Association between childhood family structure and longitudinal health behaviour changes in adulthood -Northern Finland birth cohort 1966 study.

BACKGROUND: Childhood family structure is considered to play a role in person's health and welfare. This study investigated the relationships between the longitudinal changes of adult health behaviours and childhood family structure. METHODS: From Northern Finland Birth Cohort 1966 questionnaires, we collected data on childhood family structure at the age of 14 ('two-parent family', 'one parent not living at home/no information on father', and 'father or mother deceased'), and on health behaviours (smoking, alcohol consumption and physical activity status) at the ages of 31 and 46. We used the multinomial logistic regression model to estimate the unadjusted and adjusted associations between childhood family structures and the longitudinal changes between 31 and 46 years of health behaviours (four-category variables). RESULTS: Of the study sample (n = 5431; 55.5% females), 7.1% of the offspring were represented in the 'One parent not living at home/no information on father' subgroup, 6.3% in the 'Father or mother deceased' subgroup and 86.6% in the 'Two-parent family'. 'One parent not living at home/no information on father' offspring were approximately twice as likely to smoke (adjusted OR 2.19, 95% CI 1.70-2.81) and heavily consume alcohol (adjusted OR 1.99, 95% CI 1.25-3.16) at both times in adulthood, relative to not smoking or not heavily consume alcohol, and compared with 'two-parent family' offspring. We found no statistically significant associations between childhood family structure and physical activity status changes in adulthood. CONCLUSIONS: Our findings suggest that the offspring of single-parent families in particular should be supported in early life to diminish their risk of unhealthy behaviours in adulthood.

Women with a history of gestational diabetes mellitus present an accumulation of cardiovascular risk factors at age 46-A birth cohort study.

INTRODUCTION: The incidence of gestational diabetes mellitus (GDM) is globally increasing, and it has been associated with later type 2 diabetes, metabolic syndrome (MetS), and cardiovascular disease (CVD). However, long-term population-based studies investigating common CVD risk factors years after pregnancy are lacking. To evaluate the future mortality and morbidity in cardiovascular and metabolic diseases, we conducted a thorough investigation of midlife risk factors in women with and without previous GDM. MATERIAL AND METHODS: A prospective population-based cohort study was conducted of 3173 parous women from the Northern Finland Birth Cohort, 1966. Study participants were obtained from the national register or patient records. Those with a GDM diagnosis formed the GDM cohort (n = 271), and those without a previous GDM diagnosis formed the control cohort (n = 2902). Clinical examinations were performed on participants at the age of 46 and included anthropometric measurements, oral glucose tolerance test (OGTT), biochemical measurements, and cardiovascular assessment. RESULTS: At the age of 46, women in the GDM cohort had a higher body mass index (BMI, 29.0 kg/m2 vs 26.3 kg/m2, p < 0.001) and greater waist circumference (94.1 cm vs 86.5 cm, p < 0.001) than the control cohort. In the GDM cohort, a higher incidence of impaired glucose tolerance (12.6% vs 7.3%, p = 0.002), more previously diagnosed and OGTT-detected type 2 diabetes (23.3% vs 3.9%, p < 0.001), lower high-density lipoprotein (1.53 mmol/L vs 1.67 mmol/L, p = 0.011), higher triglycerides (1.26 mmol/L vs 1.05 mmol/L, p = 0.002) and a higher fatty liver index (6.82 vs 2.47, p < 0.001), were observed even after adjusting for BMI, polycystic ovary syndrome, parity, level of education, physical activity, smoking, and alcohol consumption. The women in the GDM cohort also had more MetS (42.6% vs 21.9%, p < 0.001) and higher risk scores for CVD and fatal events (Framingham 4.95 vs 3.60, p < 0.001; FINRISK 1.71 vs 1.08, p < 0.001). CONCLUSIONS: Women with a previous diagnosis of GDM exhibit more risk factors for CVD in midlife and are at a higher risk for cardiovascular events later in life.

The interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study.

Objective: To leverage large scale genetic association data to investigate the interplay between circulating cytokines and cardiometabolic traits, and thus identifying potential therapeutic targets. Design: Bi-directional Mendelian randomisation study. Setting: Genome-wide association studies from three Finnish cohorts (Northern Finland Birth Cohort 1966, Young Finns Study, or FINRISK study), and genetic association summary statistics pooled from observational studies for expression quantitative trait loci and cardiometabolic traits. Participants: Data for 47 circulating cytokines in 13 365 individuals from genome-wide association studies, summary statistic data for up to 21 735 individuals on circulating cytokines, summary statistic gene expression data across 49 tissues in 838 individuals, and summary statistic data for up to 1 320 016 individuals on cardiometabolic traits. Interventions: Relations between circulating cytokines and cardiovascular, anthropometric, lipid, or glycaemic traits (coronary artery disease, stroke, type 2 diabetes mellitus, body mass index, waist circumference, waist to hip ratio, systolic blood pressure, glycated haemoglobin, high density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, triglycerides, C reactive protein, glucose, fasting insulin, and lifetime smoking). Main outcome methods: Genetic instrumental variables that are biologically plausible for the circulating cytokines were generated. The effects of cardiometabolic risk factors on concentrations of circulating cytokines, circulating cytokines on other circulating cytokines, and circulating cytokines on cardiometabolic outcomes were investigated. Results: Genetic evidence (mendelian randomisation P<0.0011) suggests that higher body mass index, waist circumference, smoking, higher concentrations of lipids, and systolic blood pressure increase circulating concentrations of several inflammatory cytokines and C reactive protein. Evidence for causal relations (mendelian randomisation P<0.0011) were noted between circulating cytokines, including a key role of vascular endothelial growth factor on influencing the concentrations of 10 other cytokines. Both mendelian randomisation (P<0.05) and colocalisation (posterior probability >0.5) suggested that coronary artery disease risk is increased by higher concentrations of circulating tumour necrosis factor related apoptosis-inducing ligand (TRAIL), interleukin-1 receptor antagonist (IL1RA), and macrophage colony-stimulating factor (MCSF). Conclusion: This study offers insight into inflammatory mediators of cardiometabolic risk factors, cytokine signalling cascades, and effects of circulating cytokines on different cardiometabolic outcomes.

Inflammatory Diseases, Inflammatory Biomarkers, and Alzheimer Disease: An Observational Analysis and Mendelian Randomization.

BACKGROUND AND OBJECTIVES: Whether chronic autoimmune inflammatory diseases causally affect the risk of Alzheimer disease (AD) is controversial. We characterized the relationship between inflammatory diseases and risk of AD and explored the role of circulating inflammatory biomarkers in the relationships between inflammatory diseases and AD. METHODS: We performed observational analyses for chronic autoimmune inflammatory diseases and risk of AD using data from 2,047,513 participants identified in the UK Clinical Practice Research Datalink (CPRD). Using data of a total of more than 1,100,000 individuals from 15 large-scale genome-wide association study data sets, we performed 2-sample Mendelian randomizations (MRs) to investigate the relationships between chronic autoimmune inflammatory diseases, circulating inflammatory biomarker levels, and risk of AD. RESULTS: Cox regression models using CPRD data showed that the overall incidence of AD was higher among patients with inflammatory bowel disease (hazard ratio [HR] 1.17; 95% CI 1.15-1.19; p = 2.1 × 10-4), other inflammatory polyarthropathies and systematic connective tissue disorders (HR 1.13; 95% CI 1.12-1.14; p = 8.6 × 10-5), psoriasis (HR 1.13; 95% CI 1.10-1.16; p = 2.6 × 10-4), rheumatoid arthritis (HR 1.08; 95% CI 1.06-1.11; p = 4.0 × 10-4), and multiple sclerosis (HR 1.06; 95% CI 1.04-1.07; p = 2.8 × 10-4) compared with the age (±5 years) and sex-matched comparison groups free from all inflammatory diseases under investigation. Bidirectional MR analysis identified relationships between chronic autoimmune inflammatory diseases and circulating inflammatory biomarkers. Particularly, circulating monokine induced by gamma interferon (MIG) level was suggestively associated with a higher risk of AD (odds ratio from inverse variance weighted [ORIVW] 1.23; 95% CI 1.06-1.42; p IVW = 0.007) and lower risk of Crohn disease (ORIVW 0.73; 95% CI -0.62 to 0.86; p IVW = 1.3 × 10-4). Colocalization supported a common causal single nucleotide polymorphism for MIG and Crohn disease (posterior probability = 0.74), but not AD (posterior probability = 0.03). Using a 2-sample MR approach, genetically predicted risks of inflammatory diseases were not associated with higher AD risk. DISCUSSION: Our data suggest that the association between inflammatory diseases and risk of AD is unlikely to be causal and may be a result of confounding. In support, although inflammatory biomarkers showed evidence for causal associations with inflammatory diseases, evidence was weak that they affected both inflammatory disease and AD.

A Natural History of Erectile Dysfunction in Elderly Men: A Population-Based, Twelve-Year Prospective Study.

There is a wide variation in the development and course of erectile dysfunction (ED) in men, which confirms the need for prospective studies. We conducted a cross-sectional analysis among the general male population at the baseline (n = 359) and in a follow-up survey (n = 218) 12 years later. The prospective 12-year study included 189 men. ED was assessed using the International Index of Erectile Function questionnaire. The mean age of the participants was 62.0 years at the baseline, while at the 12-year follow-up it was 71.6 years. The crude prevalence of ED was 61.6% at the baseline and 78.9% at the follow-up, and the prevalence tended to increase with age. All of the men aged 75 years or more had at least mild ED. The incidence of ED in every thousand person years was 53.5. A total of 54.5% of the men experienced ED progression, while 39.2% reported no changes in erectile function, and 6.3% experienced ED regression during the 12-year study. The likelihood of ED progression was higher in the older compared with younger age group (odds ratio, OR 5.2 (95% CI: 1.1-26.2)), and the likelihood of ED regression was lower among men with increased depression symptoms (OR 0.3 (95% CI: 0.1-0.6)) and among men with a decreased interest in their sexual life (OR 0.1 (95% CI: 0.0-0.6)). Lifestyle factors such as the consumption of alcohol and smoking were not significantly associated with ED.

Skin cancers and their risk factors in older persons: a population-based study.

BACKGROUND: The number of skin cancer is increasing rapidly. However, little is known about the risk factors of skin cancer in older persons. Our objectives were to determine the risk factors for skin cancer or its precursors in an older population. More specifically, to study the association of new skin cancers with previous skin cancer, sex, age, Fitzpatrick's skin type, history of outdoor work and socioeconomic status (SES). METHODS: In this retrospective cross-sectional study of a large, well documented historical cohort data set a total body skin examination (TBSE) was performed for 552 participants aged between 70 and 93 years by dermatologists. The information gathered was augmented with health register data and self-reported data. The associations between skin cancer and its risk factors were studied by using the logistic regression analyses. RESULTS: According to the TBSE skin cancer/precursor was present in 25.5% of participants and was more common in males than in females (34.5% vs 20.2%, p < 0.001). Previous skin cancer increased the risk of subsequent skin cancer 2.6-fold (OR 2.56, 95% CI 1.43-4.55) and male sex nearly 2-fold (1.97, 95% CI 1.26-3.08). Specific risk factors for the first occurrence of skin cancer were male sex and outdoor work. There was also association between skin cancer and age and socioeconomic status. CONCLUSIONS: TBSE is recommend for physicians treating older persons to allow early recognition of skin cancers or their precursors. Older males need particularly close attention.

Circulating inflammatory cytokines and risk of five cancers: a Mendelian randomization analysis.

BACKGROUND: Epidemiological and experimental evidence has linked chronic inflammation to cancer aetiology. It is unclear whether associations for specific inflammatory biomarkers are causal or due to bias. In order to examine whether altered genetically predicted concentration of circulating cytokines are associated with cancer development, we performed a two-sample Mendelian randomisation (MR) analysis. METHODS: Up to 31,112 individuals of European descent were included in genome-wide association study (GWAS) meta-analyses of 47 circulating cytokines. Single nucleotide polymorphisms (SNPs) robustly associated with the cytokines, located in or close to their coding gene (cis), were used as instrumental variables. Inverse-variance weighted MR was used as the primary analysis, and the MR assumptions were evaluated in sensitivity and colocalization analyses and a false discovery rate (FDR) correction for multiple comparisons was applied. Corresponding germline GWAS summary data for five cancer outcomes (breast, endometrial, lung, ovarian, and prostate), and their subtypes were selected from the largest cancer-specific GWASs available (cases ranging from 12,906 for endometrial to 133,384 for breast cancer). RESULTS: There was evidence of inverse associations of macrophage migration inhibitory factor with breast cancer (OR per SD = 0.88, 95% CI 0.83 to 0.94), interleukin-1 receptor antagonist with endometrial cancer (0.86, 0.80 to 0.93), interleukin-18 with lung cancer (0.87, 0.81 to 0.93), and beta-chemokine-RANTES with ovarian cancer (0.70, 0.57 to 0.85) and positive associations of monokine induced by gamma interferon with endometrial cancer (3.73, 1.86 to 7.47) and cutaneous T-cell attracting chemokine with lung cancer (1.51, 1.22 to 1.87). These associations were similar in sensitivity analyses and supported in colocalization analyses. CONCLUSIONS: Our study adds to current knowledge on the role of specific inflammatory biomarker pathways in cancer aetiology. Further validation is needed to assess the potential of these cytokines as pharmacological or lifestyle targets for cancer prevention.

Factors predicting 31-year survival among a population cohort in Northern Finland.

We evaluated the survival of a subarctic population and the significance of traditional risk factors for mortality, causes of death and their seasonal variation from the period of 1984-2014. By the end of 2014 (follow-up), 644 (34.4% from 1,869) participants had died (42.1% of cardiovascular causes, 22.4% of neoplastic diseases). The average age at death±SD was 74.6±11.4 years for women (n=284) and 70.2±12.0 years for men (n=360). After adjusting for baseline age, the major risk factors predicting death were male sex (hazard ratio [HR] 1.80; 95% confidence interval [CI] 1.54-2.10), current smoking (HR 1.85; 95% CI 1.58-2.17), obesity (HR 1.75; 95% CI 1.45-2.12), high blood pressure (HR 1.46; 95% CI 1.24-1.72), cardiovascular disease (HR 1.62; 95% CI 1.36-1.93) and depression (HR 1.61; 95% CI 1.21-2.14) at baseline.The most common causes of death and the main risk factors predicting death in this population were the same as reported globally. Lifestyle factors had an important impact in predicting survival. The most common causes of death were the same for men and women. There was no significant difference in overall mortality rate between winter and summer, but cerebrovascular and pulmonary causes of death were more common during winter.

Inflammation, hippocampal volume, and cognition in schizophrenia: results from the Northern Finland Birth Cohort 1966.

Increased blood interleukin-6 (IL-6) levels are a replicated abnormality in schizophrenia, and may be associated with smaller hippocampal volumes and greater cognitive impairment. These findings have not been investigated in a population-based birth cohort. The general population Northern Finland Birth Cohort 1966 was followed until age 43. Subjects with schizophrenia were identified through the national Finnish Care Register. Blood IL-6 levels were measured in n = 82 subjects with schizophrenia and n = 5373 controls at age 31. Additionally, 31 patients with schizophrenia and 63 healthy controls underwent brain structural MRI at age 34, and cognitive testing at ages 34 and 43. Patients with schizophrenia had significantly higher median (interquartile range) blood IL-6 levels than controls (5.31, 0.85-17.20, versus 2.42, 0.54-9.36, p = 0.02) after controlling for potential confounding factors. In both schizophrenia and controls, higher blood IL-6 levels were predictors of smaller hippocampal volumes, but not cognitive performance at age 34. We found evidence for increased IL-6 levels in patients with midlife schizophrenia from a population-based birth cohort, and replicated associations between IL-6 levels and hippocampal volumes. Our results complement and extend the previous findings, providing additional evidence that IL-6 may play a role in the pathophysiology of schizophrenia and associated brain alterations.

Onset of the climacteric phase by the mid-forties associated with impaired insulin sensitivity: a birth cohort study.

OBJECTIVE: To investigate whether the early-onset menopausal transition is associated with deteriorated glucose tolerance in women in their mid-forties. METHODS: A cross-sectional analysis of a cohort study including 2,632 women of the Northern Finland Birth Cohort 1966. The participants were divided into two groups by their menstrual history and follicle-stimulating hormone values at age 46: climacteric and preclimacteric women. Glucose and insulin parameters, as well as mathematical indices derived from them to evaluate insulin sensitivity, were compared between the groups. The results were adjusted for measured body mass index and smoking. The possible effect of hormone therapy was investigated in subanalyses excluding hormone therapy users. RESULTS: Climacteric women (n = 379) were more often current smokers at age 46 (P = 0.008), and their body mass indices increased more from 31 to 46 years (P = 0.013), compared to preclimacteric women (n = 2,253). In a multivariable generalized linear model, being climacteric at age 46 was associated with several findings suggesting decreased insulin sensitivity: increased glycated hemoglobin (P < 0.001), 2-hour oral glucose tolerance test 30- and 60-minute insulin (P = 0.040 and 0.006, respectively), and area under the insulin curve (P = 0.005). Being climacteric also was associated with a decreased the McAuley (P = 0.024) and Belfiore indices (P = 0.027) and glucose tolerance test 60-minute glucose (P = 0.015). In subanalyses excluding hormone therapy users (n = 94), the results did not change significantly. CONCLUSIONS: Earlier onset of climacteric transition is associated with impaired insulin sensitivity in middle-aged women.

Video Summary:http://links.lww.com/MENO/A648.

The High Prevalence of Skin Diseases in Adults Aged 70 and Older.

BACKGROUND/OBJECTIVES: To determine the prevalence of skin findings and skin diseases in adults aged 70 and older, and to study the association between cutaneous diseases and socioeconomic status (SES), sex, and living status in the older population. DESIGN: Cross-sectional study of Finnish adults aged 70 to 93 as part of the Northern Finland Birth Cohort 1966 Study. SETTINGS: Skin examination data were available for 552 adults. MEASUREMENTS: A whole-body skin examination was performed by dermatologists. The associations between skin diseases and SES, sex, and living status were analyzed. RESULTS: Nearly 80% of the adults had at least one skin disease that required further treatment or follow-up. More than one-third of the study cases (39.1%) had three or more simultaneous skin diseases. Skin diseases were more common in men than in women (P < .001). The most common skin diseases were tinea pedis (48.6%), onychomycosis (29.9%), rosacea (25.6%), actinic keratosis (22.3%), and asteatotic eczema (20.8%). Some association was found between skin diseases and SES and living status. CONCLUSION: A whole-body clinical skin examination is important because it reveals important diagnoses.

Vitamin D Deficiency Induces Insulin Resistance and Re-Supplementation Attenuates Hepatic Glucose Output via the PI3K-AKT-FOXO1 Mediated Pathway.

BACKGROUND: Pandemic vitamin D deficiency is associated with insulin resistance and type 2 diabetes. Vitamin D supplementation has been reported to have improved glucose homeostasis. However, its mechanism to improve insulin sensitivity remains unclear. METHODS AND RESULTS: Male C57BL/6J mice are fed with/without vitamin D control (CD) or Western (WD) diets for 15 weeks. The vitamin-D-deficient lean (CDVDD) and obese (WDVDD) mice are further subdivided into two groups. One group is re-supplemented with vitamin D for 6 weeks and hepatic insulin signaling is examined. Both CD and WD mice with vitamin D deficiency developed insulin resistance. Vitamin D supplementation in CDVDD mice significantly improved insulin sensitivity, hepatic inflammation, and antioxidative capacity. The hepatic insulin signals like pAKT, pFOXO1, and pGSK3ß are increased and the downstream Pepck, G6pase, and Pgc1α are reduced. Furthermore, the lipogenic genes Srebp1c, Acc, and Fasn are decreased, indicating that hepatic lipid accumulation is inhibited. CONCLUSION: The results demonstrate that vitamin D deficiency induces insulin resistance. Its supplementation has significant beneficial effects on pathophysiological mechanisms in type 2 diabetes but only in lean and not in the obese phenotype. The increased subacute inflammation and insulin resistance in obesity cannot be significantly alleviated by vitamin D supplementation. This needs to be taken into consideration in the design of new clinical trials.

Validation of the Zung self-rating depression scale (SDS) in older adults.

Objective: The main objective of this study was to investigate the psychometric properties of the Zung Self-Rating Depression Scale (SDS) and evaluate screening parameters capability of the SDS with the Beck Depression Inventory (BDI-21) among the elderly population. Design: A population-based study Setting: Community Subjects: 520 adults, aged 72-73 years, living in the city of Oulu, Finland. Main outcome measures: The screening parameters of the SDS questions and BDI-21 for detecting severity of depression. The Mini Neuropsychiatric Interview for diagnosing major depression. Results: The optimal cut-off point for the SDS was 39. The sensitivity and specificity parameters for this cut-off point were 79.2% (95% CI 57.8-92.9) and 72.2% (95% CI 67.9-76.1), respectively. Positive and negative predictive values were 12.5% (95% CI 7.7-18.8) and 98.6% (95% CI 96.7-99.5), respectively. Moreover, there was no statistically significant difference in diagnostic accuracy indices of the cut-off points 39 and 40. In a receiver operating characteristic analysis, the area under the curve was 0.85 (95%CI 0.77-0.92) for the SDS total score and 0.89 (95% CI 0.83-0.96) for the BDI-21 (p = 0.137). Conclusion: Using the traditional cut-off point, the SDS was convenient for identifying clinically meaningful depressive symptoms in an elderly Finnish population when compared with the BDI-21 which is one of the most commonly used depression screening scales. The sensitivity and specificity of these two screening tools are comparable. Based on our study, the SDS is convenient for identifying clinically meaningful depressive symptoms among older adults at the community level. Key points The widely used Zung Self-Rating Depression Scale (SDS) has not previously been validated among elderly people at the community level. The sensitivity and specificity of SDS (cut-off point 39) were 79.2% and 72.2%. The positive and negative predictive values for SDS were 12.5% and 98.6%. SDS is convenient for identifying major depression in an elderly population and regarding sensitivity and specificity comparable to BDI-21.

Impaired glucose metabolism is associated with tooth loss in middle-aged adults: The Northern Finland Birth Cohort Study 1966.

AIM: We investigated the association of impaired glucose metabolism with tooth loss in adults in the Northern Finland Birth Cohort Study 1966 (NFBC1966). METHODS: We examined 4394 participants from the 46-year follow-up of the NFBC1966. Self-reported number of teeth as well as insulin and glucose values, taken during a standard oral glucose tolerance test (OGTT), served as the primary study variables. A multinomial logistic regression model served to analyse (unadjusted, smoking-adjusted and fully adjusted) the association between number of teeth (0-24, 25-27, 28-32) and glucose metabolism in women and men. RESULTS: Among women, type 2 diabetes - whether previously known or detected during screening - pointed to a higher likelihood of 0-24 teeth (fully adjusted OR = 2.99, 95%CI = 1.54-5.80) and 25-27 teeth (OR = 1.91, 95%CI = 1.18-3.08) than did normal glucose tolerance. Similarly, impaired fasting glucose and impaired glucose tolerance together indicated a higher likelihood of 0-24 teeth (OR = 1.71, 95%CI = 1.09-2.69) than did normal glucose tolerance. A similar, statistically non-significant, pattern emerged among men. Number of teeth associated with OGTT insulin and glucose curves as well as with the Matsuda index in both women and men. CONCLUSIONS: Tooth loss strongly associated with impaired glucose metabolism in middle-aged Finnish women.

Accumulated exposure to unemployment is related to impaired glucose metabolism in middle-aged men: A follow-up of the Northern Finland Birth Cohort 1966.

AIMS: We explored whether registered unemployment is associated with impaired glucose metabolism in general population. METHODS: Based on Northern Finland Birth Cohort 1966 at 46 years, we analyzed the oral glucose tolerance tests of 1970 men and 2544 women in relation to their preceding three-year employment records in three categories of unemployment exposure: no (employed), low (≤1-year) and high exposure (>1-year). RESULTS: Among men, pre-diabetes was found in 19.2% of those with no unemployment, 23.0% with low and 27.0% with high exposure, the corresponding figures for screen-detected type 2 diabetes were 3.8%, 3.8% and 9.2% (p<0.01). Among women, analogous figures for pre-diabetes were 10.0%, 12.6% and 16.2% and for screen-detected type 2 diabetes 1.7%, 3.4% and 3.6% (p<0.01). Men with high exposure to unemployment had a higher risk for pre-diabetes (OR 1.61, CI 95% 1.03-2.51) and screen-detected type 2 diabetes (OR 2.58 95% CI 1.23-5.44) than employed men, after adjustment for education, smoking, alcohol intake, physical activity and body mass index. Among women, associations were attenuated in the adjusted models. CONCLUSIONS: High exposure to unemployment may predispose to type 2 diabetes in middle-aged men. For clinicians, awareness of the patient's unemployment status may be helpful in recognizing undiagnosed cases.

Primary health care utilisation and its costs among middle-aged smokers.

OBJECTIVE: To study and compare the utilisation of primary health care services among 46-year-old current smokers, ex-smokers and never-smokers, and to estimate the corresponding costs. METHODS: This population-based cohort study is based on the Northern Finland Birth Cohort 1966, which is a longitudinal research program in Finland's two northernmost provinces. The study is based on data collected at the 46-year follow-up, during which a total of 4997 individuals completed questionnaires on their primary health care service utilisation. Primary health care covered visits to both occupational and public health care (typically community health centres). RESULTS: Current smokers visited primary health care professionals more often per year than never-smokers, regardless of gender (RR 1.24, 95 % confidence interval 1.10-1.43 for men; RR 1.10, 1.01-1.22 for women). When primary health care services were categorised based on the type of service provided, current smokers of both genders were more likely to visit a dentist (RR 1.56, 1.32-1.84 for men; RR 1.34, 1.15-1.55 for women) or a physician (RR 1.20, 1. 03-1.40 for men; RR 1.15, 1.02-1.30 for women) than their never-smoking counterparts (BMI adjusted for). For men, the total annual costs of primary health care visits were 28 % higher for current smokers versus never-smokers (P < 0.001). For women, the difference was 21 % (P < 0.01). CONCLUSIONS: Smokers visit primary health care professionals more often already at the age of 46, before the expected diagnosis of fatal smoking-related illnesses. This phenomenon not only predicts an elevated incidence of serious illnesses in later life (such as cardiovascular disease), but also causes an economic burden on the health care system.

Uterine fibroids and cardiovascular risk.

STUDY QUESTION: Are uterine fibroids associated with increased cardiovascular risk? SUMMARY ANSWER: This study reports an association between increased serum lipids and metabolic syndrome with an increased risk of uterine fibroids. WHAT IS KNOWN ALREADY: Recent studies suggest similarities in biological disease mechanisms and risk factors for fibroids and atherosclerosis: obesity, hypertension and abnormal serum lipids. These findings are awaiting confirmation that a population-based follow-up study could offer with extensive health examination data collection linked with a national hospital discharge register. STUDY DESIGN, SIZE, DURATION: The Northern Finland Birth Cohort (NFBC1966) is a population-based long-term follow-up study including all children with estimated date of delivery in 1966 in the Northern Finland area. The data were collected from national registries, postal questionnaires and clinical health examinations. The study population for this study comprised all females included in the NFBC1966 that underwent an extensive clinical health examination at age 46 years (n = 3635). PARTICIPANTS/MATERIALS, SETTING, METHODS: All females included in the NFBC1966 who were alive and traceable (n = 5118) were invited for the 46-year follow-up study; 3268 (63.9%) responded, returned the postal questionnaire and attended the clinical examination. Uterine fibroid cases were identified through the national hospital discharge register that has data on disease diagnoses based on WHO ICD-codes. Uterine fibroid codes, ICD-9: 218 and ICD-10: D25 were used for case identification. Self-reported fibroid cases were identified through the postal questionnaire. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 729 fibroid cases were identified, including 293 based on hospital discharge registries. With adjustment for BMI, parity, education and current use of exogenous hormones the risk of prevalent fibroids rose significantly for every 1 mmol/l increase in LDL (OR = 1.13, 95% CI: 1.02-1.26 for all cases) and triglycerides (OR = 1.27, 95% CI: 1.09-1.49 for all cases). Metabolic syndrome associated with hospital discharge-based fibroid diagnosis (OR = 1.48, 95% CI: 1.09-2.01). Additionally every 1 unit increase in waist-hip ratio associated with fibroids (OR = 1.32, 95% CI: 1.10-1.57). LIMITATIONS, REASONS FOR CAUTION: The case ascertainment may present some limitations. There was likely an under-identification of cases and misclassification of some cases as controls; this would have diluted the effects of reported associations. The data analysed were cross-sectional and therefore cause and effect for the associations observed cannot be distinguished. WIDER IMPLICATIONS OF THE FINDINGS: Increased serum lipids and metabolic syndrome are associated with increased risk of uterine fibroids. Along with central obesity these findings add to an increased risk for cardiovascular disease among women with fibroids. These observations may suggest that there are shared predisposing factors underlying both uterine fibroids and adverse metabolic and cardiac disease risk, or that metabolic factors have a role in biological mechanisms underlying fibroid development. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Academy of Finland, University Hospital Oulu, University of Oulu, Finland, Northern Finland Health Care Foundation, Duodecim Foundation, ERDF European Regional Development Fund-Well-being and health: Research in the Northern Finland Birth Cohort 1966. The authors declare no conflict of interest.

Cardiovascular disease risk factors in relation to smoking behaviour and history: a population-based cohort study.

OBJECTIVE: To investigate how individual risk factors for cardiovascular disease (CVD) (blood pressure, lipid levels, body mass index, waist and hip circumference, use of antihypertensive or hypolipidemic medication, and diagnosed diabetes) differ in people aged 46 years with different smoking behaviour and history. METHODS: This population-based cohort study is based on longitudinal data from the Northern Finland Birth Cohort 1966 project. Data were collected at the 31-year and 46-year follow-ups, when a total of 5038 and 5974 individuals participated in clinical examinations and questionnaires. Data from both follow-ups were available for 3548 participants. In addition to individual CVD risk factors, Framingham and Systematic Coronary Risk Evaluation (SCORE) algorithms were used to assess the absolute risk of a CVD event within the next decade. RESULTS: The differences in individual risk factors for CVD reached statistical significance for some groups, but the differences were not consistent or clinically significant. There were no clinically significant differences in CVD risk as measured by Framingham or SCORE algorithms between never smokers, recent quitters and former smokers (7.5%, 7.4%, 8.1% for men; 3.3%, 3.0%, 3.2% for women; p<0.001). CONCLUSIONS: The effect of past or present smoking on individual CVD risk parameters such as blood pressure and cholesterol seems to be of clinically minor significance in people aged 46 years. In other words, smoking seems to be above all an independent risk factor for CVD in the working-age population. Quitting smoking in working age may thus reduce calculated CVD risk nearly to the same level with people who have never smoked.

Association between Birth Characteristics and Cardiovascular Autonomic Function at Mid-Life.

BACKGROUND: Low birth weight is associated with an increased risk of cardiovascular diseases in adulthood. As abnormal cardiac autonomic function is a common feature in cardiovascular diseases, we tested the hypothesis that low birth weight may also be associated with poorer cardiac autonomic function in middle-aged subjects. METHODS: At the age of 46, the subjects of the Northern Finland Birth Cohort 1966 were invited to examinations including questionnaires about health status and life style and measurement of vagally-mediated heart rate variability (rMSSD) from R-R intervals (RRi) and spontaneous baroreflex sensitivity (BRS) in both seated and standing positions. Maternal parameters had been collected in 1965-1966 since the 16th gestational week and birth variables immediately after delivery. For rMSSD, 1,799 men and 2,279 women without cardiorespiratory diseases and diabetes were included and 902 men and 1,020 women for BRS. The analyses were adjusted for maternal (age, anthropometry, socioeconomics, parity, gestational smoking) and adult variables (life style, anthropometry, blood pressure, glycemic and lipid status) potentially confounding the relationship between birth weight and autonomic function. RESULTS: In men, birth weight correlated negatively with seated (r = -0.058, p = 0.014) and standing rMSSD (r = -0.090, p<0.001), as well as with standing BRS (r = -0.092, p = 0.006). These observations were verified using relevant birth weight categories (<2,500 g; 2,500-3,999 g; ≥4,000 g). In women, birth weight was positively correlated with seated BRS (r = 0.081, p = 0.010), but none of the other measures of cardiovascular autonomic function. These correlations remained significant after adjustment for potential confounders (p<0.05 for all). CONCLUSIONS: In men, higher birth weight was independently associated with poorer cardiac autonomic function at mid-life. Same association was not observed in women. Our findings suggest that higher, not lower, birth weight in males may contribute to less favourable cardiovascular autonomic regulation and potentially to an elevated cardiovascular risk in later life.

The association between impaired glucose tolerance and soluble CD40 ligand: a 15-year prospective cohort study.

BACKGROUND AND AIMS: The aim of the present study was to assess soluble CD40 Ligand (sCD40L) levels in relation to impaired glucose tolerance (IGT) at population level. METHODS: This study is part of a prospective, population-based cohort study, carried out from 1990 to 2008 in northern Finland. Study members, born in 1935 and living in the City of Oulu, underwent oral glucose tolerance test (OGTT) and measurement of plasma sCD40L at three different time points during the 15-year follow-up. The total number of study members who underwent OGTT was 768 at the baseline, 557 at the first and 467 at the second follow-up. SCD40L levels in patients with IGT were compared with those in subjects with normal glucose tolerance or impaired fasting glucose (non-IGT). RESULTS: Geometric mean level of sCD40L was significantly higher in the IGT group compared with the non-IGT group at the baseline (0.42 vs. 0.27 ng/mL) and at the first follow-up (1.50 vs. 0.36 ng/mL) (repeated measures mixed models ANOVA, p < 0.05). At the second follow-up (age 72-73 years), however, the difference was not statistically significant (9.44 vs. 7.24 ng/mL). During the entire follow-up, the levels of sCD40L increased significantly both in IGT and non-IGT groups. CONCLUSION: We found that plasma sCD40L level increases with age as well as there are elevated levels of plasma sCD40L in subjects with IGT compared with non-IGT. This may indicate an increased cardiovascular risk in older age and in subjects with IGT.