Importance:Hypertensive disorders of pregnancy (HDP) are one of the leading causes of maternal morbidity and death. There is an urgent need to improve early identification of women at risk of HDP, and assessment of pregestational cardiometabolic biomarkers is a potential way forward. Objective:To investigate pregestational cardiometabolic disturbances with regard to risk of HDP. Design, Setting, and Participants:This prospective cohort study used data from the Apolipoprotein-Related Mortality Risk (AMORIS) cohort, a population-based study set in the greater Stockholm area of Sweden, linked to the Swedish Medical Birth Register from January 1, 1985, to December 31, 2020. Participants were nulliparous women 18 years of age or older with blood biomarker data obtained before their first completed pregnancy. Data analyses were conducted from January 1 to October 31, 2025. Exposures:Pregestational cardiometabolic disturbances, identified through biomarkers of lipid and glucose metabolism and low-grade inflammation. Median time between blood sampling and the start of pregnancy was 4 to 6 years (range, 0-31 years). Main Outcomes and Measures:HDP, defined as gestational hypertension, preeclampsia, or superimposed preeclampsia. Results:Of 35 189 women included (mean [SD] age at delivery, 30.9 [4.8] years), 1938 (5.5%) had HDP. In groups identified with pregestational cardiometabolic disturbances, the percentages with HDP were between 5.5% and 12.8%, whereas the percentages in the comparison categories were between 4.1% and 5.3%. In multivariable logistic regression models, associations with increased risk of HDP were observed for quartile (Q) 4 (vs Q1) for total cholesterol (adjusted odds ratio [AOR], 1.23 [95% CI, 1.06-1.41]), low-density lipoprotein cholesterol (AOR, 1.41 [95% CI, 1.05-1.89]), triglycerides (AOR, 1.19 [95% CI, 1.03-1.37]), haptoglobin (AOR, 1.20 [95% CI, 1.02-1.42]), apolipoprotein (Apo) B (AOR, 1.90 [95% CI, 1.36-2.65]), ApoB/ApoA1 ratio (AOR, 1.59 [95% CI, 1.10-2.30]), and the triglyceride-glucose index (AOR, 1.21 [95% CI, 1.04-1.40]). For C-reactive protein (AOR, 0.97 [95% CI, 0.80-1.17]) and leukocyte counts (AOR, 0.98 [95% CI, 0.80-1.20]), there was no association with HDP risk. Conclusions and Relevance:In this cohort study, pregestationally assessed cardiometabolic biomarkers were associated with increased risk of HDP in nulliparous women. For some biomarkers, the increased risk was observed below standard cutoff levels for a clinical diagnosis, that is, at subclinical levels. These results suggest that assessment of cardiometabolic biomarkers may improve identification of women at risk of HDP, both in preconceptional counseling settings and at enrollment in antenatal health care.

BACKGROUND: Binding of ANGPTL (angiopoietin-like protein)-3 to ANGPTL8 generates a protein complex (ANGPTL3/8) that strongly inhibits LPL (lipoprotein lipase) activity, as compared with ANGPTL3 alone, suggesting that ANGPTL3/8 concentrations are critical for the regulation of circulation lipoprotein concentrations and subsequent increased coronary heart disease (CHD) risk. To test this hypothesis in humans, we evaluated the associations of circulating free ANGPTL3 and ANGPTL3/8 complex concentrations with lipoprotein concentrations and CHD risk in 2 prospective cohort studies. METHODS: Fasting blood samples were obtained in conjunction with the baseline evaluation of 9479 subjects from 2 population-based Swedish cohorts of middle-aged men and women. Standard biochemical blood analyses, including all lipid/lipoprotein measurements, were performed in these samples at baseline. Additional serum samples were stored at −80 °C and used at a later stage for ANGPTL3 and ANGPTL3/8 concentration measurements. Information about incident CHD was obtained for both cohorts by matching to the Swedish National Patient Register and the Cause of Death Register. RESULTS: ANGPTL3 concentrations showed modest, positive associations with all lipoprotein concentrations but were not associated with CHD risk. In contrast, ANGPTL3/8 concentrations were associated in both cohorts with an atherogenic lipoprotein profile (characterized by increased triglyceride and LDL [low-density lipoprotein] concentrations and reduced HDL [high-density lipoprotein] concentrations). In the combined cohort, ANGPTL3/8 was associated with increased CHD risk. Hazard ratio per 1 SD increase was 1.10 (95% CI, 1.03–1.17) after adjustment for age, sex, cohort, smoking, and hypertension. CONCLUSIONS: Elevated concentrations of ANGPTL3/8, but not ANGPTL3, are associated with an atherogenic lipoprotein profile and increased CHD risk in humans.

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.

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.

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.

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.

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.

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.

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.

Contraceptive choices postpartum have not previously been studied in Sweden. Being foreign born is a risk factor for induced abortion. Improving postpartum contraceptive counseling could potentially fulfill unmet needs for contraception. This is an organizational case study using a Quality Improvement Collaborative (QIC) within the regular healthcare setting at 3 maternal health clinics in Stockholm. The active phase of the study was Sep2018-Sep2019. Quantitative and qualitative methods were combined. Routine registration of choice of postpartum contraception was introduced at the clinics and analyzed focusing on Swedish born and foreign-born women. Midwives and researchers met continuously, and during the active phase every 2-3 months in learning seminars with around 20 participants. During the learning seminars PDSA-cycles were used and areas of improvements for continuous performance measures were chosen. The midwives decided on and tested multiple evidence-based changes in contraceptive counselling and services during action periods. Goals were set and competency building in areas chosen by the midwifes were held. In addition, both foreign- and Swedish born women gave their input to the improvement areas. Qualitative data was analyzed through content analysis from field notes and verbatim transcripts. Preliminary results show that the proportion of women choosing an effective contraceptive method (SARC or LARC) among immigrant women increased from 40% to 55% when comparing the start and the end of the project. The midwives reported how they had changed their approach when counselling women who were skeptical about contraception and tried to find a new way to meet women's needs. As much as the QIC showed positive results, it was a small-scale study in 3 clinics in one geographical area. A larger study to determine and explain the effectiveness of QIC on the proportion of immigrant women choosing an effective contraceptive method postpartum is planned for 2021-2024.

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.

Background: Atherosclerosis is an inflammatory disease where hardening and narrowing of arteries can be seen. IgG antibodies against Phosphorylcholine (anti-PC) can also be used as a novel risk mar...

Background: With an aging population, morbidity, fall injuries, polypharmacy and risk of drug-drug interactions increase. The risk of adverse drug-drug interactions (DDIs) increases with more frequent polypharmacy. Antidepressants have been associated with fall injuries in several studies. Adverse effects that could increase the risk of falls, such as syncope, postural hypotension and dizziness, are more pronounced during the first few weeks after initiation of the drug. Many antidepressants are metabolized through CYP2D6 and inhibited metabolism results in increased concentrations. This study explores if use of drugs that inhibit CYP2D6 increases the risk of fall injuries in patients with newly initiated treatment of antidepressants, such as citalopram and venlafaxine.

Background: IgM antibodies against phosphorylcholine (anti-PC) may be protective in atherosclerosis, cardiovascular disease (CVD) and systemic lupus erythematosus (SLE). Less is known about other anti-PC isotypes and subclasses. In this study, we study the role of IgG1 and IgG2 anti-PC, with focus on atherosclerosis and SLE. Objectives: To study the role of IgG1 and IgG2 anti-PC, with focus on atherosclerosis and SLE, both in a clinical setting and by experimental studies, where we use our in-house produced monoclonal IgG1 anti-PC. Methods: We determined IgG1 and IgG2 anti-PC in our SLE cohort study (SLEVIC), among 116 SLE-patients from Karolinska University Hospital Huddinge and 110 population controls matched for age and gender. The level of antibodies was measured by ELISA. For functional studies, we used three of our in-house generated, fully human monoclonal IgG1 anti-PC (A01, D05, E01). Primary human macrophages were derived from peripheral blood. Apoptosis was induced in Jurkat T-cells and pre-incubated with A01, D05, E01 or isotype control IgG1 and effect on phagocytosis by marcophages studied. Anti-PC peptide/protein characterization was determined in anti-PC clones compared to isotype control using a proteomics de novo sequencing approach. Results: IgG1 but not IgG2 anti-PC levels were higher among SLE patients than controls (p=0.02). IgG1 anti-PC was negatively associated with prevalence of atherosclerotic plaques, below 10thpercentile, (OR: 2.48, CI: 0.69-9.00). IgG1 Anti-PC was negatively associated with CVD, SLICC and SLEDAI (OR: 4.74 CI: 1.29-17.39, OR: 2,978 CI: 0.876-10.098, OR: 5.108 CI 1.3 20.067 respectively). Monoclonal D05 had maximum effect on macrophage efferocytosis efficiency, followed by A01 and E01. This is because anti-PC IgG1s bind to phosphorylcholine exposed on apoptotic cells and facilitate the uptake by macrophage. The in-house produced monoclonal antibodies showed differential binding specificity to PC and PC associated neo-epitopes. Peptide analysis showed difference in the CDR3 region of the three anti-PC IgG1 clones which are crucial for recognition of the phosphorylcholine on the apoptotic cell surface and other neo-epitopes. Conclusion: anti-PC IgG1 is negatively associated with disease activity and atherosclerosis in SLE. One potential underlying mechanism could be increased phagocytosis and clearance of dead cells. Our findings raise the possibility of prevention and/or treatment of SLE (and atherosclerosis) to raise anti-PC levels, by passive or active immunization. References: [1] Frostegard J. Immunity, atherosclerosis and cardiovascular disease. BMC Med. 2013;11:117. [2] Anania C, Gustafsson T, Hua X, Su J, Vikstrom M, de Faire U, Heimburger M, Jogestrand T and Frostegard J. Increased prevalence of vulnerable atherosclerotic plaques and low levels of natural IgM antibodies against phosphorylcholine in patients with systemic lupus erythematosus. Arthritis Res Ther. 2010;12:R214. Disclosure of Interests: Divya Thiagarajan: None declared, Nina Oparina: None declared, Johanna Steen: None declared, Mizanur Rahman: None declared, Max Vikström: None declared, Roman Zubarev: None declared, Susanna Lundström: None declared, Johan Frostegård Shareholder of: Minor shareholder and inventor in startup-company Athera Biotechnologies, but they do not produce drugs yet and rheumatology is not in their focus.

Introduction - Low socioeconomic status (SES) has been reported to negatively influence cardiovascular morbidity and mortality. The prognostic implication of SES on the outcome of abdominal aortic aneurysm (AAA) has never been investigated in a large population-based study. The aim of this study was to compare the SES distribution in patients with intact (iAAA) and ruptured AAA (rAAA), with the particular aim to elucidate the influence of SES on intervention rate and outcome for rAAA patients.

ObjectivePhosphatidylserine 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).MethodsAmong 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.ResultsAnti-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.ConclusionsIgM 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.

Purpose. To evaluate a 21-item food frequency questionnaire (FFQ) in men participating in alarge cohort of Swedish 60-year-old adults (60YO).Methods. A self-reported FFQ (including 21 quali ...

Arterial wall remodeling is a central multifactorial process in the development and progression of cardiovascular diseases. We employed an approach aimed at observing genetic variants associated with the progression of carotid intima-media thickness (cIMT) in order to identify novel pathways effecting vessel remodeling. This was achieved by conducting gene-centric analysis of 400,000 variants in 3,042 subjects with repeated cIMT measurements. Rs16997464 on chr22 intergenic between neutrophil cytosolic factor-4 ( NCF4) and colony stimulating factor 2 receptor beta ( CSF2RB ) was associated with cIMT progression at array-wide significance (p <4.5x10 -7 ). The potential causative genes within this locus were investigated using a human vascular and non-vascular tissue biobank. Expression of 9 genes near rs16997464, were analyzed with the most significant association being with NCF4 in aortic adventitia. The effect of the variant on the function of the NCF4 gene product was further analyzed by comparing the oxidative burst capacity of neutrophils from subjects with different rs16997464 genotypes. We observed that neutrophils homozygous for the minor T allele, associated with slower cIMT progression, produced more extracellular ROS than neutrophils homozygous for the G allele, indicating a functional effect of rs16997464 on the NCF4 gene product p40 phox , a component of the NADPH oxidase 2 complex (NOX2). In parallel, we investigated if the chr22 locus also influenced the cellular composition of the atherosclerotic plaque, by utilizing data from the Athero-Express Biobank. Here we found that the minor T allele associated with a higher smooth muscle cell (SMC) content in the plaque. Finally, using a partial ligation model in mice where ncf4 is mutated, resulting in a reduced but not absent NOX2-associated ROS formation, we observed a reduced neointima formation in the ncf4 -mutated strain compared with wild-type littermates. Thus, this study identified rs16997464 in the NCF4-CSF2RB locus as a novel genetic determinant of cIMT progression, and provides evidence suggesting that NCF4 is involved in SMC proliferation and alteration of vessel wall pathophysiology.

Serum Pentadecanoic Acid, A Biomarker Of Dairy Fat Intake, Is Associated With Lower Risk Of Incident Cardiovascular Disease And All-Cause Mortality In Swedish Men And Women