Agneta Hilding

Long term exposure to ambient air pollution and incidence of acute coronary events: prospective cohort study and meta-analysis in 11 European cohorts from the ESCAPE Project

Objectives To study the effect of long term exposure to airborne pollutants on the incidence of acute coronary events in 11 cohorts participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Design Prospective cohort studies and meta-analysis of the results. Setting Cohorts in Finland, Sweden, Denmark, Germany, and Italy. Participants 100 166 people were enrolled from 1997 to 2007 and followed for an average of 11.5 years. Participants were free from previous coronary events at baseline. Main outcome measures Modelled concentrations of particulate matter <2.5 μm (PM2.5), 2.5-10 μm (PMcoarse), and <10 μm (PM10) in aerodynamic diameter, soot (PM2.5 absorbance), nitrogen oxides, and traffic exposure at the home address based on measurements of air pollution conducted in 2008-12. Cohort specific hazard ratios for incidence of acute coronary events (myocardial infarction and unstable angina) per fixed increments of the pollutants with adjustment for sociodemographic and lifestyle risk factors, and pooled random effects meta-analytic hazard ratios. Results 5157 participants experienced incident events. A 5 μg/m3 increase in estimated annual mean PM2.5 was associated with a 13% increased risk of coronary events (hazard ratio 1.13, 95% confidence interval 0.98 to 1.30), and a 10 μg/m3 increase in estimated annual mean PM10 was associated with a 12% increased risk of coronary events (1.12, 1.01 to 1.25) with no evidence of heterogeneity between cohorts. Positive associations were detected below the current annual European limit value of 25 μg/m3 for PM2.5 (1.18, 1.01 to 1.39, for 5 μg/m3 increase in PM2.5) and below 40 μg/m3 for PM10 (1.12, 1.00 to 1.27, for 10 μg/m3 increase in PM10). Positive but non-significant associations were found with other pollutants. Conclusions Long term exposure to particulate matter is associated with incidence of coronary events, and this association persists at levels of exposure below the current European limit values.

Psychological distress and risk of pre-diabetes and Type 2 diabetes in a prospective study of Swedish middle-aged men and women.

Aims  To determine the role of psychological distress as a predictor of pre‐diabetes and Type 2 diabetes.

Long-term exposure to ambient air pollution and incidence of cerebrovascular events: results from 11 European cohorts within the ESCAPE project.

Background: Few studies have investigated effects of air pollution on the incidence of cerebrovascular events. Objectives: We assessed the association between long-term exposure to multiple air pollutants and the incidence of stroke in European cohorts. Methods: Data from 11 cohorts were collected, and occurrence of a first stroke was evaluated. Individual air pollution exposures were predicted from land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE). The exposures were: PM2.5 [particulate matter (PM) ≤ 2.5 μm in diameter], coarse PM (PM between 2.5 and 10 μm), PM10 (PM ≤ 10 μm), PM2.5 absorbance, nitrogen oxides, and two traffic indicators. Cohort-specific analyses were conducted using Cox proportional hazards models. Random-effects meta-analysis was used for pooled effect estimation. Results: A total of 99,446 study participants were included, 3,086 of whom developed stroke. A 5-μg/m3 increase in annual PM2.5 exposure was associated with 19% increased risk of incident stroke [hazard ratio (HR) = 1.19, 95% CI: 0.88, 1.62]. Similar findings were obtained for PM10. The results were robust to adjustment for an extensive list of cardiovascular risk factors and noise coexposure. The association with PM2.5 was apparent among those ≥ 60 years of age (HR = 1.40, 95% CI: 1.05, 1.87), among never-smokers (HR = 1.74, 95% CI: 1.06, 2.88), and among participants with PM2.5 exposure < 25 μg/m3 (HR = 1.33, 95% CI: 1.01, 1.77). Conclusions: We found suggestive evidence of an association between fine particles and incidence of cerebrovascular events in Europe, even at lower concentrations than set by the current air quality limit value. Citation: Stafoggia M, Cesaroni G, Peters A, Andersen ZJ, Badaloni C, Beelen R, Caracciolo B, Cyrys J, de Faire U, de Hoogh K, Eriksen KT, Fratiglioni L, Galassi C, Gigante B, Havulinna AS, Hennig F, Hilding A, Hoek G, Hoffmann B, Houthuijs D, Korek M, Lanki T, Leander K, Magnusson PK, Meisinger C, Migliore E, Overvad K, Östenson CG, Pedersen NL, Pekkanen J, Penell J, Pershagen G, Pundt N, Pyko A, Raaschou-Nielsen O, Ranzi A, Ricceri F, Sacerdote C, Swart WJ, Turunen AW, Vineis P, Weimar C, Weinmayr G, Wolf K, Brunekreef B, Forastiere F. 2014. Long-term exposure to ambient air pollution and incidence of cerebrovascular events: results from 11 European cohorts within the ESCAPE project. Environ Health Perspect 122:919–925; http://dx.doi.org/10.1289/ehp.1307301

Aircraft noise and incidence of hypertension.

Background: An association between aircraft noise exposure and hypertension prevalence has been suggested but there are no longitudinal studies of this association. Our aim was to investigate the influence of aircraft noise on the incidence of hypertension. Methods: A cohort of 2754 men in 4 municipalities around Stockholm Arlanda airport was followed between 1992–1994 and 2002–2004. The cohort was based on the Stockholm Diabetes Preventive Program; half of the study subjects had a family history of diabetes. Residential aircraft noise exposure (expressed as time-weighted equal energy and maximal noise levels) was assessed by geographical information systems techniques among those living near the airport. Incident cases of hypertension were identified by physical examinations, including blood pressure measurements, and questionnaires in which subjects reported treatment or diagnosis of hypertension and information on cardiovascular risk factors. Analyses were restricted to 2027 subjects who completed the follow-up examination, were not treated for hypertension, and had a blood pressure below 140/90 mm Hg at enrollment. Results: For subjects exposed to energy-averaged levels above 50 dB(A) the adjusted relative risk for hypertension was 1.19 (95% CI = 1.03–1.37). Maximum aircraft noise levels presented similar results, with a relative risk of 1.20 (1.03–1.40) for those exposed above 70 dB(A). Stronger associations were suggested among older subjects, those with a normal glucose tolerance, nonsmokers, and subjects not annoyed by noise from other sources. Conclusion: These findings suggest that long-term aircraft noise exposure may increase the risk for hypertension.

Growth hormone treatment improves body composition in adults with Prader-Willi syndrome

objective Low growth hormone (GH) secretion and hypogonadism are common in patients with Prader–Willi syndrome (PWS). In this study we present the effects of GH treatment on body composition and metabolism in adults with PWS.

Work Stress, Sense of Coherence, and Risk of Type 2 Diabetes in a Prospective Study of Middle-Aged Swedish Men and Women

OBJECTIVE To investigate the prospective influence of work stress on type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS This population-based cohort included 3,205 women and 2,227 men, aged 35–56 years, with baseline normal glucose tolerance measured with oral glucose tolerance test. At follow-up 8–10 years later, T2D was diagnosed in 60 women and 111 men. Work stress factors evaluated by questionnaire (i.e., demands, decision latitude, job strain, shift work, overtime work, and also sense of coherence) were studied in association with T2D. Odds ratios (ORs) and 95% CIs adjusted for age, education, BMI, physical activity, smoking, family history of diabetes, and psychological distress were calculated. RESULTS In women, low decision latitude was associated with T2D on its own (OR 2.4 [95% CI 1.1–5.2]) and combined with high demands: job strain (OR 4.2 [2.0–8.7]), adjusted for all available potential confounders. Also, shift work increased the risk of T2D in women (OR 2.2 [1.0–4.7]) when adjusted for age, education, and psychological distress, although this risk was diluted after multifactor adjustment (OR 1.9 [0.8–4.4]). In men, high work demands and high strain decreased the risk of T2D (OR 0.5 [0.3–0.9]) for both measures, as did an active job (high demands and high decision latitude, OR 0.4 [0.2–0.9]). CONCLUSIONS Work stress and shift work may contribute to the development of T2D in women. In men, the risk was decreased by high work demands, high strain, and an active job.

Alcohol consumption and risk of pre-diabetes and type 2 diabetes development in a Swedish population

Diabet. Med. 29, 441–452 (2012)

Characterisation of subjects with early abnormalities of glucose tolerance in the Stockholm Diabetes Prevention Programme: the impact of sex and type 2 diabetes heredity

Aims/hypothesisWe evaluated the impact of sex and type 2 diabetes heredity on the prevalence and pathogenesis of early abnormalities of glucose homeostasis in subjects participating in the Stockholm Diabetes Prevention Programme.MethodsA sample of 3,128 men and 4,821 women, of whom approximately half had a family history of type 2 diabetes (FHD) was categorised according to an OGTT: NGT, IFG, IGT, combined glucose intolerance and type 2 diabetes. The homeostasis model assessment was used to determine insulin sensitivity and beta cell function.ResultsPrevalence of early abnormalities of glucose metabolism was two to three times higher in subjects with FHD and two to three times higher in men compared to women. Both maternal and paternal heredity of type 2 diabetes were associated with an increased risk of having early abnormalities of glucose metabolism. However, in women with type 2 diabetes heredity on the father’s side seems to have less impact on an increased risk of having type 2 diabetes. Both waist circumference and systolic blood pressure were increased in subjects with abnormalities of glucose homeostasis, whereas insulin sensitivity and beta cell function were decreased. Subjects with IFG had more pronounced impairment of beta cell function and insulin sensitivity than subjects with IGT.Conclusion/interpretationAn FHD and male sex increased the prevalence of abnormalities of glucose homeostasis. Subjects with IFG had more pronounced defects of insulin secretion and action than subjects with IGT.

Arterial Blood Pressure and Long-Term Exposure to Traffic-Related Air Pollution: An Analysis in the European Study of Cohorts for Air Pollution Effects (ESCAPE)

Background: Long-term exposure to air pollution has been hypothesized to elevate arterial blood pressure (BP). The existing evidence is scarce and country specific. Objectives: We investigated the cross-sectional association of long-term traffic-related air pollution with BP and prevalent hypertension in European populations. Methods: We analyzed 15 population-based cohorts, participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE). We modeled residential exposure to particulate matter and nitrogen oxides with land use regression using a uniform protocol. We assessed traffic exposure with traffic indicator variables. We analyzed systolic and diastolic BP in participants medicated and nonmedicated with BP-lowering medication (BPLM) separately, adjusting for personal and area-level risk factors and environmental noise. Prevalent hypertension was defined as ≥ 140 mmHg systolic BP, or ≥ 90 mmHg diastolic BP, or intake of BPLM. We combined cohort-specific results using random-effects meta-analysis. Results: In the main meta-analysis of 113,926 participants, traffic load on major roads within 100 m of the residence was associated with increased systolic and diastolic BP in nonmedicated participants [0.35 mmHg (95% CI: 0.02, 0.68) and 0.22 mmHg (95% CI: 0.04, 0.40) per 4,000,000 vehicles × m/day, respectively]. The estimated odds ratio (OR) for prevalent hypertension was 1.05 (95% CI: 0.99, 1.11) per 4,000,000 vehicles × m/day. Modeled air pollutants and BP were not clearly associated. Conclusions: In this first comprehensive meta-analysis of European population-based cohorts, we observed a weak positive association of high residential traffic exposure with BP in nonmedicated participants, and an elevated OR for prevalent hypertension. The relationship of modeled air pollutants with BP was inconsistent. Citation: Fuks KB, Weinmayr G, Foraster M, Dratva J, Hampel R, Houthuijs D, Oftedal B, Oudin A, Panasevich S, Penell J, Sommar JN, Sørensen M, Tittanen P, Wolf K, Xun WW, Aguilera I, Basagaña X, Beelen R, Bots ML, Brunekreef B, Bueno-de-Mesquita HB, Caracciolo B, Cirach M, de Faire U, de Nazelle A, Eeftens M, Elosua R, Erbel R, Forsberg B, Fratiglioni L, Gaspoz JM, Hilding A, Jula A, Korek M, Krämer U, Künzli N, Lanki T, Leander K, Magnusson PK, Marrugat J, Nieuwenhuijsen MJ, Östenson CG, Pedersen NL, Pershagen G, Phuleria HC, Probst-Hensch NM, Raaschou-Nielsen O, Schaffner E, Schikowski T, Schindler C, Schwarze PE, Søgaard AJ, Sugiri D, Swart WJ, Tsai MY, Turunen AW, Vineis P, Peters A, Hoffmann B. 2014. Arterial blood pressure and long-term exposure to traffic-related air pollution: an analysis in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Environ Health Perspect 122:896–905; http://dx.doi.org/10.1289/ehp.1307725

Serum Levels of Insulin-like Growth Factor Binding Proteins (IGFBP)–4 and –5 Correlate with Bone Mineral Density in Growth Hormone (GH)–Deficient Adults and Increase with GH Replacement Therapy†

Adults with growth hormone deficiency (GHD) exhibit low bone mineral density (BMD) which improves by growth hormone (GH) replacement therapy. The insulin‐like growth factor (IGF) system has an established role in mediating the effects of GH on bone and IGF binding proteins (IGFBP)‐4 and IGFBP‐5 have been shown to modulate the effects of IGFs in bone. Therefore, we studied serum levels of IGFBP‐4 and IGFBP‐5 and their relationship to serum levels of bone biochemical markers and BMD in adults with GH deficiency (GHD) before and during GH therapy. Serum levels of IGFBP‐5 and IGFBP‐4 were measured on samples from 20 patients (11 males) 22–57 years of age. All had IGF‐I serum values below –2 standard deviation score. The first 6 months were placebo controlled and all recieved 3 years of active treatment with the mean dose 0.23 ± 0.01 IU/kg/week divided into daily subcutaneous injections. Serum IGFBP‐5 levels in GHD adults were low at baseline and positively related to total body, femoral neck, trochanter, and Wards triangle BMD (r = 0.471, 0.549, 0.462, and 0.470, respectively, p < 0.05). The mean serum IGFBP‐5 level increased by about 2‐fold within 3 months after the initiation of GH therapy and was correlated with serum IGF‐I (r = 0.719, 0.801, and 0.722 before and after 18 and 36 months, respectively, p < 0.001). A positive correlation between serum IGFBP‐5 levels and lumbar spine BMD was found during GH treatment but not before. The percentage increase of serum IGFBP‐5 after GH therapy showed a positive correlation with the percentage increase of total alkaline phosphate activity (r = 0.347 p < 0.05). In contrast to IGFBP‐5, serum IGFBP‐4 levels were positively related to body mass index (r = 0.607, p < 0.01). Baseline serum IGFBP‐4 levels also correlated with total body, femoral neck, trochanter, and Wards triangle BMD (r = 0.502, 0.590, 0.612, and 0.471, respectively, p < 0.05). The mean serum IGFBP‐4 level was increased by 25% within 3 months after initiation of GH therapy and did not correlate with serum IGF‐I levels. Although the above findings are consistent with the idea that GH‐induced changes in serum IGFBP‐5 and IGFBP‐4 levels may in part mediate the anabolic effects of GH on bone tissue in adults with GHD, further studies are needed to establish the cause and effect relationship.