on increasing adherence to the program, as half of all the fatal cases were in the non-attender group. Further assessments regarding the potential preventive impact of extending screening to women over the current screening age should be considered.

The role of cardiovascular risk factors in maternal cardiovascular disease according to offspring birth characteristics in the HUNT study.

A history of preterm or small (SGA) or large (LGA) for gestational age offspring is associated with smoking and unfavorable levels of BMI, blood pressure, glucose and lipids. Whether and to what extent the excess cardiovascular risk observed in women with these pregnancy complications is explained by conventional cardiovascular risk factors (CVRFs) is not known. We examined the association between a history of SGA, LGA or preterm birth and cardiovascular disease among 23,284 parous women and quantified the contribution of individual CVRFs to the excess cardiovascular risk using an inverse odds weighting approach. The hazard ratios (HR) between SGA and LGA offspring and CVD were 1.30 (95% confidence interval (CI) 1.15, 1.48) and 0.89 (95% CI 0.76, 1.03), respectively. Smoking explained 49% and blood pressure may have explained ≈12% of the excess cardiovascular risk in women with SGA offspring. Women with preterm birth had a 24% increased risk of CVD (HR 1.24, 95% CI 1.06, 1.45), but we found no evidence for CVRFs explaining any of this excess cardiovascular risk. While smoking explains a substantial proportion of excess cardiovascular risk in women with SGA offspring and blood pressure may explain a small proportion in these women, we found no evidence that conventional CVRFs explain any of the excess cardiovascular risk in women with preterm birth.

Risk Factors for Unruptured Intracranial Aneurysms and Subarachnoid Hemorrhage in a Prospective Population-Based Study.

Background and Purpose- We wanted to evaluate potential risk factors for unruptured intracranial aneurysms (UIAs) and aneurysmal subarachnoid hemorrhage (aSAH) in a large, prospective study of the general population with risk factors collected before the detection of UIA or aSAH. Methods- All residents ≥20 years were invited to the HUNT (The Nord-Trøndelag Health Study). In this study, 89 951 participants were included. The study included standardized measurements of blood pressure and self-administered questionnaires. Cases of UIA and aSAH from 1999 to 2014 were identified using hospital records and the Norwegian Cause of Death Register. Hazard ratios with CIs were estimated using Cox regression analysis. Results- The detection rate of UIA was 8.2 per 100 000 person-years (97 patients). Current smoking (hazard ratio, 4.1; 95% CI, 2.4-7.1) and female sex (hazard ratio, 2.8; 95% CI, 1.7-4.5) were associated with markedly increased risk of UIA, but we found no association with systolic blood pressure (P for trend 0.62). The incidence of aSAH was 9.9 per 100 000 person-years (117 patients). The most important risk factors for aSAH were current smoking, female sex and increasing blood pressure (P for trend 0.006 for systolic blood pressure). Conclusions- In contrast to previous studies on risk factors of UIA, we found no association with systolic blood pressure. However, there was a strong association between systolic blood pressure and aSAH in the same population. Current smoking and female sex were associated with both diseases.

Female sex hormones and risk of incident abdominal aortic aneurysm in Norwegian women in the HUNT study.

OBJECTIVE: The delayed development of abdominal aortic aneurysm (AAA) in women compared with men might be secondary to a protective effect from endogenous estrogens. The role of postmenopausal hormone therapy remains unclear. The aim of the present study was to evaluate the effect of female sex hormones compared with other risk factors associated with AAA through a long-term study of a large female cohort. METHODS: The present prospective cohort study included 20,024 postmenopausal women from the Norwegian Nord-Trøndelag Health Study. A total of 201 cases of AAA were identified during a median follow-up period of 18 years (295,554 person-years; 1995-2014). The data were recorded from questionnaires, physical measurements, medical records, blood sample test results, and the Norwegian Cause of Death Registry. The effect of risk factors was evaluated in a multiple Cox regression analysis. Multiple imputation was performed for missing data (n = 50 data sets). The serum estradiol concentrations in women with and without incidental AAAs were compared. The median interval from blood sample collection to the AAA diagnosis was 7 years. RESULTS: Current smokers had >10-fold increased risk of incident AAA during the follow-up period (hazard ratio [HR], 10.9; 95% confidence interval [CI], 7.4-16.1). Positive associations were found for hypertension (HR, 2.0; 95% CI, 1.4-3.0) and coronary heart disease (HR, 2.2; 95% CI, 1.6-3.2). The HR associated with the current use of postmenopausal hormone therapy was 0.58 (95% CI, 0.6-1.5). No substantial difference in estradiol concentrations was found between women with and without AAA (P = .075). CONCLUSIONS: The effect of female sex hormones on the risk of incident AAAs in women, as evaluated by the serum concentrations of estradiol and the use of postmenopausal hormone therapy, is clinically less important than the strong associations found with smoking, hypertension, and coronary heart disease.

Does pregnancy complication history improve cardiovascular disease risk prediction? Findings from the HUNT study in Norway.

AIM: To evaluate whether history of pregnancy complications [pre-eclampsia, gestational hypertension, preterm delivery, or small for gestational age (SGA)] improves risk prediction for cardiovascular disease (CVD). METHODS AND RESULTS: This population-based, prospective cohort study linked data from the HUNT Study, Medical Birth Registry of Norway, validated hospital records, and Norwegian Cause of Death Registry. Using an established CVD risk prediction model (NORRISK 2), we predicted 10-year risk of CVD (non-fatal myocardial infarction, fatal coronary heart disease, and non-fatal or fatal stroke) based on established risk factors (age, systolic blood pressure, total and HDL-cholesterol, smoking, anti-hypertensives, and family history of myocardial infarction). We evaluated whether adding pregnancy complication history improved model fit, calibration, discrimination, and reclassification. Among 18 231 women who were parous, ≥40 years of age, and CVD-free at start of follow-up, 39% had any pregnancy complication history and 5% experienced a CVD event during a median follow-up of 8.2 years. While pre-eclampsia and SGA were associated with CVD in unadjusted models (HR 1.96, 95% CI 1.44-2.65 for pre-eclampsia and HR 1.46, 95% CI 1.18-1.81 for SGA), only pre-eclampsia remained associated with CVD after adjusting for established risk factors (HR 1.60, 95% CI 1.16-2.17). Adding pregnancy complication history to the established prediction model led to small improvements in discrimination (C-index difference 0.004, 95% CI 0.002-0.006) and reclassification (net reclassification improvement 0.02, 95% CI 0.002-0.05). CONCLUSION: Pre-eclampsia independently predicted CVD after controlling for established risk factors; however, adding pre-eclampsia, gestational hypertension, preterm delivery, and SGA made only small improvements to CVD prediction among this representative sample of parous Norwegian women.

Clinical performance of Anyplex II HPV28 by human papillomavirus type and viral load in a referral population.

Anyplex II HPV28 (`Anyplex`) is a semi-quantitative DNA PCR assay divided into set A, comprising 14 high risk (hr)HPV types; and set B, comprising 5 possibly hrHPV types and 9 low risk (lr)HPV types. We compared the ability of Anyplex to that of Hybrid Capture 2 (HC2) and PreTect HPV-Proofer (`Proofer`) to detect cervical intraepithelial neoplasia grade two or worse (CIN2+) by HPV types and viral load. This cross-sectional study included 296 women referred to colposcopy with abnormal cervical cytology and/or persistent HPV infection. CIN2+ was identified in 175/296 women. Liquid based cytology samples were used to perform HPV testing. The sensitivity of Anyplex to detect CIN2+ was 98.9% (95% CI 95.9-99.9) and specificity 43.0% (95% CI 34.0-52.3). Restricting to medium and high viral loads in Anyplex set A, sensitivity and specificity were 97.1% (95% CI 93.5-99.1) and 59.5% (95% CI 50.2-68.3) with positive (PPV) and negative predictive value (NPV) 77.6% and 93.5%, respectively, comparable to HC2. Restricting Anyplex to the hrHPV types in Proofer, HPV16, 18, 31, 33 and 45, sensitivity and specificity for CIN2+ were 85.1% (95% CI 79.0-90.1) and 71.1% (95% CI 62.1-79.0), comparable to Proofer`s. When adding HPV52 and 58, the sensitivity for CIN2+ was 92.6% (95% CI 87.6-96.0) and CIN3+ 96.5% (95% CI 92.0-98.8). No value of Anyplex set B was found in detecting CIN2+. In conclusion, the clinical performance of medium and high viral loads in Anyplex set A was comparable to HC2. Restricting the test to the 7 hrHPV types included in the 9-valent HPV-vaccine, HPV16, 18, 31, 33, 45, 52 and 58, satisfies the international criteria for cervical cancer screening with relative sensitivity compared to HC2 for CIN2+ and CIN3+ of 0.98 and 1.01, respectively. Detecting all 28 Anyplex HPV types adds no benefit in a referral population.

Is smoking heaviness causally associated with alcohol use? A Mendelian randomization study in four European cohorts.

Background: Observational studies have shown that tobacco and alcohol use co-occur, but it is not clear whether this relationship is causal. Methods: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK Biobank, we used observational methods to test the hypothesis that smoking heaviness increases alcohol consumption. Mendelian randomization (MR) analyses were then used to test the causal relationship between smoking heaviness and alcohol consumption using 55 967 smokers from four European studies [ALSPAC, The Nord-Trøndelag Health Study (HUNT), the Copenhagen General Population Study (CGPS) and UK Biobank]. MR analyses used rs1051730/rs16969968 as a genetic proxy for smoking heaviness. Results: Observational results provided evidence of an association between cigarettes per day and weekly alcohol consumption (increase in units of alcohol per additional cigarette smoked per day = 0.10, 95% confidence interval (CI) 0.05 to 0.15, P ≤ 0.001 in ALSPAC; and 0.48, 95% CI 0.45 to 0.52, P ≤ 0.001 in UK Biobank). However, there was little evidence for an association between rs1051730/rs16969968 and units of alcohol consumed per week across ALSPAC, HUNT, CGPS and UK Biobank (standard deviation increase in units of alcohol per additional copy of the risk allele = -0.004, 95% CI -0.023 to 0.016, P=0.708, I2 = 51.9%). We had 99% and 88% power to detect a change of 0.03 and 0.02 standard deviation units of alcohol per additional copy of the risk allele, respectively. Conclusions: Previously reported associations between smoking and alcohol are unlikely to be causal, and may be the result of confounding and/or reverse causation. This has implications for public health research and intervention research.

White Blood Cell BRCA1 Promoter Methylation Status and Ovarian Cancer Risk.

Background: The role of normal tissue gene promoter methylation in cancer risk is poorly understood. Objective: To assess associations between normal tissue BRCA1 methylation and ovarian cancer risk. Design: 2 case-control (initial and validation) studies. Setting: 2 hospitals in Norway (patients) and a population-based study (control participants). Participants: 934 patients and 1698 control participants in the initial study; 607 patients and 1984 control participants in the validation study. Measurements: All patients had their blood sampled before chemotherapy. White blood cell (WBC) BRCA1 promoter methylation was determined by using methylation-specific quantitative polymerase chain reaction, and the percentage of methylation-positive samples was compared between population control participants and patients with ovarian cancer, including the subgroup with high-grade serous ovarian cancer (HGSOC). Results: In the initial study, BRCA1 methylation was more frequent in patients with ovarian cancer than control participants (6.4% vs. 4.2%; age-adjusted odds ratio [OR], 1.83 [95% CI, 1.27 to 2.63]). Elevated methylation, however, was restricted to patients with HGSOC (9.6%; OR, 2.91 [CI, 1.85 to 4.56]), in contrast to 5.1% and 4.0% of patients with nonserous and low-grade serous ovarian cancer (LGSOC), respectively. These findings were replicated in the validation study (methylation-positive status in 9.1% of patients with HGSOC vs. 4.3% of control participants-OR, 2.22 [CI 1.40 to 3.52]-4.1% of patients with nonserous ovarian cancer, and 2.7% of those with LGSOC). The results were not influenced by tumor burden, storage time, or WBC subfractions. In separate analyses of young women and newborns, BRCA1 methylation was detected in 4.1% (CI, 1.8% to 6.4%) and 7.0% (CI, 5.0% to 9.1%), respectively. Limitations: Patients with ovarian cancer were recruited at the time of diagnosis in a hospital setting. Conclusion: Constitutively normal tissue BRCA1 promoter methylation is positively associated with risk for HGSOC. Primary Funding Source: Norwegian Cancer Society.

Maternal Smoking in Pregnancy and Offspring Depression: a cross cohort and negative control study.

Previous reports suggest that offspring of mothers who smoke during pregnancy have greater risk of developing depression. However, it is unclear whether this is due to intrauterine effects. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) from the UK (N = 2,869), the Nord-Trøndelag health study (HUNT) from Norway (N = 15,493), the Pelotas 1982 Birth Cohort Study from Brazil (N = 2,626), and the Swedish Sibling Health Cohort (N = 258 sibling pairs), we compared associations of maternal smoking during pregnancy and mother's partner's smoking during pregnancy with offspring depression and performed a discordant sibling analysis. In meta-analysis, maternal smoking during pregnancy was associated with higher odds of offspring depression (OR 1.20, 95% CI:1.08,1.34), but mother's partner's smoking during pregnancy was not (OR 1.05, 95% CI:0.94,1.17). However, there was only weak statistical evidence that the odds ratios for maternal and mother's partner's smoking differed from each other (p = 0.08). There was no clear evidence for an association between maternal smoking during pregnancy and offspring depression in the sibling analysis. Findings do not provide strong support for a causal role of maternal smoking during pregnancy in offspring depression, rather observed associations may reflect residual confounding relating to characteristics of parents who smoke.

Cancer cachexia associates with a systemic autophagy-inducing activity mimicked by cancer cell-derived IL-6 trans-signaling.

The majority of cancer patients with advanced disease experience weight loss, including loss of lean body mass. Severe weight loss is characteristic for cancer cachexia, a condition that significantly impairs functional status and survival. The underlying causes of cachexia are incompletely understood, and currently no therapeutic approach can completely reverse the condition. Autophagy coordinates lysosomal destruction of cytosolic constituents and is systemically induced by starvation. We hypothesized that starvation-mimicking signaling compounds secreted from tumor cells may cause a systemic acceleration of autophagy during cachexia. We found that IL-6 secreted by tumor cells accelerates autophagy in myotubes when complexed with soluble IL-6 receptor (trans-signaling). In lung cancer patients, were cachexia is prevalent, there was a significant correlation between elevated IL-6 expression in the tumor and poor prognosis of the patients. We found evidence for an autophagy-inducing bioactivity in serum from cancer patients and that this is clearly associated with weight loss. Importantly, the autophagy-inducing bioactivity was reduced by interference with IL-6 trans-signaling. Together, our findings suggest that IL-6 trans-signaling may be targeted in cancer cachexia.

Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium.

Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0·68, 95% confidence interval (CI): 0·61, 0·76; P < 0·001) and allergic sensitization (OR = 0·74, 95% CI: 0·64, 0·86; P < 0·001), but similar asthma risk (OR = 1·00, 95% CI: 0·91, 1·09; P = 0·967). Mendelian randomization analyses in current smokers showed a slightly lower risk of hay fever (OR = 0·958, 95% CI: 0·920, 0·998; P = 0·041), a lower risk of allergic sensitization (OR = 0·92, 95% CI: 0·84, 1·02; P = 0·117), but higher risk of asthma (OR = 1·06, 95% CI: 1·01, 1·11; P = 0·020) per smoking-increasing allele. Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.

Cardiovascular mortality - Comparing risk factor associations within couples and in the total population - The HUNT Study.

BACKGROUND: To compare associations of conventional risk factors with cardiovascular death within couples and in the population as a whole. METHODS: We analysed baseline data (1995-97) from the HUNT2 Study in Norway linked to the national Causes of Death Registry. We compared risk within couples using stratified Cox regression. RESULTS: During 914776 person-years, 3964 cardiovascular deaths occurred, and 1658 of the deaths occurred among 1494 couples. There were consistently stronger associations of serum lipids and blood pressure with cardiovascular mortality within couples compared to the population as a whole. For instance, for systolic blood pressure (per 20mmHg), the hazard ratio (HR) within couples was 1.28 (95% confidence interval: 1.17, 1.40) compared to 1.16 (1.12, 1.20) in the total population, and for diastolic pressure (per 10mmHg), the corresponding HRs were 1.16 (1.07, 1.26) and 1.11 (1.08, 1.13). Anthropometric factors (BMI, waist circumference, waist-hip ratio) as well as diabetes, smoking, physical activity, and education, showed nearly identical positive associations within couples and in the total population. CONCLUSIONS: Prospective population studies may tend to slightly underestimate associations of these factors with cardiovascular mortality.

Premature Adult Death in Individuals Born Preterm: A Sibling Comparison in a Prospective Nationwide Follow-Up Study.

BACKGROUND: Close to one in ten individuals worldwide is born preterm, and it is important to understand patterns of long-term health and mortality in this group. This study assesses the relationship between gestational age at birth and early adult mortality both in a nationwide population and within sibships. The study adds to existing knowledge by addressing selected causes of death and by assessing the role of genetic and environmental factors shared by siblings. METHODS: Study population was all Norwegian men and women born from 1967 to 1997 followed using nation-wide registry linkage for mortality through 2011 when they were between 15 and 45 years of age. Analyses were performed within maternal sibships to reduce variation in unobserved genetic and environmental factors shared by siblings. Specific outcomes were all-cause mortality and mortality from cardiovascular diseases, cancer and external causes including accidents, suicides and drug abuse/overdoses. RESULTS: Compared with a sibling born in week 37-41, preterm siblings born before 34 weeks gestation had 50% increased mortality from all causes (adjusted Hazard Ratio (aHR) 1.54, 95% confidence interval (CI) 1.17, 2.03). The corresponding estimate for the entire population was 1.27 (95% CI 1.09, 1.47). The majority of deaths (65%) were from external causes and the corresponding risk estimates for these deaths were 1.52 (95% CI 1.08, 2.14) in the sibships and 1.20 (95% CI 1.01, 1.43) in the population. CONCLUSION: Preterm birth before week 34 was associated with increased mortality between 15 and 45 years of age. The results suggest that increased premature adult mortality in this group is related to external causes of death and that the increased risks are unlikely to be explained by factors shared by siblings.

Colposcopy and additive diagnostic value of biopsies from colposcopy-negative areas to detect cervical dysplasia.

INTRODUCTION: We evaluated colposcopy in the routine diagnostic workup of women with abnormal cervical cytology, as well as the diagnostic value of endocervical curettage material and biopsies taken from colposcopy-positive and colposcopy-negative quadrants of the cervix. MATERIAL AND METHODS: This cross-sectional study included 297 nonpregnant women with abnormal cervical cytology and no prior treatment for cervical dysplasia or cancer. All women underwent gynecological examination, colposcopy, endocervical curettage, and had cervical biopsies taken. Colposcopy was considered satisfactory if the squamocolumnar junction was fully visible, and biopsies were taken from all four quadrants of the cervix, regardless of colposcopy results. RESULTS: In all, 130 of the women in our study had satisfactory colposcopy results and were diagnosed with cervical intraepithelial neoplasia grade 2 or worse (CIN2+), 61% via a colposcopy-positive biopsy and 39% via a colposcopy-negative biopsy. Eighty-seven of them had positive colposcopy results, but CIN2+ was histologically verified from colposcopy-positive biopsies in 91% (n = 79) and from colposcopy-negative biopsies in 9% (n = 8). The remaining 43 women with CIN2+ had negative colposcopy findings, so their diagnosis was verified in colposcopy-negative biopsies. The sensitivity of colposcopy alone to detect CIN2+ was 61% (95% CI 52-69). CONCLUSIONS: In the present study, colposcopy was not a stand-alone diagnostic method. Colposcopy-negative biopsies had a clear additive value, identifying a substantial proportion of women with both positive and negative colposcopy results with treatment-worthy cervical dysplasia. Endocervical curettage material had little diagnostic value in this study.

Health care contact following a new incident neck or low back pain episode in the general population; the HUNT study.

BACKGROUND: Low back and neck pain are commonly reported in the general population and represent frequent causes for health care consultations. The main aim of this study was to describe the determinants of health care contact during a 1-year period in a general population with recent onset spinal pain. METHODS: From 9056 participants in a general health survey in Norway we identified 219 persons reporting a recent onset (<1 month) of low back or neck pain. Questionnaires were given at 1 (baseline), 2, 3, 6 and 12 months after pain debut. The main outcome was self-reported health care contact due to spinal pain. Associations between health care contact and pain-related factors, other somatic and mental health factors, pain-related work limitations, physical activity and sociodemographic factors were explored. RESULTS: Conventional health care was sought by 93 persons (43 %) at least once throughout the year following the onset of pain. 18 persons (8 %) sought alternative health care only and 108 persons (49 %) sought no kind of health care. Baseline reports of coexisting low back and neck pain of equal intensity, poor self-reported health, symptoms of anxiety or depression, obesity and smoking were all associated with an increased tendency to seek conventional health care. Pain intensity and pain-related work limitations at each occasion were strongly associated with concurrent health care contact throughout the year. Higher education was associated with a reduced tendency to contact health care and no association was found for physical activity. CONCLUSION: The main finding in this study was that people from the general population who seek health-care for a new incident of neck or low back pain report more symptoms of mental distress, poorer self-reported health and more intense pain with stronger work limitations compared to those who do not. The findings suggest that identification of complementary symptoms is highly relevant in the examination of spinal pain patients, even for those with recent onset of symptoms.

On the HUNT for cardiovascular risk factors and disease in patients with psoriatic arthritis: population-based data from the Nord-Trøndelag Health Study.

OBJECTIVE: To compare the presence of cardiovascular (CV) risk factors and established CV disease in patients with psoriatic arthritis (PsA) and the general population and to compare the 10-year risk of a fatal CV event calculated by the Systematic Coronary Risk Evaluation (SCORE) algorithm. METHODS: Patients with PsA (n=338) and controls (n=50 468) were recruited from the Nord-Trøndelag Health Study 3. Age-adjusted and sex-adjusted prevalence rates of CV risk factors and comorbidity were calculated and the SCORE algorithm was applied. RESULTS: There was an increased prevalence of angina pectoris (5.0% vs 3.6%, p=0.01), history of percutaneous coronary intervention (2.4% vs 1.4%, p=0.04), hypertension (45.3% vs 39.3%, p=0.01), obesity (32.0% vs 22.4%) and tobacco smoking (21.3% vs 16.4%, p=0.02) in patients with PsA compared with controls. Patients with PsA had elevated levels of C reactive protein (CRP; p<0.001), body mass index (BMI; p<0.001) and triglycerides (p=0.01). The median calculated CV risk in patients with PsA was low and comparable with controls (0.87 vs 0.83, p=0.24). The distribution across CV risk classes was similar among patients with PsA and controls. CONCLUSIONS: Patients with PsA have a higher risk of CV disease than the background population, although there was no difference between groups in 10-year risk of a fatal CV event estimated by SCORE. However, patients with PsA had elevated levels of CV risk factors not included in the SCORE algorithm, such as BMI, triglycerides and CRP.

Mortality and work disability in a cohort of Norwegian couples--the HUNT study.

BACKGROUND: Poor health is clustered in families, and partners might influence each other. We studied possible consequences of living with a spouse with poor health or unhealthy lifestyle on mortality and work disability. METHODS: In total, 18 943 couples from the HUNT2 Study (1995-97) were linked to national registries and followed until December 2007, identifying deaths and disability pension retirements. Couple's mean exposures were included together with the individual's deviation from the couple mean in discrete time multilevel logistic regression. RESULTS: There was weak evidence of associations between partner's health and risk of dying. Associations between couples slightly exceeded associations within couples for smoking [odds ratio (OR) within 1.57 (95% confidence interval (CI): 1.38-1.78); OR between 1.88 (95% CI: 1.70-2.08), P value for difference 0.027] and education [OR within 1.07 (95% CI: 0.99-1.15); OR between 1.17 (1.11-1.23), P value for difference 0.065]. Indicators of partner's health, such as self-rated health [OR within 3.17 (95% CI: 2.80-3.58); OR between 3.92 (95% CI: 3.50-4.40), P value for difference 0.014], insomnia [OR within 1.39 (95% CI: 1.18-1.64); OR between 2.11 (95% CI: 1.86-2.53), P value for difference <0.001] and symptoms of depression [OR within 1.45 (95% CI: 1.22-1.71); OR between 1.98 (95% CI: 1.69-2.31) P value for difference 0.009] were, however, associated with risk of work disability. Self-rated health and symptoms displayed stronger associations with work disability among partners than reported somatic diseases. CONCLUSIONS: This study did not indicate strong consequences of living with a spouse with poor health or unhealthy lifestyle on mortality. It did, however, indicate associations of partner's health with work disability.

Modern mammography screening and breast cancer mortality: population study.

OBJECTIVE: To evaluate the effectiveness of contemporary mammography screening using individual information about screening history and breast cancer mortality from public screening programmes. DESIGN: Prospective cohort study of Norwegian women who were followed between 1986 and 2009. Within that period (1995-2005), a national mammography screening programme was gradually implemented, with biennial invitations sent to women aged 50-69 years. PARTICIPANTS: All Norwegian women aged 50-79 between 1986 and 2009. MAIN OUTCOME MEASURES: Multiple Poisson regression analysis was used to estimate breast cancer mortality rate ratios comparing women who were invited to screening (intention to screen) with women who were not invited, with a clear distinction between cases of breast cancer diagnosed before (without potential for screening effect) and after (with potential for screening effect) the first invitation for screening. We took competing causes of death into account by censoring women from further follow-up who died from other causes. Based on the observed mortality reduction combined with the all cause and breast cancer specific mortality in Norway in 2009, we used the CISNET (Cancer Intervention and Surveillance Modeling Network) Stanford simulation model to estimate how many women would need to be invited to biennial mammography screening in the age group 50-69 years to prevent one breast cancer death during their lifetime. RESULTS: During 15 193 034 person years of observation (1986-2009), deaths from breast cancer occurred in 1175 women with a diagnosis after being invited to screening and 8996 women who had not been invited before diagnosis. After adjustment for age, birth cohort, county of residence, and national trends in deaths from breast cancer, the mortality rate ratio associated with being invited to mammography screening was 0.72 (95% confidence interval 0.64 to 0.79). To prevent one death from breast cancer, 368 (95% confidence interval 266 to 508) women would need to be invited to screening. CONCLUSION: Invitation to modern mammography screening may reduce deaths from breast cancer by about 28%.

Causal associations of tobacco smoking with cardiovascular risk factors: a Mendelian randomization analysis of the HUNT Study in Norway.

BACKGROUND: Tobacco smoking has been associated with cardiovascular risk factors including adverse serum lipid levels, central obesity and higher resting heart rate, but lower blood pressure and body mass index (BMI). We used a Mendelian randomization approach to study whether these associations may be causal. If smoking affects cardiovascular risk factors then rs1051730 T alleles, predictors of increased smoking quantity, should be associated with cardiovascular risk factors among smokers, but not among never smokers. METHODS: Among 56,625 participants of a population-based study, we estimated associations of rs1051730 T alleles with cardiovascular risk factors and examined whether the associations differed by smoking status. RESULTS: Rs1051730 T alleles were associated with lower BMI and waist and hip circumferences and higher resting heart rate and estimated glomerular filtration rate (eGFR), and the associations were strongest among current smokers (P interaction 5×10(-9) to 0.01). Rs1051730 T alleles were associated with lower systolic blood pressure and pulse pressure and higher HDL cholesterol concentrations, but these associations did not robustly differ by smoking status. There were no convincing associations of rs1051730 T alleles with waist-hip ratio, diastolic blood pressure and non-fasting serum concentrations of non-HDL cholesterol, triglycerides, glucose and C-reactive protein. CONCLUSIONS: This Mendelian randomization analysis provides evidence that smoking may cause lower BMI and waist and hip circumferences and higher resting heart rate and eGFR. The findings further suggest that smoking is not a major determinant of waist-hip ratio or adverse blood pressure, serum lipid or glucose levels.

Reproductive history and the risk of molecular breast cancer subtypes in a prospective study of Norwegian women.

PURPOSE: Breast cancer can be classified into molecular subtypes that differ in clinical characteristics and prognosis. There is some but conflicting evidence that reproductive risk factors may differ between distinct breast cancer subtypes. METHODS: We investigated associations of reproductive factors with the risk for six molecular breast cancer subtypes in a cohort of 21,532 Norwegian women who were born between 1886 and 1928 and followed up for breast cancer incidence between 1961 and 2008. We obtained stored tumor tissue from incident breast cancers and used immunohistochemistry and in situ hybridization to classify 825 invasive tumors into three luminal subtypes [Luminal A, Luminal B (HER2-) and Luminal B (HER2+)] and three non-luminal subtypes [human epidermal growth factor receptor 2 (HER2) subtype, basal-like phenotype (BP) and five negative phenotype (5NP)]. We used Cox regression to assess reproductive factors and risk for each subtype. RESULTS: We found that young age at menarche, old age at first birth and low parity were associated with increased risk for luminal breast cancer subtypes. For the HER2 subtype, we either found no association or associations in the opposite direction compared to the luminal subtypes. The BP subtype appeared to have a similar reproductive risk profile as the luminal subtypes. Breastfeeding was associated with a reduced risk for HER2 and 5NP subtypes, but was not associated with any other subtype. CONCLUSIONS: The results suggest that molecular breast cancer subtypes differ in their reproductive risk factors, but associations with non-luminal subtypes are still poorly understood and warrant further study.