Differences in SARS-CoV-2 antibodies depending on age, blood group, and sex in a Swedish blood donor cohort.

This study aimed to describe differences in prevalence and the long-term presence of nucleocapsid antibodies (N-antibodies) elicited by SARS-CoV-2 infection in a Swedish blood donor population not subjected to lockdown. We tested 20,651 blood donor samples for nucleocapsid antibodies from the beginning of March 2020 and 27 months onwards using the Roche Elecsys Anti-SARS-CoV-2 assay. The proportion of positive SARS-CoV-2 antibody samples was determined each week. After the exclusions of one-time donors and subjects with incomplete data, 19,726 samples from 4003 donors remained. Differences in antibody prevalences stratified for age, sex, and blood groups (ABO and RhD) were determined, as well as antibody loss and recovery. Lower antibody prevalence was seen for older donors, blood group AB, and RhD-negative subjects. A significant decrease in antibody titer between the first and the second antibody-positive donation was seen for the whole study group, females, older subjects, blood group O, AB, and RhD-positive subjects. The titer waned below the detection limit in 60 (3.0%) of 1983 N-antibody-positive donors, and for 18 of these donors, a second episode with antibodies was detected. We showed that N-antibodies persist for months or years and that surprisingly few antibody-positive donors lost their antibodies. We also conclude that antibody prevalence in a Swedish population never subject to lockdown did not apparently differ from populations that were subject to stricter regulations.

ABO Blood Groups, RhD Factor and Their Association with Subclinical Atherosclerosis Assessed by Carotid Ultrasonography.

Background: The ABO blood group system has previously been associated with cardiovascular disease (CVD), where non-O blood group individuals have shown an increased risk. Studies assessing early atherosclerotic disease while also including RhD are few. We aimed to determine whether the ABO and RhD blood groups are associated with subclinical atherosclerosis in a healthy population. Methods: We included 3532 participants from the VIPVIZA trial with available carotid ultrasonography results to assess subclinical disease. Information about blood groups was obtained from the SCANDAT-3 database, where 85% of VIPVIZA participants were registered. Results: RhD- individuals aged 40 years showed increased carotid intima-media thickness (B 1.09 CI 95% 1.03; 1.14) compared to RhD+ individuals. For ABO, there were no differences in ultrasonography results when assessing the whole study population. However, 60-year-old individuals with heredity for CVD and a non-O blood group had decreased odds for carotid plaques (OR 0.54 CI 95% 0.33; 0.88). Conclusions: RhD blood group is associated with subclinical atherosclerosis in younger individuals, indicating a role as a mediator in the atherosclerotic process. In addition, a non-O blood group was associated with decreased subclinical atherosclerosis in individuals aged 60 and with heredity (corresponding to the group with the highest atherosclerotic burden).

Factors influencing antibiotic prescribing for respiratory tract infections in primary care - a comparison of physicians with different antibiotic prescribing rates.

BACKGROUND: There has been a notable decrease in antibiotic prescribing in the last thirty years in Sweden. Little is known about factors influencing antibiotic prescribing over several years. OBJECTIVE: To compare primary care physicians who, over time, reduced their antibiotic prescribing for respiratory tract infections with those who remained either high or low prescribers regarding potentially influencing factors. DESIGN AND SETTING: A register-based study including all RTI visits in primary care in Region Kronoberg, Sweden 2006-2014. The data were divided into three 3-year periods. SUBJECTS: The data comprised all physicians who had diagnosed at least one RTI for each of the three-year periods. The antibiotic prescribing rate adjusted for the patients' sex and age group was calculated for each physician and period, and based on the change between the first and the third period, the physicians were divided into three prescriber groups: The High Prescribing Group, the Decreasing Prescribing Group, and the Low Prescribing Group. MAIN OUTCOME MEASURES: For the three prescriber groups, we compared factors influencing antibiotic prescribing such as the characteristics of the physicians, their use of point-of-care tests, their choice of diagnoses, and whether the patients returned and received antibiotics. RESULTS: The High Prescribing Group ordered more point-of-care tests, registered more potential bacterial diagnoses, prescribed antibiotics at lower C-reactive protein levels, and prescribed antibiotics more often despite negative group A Streptococci test than in the Low Prescribing Group. The Decreasing Prescribing Group was between the High Prescribing Group and the Low Prescribing Group regarding these variables. The lower prescription rate in the Low Prescribing Group did not result in more return visits or new antibiotic prescriptions within 30 days. CONCLUSION: Point-of-care testing and its interpretation differed between the prescriber groups. Focus on interpreting point-of-care test results could be a way forward in antibiotic stewardship.

High prescribers used antibiotics at lower CRP levels and were more likely to identify a potential bacterial diagnosis.Many physicians reduced their antibiotic prescribing during the study period. Nine out of ten low prescribers remained low prescribers.Seeing a low-prescribing physician did not lead to more return visits or antibiotic changes.

Detection of subarachnoid haemorrhage with spectrophotometry of cerebrospinal fluid - a comparison of two methods.

OBJECTIVES: Spectrophotometric absorption curve analysis of cerebrospinal fluid (CSF) for oxyhaemoglobin and bilirubin is necessary to accurately diagnose subarachnoid haemorrhage (SAH) in patients with typical symptoms but with negative findings on X-ray examinations. In this study, we evaluated the performance of two methods for interpreting absorption curves; one method from the United Kingdom National External Quality Assessment Service (UK-NEQAS) and the other from the national quality assurance programme in Sweden (Equalis). METHODS: Consecutive absorbance curves (n=336) were interpreted with two different methods, and their performance was compared to the diagnosis as stated in the patient records. RESULTS: The UK-NEQAS method displayed equal sensitivity to the Equalis method, but the specificity of the UK-NEQAS method was significantly higher than the Equalis method resulting in fewer false positive results. For UK-NEQAS, a positive predictive value (PPV) of 84.6% and a negative predictive value (NPV) of 99.7% were observed, whereas the Equalis method had a PPV of 27.5% and an NPV of 99.7%. CONCLUSIONS: The semi-automated method based on the guidelines from UK-NEQAS provides an efficient and correct interpretation of absorbance curves with short turn-around times. We propose using this method for the routine interpretation of CSF spectrophotometric curves.

High-throughput immunoassays for SARS-CoV-2 - considerable differences in performance when comparing three methods.

BACKGROUND: The recently launched high-throughput assays for detecting antibodies against SARS-CoV-2 has contributed to the managing strategies for the COVID-19 pandemic. This study aimed to investigate the performance of three high-throughput assays and one rapid lateral flow test relative to regulatory authorities' recommended criteria. METHODS: A total of 315 samples, including 150 pre-pandemic samples, 152 samples from SARS-CoV-2 RT-PCR positive individuals and 13 potentially cross-reactive samples were analysed with SARS-CoV-2 IgG (Abbott, Abbott Park, IL), Elecsys Anti-SARS-CoV-2 (Roche, Solna, Sweden), LIAISON SARS-CoV-2 S1/S2 IgG (DiaSorin, Saluggia, Italy) and 2019-nCOV IgG/IgM Rapid Test (Dynamiker Biotechnology Co., Tianjin, China). RESULTS: All assays performed with a high level of specificity ranging from 96.7% to 99.3%. Sensitivity differed more between the assays, Roche exhibiting the highest sensitivity of 98.7%. The corresponding figures for Abbott, DiaSorin and Dynamiker Biotechnology were 80.9%, 89.0% and 72.4%, respectively. CONCLUSIONS: The results of the evaluated SARS-CoV-2 assays vary considerably, as well as their ability to fulfil the performance criteria proposed by regulatory authorities. Introduction into clinical use in low-prevalent settings, should, therefore, be made with caution.

Diagnosis-linked antibiotic prescribing in Swedish primary care - a comparison between in-hours and out-of-hours.

BACKGROUND: The rise in antibiotic resistance is a global public health concern, and antibiotic overuse needs to be reduced. Earlier studies of out-of-hours care have indicated that antibiotic prescribing is less appropriate than that of in-hours care. However, no study has compared the out-of-hours treatment of infections to in-hours treatment within the same population. METHODS: This retrospective, descriptive study was based on data retrieved from the Kronoberg Infection Database in Primary Care (KIDPC), which consists of all visits to primary care with an infection diagnosis or prescription of antibiotics during 2006-2014. The purpose was to study the trends in antibiotic prescribing and to compare consultations and prescriptions between in-hours and out-of-hours. RESULTS: The visit rate for all infections was 434 visits per 1000 inhabitants per year. The visit rate was stable during the study period, but the antibiotic prescribing rate decreased from 266 prescriptions per 1000 inhabitants in 2006 to 194 prescriptions in 2014 (mean annual change - 8.5 [95% CI - 11.9 to - 5.2]). For the out-of-hours visits (12% of the total visits), a similar reduction in antibiotic prescribing was seen. The decrease was most apparent among children and in respiratory tract infections. When antibiotic prescribing during out-of-hours was compared to in-hours, the unadjusted relative risk of antibiotic prescribing was 1.37 (95% CI 1.36 to 1.38), but when adjusted for age, sex, and diagnosis, the relative risk of antibiotic prescribing was 1.09 (95% CI 1.08 to 1.10). The reduction after adjustment was largely explained by a higher visit rate during out-of-hours for infections requiring antibiotics (acute otitis media, pharyngotonsillitis, and lower urinary tract infection). The choices of antibiotics used for common diagnoses were similar. CONCLUSIONS: Although the infection visit rate was unchanged over the study period, there was a significant reduction in antibiotic prescribing, especially to children and for respiratory tract infections. The higher antibiotic prescribing rate during out-of-hours was small when adjusted for age, sex, and diagnosis. No excess prescription of broad-spectrum antibiotics was seen. Therefore, interventions selectively aiming at out-of-hours centres seem to be unmotivated in a low-prescribing context.

Von Willebrand factor, ABO blood group, and risk of first-ever intracerebral hemorrhage: A prospective nested case-control study.

BACKGROUND AND PURPOSE: Low levels of von Willebrand factor (VWF) were associated with intracerebral hemorrhage (ICH) in a previous study. Persons with blood group O have lower VWF levels than other ABO blood groups. This study aimed to investigate the association between VWF and the risk of ICH in adults, as well as the association between ABO blood group and risk of ICH. METHODS: This population-based, nested case-control study was conducted using data and blood samples from health examinations between 1985 and 2007. All participants were followed, and cases with first-ever ICH were identified and validated. One or two controls were matched to each case. RESULTS: During a median follow-up time from blood sampling to ICH of 5.6 years, 176 cases with ICH were identified. The mean age at health examination was 57 years; 50% of participants were women. There was an association between hypertension and risk of ICH, but there was no association between VWF level and risk of ICH. There was no association between blood group O and risk of ICH. CONCLUSIONS: To our knowledge this is the largest prospective study investigating the association between VWF, ABO blood group and ICH. We found no association between VWF or blood group O and risk of future ICH.

Patients developing inflammatory bowel disease have iron deficiency and lower plasma ferritin years before diagnosis: a nested case-control study.

BACKGROUND: Iron deficiency is common among inflammatory bowel disease (IBD) patients, generally reported without comparisons with controls. The aim of this study was to analyse if iron deficiency was more common among those later developing IBD compared to matched controls in a prospective setting. METHODS: We included 96 healthy subjects later developing IBD and 191 matched controls from the Northern Sweden Health and Disease Study. We analysed iron, ferritin, transferrin, and calculated transferrin saturation in plasma sampled at least 1 year prior to IBD diagnosis. Iron deficiency was defined as plasma ferritin <30 µg/L if C-reactive protein (CRP) was <3 mg/L. When CRP was >3 mg/L, iron deficiency could not be excluded if ferritin was <100 µg/L. RESULTS: Iron deficiency could not be excluded among more male cases vs controls (25.0% vs 2.2%; P < 0.001), whereas with no differences for women (39.6% vs 35.3%; P = 0.538). Ferritin was lower among male IBD cases (P = 0.001) and for ulcerative colitis (P = 0.016 for males and 0.017 for females), but not for Crohn's disease. Ferritin was associated with a lower risk for IBD and in the ulcerative colitis subgroup when using sex-based z-scores. Ferritin quartiles 2-4 had a 65% lower odds ratio for all IBD, ulcerative colitis, and Crohn's disease in multivariable analysis. CONCLUSIONS: Lower ferritin was associated with higher risk for developing IBD in a prospective setting. Iron deficiency was more common among healthy males years later developing IBD compared to matched controls, but not among women.

Evaluation of urine dipsticks for quality control of residual erythrocytes and leukocytes in leukocyte-depleted donor plasma.

Currently used methodologies for quality control of residual leukocytes and erythrocytes in leukocyte-depleted plasma are either expensive or time-consuming. It has been proposed that urine dipsticks could be used as a screening method for residual erythrocytes. The aim was, therefore, to evaluate if urine dipsticks could be used to detect residual erythrocytes and also residual leukocytes in leukocyte-depleted plasma. Dilution series ranging over the decision limits for residual erythrocytes and leukocytes were prepared. Positive, negative and overall agreements, as well as the precision and joint frequency distributions, were calculated for five dipstick analyzers and their corresponding dipsticks. Twenty-four consecutive leukocyte-depleted donor plasma samples were also tested. None of the dipstick analyzers had both a high positive and a high negative agreement. Accordingly, none of the analyzers were able to discriminate between cell concentrations close to the decision limits. The inconsistency count revealed differences in precision between the dipstick analyzers. In the 24 consecutive donor samples, no significant correlation between the dipstick analyzers and the reference methods were found. In conclusion, urine dipsticks are not suitable for quality control of residual leukocytes and erythrocytes in leukocyte-depleted donor plasma.

Evaluation of a routine hematology analyzer for quality control of leukoreduced plasma.

BACKGROUND: Quality control of residual white blood cells (WBCs) and red blood cells (RBCs) in leukoreduced plasma is mandatory. Although technological advances have been made, analysis of quality controls using routine hematology analyzers has not generally been introduced. The aim of this study was to evaluate if the routine hematology analyzer Sysmex XN-10, (Sysmex Nordic ApS) could be used for quality control of residual WBCs and RBCs in leukoreduced plasma. STUDY DESIGN AND METHODS: Linearity, accuracy, and precision were established for two Sysmex XN-10 analyzers using spiked donor plasma. ADAM rWBC (NanoEnTek) and manual counting in the Bürker chamber (NanoEnTek) were reference methods for WBCs and RBCs, respectively. Twenty-five consecutive leukoreduced donor plasma samples were also tested. RESULTS: For WBCs, the linearity criteria were met for the ADAM rWBC, but not for the Sysmex XN-10 instruments. Precision on both Sysmex XN-10 instruments was accurate only at 6 cells/µL, and accuracy was consistently acceptable only at 5 to 6 cells/µL. The precision and accuracy of the ADAM rWBC were acceptable at 2 to 6 cells/µL. For RBCs, both Sysmex XN-10 instruments and manual counting in the Bürker chamber were linear and fulfilled the precision criteria. Accuracy was acceptable for both Sysmex instruments at 6 to 12 × 109 WBCs/L but fluctuated within the study's measuring range for the Bürker chamber. No false-positive results were seen in the 25 consecutive donor plasma samples tested. CONCLUSION: For quality control purposes of leukoreduced plasma, the Sysmex XN-10 analyzer is suitable for the enumeration of residual RBCs but not of residual WBCs.

Introduction of cost display reduces laboratory test utilization.

OBJECTIVES: To study the effects on the number of laboratory tests ordered after introduction of cost display (showing the cost in the computerized test ordering system at test ordering and test result delivery) and cost charge (requiring all primary healthcare centers to pay full laboratory costs of the ordered tests). STUDY DESIGN: The study included cost display for secondary healthcare centers (inpatient hospitals, emergency departments, and outpatient specialist providers) as well as publicly and privately operated primary healthcare centers (sites of nonemergency, nonspecialist healthcare). After 3 months, cost charge was introduced by management for all primary healthcare centers. METHODS: Information on laboratory test cost was appended to the laboratory test name in the test ordering system, resulting in cost display both at the moment of test ordering and at the presentation of the test result. Numbers of laboratory tests were obtained from the laboratory information system and calculated as tests per physician visit. Cost charge was managed through the established laboratory invoicing system. RESULTS: In the publicly operated primary healthcare centers, neither of the interventions had any effect on laboratory test volume, nor did cost display have an effect in the privately operated primary healthcare centers. However, introduction of cost charge significantly decreased laboratory test ordering in the privately operated primary healthcare centers. In contrast, secondary healthcare centers lowered test volumes when cost display was introduced. CONCLUSIONS: The results support cost awareness and cost charge as means of reducing laboratory utilization. However, the outcome varies with the setting.

Interaction of Dietary and Genetic Factors Influencing Body Iron Status and Risk of Type 2 Diabetes Within the EPIC-InterAct Study.

OBJECTIVE: Meat intake has been consistently shown to be positively associated with incident type 2 diabetes. Part of that association may be mediated by body iron status, which is influenced by genetic factors. We aimed to test for interactions of genetic and dietary factors influencing body iron status in relation to the risk of incident type 2 diabetes. RESEARCH DESIGN AND METHODS: The case-cohort comprised 9,347 case subjects and 12,301 subcohort participants from eight European countries. Single nucleotide polymorphisms (SNPs) were selected from genome-wide association studies on iron status biomarkers and candidate gene studies. A ferritin-related gene score was constructed. Multiplicative and additive interactions of heme iron and SNPs as well as the gene score were evaluated using Cox proportional hazards regression. RESULTS: Higher heme iron intake (per 1 SD) was associated with higher ferritin levels (ß = 0.113 [95% CI 0.082; 0.144]), but not with transferrin (-0.019 [-0.043; 0.006]) or transferrin saturation (0.016 [-0.006; 0.037]). Five SNPs located in four genes (rs1799945 [HFE H63D], rs1800562 [HFE C282Y], rs236918 [PCK7], rs744653 [SLC40A1], and rs855791 [TMPRSS6 V736A]) were associated with ferritin. We did not detect an interaction of heme iron and the gene score on the risk of diabetes in the overall study population (Padd = 0.16, Pmult = 0.21) but did detect a trend toward a negative interaction in men (Padd = 0.04, Pmult = 0.03). CONCLUSIONS: We found no convincing evidence that the interplay of dietary and genetic factors related to body iron status associates with type 2 diabetes risk above the level expected from the sum or product of the two individual exposures.

Methods for counting residual leukocytes in leukocyte-depleted plasma-a comparison between a routine hematology instrument, the Nageotte chamber, flow cytometry, and a fluorescent microscopy analyzer.

BACKGROUND: Counting very low levels of leukocytes is technically challenging but mandatory for quality control of leukocyte-depleted plasma. Established assays, such as flow cytometry and counting in the Nageotte chamber, are laborious and expensive. The aim of this study was to test two alternative assays, the cerebrospinal fluid program in the routine hematology analyzer ADVIA 2120 and a fluorescence microscopy analyzer, the ADAM-rWBC. STUDY DESIGN AND METHODS: Linearity, accuracy, and precision were established for the ADVIA 2120, the ADAM-rWBC analyzer and the Nageotte chamber with flow cytometry as the reference method. Two hundred consecutive leukocyte-depleted donor plasma samples were also tested. RESULTS: The ADAM-rWBC analyzer and the Nageotte chamber fulfilled all quality requirements. Flow cytometry fulfilled the requirements for linearity and precision. The ADVIA 2120 analyzer did not fully reach the quality criteria, and flow cytometry did not reach quality criteria on accuracy. No false-positive results on donor plasma samples were recorded. CONCLUSION: The ADAM-rWBC is suitable for the purpose of quality control of residual leukocytes in leukocyte-depleted plasma. For the ADVIA 2120, further improvements and studies are needed to reach the quality requirements stated in this study.

Iron biomarkers in plasma, HFE genotypes, and the risk for colorectal cancer in a prospective setting.

BACKGROUND: High iron levels can increase the formation of noxious oxygen radicals, which are thought to promote carcinogenesis. OBJECTIVE: The aim of this prospective study was to determine whether iron biomarkers and HFE genotypes, which influence iron regulation, constitute risk factors for colorectal cancer. DESIGN: This is a prospective nested case-referent study. SETTINGS: The study was performed within the population-based Northern Sweden Health and Disease Study. PATIENTS: The study included 226 cases of colorectal cancer and 437 matched referents. MAIN OUTCOME MEASURES: Conditional regression analysis was performed. Adjustments for smoking, smoking and BMI, and HFE C282Y and H63D were performed. RESULTS: The highest quintile of total iron-binding capacity showed significantly higher risk for colorectal cancer, unadjusted OR 2.35 (95% CI 1.38-4.02). When stratified by sex, the findings were only present in women (OR 3.34 (95% CI 1.59-7.02)). Ferritin was associated with reduced risk throughout quintiles 2 to 5 both in univariate and multivariate models. LIMITATIONS: Colorectal cancer may influence iron markers because of occult bleeding. Homozygotes for HFE C282Y were too few to make conclusions for this group. The relatively short follow-up time might be insufficient to detect risk of iron biomarkers. CONCLUSIONS: High iron levels do not increase the risk of colorectal cancer. HFE genotypes influencing iron uptake had no effect on colorectal cancer risk.

Iron stores and HFE genotypes are not related to increased risk of first-time myocardial infarction: a prospective nested case-referent study.

OBJECTIVES: Our objectives were to study the relationship between iron stores, HFE genotypes and the risk for first-ever myocardial infarction. METHODS: First-ever myocardial infarction cases (n=618) and double matched referents from the Northern Sweden Health and Disease Cohort Study were studied in a prospective nested case-referent setting. Plasma iron, total iron binding capacity, transferrin iron saturation and ferritin were analyzed, as well as several confounders. HFE C282Y and H63D genotypes were determined. RESULTS: There was an inverse risk association for myocardial infarction in the highest quartiles of iron (OR 0.68; 95% CI 0.48-0.96) and transferrin iron saturation (OR 0.62; 95% CI 0.42-0.89) in men. This association, however, was lost after adjusting for C-reactive protein. Women homozygous for H63D had a higher risk for myocardial infarction. CONCLUSIONS: No risk association between high iron stores and first-ever myocardial infarction was found. The higher risk in female H63D homozygotes is probably not related to iron metabolism.

Bilirubin and UGT1A1*28 are not associated with lower risk for ischemic stroke in a prospective nested case-referent setting.

BACKGROUND: Bilirubin, an antioxidant, has been associated with reduced cardiovascular disease risk. A major cause of elevated plasma bilirubin is the common UGT1A1*28 promoter polymorphism in the gene of the bilirubin-conjugating enzyme UDP-glucuronosyltransferase 1A1, which reduces transcription by 70%. Earlier studies reporting a protective effect of bilirubin on stroke have not included analysis of UGT1A1*28. The purpose of this study is to investigate if bilirubin and UGT1A1*28 are protective against ischemic stroke in a prospective case-referent setting. METHODS: Cases with first-ever ischemic stroke (n = 231; median lag time 4.9 years) and 462 matched referents from the Northern Sweden Health and Disease Study Cohort were included. Plasma bilirubin was measured and UGT1A1*28 was analyzed by fragment analysis. RESULTS: Plasma bilirubin was lower in cases than in referents, but the difference reached significance only for women. The UGT1A1*28 polymorphism (allele frequency 30%) showed a strong gene-dose relationship with bilirubin levels both among cases and referents, but was not associated with risk for stroke. Among multiple other variables analyzed, the strongest correlation with bilirubin was found for plasma iron. CONCLUSIONS: There was no evidence for a protective effect of the UGT1A1*28 polymorphism against stroke and consequently neither for bilirubin. The findings suggest that other factors influencing the risk for stroke might also affect bilirubin levels.

Plasma bilirubin and UGT1A1*28 are not protective factors against first-time myocardial infarction in a prospective, nested case-referent setting.

BACKGROUND: Bilirubin, an effective antioxidant, shows a large variation in levels between individuals and has been positively associated with reduced cardiovascular disease risk. A major reason for the variability is a common promoter polymorphism, UGT1A1*28, which reduces the transcription of the enzyme that conjugates bilirubin, UDP-glucuronosyltransferase 1A1. The aim of the study was to evaluate a possible protective effect of plasma bilirubin and the UGT1A1*28 polymorphism against myocardial infarction in a prospective case-referent setting. METHODS AND RESULTS: Subjects (n=618) with a first-ever myocardial infarction (median event age, 60.5 years; median lag time, 3.5 years) and 1184 matched referents were studied. Plasma bilirubin was lower in cases versus referents. Despite a strong gene-dosage effect on bilirubin levels in both cases and referents, the UGT1A1*28 polymorphism did not influence the risk of myocardial infarction. Among multiple other variables, serum iron showed one of the strongest associations with bilirubin levels. CONCLUSIONS: We found no evidence for a protective effect of the UGT1A1*28 polymorphism against myocardial infarction and consequently neither for bilirubin. The lower bilirubin levels in cases might be caused by decreased production, increased degradation, or increased elimination.

Iron stores and HFE genotypes are not related to increased risk of ischemic stroke. A prospective nested case-referent study.

BACKGROUND: High iron levels can increase the formation of noxious oxygen radicals, which are thought to contribute to cerebrovascular disease. The aim of this prospective study was to determine if iron status and HFE genotypes constitute risk factors for stroke. METHODS: First-ever stroke cases (231 ischemic and 42 hemorrhagic) and matched double referents from the population-based Northern Sweden cohorts were studied in a nested case-referent setting. RESULTS: For total iron binding capacity, an increased risk of ischemic stroke was seen in the highest quartile (OR 1.80; 95% CI 1.14-2.83; p for trend 0.012). The highest quartile of transferrin iron saturation showed a decreased risk of ischemic stroke in men (OR 0.44; 95% CI 0.22-0.87; p for trend 0.028), but not in women. There was an increased risk of hemorrhagic stroke in the second (OR 4.07; 95% CI 1.09-15.20) and third quartile (OR 4.22; 95% CI 1.08-16.42) of ferritin. Neither quartiles of plasma iron concentrations nor the HFE C282Y and H63D genotypes were associated with ischemic or hemorrhagic stroke. CONCLUSIONS: Iron stores were not positively related to increased risk of ischemic stroke. Furthermore, HFE genotypes did not influence the risk of ischemic or hemorrhagic stroke.