A Swedish primary healthcare prevention programme focusing on promotion of physical activity and a healthy lifestyle reduced cardiovascular events and mortality: 22-year follow-up of 5761 study participants and a reference group.

OBJECTIVE: To evaluate long-term risk of first cardiovascular (CV) events, CV deaths and all-cause deaths in community-dwelling participants of a cardiovascular disease (CVD) prevention programme delivered in a primary care setting. METHODS: Individuals who visited a primary healthcare service in Sollentuna (Sweden) and agreed to participate in the programme between 1988 and 1993 were followed. They had at least one CV risk factor but no prior myocardial infarction and received support to increase physical activity using the programme Physical Activity on Prescription and to adopt health-promoting behaviours including cooking classes, weight reduction, smoking cessation and stress management. Participants (n=5761) were compared with a randomly selected, propensity score-matched reference group from the general population in Stockholm County (n=34 556). All individuals were followed in Swedish registers until December 2011. RESULTS: In the intervention group and the reference group there were 698 (12.1%) and 4647 (13.4%) first CV events, 308 (5.3%) and 2261 (6.5%) CV deaths, and 919 (16.5%) and 6405 (18.5%) all-cause deaths, respectively, during a mean follow-up of 22 years. The HR (95% CI) in the intervention group compared with the reference group was 0.88 (0.81 to 0.95) for first CV events, 0.79 (0.70 to 0.89) for CV deaths and 0.83 (0.78 to 0.89) for all-cause deaths. CONCLUSIONS: Participation in a CVD prevention programme in primary healthcare focusing on promotion of physical activity and healthy lifestyle was associated with lower risk of CV events (12%), CV deaths (21%) and all-cause deaths (17%) after two decades. Promoting physical activity and healthy living in the primary healthcare setting may prevent CVD.

Polyunsaturated Fat Intake Estimated by Circulating Biomarkers and Risk of Cardiovascular Disease and All-Cause Mortality in a Population-Based Cohort of 60-Year-Old Men and Women.

BACKGROUND: High intake of polyunsaturated fatty acids (PUFAs) may reduce the risk of cardiovascular disease (CVD) and mortality. Large, prospective studies including both sexes and circulating PUFAs as dietary biomarkers are needed. We investigated sex-specific associations of the major dietary PUFAs, eicosapentaenoic acid, docohexaenoic acid, linoleic acid, and α-linolenic acid, with incident CVD and all-cause mortality in a population-based cohort. METHODS AND RESULTS: PUFAs in serum cholesterol esters were measured at baseline in 60-year-old Swedish women (n=2193) and men (n=2039). With the use of national registers, 484 incident CVD events (294 men and 190 women) and 456 all-cause deaths (265 men and 191 women) were identified during follow-up (median, 14.5 years) in individuals without prior CVD at baseline. Associations of PUFAs with CVD and mortality were evaluated with Cox proportional hazard models. In multivariable-adjusted models, 1-SD increases in eicosapentaenoic acid and docohexaenoic acid were associated with lower risk of incident CVD among women (hazard ratio [HR], 0.79 [95% confidence interval (CI), 0.64-0.97] and 0.74 [95% CI, 0.61-0.89], respectively). α-Linolenic acid was associated with moderately increased CVD risk in women (HR, 1.16; 95% CI, 1.02-1.32). Inverse associations with all-cause mortality were observed for eicosapentaenoic acid and docohexaenoic acid among all participants (HR, 0.81 [95% CI, 0.72-0.91] and 0.80 [95% CI, 0.72-0.89], respectively) and for linoleic acid in men (HR, 0.73; 95% CI, 0.64-0.83). CONCLUSIONS: Serum linoleic acid and very-long-chain n-3 PUFAs, partly reflecting vegetable oil and fish intake, respectively, were inversely associated with all-cause mortality. Inverse associations of eicosapentaenoic acid and docohexaenoic acid with incident CVD were observed only in women.

Interleukin-26 in antibacterial host defense of human lungs. Effects on neutrophil mobilization.

RATIONALE: The role of the presumed Th17 cytokine IL-26 in antibacterial host defense of the lungs is not known. OBJECTIVES: To characterize the role of IL-26 in antibacterial host defense of human lungs. METHODS: Intrabronchial exposure of healthy volunteers to endotoxin and vehicle was performed during bronchoscopy and bronchoalveolar lavage (BAL) samples were harvested. Intracellular IL-26 was detected using immunocytochemistry and immunocytofluorescence. This IL-26 was also detected using flow cytometry, as was its receptor complex. Cytokines and phosphorylated signal transducer and activator of transcription (STAT) 1 plus STAT3 were quantified using ELISA. Gene expression was analyzed by real-time polymerase chain reaction and neutrophil migration was assessed in vitro. MEASUREMENTS AND MAIN RESULTS: Extracellular IL-26 was detected in BAL samples without prior exposure in vivo and was markedly increased after endotoxin exposure. Alveolar macrophages displayed gene expression for, contained, and released IL-26. Th and cytotoxic T cells also contained IL-26. In the BAL samples, IL-26 concentrations and innate effector cells displayed a correlation. Recombinant IL-26 potentiated neutrophil chemotaxis induced by IL-8 and fMLP but decreased chemokinesis for neutrophils. Myeloperoxidase in conditioned media from neutrophils was decreased. The IL-26 receptor complex was detected in neutrophils and IL-26 decreased phosphorylated STAT3 in these cells. In BAL and bronchial epithelial cells, IL-26 increased gene expression of the IL-26 receptor complex and STAT1 plus STAT3. Finally, IL-26 increased the release of neutrophil-mobilizing cytokines in BAL but not in epithelial cells. CONCLUSIONS: This study implies that alveolar macrophages produce IL-26, which stimulates receptors on neutrophils and focuses their mobilization toward bacteria and accumulated immune cells in human lungs.

The importance of non-exercise physical activity for cardiovascular health and longevity.

BACKGROUND: Sedentary time is increasing in all societies and results in limited non-exercise physical activity (NEPA) of daily life. The importance of low NEPA for cardiovascular health and longevity is limited, especially in elderly. AIM: To examine the association between NEPA and cardiovascular health at baseline as well as the risk of a first cardiovascular disease (CVD) event and total mortality after 12.5 years. STUDY DESIGN: Cohort study. MATERIAL AND METHODS: Every third 60-year-old man and woman in Stockholm County was invited to a health screening study; 4232 individuals participated (78% response rate). At baseline, NEPA and exercise habits were assessed from a self-administrated questionnaire and cardiovascular health was established through physical examinations and laboratory tests. The participants were followed for an average of 12.5 years for the assessment of CVD events and mortality. RESULTS: At baseline, high NEPA was, regardless of regular exercise and compared with low NEPA, associated with more preferable waist circumference, high-density lipoprotein cholesterol and triglycerides in both sexes and with lower insulin, glucose and fibrinogen levels in men. Moreover, the occurrence of the metabolic syndrome was significantly lower in those with higher NEPA levels in non-exercising and regularly exercising individuals. Furthermore, reporting a high NEPA level, compared with low, was associated with a lower risk of a first CVD event (HR=0.73; 95% CI 0.57 to 0.94) and lower all-cause mortality (0.70; 0.53 to 0.98). CONCLUSIONS: A generally active daily life was, regardless of exercising regularly or not, associated with cardiovascular health and longevity in older adults.

Low levels of IgM antibodies to oxidized cardiolipin increase and high levels decrease risk of cardiovascular disease among 60-year olds: a prospective study.

BACKGROUND: Antibodies against cardiolipin (aCL) are associated with increased risk of cardiovascular disease (CVD). We here determine the role of antibodies against oxidized CL (aOxCL). METHODS: One third of sixty-year olds from the Stockholm County were screened (2039 men, 2193 women), where 211 incident CVD-cases and 633 age- and sex-matched controls were identified (5-7 year follow-up). Antibodies were determined by ELISA and uptake of oxLDL in macrophages by FACScan. RESULTS: IgM aOxCL was lower among CVD cases than controls (p=0.024). aOxCL-levels were divided in quartiles with the highest quartile set as the reference group. After adjustment for smoking, BMI, type II diabetes, hypercholesterolaemia and hypertension, an increased risk was determined in the lowest quartile of IgM aOxCL (OR: 1.80, CI: 1.12-2.91, p=0.0159); OR for men in the lowest quartile was 2.46 (CI 1.34-4.53, p=0.0037) for CVD and for stroke: 12.28 (CI: 1.48-101.77, p=0.02). IgG aOxCL levels did not differ between quartiles in CVD-risk. High levels of IgM aOxCL (reaching significance above 86th) and IgG aOxCL (above 95th percentile) were associated with decreased risk of CVD (OR: 0.485, CI: 0.283-0.829; p=0.0082 and OR: 0.23, CI: 0.07-0.69; p=0.0091). aCL were not associated with CVD. oxCL but not CL competed out uptake of OxLDL in macrophages, and aOxLDL recognized oxCL but not CL. In contrast to aCL, aOxCL was not dependent on co-factor Beta2-glycoprotein-I. CONCLUSIONS: aOxCL is a novel risk/protection marker for CVD, with therapeutic implications. OxCL competes with oxLDL for uptake in macrophages and the possibility that aOxCL inhibits such uptake by interfering with same or similar epitopes in oxCL and oxLDL should be further studied.

Metal ratios as possible biomarkers for amyotrophic lateral sclerosis.

BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown aetiology. Metals have been suspected to contribute to ALS pathogenesis since mid-19th century, yet studies on measured metal concentrations in ALS patients have often yielded conflicting results, with large individual variation in measured values. Calculating metal concentration ratios can unveil possible synergistic effects of neurotoxic metals in ALS pathogenesis. The aim of this study was to investigate if ratios of different metal concentrations in cerebrospinal fluid (CSF) and blood plasma, respectively, differ between ALS patients and healthy controls. METHODS: Cerebrospinal fluid and blood plasma were collected from 17 ALS patients and 10 controls. Samples were analysed for 22 metals by high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS), and all possible 231 metal ratios calculated in each body fluid. RESULTS: Fifty-three metal ratios were significantly elevated in ALS cases as compared to controls (p < 0.05); five in blood plasma, and 48 in CSF. The finding of fewer elevated ratios in blood plasma may indicate specific transport of metals into the central nervous system. The elevated metal ratios in CSF include Cd/Se (p = 0.031), and 16 ratios with magnesium, such as Mn/Mg (p = 0.005) and Al/Mg (p = 0.014). CONCLUSION: Metal ratios may be used as biomarkers in ALS diagnosis and as guidelines for preventive measures.

Antibodies against malondialdehyde among 60-year-olds: prediction of cardiovascular disease.

Malondialdehyde (MDA) is generated in oxidized LDL. It forms covalent protein adducts, and is recognized by antibodies (anti-MDA). We previously studied IgM anti-MDA, and here we focus on IgG, IgG1 and IgG2 anti-MDA in predicting cardiovascular disease (CVD). We determined, by ELISA, anti-MDA in a 7-year follow-up of 60-year-old men and women from Stockholm County (2039 men, 2193 women). We identified 210 incident CVD cases (defined as new events of myocardial infarction (MI), and hospitalization for angina pectoris) and ischemic stroke, and 620 age- and sex-matched controls. IgG anti-MDA was not associated with CVD. Median values only differed significantly for IgG1 anti-MDA among men, with lower levels among cases than controls (p = 0.039). High IgG1 anti-MDA (above 75th percentile) was inversely associated with CVD risk after adjustment for smoking, body mass index, type 2 diabetes, hyperlipidemia, and hypertension, (OR and 95% CI: 0.59; 0.40-0.89). After stratification by sex, this association emerged in men (OR and 95% CI: 0.46; 0.27-0.77), but not in women. IgG2 anti-MDA were associated with protection in the whole group and among men though weaker than IgG1 anti-MDA. IgG2 anti-MDA above the 75th percentile was associated with an increased risk of MI/angina in women (OR and 95% CI: 2.57; (1.08-6.16)). IgG1 and less so IgG2 anti-MDA are protection markers for CVD and MI/angina in the whole group and among men. However, IgG2 anti-MDA was a risk marker for MI/angina among women. These findings could have implications for both prediction and therapy.

Chromosome 1p13 genetic variants antagonize the risk of myocardial infarction associated with high ApoB serum levels.

BACKGROUND: Genetic variation at 1p13 modulates serum lipid levels and the risk of coronary heart disease through the regulation of serum lipid levels. Here we investigate if the interaction between genetic variants at 1p13 and serum lipid levels affects the risk of non-fatal myocardial infarction (MI) in the Stockholm Heart Epidemiology Program (SHEEP), a large population based case control study. METHODS: In the present study only non fatal MI cases (n = 1213, men/women: 852/361) and controls (n = 1516, men/women =1054/507) matched by age, sex and residential area, were included. Three SNPs 12740374 G/T, rs599839A/G and rs646776T/C mapping at 1p13 were analysed for association with serum lipid levels and the risk of MI by a weighted least square regression and logistic regression analyses, respectively. To analyse the effect of the interaction between genetic variants and serum lipid levels on the risk of MI, we applied the biological model of interaction that estimates the difference in risk, expressed as OR (95%CI), observed in the presence and in the absence of both exposures. One derived measure is the Synergy index (S) and 95%CI, where S > 1 indicates synergy and S < 1 antagonism between the two interaction terms. RESULTS: Rs12740374G/T and rs646776T/C were in strong linkage disequilibrium (LD) (r2 = 0.99), therefore only rs599839A/G and rs646776 were included in the analysis. Consistently with published data, presence of the rare genotypes was associated with reduced total-, LDL-cholesterol and ApoB serum levels (all p < 0.05) as compared to the reference genotype, but was not associated with the risk of MI.However, the increased risk of MI observed in individual exposed to high (≥75th percentile) serum lipid levels was offset in subjects carrying the rare alleles G and C. In particular, the risk of MI associated with high ApoB serum levels OR (95%CI) 2.27 (1.86-2.77) was reduced to 1.76 (1.33-2.34) in the presence of the G allele at rs599839 with an S of 0.47 (0.20-0.90). CONCLUSIONS: These results indicate that an antagonism between ApoB serum levels and genetic variants at 1p13 contributes to reduce the risk of non-fatal MI in the presence of high ApoB serum levels.

The metabolic syndrome and left ventricular hypertrophy--the influence of gender and physical activity.

AIMS: To investigate associations between the metabolic syndrome (MetS) and left ventricular hypertrophy (LVH) as well as the influence of gender and physical activity (PA) in a population-based cross-sectional study of 60-year-old men (n = 1822) and women (n = 2049). MAJOR FINDINGS: In total, 908 (23.5%) study participants fulfilled the criteria for MetS (54.2% men). Among those, 104 (11.5%) exhibited signs of LVH (60.6% men), compared with 182 (6.1%) among those without MetS (60.4% men). Of the individual factors contained in MetS, hypertension was independently associated with LVH in both men and women (OR = 3.4; 95% CI 2.0-5.8 and 4.4; 2.5-7.8 respectively), whereas waist circumference (OR = 1.6; 95% CI 1.0-2.6), high glucose levels (OR = 1.8; 95% CI 1.1-2.8) and hyperinsulinaemia (OR = 1.7; 95% CI 1.1-2.6) were independently related to risks for LVH exclusively in women. PA did not significantly affect the association. PRINCIPAL CONCLUSION: Participants with MetS were at an increased risk of LVH, independently of PA level. Of the various components in MetS, hypertension was most strongly and independently related to LVH in both men and women. In women, abdominal obesity, high glucose levels and hyperinsulinaemia were independently related to LVH, suggesting a gender differences in the mechanisms behind development of LVH.

Antibodies Against Phosphorylcholine Among 60-Year-Olds: Clinical Role and Simulated Interactions.

Aims: Antibodies against phosphorylcholine (anti-PC) are implicated as protection markers in atherosclerosis, cardiovascular disease (CVD), and other chronic inflammatory conditions. Mostly, these studies have been focused on IgM. In this study, we determined IgG, IgG1, and IgG2 anti-PC among 60-year-olds. Methods: Based on a 7-year follow-up of 60-year-olds (2,039 men and 2,193 women) from Stockholm County, we performed a nested case-control study of 209 incident CVD cases with 620 age- and sex-matched controls. Anti-PC was determined using ELISA. We predicted the binding affinity of PC with our fully human, in-house-produced IgG1 anti-PC clones (i.e., A01, D05, and E01) using the molecular docking and molecular dynamics simulation approach, to retrieve information regarding binding properties to PC. Results: After adjustment for confounders, IgG and IgG2 anti-PC showed some significant associations, but IgG1 anti-PC was much stronger as a protection marker. IgG1 anti-PC was associated with an increased risk of CVD below 33rd, 25th, and 10th percentile and of stroke below 33rd and 25th, and of myocardial infarction (MI) below 10th percentile. Among men, a strong association with stroke was determined below the 33rd percentile [HR 9.20, CI (2.22-38.12); p = 0.0022]. D05 clone has higher binding affinity followed by E01 and A01 using molecular docking and further have been confirmed during the course of 100 ns simulation. The stability of the D05 clone with PC was substantially higher. Conclusion: IgG1 anti-PC was a stronger protection marker than IgG anti-PC and IgG2 anti-PC and also separately for men. The molecular modeling approach helps in identifying the intrinsic properties of anti-PC clones and atomistic interactions with PC.

Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease: An Individual-Level Meta-Analysis.

Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD. Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed. Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged ≥65, 2) individuals with renal impairment, and 3) antiplatelet users. Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline.

Physical activity attenuates cardiovascular risk and mortality in men and women with and without the metabolic syndrome - a 20-year follow-up of a population-based cohort of 60-year-olds.

AIMS: The purpose of this study was to analyse the association of leisure-time physical activity of different intensities at baseline, and cardiovascular disease incidence, cardiovascular disease mortality and all-cause mortality in a population-based sample of 60-year-old men and women with and without established metabolic syndrome, for more than 20 years of follow-up. A secondary aim was to study which cardiometabolic factors may mediate the association between physical activity and long-term outcomes. METHODS: A total of 3693 participants (53% women) underwent physical examination and laboratory tests, completed an extensive questionnaire at baseline 1997-1999 and were followed until their death or until 31 December 2017. First-time cardiovascular disease events and death from any cause were ascertained through regular examinations of national registers. RESULTS: Metabolic syndrome prevalence was 23.0%. In metabolic syndrome participants, light physical activity attenuated cardiovascular disease incidence (hazard ratio = 0.71; 95% confidence interval 0.50-1.00) compared to sedentary (reference) after multi-adjustment. Moderate/high physical activity was inversely associated with both cardiovascular disease and all-cause mortality, but became non-significant after multi-adjustment. Sedentary non-metabolic syndrome participants had lower cardiovascular disease incidence (0.47; 0.31-0.72) but not significantly different cardiovascular disease (0.61; 0.31-1.19) and all-cause mortality (0.92; 0.64-1.34) compared to sedentary metabolic syndrome participants. Both light and moderate/high physical activity were inversely associated with cardiovascular disease and all-cause mortality in non-metabolic syndrome participants (p<0.05). There were significant variations in several central cardiometabolic risk factors with physical activity level in non-metabolic syndrome participants. Fibrinogen mediated the protective effects of physical activity in non-metabolic syndrome participants. CONCLUSION: Physical activity of different intensities attenuated cardiovascular risk and mortality in 60-year old men and women with metabolic syndrome during a 20-year follow-up.

CYP2D6-inhibiting drugs and risk of fall injuries after newly initiated antidepressant and antipsychotic therapy in a Swedish, register-based case-crossover study.

Drug-drug interactions have been shown to affect the risk of fall injuries when opioids are used concomitantly with drugs inhibiting the cytochrome P450 2D6 (CYP2D6) enzyme in a previous pharmacoepidemiological study. The aim of this study was to determine whether CYP2D6-inhibiting drugs reinforce the risk of fall injuries when used concomitantly with antidepressants or antipsychotics. We identified all 252,704 adults with a first fall injury leading to hospitalisation from the National Patient Register in Sweden 2006-2013. Data on dispensed drugs was linked from the Swedish Prescribed Drug Register. We applied a case-crossover design to analyse newly dispensed (28 days preceding the fall injury, preceded by a 12-week washout period) antidepressants and antipsychotics, respectively, in relation to risk of a fall injury and according to concomitant use of CYP2D6-inhibiting drugs. Newly dispensed drugs were assessed correspondingly in a control period of equal length, 28 days prior to the 12-week washout period. Overall, the risk of fall injury was increased after newly initiated antidepressant and antipsychotic treatment. For antidepressants, concomitant CYP2D6 inhibitor use further elevated the risk estimates compared to non-use, most pronounced for the groups selective serotonin reuptake inhibitors (sertraline excluded) [OR = 1.47 (95% CI 1.19-1.80) vs. OR = 1.19 (95% CI 1.13-1.26)], and tricyclic antidepressants [OR = 1.71 (95% CI 1.17-2.51) vs. 1.27 (95% CI 1.11-1.47)] as well as for sertraline [OR = 1.61 (95% CI 1.05-2.38) vs. 1.12 (95% CI 1.00-1.26)]. For antipsychotics, the risk of fall injury was not altered by concomitant use of CYP2D6-inhibiting drugs. In conclusion, concomitant use of CYP2D6 inhibiting drugs tends to further increase the risk of fall injury in newly initiated antidepressant treatment, but not in antipsychotic treatment.

Low levels of antibodies against phosphorylcholine predict development of stroke in a population-based study from northern Sweden.

BACKGROUND AND PURPOSE: Natural immunoglobulin M antibodies specific for phosphorylcholine (anti-PC) have been implicated in atherosclerosis. We have shown previously that high levels of anti-PC predict a slower progression of atherosclerosis in humans and that low levels of anti-PC are associated with higher risk for cardiovascular disease. Here we determine the association between anti-PC and the incidence of stroke. METHODS: Using a nested case control study design, we examined 227 incident cases (125 men and 102 women) of first-time stroke and 455 age- and sex-matched controls identified during a 13-year time period (1985 to 1999) within the population-based cohorts of the Västerbotten Intervention Project (VIP) and the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease (WHO MONICA) project in Northern Sweden. Odds ratios of stroke with 95% CIs with adjustments for age, gender, smoking, serum cholesterol, diabetes, body mass index, and blood pressure were determined. Anti-PC levels were measured using ELISA. RESULTS: A significant association between low levels of anti-PC at baseline and incident stroke was seen for the whole group of anti-PC levels below the 30th percentile (multivariately adjusted odds ratio, 1.62; CI, 1.11 to 2.35). Analyses of gender-specific associations indicated fairly strong associations for females, especially at the lowest 30th percentile (multivariately adjusted odds ratio, 2.65; CI, 1.41 to 4.95). No associations were noted for men. CONCLUSION: Low anti-PC is a novel independent risk marker for development of stroke. Measurements of anti-PC could be used to identify immunodeficient subjects at an increased risk for stroke. The possibility that such subjects might be targets for novel modes of treatment such as immunotherapies deserves further investigation.

Pesticide exposure among Bolivian farmers: associations between worker protection and exposure biomarkers.

The use of pesticides has increased during the past decades, also increasing the risk of exposure to toxic pesticides that can cause detrimental health effects in the future. This is of special concern among farmers in low-to-middle-income countries that may lack proper training in the safe use of these chemicals. To assess the situation in Bolivia a cross-sectional study in three agricultural communities was performed (n = 297). Handling, use of personal protective equipment (PPE) and pesticide exposure were assessed by a questionnaire and measurements of urinary pesticide metabolites (UPMs). Results showed that methamidophos (65%) and paraquat (52%) were the most commonly used pesticides and that 75% of the farmers combined several pesticides while spraying. Notably, only 17% of the farmers used recommended PPEs while 84% reported to have experienced symptoms of acute pesticide poisoning after spraying. UPM measurements indicated high levels of exposure to chlorpyrifos, pyrethroids and 2,4D and that men generally were more highly exposed compared to women. Our study demonstrates that farmers who are better at following recommendations for pesticide handling and use of PPE had a significantly lower risk of having high UPM levels of most measured pesticides. Our results thus confirm the need of proper training of farmers in low-to-middle-income countries in proper protection and pesticide handling in order to reduce exposure levels and health problems.

Correction to: Pesticide exposure among Bolivian farmers: associations between worker protection and exposure biomarkers.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.In the original Article, co-author Ulla Stenius' surname was misspelled as Ulla Steinus. This has been corrected in the PDF, HTML and XML versions of this Article.

Variants in the coagulation factor 2 receptor (F2R) gene influence the risk of myocardial infarction in men through an interaction with interleukin 6 serum levels.

Thrombin-activated factor 2 receptor (F2R) links thrombosis to inflammation modulating interleukin (IL)6 synthesis. We have investigated the role of F2R genetic variants and their interaction with IL6 serum levels in the occurrence of myocardial infarction (MI) in the Stockholm Heart Epidemiology Program (SHEEP). Seven SNPs -1738 G/A, -506-/GGCCGCGGGAAGC (D/I), 2860 G/A, 2930 T/C, 9113 C/A, 9333 C/T and 120813 T/C within F2R locus were genotyped in the SHEEP (n=2,774). The C allele at position 2930 was associated with a slight reduction in MI risk in men. IL6 serum levels were higher in male cases carrying genotypes AA at the -1738 (p= 0.01) and GG at the 2860 loci (p= 0.03) and both alleles were found to differentially modulate IL6 serum levels in the context of selective haplotypes. High IL6 serum levels (>75(th) percentile), were independently associated with an increased risk of MI in men with an odds ratio (OR) (95% confidence interval [CI]) of 2.44 (1.72-3.46), (p=0.0016), but not in women ( OR 0.83 [95%CI 0.50-1.36], p=0.64). In the presence of high IL6 serum levels, the -1738A allele increased and the 2860A allele reduced the risk of MI (all p < or = 0.02). Consistently, the AG diplotype increased MI risk (OR 1.71 [95%CI 1.17-2.51], p=0.005). The -1738 and 2860 loci association with IL6 serum levels was replicated in men in the Stockholm Coronary Artery Risk Factor (SCARF) study (both p < or = 0.04). In the pooled data from the two populations, the A and G allele modulated the risk of MI in men with high IL6 serum levels (p < or = 0.03). Our results demonstrate that in men F2R genetic variants influence the risk of MI mainly through an interaction with IL6 serum levels.

Serum Fatty Acids, Desaturase Activities and Abdominal Obesity - A Population-Based Study of 60-Year Old Men and Women.

Abdominal obesity is a key contributor of metabolic disease. Recent trials suggest that dietary fat quality affects abdominal fat content, where palmitic acid and linoleic acid influence abdominal obesity differently, while effects of n-3 polyunsaturated fatty acids are less studied. Also, fatty acid desaturation may be altered in abdominal obesity. We aimed to investigate cross-sectional associations of serum fatty acids and desaturases with abdominal obesity prevalence in a population-based cohort study. Serum cholesteryl ester fatty acids composition was measured by gas chromatography in 60-year old men (n = 1883) and women (n = 2015). Cross-sectional associations of fatty acids with abdominal obesity prevalence and anthropometric measures (e.g., sagittal abdominal diameter) were evaluated in multivariable-adjusted logistic and linear regression models, respectively. Similar models were employed to investigate relations between desaturase activities (estimated by fatty acid ratios) and abdominal obesity. In logistic regression analyses, palmitic acid, stearoyl-CoA-desaturase and Δ6-desaturase indices were associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals) for highest versus lowest quartiles were 1.45 (1.19-1.76), 4.06 (3.27-5.05), and 3.07 (2.51-3.75), respectively. Linoleic acid, α-linolenic acid, docohexaenoic acid, and Δ5-desaturase were inversely associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals): 0.39 (0.32-0.48), 0.74 (0.61-0.89), 0.76 (0.62-0.93), and 0.40 (0.33-0.49), respectively. Eicosapentaenoic acid was not associated with abdominal obesity. Similar results were obtained from linear regression models evaluating associations with different anthropometric measures. Sex-specific and linear associations were mainly observed for n3-polyunsaturated fatty acids, while associations of the other exposures were generally non-linear and similar across sexes. In accordance with findings from short-term trials, abdominal obesity was more common among individuals with relatively high proportions of palmitic acid, whilst the contrary was true for linoleic acid. Further trials should examine the potential role of linoleic acid and its main dietary source, vegetable oils, in abdominal obesity prevention.

IgM antibodies to oxidized phosphatidylserine as protection markers in cardiovascular disease among 60-year olds.

OBJECTIVE: Phosphatidylserine is exposed on apoptotic cells and is prone to oxidation (OxPS). Here we analyze the association of IgM antibodies against OxPS (anti-OxPS) with the risk of cardiovascular disease (CVD). METHODS: Among sixty-year olds from Stockholm County in Sweden, previously screened for cardiovascular risk factors (2039 men, 2193 women), there were 210 incident CVD-cases identified during a 5-year follow-up. Using a nested case-control design, 622 age- and sex-matched controls were selected. Odds ratios (OR) with 95% intervals (CI) were calculated by conditional logistic regression. IgM anti-OxPS was measured by ELISA. Phagocytosis of apoptotic Jurkat-cells by macrophages was studied by flow cytometry. RESULTS: Anti-OxPS levels were lower among cases (median (interquartile range): 80.7 (60.9-101.0 vs. 84.6 (65.8-109.6); p = 0.047); among men (76.6 (55.8-99.2) vs. 82.0 (63.1-105.1); p = 0.022) and among women 89.6 (72.3-110.1) vs. 89.8 (69.9-114.4); p = 0.79). After adjustment for smoking, BMI, diabetes mellitus type II, hypercholesterolaemia and hypertension, and dividing into quartiles, using the highest quartile (quartile 4) as reference, quartile 3 was associated with a OR of 1.74 (CI 1.08-2.81). Quartiles 2 and 1 had similar associations, the later reaching statistical significance. Among men associations were stronger whereas no significant associations were observed in women. The OR of MI/angina comparing quartile 3 with quartile 4 was 2.31 (CI 1.30-4.11). The OR for quartile 2 and 1, respectively, were similar as for quartile 3. Total IgM increased uptake of apoptotic cells, which was reversed if incubated with OxPS. CONCLUSIONS: IgM anti-OxPS is a novel potential protection marker for CVD, in particular in men. Increased phagocytosis of dying/dead cells could be one potential underlying mechanism.