New insights into the optimal management of COPD: extracts from CHEST 2021 annual meeting (October 17-20, 2021).

INTRODUCTION: Discordance between real-world prescribing patterns and global treatment guidelines for the treatment of chronic obstructive pulmonary disease (COPD) with inhaled single or dual long-acting bronchodilator maintenance therapy is increasingly being reported in the literature, particularly with regard to addition of inhaled corticosteroids (ICS). Patient-related factors, e.g. inhalation technique and inspiratory flow, are key to disease control in COPD. Treatment discordance and patient-related factors can lead to high-cost side effects and sub-optimal treatment benefit; furthermore, the COVID-19 pandemic has led to new challenges in COPD management. AREAS COVERED: This article summarizes a series of presentations sponsored by Boehringer Ingelheim and delivered at the annual CHEST congress 2021 (October 17-20, 2021) that explored new insights into the optimal management of COPD. EXPERT OPINION/COMMENTARY: There is a concerning high degree of discordance with GOLD recommendations. Dual therapy without addition of ICS does not increase exacerbation risk and could reduce pneumonia risk, and unnecessary prescription of triple therapy has financial implications. Clinic-based spirometry may not reflect the home setting, and training is required; inhalers that operate independently of users' inhalation profiles should be considered. Integration of digital healthcare solutions into clinical studies is suggested in the post-COVID setting, although further evaluation is required.

Cardiovascular events and all-cause mortality in patients with chronic obstructive pulmonary disease using olodaterol and other long-acting beta2-agonists.

PURPOSE: We examined the effect of olodaterol on the risk of myocardial ischaemia, cardiac arrhythmia, and all-cause mortality compared with use of other long-acting beta2-agonists (LABAs). Channelling bias was also explored. METHODS: This Danish population-based cohort study used data linked from registries of hospital diagnoses, outpatient dispensings, and deaths. It included patients (aged ≥40 years) with a diagnosis of chronic obstructive pulmonary disease (COPD) who initiated olodaterol or another LABA. Using matching and propensity score (PS) stratification, we calculated adjusted incidence rate ratios (IRRs) using Poisson regression, followed by several additional analyses to evaluate and control channelling bias. RESULTS: The IRRs of cardiac arrhythmias or myocardial ischaemia among users of olodaterol (n = 14 239) compared to users of other LABAs (n = 51 167) ranged from 0.96 to 1.65 in various analyses, although some estimates had low precision. Initial analysis suggested an increased risk for death with olodaterol compared with other LABAs (IRR, 1.63; 95% CI, 1.44-1.84). Because olodaterol prescribing was associated with COPD severity, the mortality association was attenuated by using different methods of tighter confounding control: the IRRs were 1.26 (95% CI, 0.97-1.64) among LABA-naïve LABA/LAMA users without recent COPD hospitalisation; 1.27 (95% CI, 1.03-1.57) in a population with additional trimming from the tails of the PS distribution; and 1.32 (95% CI, 1.19-1.48) after applying overlap-weights analysis. CONCLUSIONS: Olodaterol users had a similar risk for cardiac arrhythmias or myocardial ischaemia as other LABA users. The observed excess all-cause mortality associated with olodaterol use could be due to uncontrolled channelling bias.

Treatment Transitions in Chronic Obstructive Pulmonary Disease: Retrospective Analyses of US and UK Healthcare Databases.

INTRODUCTION: Previous studies have reported that more patients receive inhaled corticosteroid (ICS)-containing therapies than would be expected based on exacerbation history, suggesting overprescribing. We aimed to describe patterns of treatment switching from first (1MT) to second maintenance therapy (2MT) among COPD patients in the US and UK. METHODS: We used healthcare data from the US IBM® MarketScan® and UK Clinical Practice Research Datalink databases (2015 - 2018) to assess transitions between 1MT and 2MT among COPD patients. Patients with a recorded asthma diagnosis prior to 1MT were excluded. We assessed whether prescribed treatments (long-acting muscarinic antagonists [LAMA], long-acting ß2-agonists [LABA], inhaled corticosteroids [ICS], as monotherapy or in combination) were consistent with global and national recommendations for COPD, identified patient characteristics associated with treatment transitions, and evaluated treatment duration. RESULTS: Overall, 7028 patients in the US and 2461 in the UK initiated 2MT within a median (IQR) 160.0 (76.0; 335.0) and 218.0 (86.0; 428.0) days after 1MT, respectively. In the US, 33.6% of patients initiating 2MT had no recorded exacerbations in the previous year, whereas 23.1% had one and 43.3% had ≥ 2. In the UK, 54.9% of patients had no recorded exacerbations in the previous year, whereas 20.9% had one and 24.2% had ≥ 2. At 2MT, most patients switched to LAMA/LABA/ICS (26.1%) or LABA/ICS (25.8%) in the US, and LAMA/LABA (39.4%) or LAMA/LABA/ICS (27.8%) in the UK; 62.2% (US) and 47.5% of patients (UK) were prescribed ICS-containing regimens. The most common treatment transition from 1MT to 2MT was LABA/ICS to LAMA/LABA/ICS (13.0%) in the US; and LAMA to LAMA/LABA (32.5%) and LAMA to LAMA/LABA/ICS (14.3%) in the UK. CONCLUSIONS: At 2MT, the proportion of patients on LAMA/LABA/ICS was similar between the US and UK, but treatment pathways were different.

People with chronic obstructive pulmonary disease (COPD) take inhaled medication to control symptoms such as breathlessness and cough. There are two types of inhaler: 'reliever' inhalers for immediate symptom relief, and 'maintenance' inhalers for long-term disease control. Maintenance inhalers can be used on their own or together, and treatment is often escalated based on the persistence of symptoms or exacerbations (flare-ups), for which inhaled corticosteroids (ICS) are often prescribed. We wanted to see whether doctors' prescribing habits are in line with clinical guidelines, so we looked at data from COPD patients who switched from their first maintenance therapy (1MT) to a second, different maintenance therapy (2MT) between 2015 and 2018. Our data sources were a US health claims database (~ 7000 patients) and a UK general practice database (~ 2500 patients). We excluded people with a diagnosis of both COPD and asthma, as similar inhalers are used to treat these two conditions, although the clinical decisions for when to prescribe them differ. On average, the time between 1MT and 2MT was 160 days (US) and 218 days (UK). Overall, 50% (UK) and 60% of patients (US) were prescribed ICS as part of their treatment regimen at 2MT, and ICS use in both countries was higher than expected based on the guidelines, which recommend ICS only for patients with severe COPD who meet certain criteria. This means that some patients are being given medication without a known clinical benefit, which puts them at risk of side effects, possibly increasing unnecessary healthcare costs.

First Maintenance Therapy for Chronic Obstructive Pulmonary Disease: Retrospective Analyses of US and UK Healthcare Databases.

INTRODUCTION: Inhaled corticosteroids (ICS) are often prescribed inappropriately alongside long-acting bronchodilators for chronic obstructive pulmonary disease (COPD). We aimed to investigate if prescribing habits in the US and UK differ from recommendations for initiation of COPD maintenance therapy. METHODS: We used healthcare data from the US IBM® MarketScan® and UK Clinical Practice Research Datalink databases to assess exacerbations and comorbidities in patients with COPD initiating first maintenance therapy (1MT) between 2015 and 2018. Patients with a recorded asthma diagnosis prior to initiation of 1MT were excluded. We evaluated time from recorded diagnosis of COPD until initiation of 1MT, and treatment regimen at 1MT (long-acting muscarinic antagonist [LAMA], long-acting ß2-agonist [LABA], ICS, as monotherapy or in combination). RESULTS: In the US and UK, median (IQR) time between recorded COPD diagnosis and 1MT was 158 (12; 839) and 29 (1; 521) days, respectively. Among the 53,473 US patients and 8786 UK patients who initiated 1MT, 50.9% and 32.4% had ≥ 1 exacerbation in the previous year. In the US, 20% of patients initiated LAMA, 1% LABA, 13% LAMA/LABA, and 66% an ICS-containing regimen (49% LABA/ICS, 13% ICS, and 4% LAMA/LABA/ICS). In the UK, 53% of patients initiated LAMA, 4% LABA, 16% LAMA/LABA, and 27% an ICS-containing regimen (14% LABA/ICS, 9% ICS, and 4% LAMA/LABA/ICS). CONCLUSIONS: At 1MT, two-thirds of patients in the US received ICS-containing therapies, with almost half on LABA/ICS. In contrast, less than one-third received ICS-containing therapy in the UK and more than half of patients received LAMA. In both countries, more patients received ICS-containing therapies at initiation of 1MT than would be expected based on their exacerbation history, suggesting overprescribing.

Chronic obstructive pulmonary disease (COPD), a smoking-related lung disease, restricts airflow in the lungs, causing symptoms such as breathlessness and coughing. To control symptoms, patients use one or more types of inhaled 'maintenance' medication, which can be prescribed alone or together. When patients have a short-term worsening of symptoms, doctors often prescribe inhaled corticosteroids (ICS). We wanted to see whether doctors' prescribing habits for maintenance inhalers are in line with clinical guidelines, so we analyzed data from a US health insurance database (~ 50,000 patients) and UK primary care medical records (~ 8000 patients). We focused on patients with a diagnosis of COPD who were prescribed their first maintenance therapy (1MT) between 2015 and 2018. We excluded people with a diagnosis of both COPD and asthma, as similar inhalers are used to treat these conditions, although the clinical decisions for when to prescribe them differ. The average time between COPD diagnosis and 1MT was longer in the US (158 days) than in the UK (29 days). A higher percentage of patients in the US (~ 65%) versus UK (~ 25%) were prescribed ICS as part of their treatment, and ICS use in both countries was higher than expected based on the guidelines, which recommend ICS only for patients with severe COPD who meet certain criteria. Our findings suggest overprescribing of ICS in both countries (particularly the US), meaning that some patients are being given medication without a known clinical benefit, which puts them at risk of side effects, possibly increasing unnecessary healthcare costs.

Effectiveness and Safety of COPD Maintenance Therapy with Tiotropium/Olodaterol versus LABA/ICS in a US Claims Database.

INTRODUCTION: In patients with chronic obstructive pulmonary disease (COPD), treatment with long-acting muscarinic antagonist (LAMA)/long-acting ß2-agonist (LABA) combination therapy significantly improves lung function versus LABA/inhaled corticosteroid (ICS). To investigate whether LAMA/LABA could provide better clinical outcomes than LABA/ICS, this non-interventional database study assessed the risk of COPD exacerbations, pneumonia, and escalation to triple therapy in patients with COPD initiating maintenance therapy with tiotropium/olodaterol versus any LABA/ICS combination. METHODS: Administrative healthcare claims and laboratory results data from the US HealthCore Integrated Research Databasesm were evaluated for patients with COPD initiating tiotropium/olodaterol versus LABA/ICS treatment (January 2013-March 2019). Patients were aged at least 40 years with a diagnosis of COPD (but not asthma) at cohort entry. A Cox proportional hazard regression model was used (as-treated analysis) to assess risk of COPD exacerbation, community-acquired pneumonia, and escalation to triple therapy, both individually and as a combined risk of any one of these events. Potential imbalance of confounding factors between cohorts was handled using fine stratification, reweighting, and trimming by exposure propensity score (high-dimensional); subgroup analyses were conducted on the basis of blood eosinophil levels and exacerbation history. RESULTS: The total population consisted of 61,985 patients (tiotropium/olodaterol n = 2684; LABA/ICS n = 59,301); after reweighting, the total was 42,953 patients (tiotropium/olodaterol n = 2600; LABA/ICS n = 40,353; mean age 65 years; female 54.5%). Patients treated with tiotropium/olodaterol versus LABA/ICS experienced a reduction in the risk of COPD exacerbations (adjusted hazard ratio 0.76 [95% confidence interval 0.68, 0.85]), pneumonia (0.74 [0.57, 0.97]), escalation to triple therapy (0.22 [0.19, 0.26]), and any one of these events (0.45 [0.41, 0.49]); the combined risk was similar irrespective of baseline eosinophils and exacerbation history. CONCLUSIONS: In patients with COPD, tiotropium/olodaterol was associated with a lower risk of COPD exacerbations, pneumonia, and escalation to triple therapy versus LABA/ICS, both individually and in combination; the combined risk was reduced irrespective of baseline eosinophils or exacerbation history. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04138758 (registered 23 October 2019).

No Evidence of Off-label Use of Olodaterol and Indacaterol in Denmark, France, and the Netherlands: A Drug Utilization Study.

To characterize the use of olodaterol and indacaterol in clinical practice and to quantify the off-label use in asthma. Drug utilization study of new users of olodaterol or indacaterol between 2014 and 2017 in the PHARMO Database Network in the Netherlands, the Danish population registers, and the IMS Real-World Evidence Longitudinal Patient Database panels in France. On-label use was defined as use among adults with a recorded diagnosis of COPD. Off-label use was defined as use among adults with a recorded diagnosis of asthma without a recorded diagnosis of COPD or as use among patients aged ≤18 years. Potential off-label use was defined as no recorded diagnosis of either COPD or asthma. The study included 4,158 new users of olodaterol and 9,966 new users of indacaterol. Prevalence of off-label use ranged from 3.5% for both drugs to 12.4% for olodaterol and 11.9% for indacaterol. Prevalence of on-label use ranged from 47.8% to 77.7% for olodaterol and from 28.7% to 70.1% for indacaterol. The remaining new users of olodaterol and indacaterol were classified as potential off-label users, with prevalence ranging from 17.3% to 48.6% for olodaterol and from 20.5% to 66.6% for indacaterol. This study provides no evidence of a major concern in Europe for olodaterol or indacaterol for off-label use in asthma or for pediatric use.

Patient database analysis of fulvestrant 500 mg in the treatment of metastatic breast cancer: A European perspective.

INTRODUCTION: Clinical guidelines recommend that patients with hormone receptor (HR)-positive metastatic breast cancer (MBC) should be preferentially treated with endocrine therapy. Fulvestrant (a selective estrogen receptor degrader) is approved for use in these patients following relapse after, or relapse or progression during, antiestrogen therapy. This descriptive study analyzed European treatment patterns for HR-positive MBC in real-world clinical practice. METHODS: The IMS Oncology Analyzer (OA), a retrospective cancer treatment database reporting physician-entered patient case histories, was used to identify records for postmenopausal women with HR-positive MBC from April 1, 2004 to June 30, 2013 in France, Germany, Italy, and Spain. Treatments were allocated to mutually exclusive categories (fulvestrant-containing, aromatase inhibitor [AI]-containing, tamoxifen-containing, or chemotherapy-containing regimens) and assessed by line of therapy for MBC. Fulvestrant use was also assessed pre- and post-2010 (when fulvestrant 500 mg dosing was approved). RESULTS: In total, 27,214 eligible patients were included (France: 6801; Germany: 6852; Italy: 7061; Spain: 6500). Chemotherapy-based regimens were the most common first-line treatments for MBC across all countries. Across countries, the proportion of patients initiating on each treatment category ranged from: chemotherapy, 57.5-70.4%; AI, 23.5-30.1%; tamoxifen, 2.7-9.8%; fulvestrant 0.8-2.6%. When administered, fulvestrant was usually given as first- or second-line treatment. Post-2010, more patients received fulvestrant 500 mg than fulvestrant 250 mg in France, Germany, and Spain; in Italy, more patients continued to receive fulvestrant 250 mg. CONCLUSION: Most patients with HR-positive MBC receive chemotherapy over endocrine therapy; fulvestrant constitutes a small proportion of treatments for such patients.

Difference in diet between a general population national representative sample and individuals with alcohol use disorders, but not individuals with depressive or anxiety disorders.

BACKGROUND: Mental disorders influence diet and food consumption, but there is a lack of consistent findings. AIMS: To investigate food consumption, nutrient intakes and serum metabolic biomarkers in depressive, anxiety and alcohol use disorders in comparison with the remaining from a population-based nationwide sample. METHODS: The study was based on the Health 2000 Survey data of which 5504 subjects aged 30 and over (3009 women and 2495 men) were used for the analysis. Depressive disorder, anxiety disorders and alcohol use disorders were diagnosed using the Composite International Diagnostic Interview (M-CIDI). The consumption of food and beverage items, and nutrient intakes were measured with a validated food frequency questionnaire, and the concentrations of biomarkers were determined in blood samples. RESULTS: Overall, no similar differences with both genders were found in the intakes of energy, dietary fibre or macronutrients or in biomarkers in depressive or anxiety disorders. Women suffering from depressed disorder consumed more soft drinks (P = 0.034) and women suffering from anxiety disorders consumed more oils (P = 0.001), polyunsaturated fatty acids (P = 0.001) and less potatoes (P = 0.002) than the remaining participants. Men suffering from depressive disorder consumed less sweets and chocolate (P = 0.001) and men with anxiety disorder consumed more tea (P = 0.033) compared with the remaining participants. In alcohol use disorders, the intake of carbohydrate was lower in both genders (P = 0.001 for women, P = 0.001 for men). CONCLUSIONS: A difference in the usual diet exists between individuals with alcohol use disorders and the remaining participants on a population level. No consistent difference in both genders between those with depressive or anxiety disorders and the remaining was found.

Consumption of red meat and whole-grain bread in relation to biomarkers of obesity, inflammation, glucose metabolism and oxidative stress.

PURPOSE: To examine the association of red meat and whole-grain bread consumption with plasma levels of biomarkers related to glucose metabolism, oxidative stress, inflammation and obesity. METHODS: Our cross-sectional study was based on 2,198 men and women who were selected as a sub-cohort for an investigation of biological predictors of diabetes and cardiovascular diseases from the European Prospective Investigation into Cancer and Nutrition-Potsdam study. Circulating levels of glycated hemoglobin, adiponectin, hs-CRP, gamma-glutamyltransferase, alanine-aminotransferase, fetuin-A, HDL-cholesterol and triglycerides were measured from random blood samples. Diet and lifestyle data were assessed by questionnaires, and anthropometric data were measured. RESULTS: After multivariable adjustment, higher consumption of whole-grain bread was significantly (P trend <0.05) associated with lower levels of GGT, ALT and hs-CRP, whereas higher consumption of red meat was significantly associated with higher levels of GGT and hs-CRP when adjusted for potential confounding factors related to lifestyle and diet. Further adjustment for body mass index and waist circumference attenuated the association between red meat and hs-CRP (P = 0.19). CONCLUSIONS: The results of this study suggest that high consumption of whole-grain bread is related to lower levels of GGT, ALT and hs-CRP, whereas high consumption of red meat is associated with higher circulating levels of GGT and hs-CRP.

Reliability of plasma fibroblast growth factor 23 as risk biomarker in epidemiological studies measured over a four-month period.

BACKGROUND: Identified as a biomarker of altered calcium-phosphorus metabolism in chronic kidney disease, fibroblast growth factor 23 (FGF-23) can also be used as a biomarker of risk for cardiovascular disease in the general population. However, it is crucial to first evaluate the reproducibility (reliability) of plasma FGF-23 concentrations. METHODS: We assessed the reliability of plasma FGF-23 concentrations using replicate blood samples taken four months apart of 207 participants from the European Prospective Investigation into Cancer and Nutrition-Potsdam Study. RESULTS: Plasma FGF-23 concentrations at baseline (geometric mean: 24.7 RU/mL; 95% confidence interval [CI] in RU/mL: 21.8-27.9) were not significantly different from those measured four months later (geometric mean: 23.7 RU/mL; 95% CI in RU/mL: 20.6-27.1; P = 0.42). The intraclass correlation coefficients were 0.69 (95% CI: 0.62-0.76) for all; 0.64 (95% CI: 0.50-0.75) for men and 0.73 (95% CI: 0.64-0.81) for women. CONCLUSIONS: Plasma FGF-23 concentrations showed good reliability over time. Our findings suggest that in epidemiological studies, a single plasma FGF-23 measurement may be sufficient to derive the relative risk in prospective cohort studies.

HbA1c measured in stored erythrocytes is positively linearly associated with mortality in individuals with diabetes mellitus.

INTRODUCTION: Observational studies have shown that glycated haemoglobin (HbA(1c)) is related to mortality, but the shape of the association is less clear. Furthermore, disease duration and medication may modify this association. This observational study explored the association between HbA(1c) measured in stored erythrocytes and mortality. Secondly, it was assessed whether disease duration and medication use influenced the estimates or were independently associated with mortality. METHODS: Within the European Prospective Investigation into Cancer and Nutrition a cohort was analysed of 4,345 individuals with a confirmed diagnosis of diabetes at enrolment. HbA(1c) was measured in blood samples stored up to 19 years. Multivariable Cox proportional hazard regression models for all-cause mortality investigated HbA(1c) in quartiles as well as per 1% increment, diabetes medication in seven categories of insulin and oral hypoglycaemic agents, and disease duration in quartiles. RESULTS: After a median follow-up of 9.3 years, 460 participants died. Higher HbA(1c) was associated with higher mortality: Hazard Ratio for 1%-increase was 1.11 (95% CI 1.06, 1.17). This association was linear (P-nonlinearity = 0.15) and persistent across categories of medication use, disease duration, and co-morbidities. Compared with metformin, other medication types were not associated with mortality. Longer disease duration was associated with mortality, but not after adjustment for HbA(1c) and medication. CONCLUSION: This prospective study showed that persons with lower HbA(1c) had better survival than those with higher HbA(1c). The association was linear and independent of disease duration, type of medication use, and presence of co-morbidities. Any improvement of HbA(1c) appears to be associated with reduced mortality risk.

The association of circulating adiponectin levels with pancreatic cancer risk: a study within the prospective EPIC cohort.

Excess body weight and type 2 diabetes mellitus, risk factors of pancreatic cancer, are characterized by decreased levels of adiponectin. In addition to anti-inflammatory and anti-proliferative actions, adiponectin has an important role in regulating glucose metabolism, i.e., decreasing circulating blood glucose levels. Prospectively, hyperglycemia has been associated with risk of pancreatic cancer. The aim of this study was to investigate the association of pre-diagnostic adiponectin levels with pancreatic cancer risk. We conducted a case-control study nested within European Prospective Investigation into Cancer and Nutrition. Blood samples of 452 pancreatic cancer cases and 452 individually matched controls were analyzed by immunoassays. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Overall, adiponectin showed no association with pancreas cancer risk; however, among never smokers, higher circulating levels of adiponectin were associated with a reduction in pancreatic cancer risk (OR = 0.44 [95% CI 0.23-0.82] for highest vs. lowest quartile), whereas among current smokers there was no significant association (OR = 1.59 [95% CI 0.67-3.76] for highest vs. lowest quartile; p-trend = 0.530; p-interaction = 0.309). In our study, lower adiponectin concentrations may be associated with the development of pancreatic cancer among never smokers, whereas the only other prospective study being conducted so far showed a decrease in risk among male smokers. Therefore, further studies are needed to clarify the role of adiponectin in pancreatic cancer development.

Associations between general and abdominal adiposity and mortality in individuals with diabetes mellitus.

Individuals with diabetes mellitus are advised to achieve a healthy weight to prevent complications. However, fat mass distribution has hardly been investigated as a risk factor for diabetes complications. The authors studied associations between body mass index, waist circumference, waist/hip ratio, and waist/height ratio and mortality among individuals with diabetes mellitus. Within the European Prospective Investigation into Cancer and Nutrition, a subcohort was defined as 5,435 individuals with a confirmed self-report of diabetes mellitus at baseline in 1992-2000. Participants were aged 57.3 (standard deviation, 6.3) years, 54% were men, the median diabetes duration was 4.6 (interquartile range, 2.0-9.8) years, and 22% of the participants used insulin. Body mass index, as indicator of general obesity, was not associated with higher mortality, whereas all measurements of abdominal obesity showed a positive association. Associations generally were slightly weaker in women. The strongest association was observed for waist/height ratio: In the fifth quintile, the hazard rate ratio was 1.88 (95% confidence interval: 1.33, 2.65) for men and 2.46 (95% confidence interval: 1.46, 4.14) for women. Measurements of abdominal, but not general, adiposity were associated with higher mortality in diabetic individuals. The waist/height ratio showed the strongest association. Respective indicators might be investigated in risk prediction models.

Estimation of the contribution of biomarkers of different metabolic pathways to risk of type 2 diabetes.

The contribution of different biological pathways to the development of type 2 diabetes was quantified in a case-cohort design based on circulating blood biomarkers from participants aged 35-65 years in the EPIC-Potsdam Study. The analytic sample included 613 participants with incident diabetes and 1965 participants without diabetes. The proportion that each biomarker contributed to the risk of diabetes was quantified using effect decomposition method. Summarized risk of each biomarker was estimated by an index based on quintiles of gamma-glutamyltransferase (GGT), HDL-cholesterol, hs-CRP, and adiponectin. Cox proportional hazard regression was used to estimate relative risks adjusted for age, sex, body mass index, waist-circumference, education, sport activity, cycling, occupational activity, smoking, alcohol intake, and consumptions of red meat, coffee and whole grain bread. Adiponectin explained a total of 32.1% (CI = 16.8, 49.1%) of the risk related to index. For the other biomarkers the corresponding proportions were 23.5% (CI = 10.1, 37.8%) by HDL-cholesterol, 21.5% (CI = 11.5, 32.8%) by GGT, and 15.5% (CI = 4.44, 27.3%) by hs-CRP. The results support the hypothesis that the different biological pathways reflected by GGT, HDL-cholesterol, hs-CRP and adiponectin independent from each other contribute to the risk of type 2 diabetes. Of these pathways the highest contribution was observed for adiponectin which contributed one-third to the risk and that equal proportion was contributed by GGT and HDL-cholesterol, although the contribution of inflammation was lower.

Fish consumption and polyunsaturated fatty acids in relation to psychological distress.

BACKGROUND: It has been suggested that high fish consumption improves mental well-being. The aim of this study was to assess whether high fish consumption or omega-3 polyunsaturated fatty acid (PUFA) intake was associated with reduced self-reported psychological distress. METHODS: We used three cross-sectional data sets, the nationwide Health 2000 Survey (n = 5840), the Fishermen Study on Finnish fishermen and their family members (n = 1282) and the Finntwin16 Study on young adults (n = 4986). Data were based on self-administered questionnaires, interviews, health examinations and blood samples. Psychological distress was measured using the 12-item and 21-item General Health Questionnaires (GHQs). Fish consumption was measured by a food frequency questionnaire (FFQ, g/day) and independent frequency questions (times/month). Dietary intake (g/day) and serum concentrations (% from fatty acids) of PUFAs were determined. Relationships were analysed using regression analysis. RESULTS: Regardless of the measure, fish consumption and omega-3 PUFA dietary intake were not associated with distress in any of the data sets. In contrast to the hypothesis, high serum docosahexaenoic acid was associated with high distress in the Fisherman Study men. Some non-linear associations were detected between serum omega-3 PUFAs or fish consumption (times/month) and distress. In the Fishermen Study, the associations were modified by alcohol consumption, smoking and physical activity. CONCLUSIONS: Our results do not support the hypothesis that fish consumption or omega-3 PUFA intake are associated with reduced psychological distress in the general population or in a population with high fish consumption.

Plant foods and the risk of cerebrovascular diseases: a potential protection of fruit consumption.

Studies on the association between plant foods and cerebrovascular diseases have given contradictory results suggesting the existence of some effect-modifying factors. The present study determines whether the consumption of plant foods (i.e. fruits and berries, vegetables, and cereals) predicts a decreased cerebrovascular disease incidence in a population with low fruit and vegetable and high wholegrain intake. This cohort study on 3932 men and women was based on data from the Finnish Mobile Clinic Health Examination Survey, conducted in 1968-72. The participants were 40-74 years of age and free of cardiovascular diseases at baseline. Data on the plant food consumption were derived from a 1-year dietary history interview. During a 24-year follow-up 625 cases of cerebrovascular diseases occurred, leading to either hospitalisation or death. An inverse association was found between fruit consumption and the incidence of cerebrovascular diseases, ischaemic stroke and intracerebral haemorrhage. The adjusted relative risks (RR) between the highest and lowest quartiles of intake of any cerebrovascular disease, ischaemic stroke and intracerebral haemorrhage were 0.75 (95 % CI 0.59, 0.94), 0.73 (95 % CI 0.54, 1.00) and 0.47 (95 % CI 0.24, 0.92), respectively. These associations were primarily due to the consumption of citrus fruits and occurred only in men. Total consumption of vegetables or cereals was not associated with the cerebrovascular disease incidence. The consumption of cruciferous vegetables, however, predicted a reduced risk of cerebrovascular diseases (RR 0.79; 95 % CI 0.63, 0.99), ischaemic stroke (RR 0.67; 95 % CI 0.49, 0.92) and intracerebral haemorrhage (RR 0.49; 95 % CI 0.25, 0.98). In conclusion, the consumption of fruits, especially citrus, and cruciferous vegetables may protect against cerebrovascular diseases.

Fish consumption and the incidence of cerebrovascular disease.

Studies of the beneficial role of fish consumption in the prevention of CVD are not consistent in their findings, particularly those studies that focus on the risk of stroke. The aim of the present study is to investigate the relationship between the consumption of different types of fish and the subsequent incidence of cerebrovascular disease (CVA). We prospectively evaluated the association between consumption of different types of fish and CVA in 3958 men and women aged 40-79 years who were free of heart disease and had participated in a health examination survey from 1967 to 1972. A total of 659 incident cases of CVA occurred during a follow-up until the end of 1994. A dietary history interview method provided data on habitual consumption of fish and other foods over the preceding year at baseline. Total fish intake did not predict CVA, but consumption of salted fish suggested an increased risk of intracerebral haemorrhage. The relative risk of intracerebral haemorrhage between the highest tertile of salted fish consumption and non-consumers was 1.98 (95 % CI 1.02, 3.84; P for trend = 0.06) after adjustment for age, sex, energy intake, smoking, BMI, physical activity, geographic area, occupation, diabetes, use of post-menopausal hormones, serum cholesterol, hypertension, and consumptions of butter, vegetables, fruits and berries. The relationship between fish consumption and stroke risk is not straightforward. How the fish is prepared for consumption may play an important role, affecting the association.

Vitamin D status and common risk factors for bone fragility as determinants of quantitative ultrasound variables in a nationally representative population sample.

Calcaneal quantitative ultrasound (QUS) can predict bone strength and fracture risk. Bone fragility has no single cause but results from a complex interplay of several etiologic or contributing factors. Vitamin D is essential for bone health even though it is still unclear how much of this vitamin is required to maintain bone strength and prevent fractures. Measurements of serum 25-hydroxyvitamin D [S-25(OH)D] have indicated a high prevalence of inadequate vitamin D status in a number of studies mostly based on selected study populations. The objective of this study was to examine the associations between S-25(OH)D, common risk factors for bone fragility, and QUS variables in a large unselected population sample. The study population consisted of 2736 men and 3299 women from a nationally representative population sample, aged 30 years or over. Information on lifestyle was elicited by means of interviews and questionnaires. Body fat mass was estimated using an impedance-meter. S-25(OH)D was measured by radioimmunoassay. Calcaneal QUS was performed on the Hologic Sahara apparatus recording broadband ultrasound attenuation (BUA) and speed of sound (SOS). The potential determinants of BUA and SOS were analysed using separate multiple linear regression models for men and women. S-25(OH)D proved to be an independent determinant of BUA (P<0.0001 for men, P<0.001 for women) and SOS (P<0.0001 for men, P<0.05 for women). BUA was also independently associated with age, height, weight, alcohol consumption, and postmenopausal status in women, and with weight, alcohol consumption, smoking and physical activity in men. All of the above variables, except for weight in women, were also found to be independent determinants of SOS in both men and women. A reverse association was found between S-25(OH)D and adiposity in spite of higher intakes of vitamin D in those with higher fat mass. In this unselected sample of men and women, vitamin D status, several lifestyle factors and physical characteristics proved to be significant determinants of BUA and SOS. Inadequate vitamin D status was common, and measures ensuring adequate intakes of vitamin D in the population thus deserve continued attention. Obesity should be taken into account in future assessments of vitamin D status in Finland as in other countries.

Identifying vegetarians and their food consumption according to self-identification and operationalized definition in Finland.

OBJECTIVES: To determine the prevalence and sociodemographic factors related to vegetarians according to different definitions in Finland and to compare the consumption of selected foodstuffs and nutritional intakes among vegetarians and omnivores. DESIGN: Information about subjects' identification as vegetarians in a survey was used as a basis for self-defined vegetarianism. Foodstuffs consumed and their frequencies of consumption were obtained, and the reported consumption frequencies of meat, fish, milk and eggs or food portions containing these foodstuffs were used as a basis for an operationalized definition of different types of vegetarianism. Reported consumption was used to estimate foodstuff and nutritional intakes. SETTING: Three large nationwide surveys in Finland. SUBJECTS: In total, 24 393 participants aged between 18 and 79 years were included. RESULTS: The proportion of self-identified vegetarians was 3.3 % of the total population in Finland. According to responses to questions on consumption frequency, 1.4 % of the population were pesco-lacto-ovo-vegetarians, 0.43 % were vegans, lacto-vegetarians or lacto-ovo-vegetarians, and 0.18 % were vegans or lacto-vegetarians. Eighty per cent of the self-identified vegetarians did not follow a vegetarian diet according to the operationalized definition, but they consumed fewer meat products (P < 0.01).ConclusionSome self-defined vegetarians do consume red meat, poultry or fish, but they follow a healthier diet than self-defined omnivores. In the same sample self-identification indicated more than double the incidence of vegetarianism than the operationalized definition. Therefore self-identification is not a good method for observing the prevalence of vegetarianism.

Serum vitamin D and subsequent occurrence of type 2 diabetes.

BACKGROUND: Low vitamin D status has been suggested as a risk factor for type 2 diabetes. Although the epidemiologic evidence is scarce, 2 recent studies have suggested an association. The present study investigated the relation of serum vitamin D with type 2 diabetes incidence using pooled data from these 2 cohorts. METHODS: Two nested case-control studies, collected by the Finnish Mobile Clinic in 1973-1980, were pooled for analysis. The study populations consisted of men and women aged 40-74 years and free of diabetes at baseline. During a follow-up period of 22 years, 412 incident type 2 diabetes cases occurred, and 986 controls were selected by individual matching. Serum vitamin D (serum 25(OH)D) was determined from frozen samples, stored at baseline. Pooled estimates of the relationship between serum vitamin D concentration and type 2 diabetes incidence were calculated. RESULTS: Men had higher serum vitamin D concentrations than women and showed a reduced risk of type 2 diabetes in their highest vitamin D quartile. The relative odds between the highest and lowest quartiles was 0.28 (95% confidence interval = 0.10-0.81) in men and 1.14 (0.60-2.17) in women after adjustment for smoking, body mass index, physical activity, and education. CONCLUSIONS: The results support the hypothesis that high vitamin D status provides protection against type 2 diabetes. Residual confounding may contribute to this association.