The characteristics of elevated blood pressure in abdominal obesity correspond to primary hypertension: a cross-sectional study.

BACKGROUND: Obesity-related hypertension and the associated metabolic abnormalities are considered as a distinct hypertensive phenotype. Here we examined how abdominal fat content, as judged by waist:height ratio, influenced blood pressure and hemodynamic profile in normotensive subjects and never-treated hypertensive patients. METHODS: The 541 participants (20-72 years) underwent physical examination and laboratory analyses and were divided into age and sex-adjusted quartiles of waist:height ratio. Supine hemodynamics were recorded using whole-body impedance cardiography, combined with analyses of radial tonometric pulse wave form and heart rate variability. RESULTS: Mean waist:height ratios in the quartiles were 0.46, 0.51, 0.55 and 0.62. Radial and aortic blood pressure, systemic vascular resistance, pulse wave velocity, markers of glucose and lipid metabolism, leptin levels and C-reactive protein were higher in quartile 4 when compared with quartiles 1 and 2 (p < 0.05 for all). Cardiac index was lower in quartile 4 versus quartile 1, while no differences were seen in heart rate variability, augmentation index, plasma renin activity, and aldosterone concentration between the quartiles. Linear regression analyses showed independent associations of abdominal obesity with higher aortic systolic and diastolic blood pressure, systemic vascular resistance, and pulse wave velocity (p < 0.05 for waist:height ratio in all regression models). CONCLUSION: Higher waist:height ratio was associated with elevated blood pressure, systemic vascular resistance, and arterial stiffness, but not with alterations in cardiac sympathovagal modulation or activation of the circulating renin-angiotensin-aldosterone system. Although obesity-related elevation of blood pressure has distinct phenotypic features, these results suggest that its main characteristics correspond those of primary hypertension. TRIAL REGISTRATION: ClinicalTrails.gov NCT01742702 (date of registration 5th December 2012).

Rapid urine screening for ethyl glucuronide from pregnant women as a tool for detecting prenatal alcohol exposure.

BACKGROUND: An increasing prevalence of alcohol consumption is a major public health problem, which has also led to an increasing number of children who have been prenatally exposed to the toxic effects of ethanol. However, obtaining reliable information on prenatal alcohol exposure through maternal self-reports has proved difficult. AIMS: Our aim was to evaluate the potential for rapid screening test for measuring ethyl glucuronide (EtG), a specific alcohol metabolite, from urine samples of pregnant women. METHODS: Five hundred five urine samples of pregnant women were collected anonymously from five prenatal units in two Finnish cities: a tertiary specialist antenatal clinic for pregnant women with problematic substance use (HAL), a regular hospital antenatal clinic (LCH = Lahti Central Hospital), a prenatal screening unit and two community maternity clinics (USR = user self-recruiting units). All samples were screened using rapid EtG test strips, and all positive, uncertain, and randomly selected negative samples were confirmed by quantitative analyses. The samples were also screened for cotinine and use of cannabis. RESULTS: In this material an EtG cut-off of 300 ng/mL suggesting heavy alcohol drinking was exceeded by 7.4% (5/68) of the samples in the HAL clinic, 1.9% (4/202) in LCH, and 0.9% (2/225) in USR. A cut-off of 100 ng/mL was exceeded by 17.6% (12/68) of samples from HAL, 7.5% (16/212) from LCH, and 6.7% (15/225) from USR. Based on confirmatory quantitative analyses, there were no false negatives nor false positives in rapid EtG screening. However, 57 (11.3%) of test results were classified as uncertain. In these cases, confirmation by quantitative analyses resulted in 56.1% rate of positive values. 73% of the samples with EtG > 300 ng/mL showed positive cotinine results suggesting smoking co-occurring with alcohol intake. CONCLUSIONS: Rapid EtG tests may be an easy and inexpensive method, which may improve the possibilities for screening alcohol use among pregnant women during routine prenatal visits. Quantitative EtG analyses are recommended to confirm screening positive and uncertain cases. TRIAL REGISTRATION: NCT04571463 Date of Registration 11/05/2020.

The prevalence of hemoglobin Tacoma in Finland detected by HbA1c capillary electrophoresis.

Previous studies have identified occasional cases of heterozygous Hb Tacoma in areas that have attracted Finnish immigrants, especially in Sweden and North America, but large studies of this slightly unstable beta variant in vitro have not been carried out. Here we determined the prevalence of hemoglobin variants across Finland. A total of 5059 samples from 11 different hospital districts were analyzed using HbA1c capillary electrophoresis and reviewed for atypical profiles (HbA1c, Capillarys 3 Tera, Sebia). 38 heterozygous Hb Tacoma cases were found (0.75%). The prevalence was highest in South Ostrobothnia (2.0%), located in western Finland, and second highest in the neighboring provinces (1.0-1.4%), but only two districts were devoid of variants. Heterozygous Hb Tacoma was confirmed by genetic testing (NM_000518.5(HBB):c.93G > T (p.Arg31Ser)). In addition, five other variants were found, suggestive of HbE, Hb Helsinki (two cases) and an alpha variant, as interpreted from the electropherograms. The fifth variant, belonging to the South Ostrobothnian cohort, remained unknown at the time of the initial analyses, but was later interpreted as homozygous Hb Tacoma and confirmed by hemoglobin fraction analysis (Hemoglobin(E), Capillarys 3 Tera). In a subsequent retrospective study of the electropherograms of routine HbA1c diagnostics, altogether nine homozygous Hb Tacoma cases were identified in South Ostrobothnia. While heterozygous Hb Tacoma is usually an incidental finding, it interferes with several HbA1c assays. The present study is the first demonstration of homozygous Hb Tacoma. The clinical presentations of homozygous Hb Tacoma are not known and need to be addressed in future studies.

Longitudinal physical activity patterns and the development of cardiometabolic risk factors during adolescence.

PURPOSE: To examine the associations between longitudinal physical activity (PA) patterns and the development of cardiometabolic risk factors from adolescence to young adulthood. METHODS: This cohort study encompassed 250 participants recruited from sports clubs and schools, and examined at mean age 15 and 19. Device-measured moderate-to-vigorous PA was grouped into five patterns (via a data-driven method, using inactivity maintainers as a reference). The outcomes were: glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), total cholesterol, HDL and LDL cholesterol, triglycerides, blood pressure, and body mass index (BMI). Linear growth curve models were applied with adjustment for sex, age, fruit/vegetable consumption, cigarette/snuff use, and change in the device wear-time. RESULTS: Insulin and BMI increased among decreasers from moderate to low PA (ß for insulin 0.23, 95% CI 0.03-0.46; ß for BMI 0.90; CI 0.02-1.78). The concentration of HDL cholesterol decreased (ß -0.18, CI -0.31 to -0.05) and that of glucose increased (ß 0.18, CI 0.02-0.35) among decreasers from high to moderate PA. By contrast, among increasers, blood pressure declined (systolic ß -6.43, CI -12.16 to -0.70; diastolic ß -6.72, CI -11.03 to -2.41). CONCLUSIONS: Already during the transition to young adulthood, changes in PA are associated with changes in cardiometabolic risk factors. Favorable blood pressure changes were found among PA increasers. Unfavorable changes in BMI, insulin, glucose, and HDL cholesterol were found in groups with decreasing PA. The changes were dependent on the baseline PA and the magnitude of the PA decline.

Urine sodium excretion is related to extracellular water volume but not to blood pressure in 510 normotensive and never-treated hypertensive subjects.

PURPOSE: High sodium intake is an accepted risk factor for hypertension, while low Na+ intake has also been associated with increased risk of cardiovascular events. In this cross-sectional study, we examined the association of 24-h urinary Na+ excretion with haemodynamics and volume status. MATERIALS AND METHODS: Haemodynamics were recorded in 510 normotensive and never-treated hypertensive subjects using whole-body impedance cardiography and tonometric radial artery pulse wave analysis. The results were examined in sex-specific tertiles of 24-h Na+ excretion, and comparisons between normotensive and hypertensive participants were also performed. Regression analysis was used to investigate factors associated with volume status. The findings were additionally compared to 28 patients with primary aldosteronism. RESULTS: The mean values of 24-h urinary Na+ excretion in tertiles of the 510 participants were 94, 148 and 218 mmol, respectively. Average tertile age (43.4-44.7 years), office blood pressure and pulse wave velocity were corresponding in the tertiles. Plasma electrolytes, lipids, vitamin D metabolites, parathyroid hormone, renin activity, aldosterone, creatinine and insulin sensitivity did not differ in the tertiles. In supine laboratory recordings, there were no differences in aortic systolic and diastolic blood pressure, heart rate, cardiac output and systemic vascular resistance. Extracellular water volume was higher in the highest versus lowest tertile of Na+ excretion. In regression analysis, body surface area and 24-h Na+ excretion were independent explanatory variables for extracellular water volume. No differences in urine Na+ excretion and extracellular water volume were found between normotensive and hypertensive participants. When compared with the 510 participants, patients with primary aldosteronism had 6.0% excess in extracellular water (p = .003), and 24-h Na+ excretion was not related with extracellular water volume. CONCLUSION: In the absence of mineralocorticoid excess, Na+ intake, as evaluated from 24-h Na+ excretion, predominantly influences extracellular water volume without a clear effect on blood pressure.

We evaluated sodium intake in 510 subjects by measuring their 24-h sodium excretion to the urine and examined whether sodium intake was related with alterations in cardiovascular function and fluid balance. All participants were without blood pressure lowering medications.Blood pressure was recorded by a device that senses the radial artery pulsations form the wrist. The amount of blood pumped by the heart, the transfer of pressure waves following cardiac contractions and body fluid status were evaluated using bioimpedance, a method recording changes in body electrical resistance.For the analyses, the participants were divided into tertiles according to their 24-h sodium excretions. We also compared results between normotensive and hypertensive subjects.The 24-h sodium excretion in the tertiles corresponded to about 6 g, 9 g and 13 g of salt intake per day, respectively. There were no differences between the tertiles in age, routine laboratory analyses, blood pressure, large arterial stiffness, amount blood pumped by the heart and resistance to blood flow in the arteries. However, there was more extracellular fluid in the highest versus the lowest tertile of sodium excretion. Further statistics indicated that extracellular fluid volume in the body was mainly determined by body size, but it was also moderately influenced by sodium intake.No differences in 24-h sodium excretion and extracellular water volume were found between normotensive and hypertensive participants.In subjects not using blood pressure lowering medications, sodium intake predominantly influences the amount of extracellular fluid without a clear effect on blood pressure.

Patterns of IgA Autoantibody Generation, Inflammatory Responses and Extracellular Matrix Metabolism in Patients with Alcohol Use Disorder.

Recent data have emphasized the role of inflammation and intestinal immunoglobulin A (IgA) responses in the pathogenesis of alcoholic liver disease (ALD). In order to further explore such associations, we compared IgA titers against antigens targeted to ethanol metabolites and tissue transglutaminase with pro- and anti-inflammatory mediators of inflammation, markers of liver status, transferrin protein desialylation and extracellular matrix metabolism in alcohol-dependent patients with or without liver disease and in healthy controls. Serum IgAs against protein adducts with acetaldehyde (HbAch-IgA), the first metabolite of ethanol, and tissue transglutaminase (tTG-IgA), desialylated transferrin (CDT), pro- and anti-inflammatory cytokines, markers of liver status (GT, ALP) and extracellular matrix metabolism (PIIINP, PINP, hyaluronic acid, ICTP and CTx) were measured in alcohol-dependent patients with (n = 83) or without (n = 105) liver disease and 88 healthy controls representing either moderate drinkers or abstainers. In ALD patients, both tTG-IgA and HbAch-IgA titers were significantly higher than those in the alcoholics without liver disease (p < 0.0005 for tTG-IgA, p = 0.006 for Hb-Ach-IgA) or in healthy controls (p < 0.0005 for both comparisons). The HbAch-IgA levels in the alcoholics without liver disease also exceeded those found in healthy controls (p = 0.0008). In ROC analyses, anti-tTG-antibodies showed an excellent discriminative value in differentiating between ALD patients and healthy controls (AUC = 0.95, p < 0.0005). Significant correlations emerged between tTG-IgAs and HbAch-IgAs (rs = 0.462, p < 0.0005), CDT (rs = 0.413, p < 0.0001), GT (rs = 0.487, p < 0.0001), alkaline phosphatase (rs = 0.466, p < 0.0001), serum markers of fibrogenesis: PIIINP (rs = 0.634, p < 0.0001), hyaluronic acid (rs = 0.575, p < 0.0001), ICTP (rs = 0.482, p < 0.0001), pro-inflammatory cytokines IL-6 (rs = 0.581, p < 0.0001), IL-8 (rs = 0.535, p < 0.0001) and TNF-α (rs = 0.591, p < 0.0001), whereas significant inverse correlations were observed with serum TGF-ß (rs = -0.366, p < 0.0001) and CTx, a marker of collagen degradation (rs = -0.495, p < 0.0001). The data indicate that the induction of IgA immune responses toward ethanol metabolites and tissue transglutaminaseis a characteristic feature of patients with AUD and coincides with the activation of inflammation, extracellular matrix remodeling and the generation of aberrantly glycosylated proteins. These processes appear to work in concert in the sequence of events leading from heavy drinking to ALD.

Higher circulating EGF levels associate with a decreased risk of IgE sensitization in young children.

BACKGROUND: Decreased exposure to microbial agents in industrialized countries and urban living areas is considered as a risk factor of developing immune-mediated diseases, such as allergies and asthma. Epithelial surfaces in the gastrointestinal and respiratory tracts and in the skin constitute the primary areas in contact with the environmental microbial load. METHODS: We analyzed the levels of 30 cytokines and growth factors in serum or plasma as markers of the immune maturation in the participants in the DIABIMMUNE study from Russian Karelia (n = 60), Estonia (n = 83) and Finland (n = 89), three neighboring countries with remarkable differences in the incidences of allergies, asthma and autoimmune diseases. RESULTS: We observed an upregulation of T helper cell signature cytokines during the first 12 months of life, reflecting natural development of adaptive immune responses. During the first years of life, circulating concentrations of epidermal growth factor (EGF) were significantly higher, especially in Russian children compared with Finnish children. The children who developed IgE sensitization showed lower levels of EGF than those without such responses. CONCLUSION: Our results suggest that low circulating EGF levels associate with the risk of allergies possibly via the effects on the epithelial integrity and mucosal homeostasis.

The role of alcohol use and adiposity in serum levels of IL-1RA in depressed patients.

BACKGROUND: The role of Interleukin-1 Receptor antagonist (IL-1Ra), an innate antagonist to pro-inflammatory cytokine IL-1, has attracted increasing attention due to its potential pathogenic and therapeutic implications in depression. However, the role of alcohol and adiposity in modulating IL-1Ra cytokine pathway in depressed patients has remainned unknown. The aim of this study was to follow the changes in IL-1Ra serum levels in depressed patients with or without simultaneous alcohol use disorder (AUD) and different degrees of adiposity during 6 months of follow-up. MATERIALS AND METHODS: A total of 242 patients with depression were followed for 6 months. At baseline 99 patients had simultaneous AUD. Levels of serum IL-1Ra and common mediators of inflammation (IL-6, hs-CRP) were measured. Clinical assessments included Body Mass Index (BMI), Montgomery-Asberg Depression Rating Scale (MADRS) and Alcohol Use Disorders Identification Test (AUDIT) scores. RESULTS: Significant reductions in clinical symptoms and IL-1Ra were observed during 6-month follow-up. In hierarchical linear regression analysis, the effect of MADRS score, age, gender, and smoking had a combined effect of 2.4% in the model. The effect of AUDIT score increased the effect to 4.2% of variance (p = 0.08), whereas adding BMI increased the effect to 18.5% (p <  0.001). CONCLUSION: Adiposity may influence the IL-1Ra anti-inflammatory response in depressed patients, whereas the effect of alcohol consumption in these patients seems insignificant. These findings should be considered in studies on the role of IL-1Ra in depression. TRIAL REGISTRATION: Ostrobothnia Depression Study in ClinicalTrials.gov , Identifier NCT02520271 .

Participation in scheduled asthma follow-up contacts and adherence to treatment during 12-year follow-up in patients with adult-onset asthma.

BACKGROUND: Poor treatment compliance is a common problem in the treatment of asthma. To our knowledge, no previous long-term follow-up studies exist on how scheduled asthma follow-up contacts occur in primary health care (PHC) versus secondary care and how these contacts relate to adherence to medication and in participation to further scheduled asthma contacts. The aim of this study was to evaluate occurrence of scheduled asthma contacts and treatment compliance in PHC versus secondary care, and to identify the factors associated with non-participation to scheduled contacts. METHODS: Patients with new adult-onset asthma (n = 203) were followed for 12 years in a real-life asthma cohort of the Seinäjoki Adult Asthma Study (SAAS). The first contacts were mainly carried out in secondary care and therefore the actual follow-up time including PHC visits was 10 years. RESULTS: A majority (71%) of the patients had ≥ 2 scheduled asthma contacts during 10-year follow-up and most of them (79%) mainly in PHC. Patients with follow-up contacts mainly in PHC had better adherence to inhaled corticosteroid (ICS) medication during the whole 12-year period compared to patients in secondary care. In the study population, 29% of the patients had only 0-1 scheduled asthma contacts during the follow-up. Heavy alcohol consumption predicted poor participation in scheduled contacts. CONCLUSIONS: Patients with mainly PHC scheduled asthma contacts were more adherent to ICS medication than patients in the secondary care. Based on our results it is necessary to pay more attention to actualization of asthma follow-up visits and systematic assessment of asthma patients including evaluation of alcohol consumption. Trial registration Seinäjoki Adult Asthma Study is retrospectively registered at www.ClinicalTrials.gov with identifier number NCT02733016. Registered 11 April 2016.

Blood Cell Responses Following Heavy Alcohol Consumption Coincide with Changes in Acute Phase Reactants of Inflammation, Indices of Hemolysis and Immune Responses to Ethanol Metabolites.

Aberrations in blood cells are common among heavy alcohol drinkers. In order to shed further light on such responses, we compared blood cell status with markers of hemolysis, mediators of inflammation and immune responses to ethanol metabolites in alcohol-dependent patients at the time of admission for detoxification and after abstinence. Blood cell counts, indices of hemolysis (LDH, haptoglobin, bilirubin), calprotectin (a marker of neutrophil activation), suPAR, CD163, pro- and anti-inflammatory cytokines and autoantibodies against protein adducts with acetaldehyde, the first metabolite of ethanol, were measured from alcohol-dependent patients (73 men, 26 women, mean age 43.8 ± 10.4 years) at baseline and after 8 ± 1 days of abstinence. The assessments also included information on the quantities of alcohol drinking and assays for biomarkers of alcohol consumption (CDT), liver function (AST, ALT, ALP, GGT) and acute phase reactants of inflammation. At baseline, the patients showed elevated values of CDT and biomarkers of liver status, which decreased significantly during abstinence. A significant decrease also occurred in LDH, bilirubin, CD163 and IgA and IgM antibodies against acetaldehyde adducts, whereas a significant increase was noted in blood leukocytes, platelets, MCV and suPAR levels. The changes in blood leukocytes correlated with those in serum calprotectin (p < 0.001), haptoglobin (p < 0.001), IL-6 (p < 0.02) and suPAR (p < 0.02). The changes in MCV correlated with those in LDH (p < 0.02), MCH (p < 0.01), bilirubin (p < 0.001) and anti-adduct IgG (p < 0.01). The data indicates that ethanol-induced changes in blood leukocytes are related with acute phase reactants of inflammation and release of neutrophil calprotectin. The studies also highlight the role of hemolysis and immune responses to ethanol metabolites underlying erythrocyte abnormalities in alcohol abusers.

Long-term prognosis of new adult-onset asthma in obese patients.

BACKGROUND: Obesity has been associated with poor outcomes of asthma in cross-sectional studies, but long-term effect of obesity on asthma remains unknown. AIMS: To study the effects of obesity, found at the time of diagnosis of adult-onset asthma, on 12-year prognosis by focusing on oral corticosteroid (OCS) use and respiratory-related hospital admissions. METHODS: Patients diagnosed with adult-onset asthma (n=203) were divided into three categories based on diagnostic body mass index (BMI) (<25 kg·m-2, 25-29.9 kg·m-2, ≥30 kg·m-2) and followed for 12 years as part of the Seinäjoki Adult Asthma Study. Self-reported and dispensed OCS were assessed for the 12-year period. Data on hospital admissions were analysed based on medical records. RESULTS: 12 years after diagnosis, 86% of the patients who were obese (BMI ≥30 kg·m-2) at diagnosis remained obese. During the follow-up, no difference was found in weight gain between the BMI categories. During the 12-year follow-up, patients obese at diagnosis reported more frequent use of OCS courses (46.9% versus 23.1%, p=0.028), were dispensed OCS more often (81.6% versus 56.9%, p=0.014) and at higher doses (median 1350 (interquartile range 280-3180) mg versus 600 (0-1650) mg prednisolone, p=0.010) compared to normal-weight patients. Furthermore, patients who were obese had more often one or more respiratory-related hospitalisations compared to normal-weight patients (38.8% versus 16.9%, p=0.033). In multivariate logistic regression analyses, obesity predicted OCS use and hospital admissions. CONCLUSIONS: In adult-onset asthma, patients obese at diagnosis mostly remained obese at long-term and had more exacerbations and respiratory-related hospital admissions compared to normal-weight patients during 12-year follow-up. Weight loss should be a priority in their treatment to prevent this outcome.

Allergy-Related Symptoms Are Poorly Predicted by IgE and Skin Prick Testing in Early Life.

INTRODUCTION: In childhood, the so-called allergic march involves progression from IgE sensitization to allergy-related symptoms. Both IgE sensitization and relevant clinical symptoms are required for the diagnosis of allergy, but concordance between test results and clinical symptoms varies greatly, creating challenges for the diagnostics and for the prediction of outcomes. We assessed the prevalence of IgE sensitization and allergy symptoms, concordance between 2 IgE sensitization testing methods, and predictive value of these tests in relation to clinical symptoms in young Finnish children. METHODS: The current study included 2 series of children: a birth cohort, in which the participants were followed prospectively from birth up to 3 years, and a young children cohort observed from 3 to 5 years of age. They were regularly monitored for sensitization by measuring serum allergen-specific IgEs (sIgEs) and performing skin prick tests (SPTs). The emergence of atopic dermatitis, wheezing, and symptoms associated with food allergies was recorded. RESULTS: Over the first 5 years of life, the prevalence of sIgE sensitization was 46%, while it was 36% for positive SPTs. Disease prevalence was 26% for atopic dermatitis, 25% for wheezing, and 19% for symptoms associated with food allergies. Concordance between sIgE and SPT results was good for aeroallergens, but poor for dietary allergens. The association between clinical symptoms and sensitization was stronger at 5 years than at 3 years of age. The proportion of children with concordant combinations of allergy symptoms and sensitization markers in contrast to those with discordant combinations increased from 3 to 5 years. CONCLUSION: In early childhood, testing for IgE sensitization predicts allergy-related symptoms in an age-dependent manner, but not particularly well. Tests predict symptoms caused by aeroallergens clearly better than those caused by dietary allergens. The clinical relevance of sensitization testing in early life is therefore limited in the prediction of true allergy.

Association of different enteroviruses with atopy and allergic diseases in early childhood.

BACKGROUND: Enterovirus (EV) infections, being among the most prevalent viruses worldwide, have been associated with reduced risk of allergic diseases. We sought to determine the association between EVs and allergic sensitization and disease in early childhood. METHODS: The study was carried out in a nested case-control setting within a prospective birth cohort in Finland. We included 138 case children who had specific IgE (s-IgE) sensitization at the age of 5 years and 138 control children without s-IgE sensitization. Allergic disease was recorded at study visits and identified with the ISAAC questionnaire. We screened for the presence of serotype-specific antibodies against 41 EVs at 1-5 years of age and assessed their association with allergic sensitization and disease. RESULTS: The overall number of EV infections did not differ between s-IgE-sensitized children and non-sensitized control children. However, there was a tendency of case children with an allergic disease having less EV infections than their controls. This observation was statistically significant for species A EVs in case children with atopic dermatitis vs. control children: OR 0.6 (95% CI 0.36-0.99), p = .048. CONCLUSION: This study supports the evidence that EV exposure and development of allergic disease are inversely associated. Interestingly, the inverse association was not observed for bare atopic IgE sensitization, but for IgE sensitization coupled with clinical atopic disease. This suggests that environmental factors influencing IgE sensitization may differ from those influencing progression to clinical allergic disease.

Plasma uric acid is related to large arterial stiffness but not to other hemodynamic variables: a study in 606 normotensive and never-medicated hypertensive subjects.

BACKGROUND: Elevated level of plasma uric acid (PUA) has been associated with cardiovascular disease, but whether uric acid is an independent risk factor or merely a marker remains controversial. METHODS: We investigated in a cross-sectional setting the association of PUA with hemodynamics in 606 normotensive and never-medicated hypertensive subjects (295 men, 311 women, age range 19-73 years) without cardiovascular disease or gout. In all except 15 individuals, PUA was within the normal range. Supine hemodynamics were recorded using whole-body impedance cardiography and radial tonometric pulse wave analysis. RESULTS: The mean concentrations of PUA in age, sex and body mass index adjusted quartiles were 234, 278, 314, and 373 µmol/l, respectively. The highest PUA quartile presented with higher aortic to popliteal pulse wave velocity (PWV) than the lowest quartile (8.7 vs. 8.2 m/s, p = 0.026) in analyses additionally adjusted for plasma concentrations of C-reactive protein, low density lipoprotein cholesterol, triglycerides, and mean aortic blood pressure. No differences in radial and aortic blood pressure, wave reflections, heart rate, cardiac output, and systemic vascular resistance were observed between the quartiles. In linear regression analysis, PUA was an independent explanatory factor for PWV (ß = 0.168, p < 0.001, R2 of the model 0.591), but not for systolic or diastolic blood pressure. When the regression analysis was performed separately for men and women, PUA was an independent predictor of PWV in both sexes. CONCLUSIONS: PUA concentration was independently and directly associated with large arterial stiffness in individuals without cardiovascular disease and PUA levels predominantly within the normal range. Trial registration ClinicalTrials.gov NCT01742702.

Relationship between age and bronchodilator response at diagnosis in adult-onset asthma.

BACKGROUND: Possible variation in bronchodilator response (BDR) according to age at the diagnosis of adult-onset asthma is unknown. Our aim was to assess if BDR in FEV1 is related to age at diagnosis of adult-onset asthma and how many subjects fulfill the 400 mL criterion of BDR, the suggested cut-off for asthma-like reversibility in asthma-COPD overlap (ACO). METHODS: A total of 1030 patients with adult-onset asthma were included; 245 from SAAS (Seinäjoki Adult Asthma Study, Finland) and 785 from COREA (Cohort for Reality and Evolution of Adult Asthma in Korea) cohorts. BDR in FEV1 at the diagnosis of asthma was assessed. Patients were divided into groups based on age at asthma diagnosis: < 40, 40-59.9, and ≥ 60 years. The cohorts were analyzed separately. RESULTS: BDR % in FEV1 did not differ between the groups of different age at asthma diagnosis and no correlation between BDR and age was found. Of patients aged ≥40 years, only 18% (SAAS-cohort) and 5% (COREA-cohort) reached the 400 mL BDR in FEV1. After exclusion of possible ACO patients, the results remained similar. CONCLUSION: By using two large cohorts of steroid-naive patients with asthma, we have shown that BDR at diagnosis of asthma is constant over large age span range, and the limit of 400 mL in BDR in FEV1 is rarely reached. TRIAL REGISTRATION: Seinäjoki Adult Asthma Study is registered at ClinicalTrials.gov with identifier number NCT02733016 .

Contrasting microbiotas between Finnish and Estonian infants: Exposure to Acinetobacter may contribute to the allergy gap.

BACKGROUND: Allergic diseases are more common in Finland than in Estonia, which-according to the biodiversity hypothesis-could relate to differences in early microbial exposures. METHODS: We aimed at defining possible microbial perturbations preceding early atopic sensitization. Stool, nasal and skin samples of 6-month-old DIABIMMUNE study participants with HLA susceptibility to type 1 diabetes were collected. We compared microbiotas of sensitized (determined by specific IgE results at 18 months of age) and unsensitized Estonian and Finnish children. RESULTS: Sensitization was differentially targeted between populations, as egg-specific and birch pollen-specific IgE was more common in Finland. Microbial diversity and community composition also differed; the genus Acinetobacter was more abundant in Estonian skin and nasal samples. Particularly, the strain-level profile of Acinetobacter lwoffii was more diverse in Estonian samples. Early microbiota was not generally associated with later sensitization. Microbial composition tended to differ between children with or without IgE-related sensitization, but only in Finland. While land-use pattern (ie green areas vs. urban landscapes around the children's homes) was not associated with microbiota as a whole, it associated with the composition of the genus Acinetobacter. Breastfeeding affected gut microbial composition and seemed to protect from sensitization. CONCLUSIONS: In accordance with the biodiversity hypothesis, our results support disparate early exposure to environmental microbes between Finnish and Estonian children and suggest a significant role of the genus Acinetobacter in the allergy gap between the two populations. The significance of the observed differences for later allergic sensitization remains open.

Early exposure to cats, dogs and farm animals and the risk of childhood asthma and allergy.

BACKGROUND: Synergistic role of exposure to cats, dogs, and farm animals during infancy on the risk of childhood asthma and allergy remains unknown. OBJECTIVES: To investigate independent and synergistic associations between exposure to indoor pets and farm animals during infancy and the risk of asthma and allergy by age 5. METHODS: We studied 3781 children participating in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study. At age 5, a validated version of the International Study of Asthma and Allergies in Childhood questionnaire was administered to collect information on asthma and allergic disease, and exposure to indoor pets and farm animals during the first year of life. Allergen-specific IgE antibodies were analyzed from serum samples. Statistical analyses employed Cox proportional hazards and logistic regression. RESULTS: Having a dog in the house was inversely associated with the risk of asthma (HR 0.60; 95% CI, 0.38-0.96), allergic rhinitis (OR 0.72; 95% CI, 0.53-0.97), and atopic sensitization (OR 0.77; 95% CI, 0.63-0.96). Having a cat was associated with a decreased risk of atopic eczema (OR 0.68; 95% CI, 0.51-0.92). Farm animals were neither independently nor in synergy with indoor pets associated with the outcomes. CONCLUSION: Having a dog or cat in the house during the first year of life may protect against childhood asthma and allergy. We did not find a synergistic association between cat, dog, and farm animal exposure on the risk of childhood asthma and allergy. Future research should identify specific causative exposures conferred by indoor pets and whether they could be recommended for allergy prevention.

Combined effects of lifestyle risk factors on fatty liver index.

BACKGROUND: Factors of lifestyle may have a major impact on liver-related morbidity and mortality. We examined independent and joint effects of lifestyle risk factors on fatty liver index (FLI), a biomarker of hepatic steatosis, in a population-based cross-sectional national health survey. METHODS: The study included 12,368 participants (5784 men, 6584 women) aged 25-74 years. Quantitative estimates of alcohol use, smoking, adiposity and physical activity were used to establish a total score of risk factors, with higher scores indicating an unhealthier lifestyle. FLI was calculated based on an algorithm including body mass index, waist circumference, serum gamma-glutamyltransferase and triglycerides. RESULTS: The occurrence of FLI ≥ 60% indicating fatty liver increased from 2.4% in men with zero risk factors to 81.9% in those with a total risk score of 7-8 (p <  0.0005 for linear trend) and in women from 0 to 73.5% (p <  0.0005). The most striking individual impacts on the likelihood for FLI above 60% were observed for physical inactivity (p <  0.0005 for both genders) and alcohol consumption (p <  0.0005 for men). Interestingly, coffee consumption was also found to increase with increasing risk factor scores (p <  0.0005 for linear trend in both genders). CONCLUSIONS: The data indicates that unfavorable combinations of lifestyle risk factors lead to a high likelihood of hepatic steatosis. Use of FLI as a diagnostic tool may benefit the assessment of interventions aimed at maintaining a healthy lifestyle and prevention of liver-related morbidity.

Plasma total calcium concentration is associated with blood pressure and systemic vascular resistance in normotensive and never-treated hypertensive subjects.

Purpose: The underlying causes of primary hypertension are not fully understood. Evidence on the relation of plasma calcium concentration with blood pressure (BP) is inconsistent and relies largely on studies utilizing office BP measurements in populations using cardiovascular drugs. In many studies adjustment for confounders was not optimal. In this cross-sectional study we examined the association of plasma total calcium concentration with the haemodynamic determinants of blood pressure.Subjects and methods: Supine haemodynamics were recorded using pulse wave analysis, whole-body impedance cardiography, and heart rate variability analysis in 618 normotensive or never-treated hypertensive subjects (aged 19-72 years) without diabetes, cardiovascular or renal disease, or cardiovascular medications. Linear regression analysis was used to investigate factors associated with haemodynamic variables.Results: Mean age was 45.0 years, body mass index 26.8 kg/m2, seated office BP 141/89 mmHg, and 307 subjects (49.7%) were male. Mean values of routine blood and plasma chemistry analyses were within the reference limits of the tests except for low-density lipoprotein cholesterol (3.05 mmol/l). In the laboratory, mean supine radial BP was 131/75 mmHg, and both systolic and diastolic BP correlated directly with plasma total calcium concentration (r = 0.25 and r = 0.22, respectively, p < 0.001 for both). In regression analysis plasma total calcium concentration was an independent explanatory variable for radial and aortic systolic and diastolic BP, and systemic vascular resistance, but not for cardiac output, pulse wave velocity, or any of the heart rate variability parameters.Conclusion: Plasma total calcium concentration was directly associated with systolic and diastolic BP and systemic vascular resistance in normotensive or never-treated hypertensive subjects without comorbidities and cardiovascular medications. Higher plasma calcium concentration potentially plays a role in primary hypertension via an effect on vascular resistance.

Development of atopic sensitization in Finnish and Estonian children: A latent class analysis in a multicenter cohort.

BACKGROUND: The prevalence of atopy is associated with a Western lifestyle, as shown by studies comparing neighboring regions with different socioeconomic backgrounds. Atopy might reflect various conditions differing in their susceptibility to environmental factors. OBJECTIVE: We sought to define phenotypes of atopic sensitization in early childhood and examine their association with allergic diseases and hereditary background in Finland and Estonia. METHODS: The analysis included 1603 Finnish and 1657 Estonian children from the DIABIMMUNE multicenter young children cohort. Specific IgE levels were measured at age 3, 4, and 5 years, respectively, and categorized into 3 CAP classes. Latent class analysis was performed with the statistical software package poLCA in R software. RESULTS: Both populations differed in terms of socioeconomic status and environmental determinants, such as pet ownership, farm-related exposure, time spent playing outdoors, and prevalence of allergic diseases (all P < .001). Nevertheless, we found similar latent classes in both populations: an unsensitized class, a food class, 2 inhalant classes differentiating between seasonal and perennial aeroallergens, and a severe atopy class. The latter was characterized by high total and specific IgE levels and strongly associated with wheeze (odds ratio [OR], 5.64 [95% CI, 3.07-10.52] and 4.56 [95% CI, 2.35-8.52]), allergic rhinitis (OR, 22.4 [95% CI, 11.67-44.54] and 13.97 [95% CI, 7.33-26.4]), and atopic eczema (OR, 9.39 [95% CI, 4.9-19.3] and 9.5 [95% CI, 5.2-17.5] for Finland and Estonia, respectively). Environmental differences were reflected in the larger seasonal inhalant atopy class in Finland, although composition of classes was comparable between countries. CONCLUSION: Despite profound differences in environmental exposures, there might exist genuine patterns of atopic sensitization. The distribution of these patterns might determine the contribution of atopic sensitization to disease onset.