Alpha-synuclein measured in cerebrospinal fluid from patients with Alzheimer's disease, mild cognitive impairment, or healthy controls: a two year follow-up study.

BACKGROUND: α-Synuclein has been proposed as a potential biomarker for Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). However, results from α-synuclein measurements in cerebrospinal fluid (CSF) have been inconclusive, and to our knowledge, longitudinal studies of changes prior to the AD diagnosis have not been investigated. METHODS: Levels of α-synuclein at baseline and after one and two years were measured in CSF, by enzyme-linked immunosorbent assay. Twenty-six patients with early AD (AD-AD), 48 patients with aMCI, subdivided as 23 that developed AD during follow-up (MCI-AD), and 25 that did not (MCI-MCI), and 25 healthy control individuals, were included. One-way ANOVA was applied to compare mean α-synuclein baseline values between all four study groups, and a linear mixed model was used to compare mean change over time between the three patient groups. Linear associations between α-synuclein and amyloid-ß 1-42 (Aß42), amyloid-ß 1-40 (Aß40), total tau and phosphorylated tau were also examined. RESULTS: A large variation in individual α-synuclein CSF levels was observed, particularly in the MCI-AD group. No significant differences were found in mean α-synuclein levels between all the study groups at baseline. When using a linear mixed model, no significant differences were found at follow-up for estimated mean changes between the patient groups. MCI-AD patients with short duration of symptoms prior to inclusion in the study (≤2 years) had considerably higher mean CSF α-synuclein levels compared to patients with a longer symptom duration (802.2 vs. 442.8 pg/mL, p = 0.01). No such difference was seen in the MCI-MCI or AD-AD groups. Significant linear associations (p < 0.0005) between α-synuclein and Aß40, total tau and phosphorylated tau were found. CONCLUSION: The observed difference in mean CSF α-synuclein level according to duration of symptoms in the MCI-AD group, may be an indication of changes related to disease progression. However, the lack of significant differences between groups, as well as the large individual variation in CSF levels of α-synuclein in the present study, suggest that α-synuclein is not a useful biomarker for AD.

Postpartum breast involution reveals regression of secretory lobules mediated by tissue-remodeling.

INTRODUCTION: A postpartum diagnosis of breast cancer is an independent predictor of metastases, however the reason is unknown. In rodents, the window of postpartum mammary gland involution promotes tumor progression, suggesting a role for breast involution in the poor prognosis of human postpartum breast cancers. Rodent mammary gland involution is characterized by the programmed elimination of the secretory lobules laid down in preparation for lactation. This tissue involution process involves massive epithelial cell death, stromal remodeling, and immune cell infiltration with similarities to microenvironments present during wound healing and tumor progression. Here, we characterize breast tissue from premenopausal women with known reproductive histories to determine the extent, duration and cellular mechanisms of postpartum lobular involution in women. METHODS: Adjacent normal breast tissues from premenopausal women (n = 183) aged 20 to 45 years, grouped by reproductive categories of nulliparous, pregnant and lactating, and by time since last delivery were evaluated histologically and by special stain for lobular area, lobular type composition, apoptosis and immune cell infiltration using computer assisted quantitative methods. RESULTS: Human nulliparous glands were composed dominantly of small (approximately 10 acini per lobule) and medium (approximately 35 acini per lobule) sized lobules. With pregnancy and lactation, a >10 fold increase in breast epithelial area was observed compared to nulliparous cases, and lactating glands were dominated by mature lobules (>100 acini per lobule) with secretory morphology. Significant losses in mammary epithelial area and mature lobule phenotypes were observed within 12 months postpartum. By 18 months postpartum, lobular area content and lobule composition were indistinguishable from nulliparous cases, data consistent with postpartum involution facilitating regression of the secretory lobules developed in preparation for lactation. Analyses of apoptosis and immune cell infiltrate confirmed that human postpartum breast involution is characterized by wound healing-like tissue remodeling programs that occur within a narrowed time frame. CONCLUSIONS: Human postpartum breast involution is a dominant tissue-remodeling process that returns the total lobular area of the gland to a level essentially indistinguishable from the nulliparous gland. Further research is warranted to determine whether the normal physiologic process of postpartum involution contributes to the poor prognosis of postpartum breast cancer.

One-year course of fatigue after post-operative radiotherapy in Norwegian breast cancer patients--comparison to general population.

INTRODUCTION: Fatigue after treatment for breast cancer (BC) is common, but poorly understood. We examined the fatigue levels during first year after radiotherapy (RT) according to the extent of RT (local or locoregional), hormonal therapy (HT) and chemotherapy (CT). The impact of comorbidity was also explored. Moreover, we compared fatigue levels in patients with the general population (GenPop) data. MATERIAL AND METHODS: BC patients (n = 250) referred for post-operative RT at St. Olavs Hospital, Trondheim, Norway, were enrolled. Fatigue was measured by the EORTC QLQ-C30-fatigue subscale, ranging from 0 to 100, before RT (baseline), after RT, and at three, six, and 12 months. Clinical and treatment-related factors were recorded at baseline. GenPop data was available from a previous survey (n = 652). Linear mixed models and analysis of covariance were applied. RESULTS: Compliance ranged from 87% to 98%. At baseline, mean value (SD) of fatigue in BC patients was 26.8 (23.4). The level increased during RT (mean change 8.3, 95% CI 5.5-11.1), but declined thereafter and did not differ significantly from pre-treatment levels at subsequent time points. In age-adjusted analyses, locoregional RT accounted for more overall fatigue than local RT (mean difference 6.6, 95% CI 1.2-12.0), but the association was weakened and not statistical significant when adjusting for CT and HT. Similar pattern was seen for CT and HT. The course of fatigue differed significantly by CT (p < 0.001, interaction test). At baseline, fatigue levels were higher in patients with than without CT, but at subsequent time points similar levels were evident, indicating a temporary adverse effect of CT. Comorbidity was significantly associated with increased level of fatigue, independent of other factors (mean difference 8.1, 95% CI 2.2-14.1). BC-patients were not significantly more fatigued than GenPop, except for immediately after ending RT, and then only among those without comorbidity (mean 35.9 vs. 25.8, p < 0.001). CONCLUSION: Comorbidity seems to be a more important determinant for fatigue levels than the cancer treatment.

Lipid Levels During Adult Lifetime in Men and Women With and Without a Subsequent Incident Myocardial Infarction: A Longitudinal Analysis of Data From the Tromsø Study 1974 to 2016.

Background The atherosclerotic effect of an adverse lipid profile is assumed to accumulate throughout life, leading to increased risk of myocardial infarction (MI). Still, little is known about age at onset and duration of unfavorable lipid levels before MI. Methods and Results Longitudinal data on serum lipid levels for 26 130 individuals (50.5% women, aged 20-89 years) were obtained from 7 population-based health surveys in Tromsø, Norway. Diagnoses of MI were obtained from national registers. A linear mixed model was applied to compare age- and sex-specific mean values of total cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglyceride concentration by MI status (MI versus non-MI). Already from young adulthood, 20 to 35 years before the incident MI, individuals with a subsequent incident MI had on average more adverse lipid levels than individuals of the same age and sex without MI. Analogous to a dose-response relationship, there was a clear trend toward more severe adverse lipid levels the lower the age at incident MI (P<0.001, test for trend through ordered categories <55, 55-74, ≥75 years). This trend was particularly pronounced for high-density lipoprotein cholesterol in percentage of total cholesterol (both sexes) and for the relative relationship between triglyceride, high-density lipoprotein cholesterol, and total cholesterol level (women). The difference in mean lipid level by MI status was just as large in women as in men, but the age pattern differed (P≤0.05, tests of 3-way interaction). Conclusions Compared with general population mean levels, adverse lipid levels were seen 20 to 35 years before the incident MI in both men and women.

Prognostic impact of depressive symptoms on all-cause mortality in individuals with abdominal aortic aneurysm and in the general population: a population-based prospective HUNT study in Norway.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a potentially life-threatening disease but the high mortality rate is linked to high age and comorbidity pattern. Depression is associated with increased mortality in the general population and individuals with cardiovascular diseases, but this is sparsely studied for AAA. The aim was to examine the prognostic impact of depressive symptoms on all-cause mortality in individuals with AAA and compare with findings in a general population of the same age and risk profile. METHODS: Population-based prospective study including 36 616 participants (52.1% women) from the Trøndelag Health Study in Norway. A total of 9428 individuals died during a median follow-up of 10 years at ages 60-90 years. Depressive symptoms were defined by a Hospital Anxiety and Depression Scale-Depression score ≥8. Data on AAA diagnoses and death were obtained from medical records and national registers. HRs from Cox proportional hazard regression models are reported. RESULTS: A total of 4832 (13.2%) individuals reported depressive symptoms, whereas 583 (1.6%) AAAs were identified. The adjusted hazard of death was 2.66 times higher in persons with AAA compared with the general population (95% CI 2.39 to 2.97). Overall, there was no significant adverse effect of depressive symptoms in individuals with AAA (HR 1.15;95% CI 0.88 to 1.51), whereas an increased risk was seen in the general population (HR 1.23;95% CI 1.17 to 1.30). CONCLUSION: The overall risk of death was considerably higher in individuals with AAA compared with a general population of the same age and risk profile. Depressive symptoms did not significantly influence the risk of death in the AAA group.

Histological type and grade of breast cancer tumors by parity, age at birth, and time since birth: a register-based study in Norway.

BACKGROUND: Some studies have indicated that reproductive factors affect the risk of histological types of breast cancer differently. The long-term protective effect of a childbirth is preceded by a short-term adverse effect. Few studies have examined whether tumors diagnosed shortly after birth have specific histological characteristics. METHODS: In the present register-based study, comprising information for 22,867 Norwegian breast cancer cases (20-74 years), we examined whether histological type (9 categories) and grade of tumor (2 combined categories) differed by parity or age at first birth. Associations with time since birth were evaluated among 9709 women diagnosed before age 50 years. Chi-square tests were applied for comparing proportions, whereas odds ratios (each histological type vs. ductal, or grade 3-4 vs. grade 1-2) were estimated in polytomous and binary logistic regression analyses. RESULTS: Ductal tumors, the most common histological type, accounted for 81.4% of all cases, followed by lobular tumors (6.3%) and unspecified carcinomas (5.5%). Other subtypes accounted for 0.4%-1.5% of the cases each. For all histological types, the proportions differed significantly by age at diagnoses. The proportion of mucinous and tubular tumors decreased with increasing parity, whereas Paget disease and medullary tumors were most common in women of high parity. An increasing trend with increasing age at first birth was most pronounced for lobular tumors and unspecified carcinomas; an association in the opposite direction was seen in relation to medullary and tubular tumors. In age-adjusted analyses, only the proportions of unspecified carcinomas and lobular tumors decreased significantly with increasing time since first and last birth. However, ductal tumors, and malignant sarcomas, mainly phyllodes tumors, seemed to occur at higher frequency in women diagnosed <2 years after first childbirth. The proportions of medullary tumors and Paget disease were particularly high among women diagnosed 2-5 years after last birth. The high proportion of poorly differentiated tumors in women with a recent childbirth was partly explained by young age. CONCLUSION: Our results support previous observations that reproductive factors affect the risk of histological types of breast cancer differently. Sarcomas, medullary tumors, and possible also Paget disease, may be particularly susceptible to pregnancy-related exposure.

Postoperative controls of ventilation tubes in children by general practitioner or otolaryngologist? Study protocol for a multicenter randomized non-inferiority study (The ConVenTu study).

BACKGROUND: Otitis media with effusion is the major cause of acquired hearing problems in children. Some of the affected children need surgery with ventilation tubes in the tympanic membrane to reduce ear complaints and to improve hearing, middle ear function, and health-related quality of life. This is one of the most common ambulatory surgeries performed on children. Postoperative controls are needed to assess that the tubes are functional, to evaluate whether hearing loss has been improved, and to handle potential complications. The follow-up may continue for years and are usually done by otolaryngologists. Nevertheless, there exist no evidence-based guidelines concerning the level of expertise needed for postoperative controls of the ventilation tubes. The aim of this protocol is to describe the ConVenTu study that evaluates whether postoperative controls performed by general practitioners (GPs) represent a safe and sufficient alternative to controls performed by otolaryngologists. METHODS/DESIGN: Multicenter randomized non-inferiority study conducted in clinical settings in seven hospitals located in Norway. Discharged children with ventilation tubes, aged 3-10 years, are allocated randomly to receive postoperative controls by either an otolaryngologist at the hospital where they had ventilation tube surgery or their regular GP. Study participants are enrolled consecutively until 200 patients are included in each group. Two years after surgery, we will compare the pure tone average of hearing thresholds (primary endpoint) and middle ear function, complication rate, health-related quality of life and the parents' evaluations of the postoperative care (secondary endpoints). DISCUSSION: This protocol describes the first randomized non-inferiority study of GPs performing postoperative controls after surgery with ventilation tubes. Results from this study may be utilized for deriving evidence-based clinical practice guidelines of the level of postoperative controls after ventilation tube surgery which is safe and sufficient. TRIAL REGISTRATION: ClinicalTrials.gov NCT02831985 . Registered on 13 July 2016.

Parity and time interval since childbirth influence survival in endometrial cancer patients.

Parity and time interval since last birth have been found to be associated with the risk of endometrial cancer, but few previous studies have examined whether these reproductive factors have prognostic impact. We examined this issue among 740 nulliparous and 3355 parous endometrial cancer patients diagnosed in Norway during the period 1961-1999. The mean age at diagnosis was 55.7 years (range, 25-74 years). Hazard ratios (HRs) with 95% confidence intervals were calculated in Cox proportional regression models. Parous women had significantly (P < 0.001) better prognosis than nulliparous women. In analyses adjusted for age at diagnosis, clinical stage, and histological type, the HR for parous versus nulliparous women was 0.68 (95% confidence interval, 0.57-0.82). The prognostic impact of parity was restricted to patients with endometrioid tumors (P = 0.014, test for interaction) and appeared to be most pronounced in women without metastases (P = 0.14, test for interaction). Moreover, the improved prognosis was strongest for women with the shortest time interval since last childbirth. The HRs (nulliparous women as reference) were 0.51, 0.60, and 0.80 for women less than 15, 15 to 24, and 25 years or more since birth (P < 0.001). The observed beneficial effect of pregnancies may be related to a strong exposure to progesterone during pregnancy. However, it is possible that tumors developing in nulliparous and parous women have different biological features. Further knowledge on this issue may provide valuable information that can be used for individualized treatment.

Prognostic impact of parity in 493 uterine sarcoma patients.

INTRODUCTION: Nulliparity has been found to negatively affect prognosis among endometrial cancer patients. Few previous studies have examined the prognostic impact of parity in patients with uterine sarcomas. METHODS: In the present nationwide, register-based study in Norway, we explore whether parity influences survival among 493 women diagnosed with malignant uterine sarcomas. Hazard ratios for total mortality were calculated in Cox proportional hazard regression analyses. RESULTS: The 5-year Kaplan-Meier survival rates for the 126 endometrial stromal sarcoma (ESS) patients, 249 leiomyosarcoma (LS) patients, and 118 carcinosarcoma (CS) patients were 74%, 68%, and 55%, respectively, but varied considerably by age at diagnosis and clinical stage. In the univariate analyses, nulliparous women had poorer prognosis than parous women among CS patients (P = 0.071, log-rank test) and ESS patients (P = 0.15). In analyses adjusted for clinical stage and age at diagnosis, nulliparity was associated with a worse outcome in ESS patients only (hazard ratio, 0.50; 95% confidence interval, 0.22-1.12; parous vs nulliparous women); a trend with increasing number of births was also observed, of borderline significance (P = 0.058). No independent prognostic impact of parity was found in LS or CS patients. However, a considerably higher proportion of nulliparous than parous CS patients was diagnosed with advanced-stage disease (P = 0.003). CONCLUSION: Nulliparity seems to be associated with poorer prognosis in ESS patients; no independent prognostic impact of parity was seen among LS or CS patients. Further knowledge on underlying biological mechanisms may be valuable for improved treatment.

Symptoms of Depression and Risk of Abdominal Aortic Aneurysm: A HUNT Study.

Background Depression is associated with cardiovascular diseases, but the evidence is scarce regarding depression and risk of abdominal aortic aneurysms (AAA). The aim was to determine whether individuals with depressive symptoms have increased risk of AAA. Methods and Results This population-based prospective study included 59 136 participants (52.4% women) aged 50 to 106 years from the HUNT (Norwegian Nord-Trøndelag Health Study). Symptoms of depression were assessed using the depression subscale of the Hospital Anxiety and Depression Scale (HADS). During a median follow-up of 13 years, there were 742 incident cases of AAA (201 women). A total of 6401 individuals (12.3%) reported depressive symptoms (defined as HADS depression scale [HADS-D]) ≥8) (52.5% women). The annual incidence rate of AAA was 1.0 per 1000 individuals. At all ages, the estimated proportion of individuals diagnosed with AAA was higher among those with depressive symptoms (log-rank test, P<0.001). People with HADS-D ≥8 were older than those with HADS-D<8 (median 57.8 versus 52.3 years, P<0.001) and a statistically significantly higher proportion of them (P<0.001) were smokers, overweight or obese, and reported a history of coronary heart disease, diabetes mellitus, and hypertension. In a Cox proportional hazard regression model adjusted for these factors, individuals with depressive symptoms had a ≈30% higher risk of AAA than those without (hazard ratio, 1.32, 95% CI 1.08-1.61, P=0.007). Conclusions This study shows that individuals with depressive symptoms have significantly higher risk of incident AAA, after adjustments for established risk factors.

Mucosal 5-aminosalicylic acid concentration, drug formulation and mucosal microbiome in patients with quiescent ulcerative colitis.

BACKGROUND: 5-aminosalicylic acid (5-ASA) is the first-line therapy for ulcerative colitis (UC). 5-ASA acts locally in the colonic mucosa by numerous proposed mechanisms, and is metabolised by N-acetyltransferase (NAT). Large variations in mucosal 5-ASA concentrations have been reported, but the underlying mechanisms are not understood. AIM: To study the relationship between 5-ASA concentration, 5-ASA formulation, NAT genotype and bacterial microbiome in patients with UC. METHODS: Patients with quiescent UC, using monotherapy of Mezavant (n = 18), Asacol (n = 14) or Pentasa (n = 10), 4.0-4.8 g/day were included. 5-ASA was measured in colonic mucosal biopsies and serum by ultra-high performance liquid chromatography. NAT genotypes were determined by Sanger sequencing. Bacterial microbiome was sequenced from faeces and mucosa by 16S rRNA sequencing using Illumina Miseq. RESULTS: Mezavant provided the highest mucosal 5-ASA levels (geometric mean 2.39 ng/mg), followed by Asacol (1.60 ng/mg, 33% lower, P = 0.50) and Pentasa (0.57 ng/mg, 76% lower, P = 0.033). Mucosal 5-ASA concentration was not associated with NAT genotype, but serum 5-ASA concentration and NAT1 genotype was associated (P = 0.044). Mucosal 5-ASA concentration was positively associated with mucosal bacterial diversity (P = 0.0005) and bacterial composition. High mucosal 5-ASA concentration was related to reduced abundance of pathogenic bacteria such as Proteobacteria, and increased abundance of several favourable bacteria such as Faecalibacterium. CONCLUSIONS: Mucosal 5-ASA concentration is positively associated with bacterial diversity and a mucosal bacterial composition that are perceived favourable in UC. Mezavant yielded higher mucosal 5-ASA concentrations than Pentasa. 5-ASA may have beneficial effects on the mucosal microbiome, and high concentrations possibly amend dysbiosis in UC.

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

OBJECTIVE: To explore whether twin births and sex of children influenced maternal risk of endometrial cancer, possibly with effect modification by age. DESIGN: Population-based prospective study. STUDY POPULATION: A total of 1,094,017 parous Norwegian women aged 30-74 years, including 3,356 endometrial cancer cases. Among the 27,158 mothers of twins, 101 cases occurred. METHODS: Incidence rate ratios (IRR) with 95% confidence intervals (CI) were calculated in Poisson regression analyses of person-years at risk. RESULTS: Women ever having experienced a twin birth had an overall higher risk of endometrial cancer than women with singleton births only (IRR=1.26, 95% CI=1.03-1.53). Women with twin boys appeared to be the main contributor to the overall elevated risk (IRR=1.57, 95% CI=1.15-2.14). The risk estimates for women with twin girls or sex-nonconcordant twins were close to unity (IRR of 1.09 and 1.12, respectively). However, age-specific analyses revealed an elevated risk also in women with twin girls, but only before age 55 years (IRR=1.92, 95% CI=1.27-2.89); a lower risk was seen at older ages (IRR=0.41, 95% CI=0.19-0.92). The risk estimates for twin boys and sex-nonconcordant twins were consistently observed across age groups. The effect modification by age was statistically significant (p=0.0024). No association was found with sex of children in singleton mothers. CONCLUSION: Mothers of twin boys had a significantly higher risk of endometrial cancer than women with singleton births only, whereas women with twin girls had an elevated risk before age 55 years. No significant association was seen with sex-noncordant twins, neither overall nor within age groups.

Antiseptic effect of low-concentration povidone-iodine applied with a depot device in the conjunctiva before cataract surgery.

PURPOSE: Examine the antiseptic effect of long-term low-concentration (0.3%) povidone-iodine (PI) before cataract surgery. SETTING: St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. DESIGN: Single-armed prospective clinical study. METHODS: Repeated measure of preoperative conjunctival samples from 51 participants were obtained the day before surgery (T1), the day of surgery after treatment with ophthalmic NSAID (T2), and after additional treatment with low-concentration PI (T3) given by placing a pledget soaked in a mix of eye-drops in fornix inferior for 20 min. RESULTS: Before surgery, and before any type of treatment (T1), bacterial growth (≥5 BC) in the conjunctiva was identified in 36 (66.7%) of the participants. After treatment with ophthalmic NSAID (T2), and after additional treatment with low-concentration PI (T3), bacteria were identified in 31 (60.8%) and 12 (23.4%) participants, respectively. All except one of the participants with a measurable change from T2 to T3 (n = 31, 60.8% of total sample), experienced a decrease in number of bacterial colonies (BC) after treatment with low-concentration PI (96.8 vs. 3.2%, p < 0.001). A complete removal of bacteria was seen in 20 (n = 31, 64,5%) of the colonized participants after treatment with PI. CONCLUSIONS: Preoperative treatment with long-term, low-concentration PI applied via a depot device in fornix inferior, seem to be an easy and effective way to reduce the number of BC in the conjunctiva.

Active range of motion as an indicator for ligament and membrane lesions in the upper cervical spine after a whiplash trauma.

In the present study, we examined whether active range of neck motion (AROM) differed between persons with and without a diagnosis of whiplash-associated disorder type 2 (WAD2) and explored whether magnetic resonance (MR)-verified lesions of specific ligaments or membranes at the craniovertebral junction was associated with increased or decreased motion in any particular direction among the WAD2 patients. A CROM goniometer was used for registration of flexion, extension, side bending (left and right) and rotation (left and right), respectively. The neck structures considered were the alar and the transverse ligaments, and the tectorial and the posterior atlanto-occipital membranes. Our study comprised 87 WAD2 patients and 29 control persons without any known neck injury. For comparing mean values of AROM between the groups, t-test and analysis of variance (ANOVA) were used. WAD patients had on average a shorter range of active motion for all movements compared with the control group. The difference was statistically significant for all measures considered, except side bending to the left. Among the WAD patients, increasing severity of lesions to the alar ligaments was associated with a decrease in maximal flexion and rotation. A similar pattern was seen for lesions to the transverse ligament, but the trend test was not significant. An abnormal posterior atlanto-occipital membrane was associated with shorter range of left rotation, with a significant trend test both in analyses with and without adjustment for lesions to other structures. No significant association was found in relation to lesions to the tectorial membrane, but very few persons had such lesions. These findings indicate that soft tissue lesions may affect neck motion as reflected by AROM. However, since lesions to different structures seem to affect the same movement, AROM alone is not a sufficient indicator for soft-tissue lesions to specific structure in the upper cervical spine.

Data on gender contrasts in the risk of incident myocardial infarction by age. The Tromsø Study 1979-2012.

The data presented in this article relate to the research article entitled "Risk of incident myocardial infarction by gender: Interactions with serum lipids, blood pressure and smoking. The Tromsø Study 1979-2012" (Albrektsen et al., 2017) [1]. Data quantify the gender differences in the risk of myocardial infarction (MI) in terms of incidence rate ratios (IRR), in subgroups defined by serum lipids, blood pressure and smoking among persons aged 35-54 years, 55-74 years and 75-94 years, respectively. Data also describe the age- and gender-specific linear associations with the coronary heart disease (CHD) risk factors. IRRs for combined categories of age, gender and a CHD risk factor, with each category compared to the same reference group, are also shown. IRRs were calculated as estimates of relative risk in Poisson regression analyses of person-years at risk. Among 33,859 individuals at risk, a total of 622, 1308 and 816 were diagnosed with MI at ages 35-54, 55-74 and 75-94 years, respectively.

Risk of incident myocardial infarction by gender: Interactions with serum lipids, blood pressure and smoking. The Tromsø Study 1979-2012.

BACKGROUND AND AIMS: Overall, men have roughly twice the risk of myocardial infarction (MI) compared to women, but what causes this contrast is unclear. Identification of subgroups where the gender contrast in risk is particularly low or high, may provide new insight. In the search for such subgroups, we focus on gender-specific effects of established coronary heart disease (CHD) risk factors. Heterogeneity across age groups is also explored. METHODS: Population-based prospective study from Tromsø, Norway, comprising 33,859 individuals (51% women); 2746 individuals (854 women) received a diagnosis of MI during follow-up at ages 35-94 years. Incidence rate ratios (IRR) were calculated as estimates of relative risk in Poisson regression analyses. RESULTS: The association between total cholesterol and risk of MI was stronger for men than women, and IRR for men vs. women accordingly increased with increasing cholesterol, but the risk was higher for men in all subgroups (IRR in range 1.63-3.27), except among older people with low cholesterol levels. The adverse effect of increasing blood pressure (BP) was stronger for women, and IRR for gender diminished with increasing systolic (from 3.90 to 1.38) and diastolic BP (from 2.87 to 1.54). The gender contrast in risk was also substantially reduced in smokers ≥75 years. Associations with high-density lipoprotein cholesterol (HDL-C) did not differ between genders. CONCLUSIONS: Gender heterogeneity in associations with total cholesterol but not HDL-C indicates gender differences in associations with non-HDL-C. The stronger association with BP in women may relate to more severe hypertension-induced left ventricular hypertrophy.

Clinical stage of breast cancer by parity, age at birth, and time since birth: a progressive effect of pregnancy hormones?

Breast cancer diagnosed during pregnancy or 1 to 2 years after birth often occurs at a late stage. Little is known about tumor characteristics in the high-risk period shortly after a childbirth. We here explore whether stage of disease differs according to timing of births. Results are based on 22,351 Norwegian breast cancer patients of parity 0 to 5, ages 20 to 74 years. The proportion of stage II to IV tumors was considerably higher among parous than nulliparous women at age <30 years (52.7% versus 36.8%, P=0.009), but similar or lower in other age groups (P(interaction)=0.029). In general, the largest proportion of stage II to IV tumors was found among women diagnosed during pregnancy or <2 years after birth. However, among women with late-age births (first or second birth >or=30 years, third birth >or=35 years), as well as women with an early second birth (<25 years), the proportion with advanced disease was rather similar or even higher among those diagnosed 2 to 6 years after birth (49.3-56.0%). The association between clinical stage and time since birth reached statistical significance among women with a late first or second birth and among all triparous women (P

Lifelong Gender Gap in Risk of Incident Myocardial Infarction: The Tromsø Study.

Importance: It is not clear to what extent the higher incidence of coronary heart disease (CHD) in men vs women is explained by differences in risk factor levels because few studies have presented adjusted risk estimates for sex. Moreover, the increase in risk of CHD in postmenopausal women, possibly hormone related, may eventually eliminate the sex contrast in risk, but age-specific risk estimates are scarce. Objective: To quantify the difference in risk of incident myocardial infarction (MI) between men and women. Design, Setting and Participants: Population-based prospective study from Tromsø, Norway, comprising 33 997 individuals (51% women). Median follow-up time during ages 35 to 102 years was 17.6 years. Incidence rates (IRs) and incidence rate ratios (IRRs, relative risk) of MI were calculated in Poisson regression analysis of person-years at risk. The data analysis was performed in November 2015. Exposures: Sex, age, birth cohort, serum lipid levels, blood pressure, lifestyle factors, diabetes. Main Outcomes and Measures: Incident MI. Results: A total of 2793 individuals (886 women) received a diagnosis of MI during follow-up in the period 1979 through 2012. The IR increased with age in both sexes, with lower rates for women until age 95 years. Adjusted for age and birth cohort, the overall IRR for men vs women was 2.72 (95% CI, 2.50-2.96). Adjustment for high-density lipoprotein cholesterol and total cholesterol levels had the strongest impact on the risk estimate for sex, followed by diastolic blood pressure and smoking. However, the sex difference remained substantial even after adjustment for these factors (IRR, 2.07; 95% CI, 1.89-2.26). Men had higher risk throughout life, but the IRRs decreased with age (3.64 [95% CI, 2.85-4.65], 2.00 [95% CI, 1.76-2.28], and 1.66 [95% CI, 1.42-1.95] for age groups 35-54, 55-74, and 75-94 years, respectively). Adjustment for systolic blood pressure, diabetes, body mass index, and physical activity had no notable impact. Conclusions and Relevance: The observed sex contrast in risk of MI cannot be explained by differences in established CHD risk factors. The gender gap persisted throughout life but declined with age as a result of a more pronounced flattening of risk level changes in middle-aged men. The minor changes in IRs when moving from premenopausal to postmenopausal age in women make it unlikely that changes in female hormone levels influence the risk of MI.