Olafur S Indridason

National University Hospital of Iceland, Reikiavik, Capital Region, Iceland

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Publications (55)176.02 Total impact

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    ABSTRACT: Chronic kidney disease (CKD) is a complex disorder with a strong genetic component. A number of common sequence variants have been found to associate with serum creatinine (SCr), estimated glomerular filtration rate (eGFR) and/or CKD. We imputed 24 million single nucleotide polymorphisms and insertions/deletions identified by whole-genome sequencing of 2,230 Icelanders into 81,656 chip-typed individuals and 112,630 relatives of genotyped individuals over the age of 18 with SCr measurements. The large set of sequenced individuals allowed accurate imputation of variants to a minor allele frequency of 0.1%. We tested the imputed variants for association with SCr. In addition to replicating established loci, we discovered missense and loss of function variants associating with SCr in three solute carriers (SLC6A19, SLC25A45, SLC47A1) and two E3 ubiquitin ligases (RNF186, RNF128). All the variants are within coding sequences and all but one are rare (minor allele frequency <2%) with SCr effects between 0.085 and 0.129 standard deviations (SD). These rare variants have a larger effect on SCr than previously reported common variants, explaining 0.5% of the variability of SCr in Icelanders in addition to the 1% already accounted for. We tested the 5 variants associating with SCr for association with CKD in an Icelandic sample of 15,594 cases and 291,428 controls. Three of the variants also associated with CKD. These variants may either affect kidney function or creatinine synthesis and excretion. Of note were four mutations in SLC6A19 that associate with reduced SCr, three of which have been shown to cause Hartnup disease.
    Human Molecular Genetics 07/2014; · 7.69 Impact Factor
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    ABSTRACT: Introduction: The Icelandic health care system ranks favourably in international comparison but patients' experience of interaction with the health service has not been well studied. The goal of this study was to examine the satisfaction of patients admitted to the Acute Cardiac Unit (ACU) at Landspitali - The National University Hospital of Iceland. Methods: A questionnaire based on the Patient Satisfaction Questionnaire III was mailed to patients admitted to the ACU between 1 January and 29 February 2012. Questions were presented as statements and participants asked to respond how strongly on a scale from 1 to 5 they agreed or disagreed with each statement. Data analysis was performed using descriptive statistics, Cronbach´s alpha for internal consistency of scales and principal components analysis, Wilcoxon-Mann-Whitney and Kruskal-Wallis tests for comparison of groups and Pearson and Spearman correlation coefficients for correlation between variables. Results: The questionnaire was mailed to 485 individuals of whom 275 (57%) responded. The median age of the participants was 62 (range, 19-95) years and 132 (48%) were women. Internal consistency of the scales was mostly high (Cronbach's alpha 0.62-0.91) and principal components analysis revealed one main factor. The mean score of the questionnaire was 6.8 ±1.0 and 91%, and 86% of the participants were pleased with their interaction with physicians and nurses, respectively. Similarly, 88% were pleased with the care they recieved but 25% felt they received insufficient explanations of their symptoms or that follow-up care was lacking. Conclusion: Patients of the ACU generally appear to be satisfied with their care. However, our results suggest that improvement is needed in several areas, including information provided at discharge and follow-up care. Key words: Health service, acute cardiac unit, heart disease, quality of care, PSQ-III questionnaire, survey. Correspondence: Ólafur Skúli Indriðason, olasi@landspitali.is 1Faculty of Medicine, University of Iceland, 2Internal Medicine Services, Landspitali - The National University Hospital of Iceland, 3Educational Testing Institute, Reykjavik, Iceland., University of Iceland.
    Laeknabladid. 06/2014; 100(7):385-390.
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    ABSTRACT: Introduction: Acute kidney injury (AKI) is a common problem in hospitalized patients, requiring extensive treatment and carries a high mortality rate. This study was designed to assess the epidemiology of AKI, and risk factors and outcome of patients with severe AKI in a tertiary care university hospital in Iceland. Material and methods: All adult patients with measured serum creatinine (SCr) in Landspitali University Hospital from January 2008 to December 2011, who had a measured baseline SCr in the preceeding six months, were included. Patients were categorized according to the RIFLE-criteria into risk (stage 1), injury (stage 2) and failure (stage 3) groups based on their highest SCr, using the lowest SCr in the previous six months as baseline. Results: A total of 17,693 individuals (out of 74,960) had a baseline SCr and their data were used for analysis. AKI occured in 3,686 (21%) with 12%, 5% and 4% of stage 1, 2 and 3, respectively. There were more females in stage 1 and stage 2 and more males in stage 3 (p< 0.001). Contributing causes for AKI in patients with stage 3 AKI were surgery (22%), circulatory shock (23%), sepsis (14%), cardiovascular insult (32%), respiratory failure (27%), bleeding (10%), trauma (7%) and AKI associated drugs (61%). Dialysis was required in 11% and in 0.7% for longer than 30 days but none > 90 days. One year survival was 52%. Conclusions: Acute kidney injury is common in Iceland and the prognosis of those with severe AKI is dismal. Majority of those patients were taking drugs that increase risk of AKI, providing a target for preventive measures. Key words: Acute kidney injury, survival, RIFLE criteria, risk factors, comorbid diseases. Correspondence: Gisli H. Sigurðsson, gislihs@landspitali.is.
    Laeknabladid 11/2013; 99(11):499-503. · 0.46 Impact Factor
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    ABSTRACT: Background/objectives:Randomised controlled trials (RCTs) evaluating the effect of fish oil supplementation on postoperative atrial fibrillation (POAF) following cardiac surgery have produced mixed results. In this study, we examined relationships between levels of red blood cell (RBC) n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) and the incidence of POAF.Subjects/methods:We used combined data (n=355) from RCTs conducted in Australia and Iceland. The primary end point was defined as POAF lasting >10 min in the first 6 days following surgery. The odds ratios (ORs) for POAF were compared between quintiles of preoperative RBC n-3 LC-PUFA levels by multivariable logistic regression.Results:Subjects with RBC docosahexaenoic acid (DHA) in the fourth quintile, comprising a RBC DHA range of 7.0-7.9%, had the lowest incidence of POAF. Subjects in the lowest and highest quintiles had significantly higher risk of developing POAF compared with those in the fourth quintile (OR=2.36: 95% CI; 1.07-5.24 and OR=2.45: 95% CI; 1.16-5.17, respectively). There was no association between RBC eicosapentaenoic acid levels and POAF incidence.Conclusions:The results suggest a 'U-shaped' relationship between RBC DHA levels and POAF incidence. The possibility of increased risk of POAF at high levels of DHA suggests an upper limit for n-3 LC-PUFAs in certain conditions.European Journal of Clinical Nutrition advance online publication, 30 October 2013; doi:10.1038/ejcn.2013.215.
    European journal of clinical nutrition 10/2013; · 3.07 Impact Factor
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    ABSTRACT: Limited data exist on the comparison of blood pressure (BP) measurements using aneroid and oscillometric devices. The purpose of the study was to investigate the difference in BP obtained using oscillometric and aneroid BP monitors in 9- to 10-year-old children. A total of 979 children were divided into group O, which underwent two oscillometric BP readings followed by two aneroid readings, and group A, which had BP measured in the reverse order. No significant difference was found between the mean (±standard deviation) of the two systolic BP readings obtained using the oscillometric and aneroid devices (111.5±8.6 vs 111.3±8.1 mm Hg; P=.39), whereas the mean diastolic BP was lower with the oscillometric monitor (61.5±8.0 vs 64.5±6.8 mm Hg; P<.001). A significant downward trend in BP was observed with each consecutive measurement, and agreement between the two monitors was limited. Multiple BP measurements are, therefore, recommended before the diagnosis of elevated BP or hypertension is made with either method.
    Journal of Clinical Hypertension 09/2013; · 2.36 Impact Factor
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    ABSTRACT: Objectives: Postoperative atrial fibrillation (POAF) has been associated with an inflammatory response to the surgical procedure. n-3 long-chain polyunsaturated fatty acids (LC-PUFA) have been proposed for the prevention of POAF. We investigated the relationship between the plasma concentration of inflammatory mediators, levels of n-3 LC-PUFA in red blood cell (RBC) membrane lipids, and the risk of POAF after coronary artery bypass grafting (CABG). Methods: A total of 125 patients who underwent CABG were studied. Inflammatory mediators in plasma and the content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in RBC membranes were assessed. Results: Sixty-two patients (49.6%) developed POAF. The POAF group had higher RBC levels of total n-3 LC-PUFA and DHA than did patients remaining in sinus rhythm (p < 0.05). Of the inflammatory mediators, only postoperative interleukin-6 levels differed, being higher in the POAF group (p < 0.05). Inflammatory mediators were not independent predictors of POAF by multivariable logistic regression analysis. Higher levels of DHA and total n-3 LC-PUFA in RBC membranes, measured immediately prior to CABG and on postoperative day 3, were linearly associated with an increased risk of POAF (p < 0.05). Conclusions: Our findings suggest that inflammatory mediators are not associated with the occurrence of POAF. Interestingly, high n-3 LC-PUFA levels in RBC membranes appear to increase the risk of POAF.
    Cardiology 08/2013; 126(2):107-114. · 1.52 Impact Factor
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    ABSTRACT: Open heart surgery is associated with a systemic inflammatory response. The n-3 long-chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the n-6 LC-PUFA arachidonic acid (AA) may contribute to modulation of the inflammatory response. We investigated whether the preoperative levels of EPA, DHA and AA in plasma phospholipids (PL) and red blood cell (RBC) membrane lipids in patients (n=168) undergoing open heart surgery were associated with changes in the plasma concentration of selected inflammatory mediators in the immediate postoperative period. The postoperative concentration of TNF-β was lower (P<0.05) and those of hs-CRP, IL-6, IL-8, IL-18 and IL-10 higher (P<0.05) than the respective preoperative concentrations. We observed that the preoperative levels of EPA and AA in plasma PL and RBC membrane lipids were associated with changes in the concentration of pro-inflammatory and anti-inflammatory mediators, suggesting a complex role in the postoperative inflammatory process.
    Prostaglandins Leukotrienes and Essential Fatty Acids 08/2013; · 2.73 Impact Factor
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    ABSTRACT: Background: Differences in body composition may lead to imprecision in estimates of glomerular filtration rate (eGFR) derived from serum creatinine. Our aims were to examine the relationship between eGFR and anthropometric and body composition measures and handgrip strength. Methods: We analyzed data from a cross-sectional study comprising 1,630 randomly selected community-dwelling adults. The Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations were used to calculate eGFR from IMDS-standardized serum creatinine. Body mass index and body surface area were calculated from measured height and weight. Body composition was determined by dual-energy x-ray absorptiometry, handgrip strength measured by a hand-held dynamometer. Regression analysis was used to examine the association between eGFR and other factors. Results: In women, eGFR determined by the MDRD equation was inversely associated with height (β = -0.08; p = 0.012), lean mass percentage (β = -0.06; p = 0.047) and handgrip strength (β = -0.15; p < 0.001) and eGFR calculated using the CKD-EPI equation was inversely associated with handgrip strength (β = -0.08; p = 0.001). In men, there was an inverse association between eGFR by the MDRD equation and lean mass percentage (β = -0.10; p = 0.013) and handgrip strength (β = -0.12; p = 0.022) and between eGFR by the CKD-EPI equation and lean mass percentage (β = -0.07; p = 0.018). The R(2) for these variables was <0.02. Conclusions: The inverse relationship between eGFR and measures of lean mass percentage and handgrip strength suggests that incorporation of these variables might improve eGFR prediction from serum creatinine in the general population. This effect appears to be small however and needs to be examined in studies that include measured GFR.
    Nephron Clinical Practice 06/2013; 123(1-2):22-27. · 1.65 Impact Factor
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    ABSTRACT: BACKGROUND Low birth weight has been associated with increased risk of hypertension later in life. The aim of this study was to evaluate the association between birth weight and blood pressure (BP) in healthy 9- to 10-year-old Icelandic children. METHODS Each child underwent 4 seated BP measurements, and the BP percentile was calculated from the mean of the 4 measurements. Height and weight were measured and birth weight retrieved from the Icelandic Birth Registry. Birth measures and anthropometric data were correlated with BP and BP percentiles. Multivariable linear regression was employed to examine the association between BP and birth measures. RESULTS Of 857 children with complete data, 445 were female (51.9%). The mean BP was 112/64 mm Hg in males and 111/63mm Hg in females. The mean birth weight was 3714±620g. No correlation was found between birth weight and absolute BP values. A significant negative correlation between birth weight and both systolic (r = -0.09, P = 0.005) and diastolic (r = -0.08, P = 0.014) BP percentiles was observed. Gestational age did not correlate with BP. CONCLUSION In contrast to many previous studies, we found no association between birth weight and absolute BP in children. However, we observed a statistically significant negative correlation between birth weight and BP percentiles. The lack of standardized BP values may partly explain the conflicting results of previous studies in children, and we suggest that BP percentiles be examined more thoroughly in association with birth weight.
    American Journal of Hypertension 01/2013; 26(1):76-82. · 3.67 Impact Factor
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    European Journal of Clinical Investigation 01/2013; · 3.37 Impact Factor
  • Olof Viktorsdottir, Olafur Skuli Indridason, Runolfur Palsson
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    ABSTRACT: Rapid correction of severe hyponatremia can result in osmotic demyelination syndrome. Patients with severe hyponatremia and renal failure requiring dialysis pose a therapeutic challenge since the use of conventional intermittent hemodialysis will result in a rapid correction of the serum sodium level. We report the case of a 52-year-old woman with extreme hyponatremia and severe acute kidney injury, who was successfully treated with continuous venovenous hemodialysis using a modified dialysate solution with a low sodium concentration that was adjusted on a daily basis. © 2013 S. Karger AG, Basel.
    Blood Purification 01/2013; 36(3-4):274-9. · 2.06 Impact Factor
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    ABSTRACT: A large body of literature suggests an inverse relationship between birth weight and blood pressure in children, adolescents and adults. The most persistent findings have been observed in children with a history of low birth weight or intrauterine growth restriction, while a large number of studies carried out in populations with normally distributed birth weight have shown conflicting results. A recently reported strong direct association between high birth weight and blood pressure, and the significant positive effect of postnatal growth on blood pressure suggests that the fetal origins of adult disease hypothesis should be expanded to include the role of excessive fetal and postnatal growth. In this paper, we review recent studies on the relationship between birth weight and blood pressure in childhood, with a focus on confounding variables that may explain the conflicting results of published work in this field.
    Current Hypertension Reports 10/2012; · 3.90 Impact Factor
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    ABSTRACT: A decrease in bone mineral density (BMD) is frequently seen in patients with anorexia nervosa (AN). This study was designed to assess BMD of young Icelandic women with current or previous history of AN and identify predictors which might be targets for preventive measures. The study was retrospective. Participants were women aged 18-40 years, with diagnosis of AN (F50.0, F50.1) attending the anorexia unit at Landspítali - The National University Hospital of Iceland - in 2001-2009, who had undergone measurement of BMD by dual-energy X-ray absorptiometry. A control group consisted of 58 healthy 30 years old women participating in a study of bone health in 2001-2003. At time of BMD measurement the median body mass index (BMI: kg/m2) in the AN group (n=40) was 17.4 (12.3-25.2) compared to 23.6 (18.1-43.7) in the control group (p<0,001). Lumbar spine and hip BMD were 15.3-17.5% lower in AN patients than in control subjects (p<0.001). In both groups there was a strong correlation between BMD and body weight (r=0.354-0.604, p<0.05) and lean mass (r=0.425-0.588, p<0.05). Among patients with AN a correlation was also seen between BMD and lowest weight during the illness (r=0.482-0.499, p<0.01). Among the 26 AN patients who had repeated BMD measurement, a significant decrease in BMD at femoral neck (-6.6%, p=0.030) was observed in those who lost weight between the measurements (n=9). Those who had BMI ≤17.5 between BMD measurements lost 5.5-7.1% of the BMD at the hip (p<0.05). Young women with AN have 15% lower bone mass than healthy young women. The relationship between BMD and body weight seems to be a continuum across disease states. Increased body weight may be the most important factor for recovery of bone mass in AN patients.
    Laeknabladid 10/2012; 98(10):523-9. · 0.46 Impact Factor
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    ABSTRACT: Recent reports show an increased occurrence of kidney stone disease worldwide. To further evaluate and quantify this observation, we examined recent trends in the incidence of kidney stone disease in the adult population of Iceland over a 24-year period. Computerized databases of all major hospitals and medical imaging centers in Iceland were searched for International Classification of Diseases, radiologic and surgical procedure codes indicative of kidney stones in patients aged 18 years and older. The time trends in stone frequency of 5945 incident patients (63% men) were assessed by Poisson regression analysis. The majority of patients (90.5%) had symptomatic stone disease. The total incidence of kidney stones rose significantly from 108 per 100,000 in the first 5-year interval of the study to 138 per 100,000 in the last interval. The annual incidence of symptomatic stones did not increase significantly in either men or women. There was, however, a significant increase in the annual incidence of asymptomatic stones over time, from 7 to 24 per 100,000 for men and from 7 to 21 per 100,000 for women. The increase in the incidence of asymptomatic stones was only significant for women above 50 years of age and for men older than 40 years. Thus, we found a significant increase in the incidence of kidney stone disease resulting from increased detection of asymptomatic stones. This was largely due to a more frequent use of high-resolution imaging studies in older patients.Kidney International advance online publication, 19 September 2012; doi:10.1038/ki.2012.320.
    Kidney International 09/2012; · 8.52 Impact Factor
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    ABSTRACT: The study aimed to investigate the effect of 6 months of endurance training of moderate intensity on physical performance and the risk of falling in haemodialysis patients. This was a prospective interventional study in which 21 of 35 eligible patients accepted to participate. The 6-minute walk test (6MWT), timed up and go (TUG), timed stand test and Romberg's test were used to evaluate physical fitness. The Borg scale was used to control the workload. The patients bicycled for 12-40 min with increasing workload according to their capabilities. Wilcoxon signed ranks and McNemar's tests were used for analysis. Of the 21 participants, 12 completed 3 months of training. Their median (range) age was 69 (37-88) years, duration of dialysis was 2.5 (1-11) years and body mass index was 25.0 (20.0-31.9). Romberg's test was positive in four participants at the beginning but in three after 3 months. Nine participants completed 6 months of training; none had a positive Romberg's test at that time. Walking distance increased significantly after 3 and 6 months of training (p = 0.002 and p = 0.012, respectively), and time for the TUG decreased significantly (p = 0.041 and p = 0.044), as did time for the timed stand test (p = 0.015 and 0.018), compared with baseline values. The TUG test was in excess of 14 s in four patients at baseline but only one at the end of training. Endurance training of moderate intensity during dialysis results in significantly increased physical performance in haemodialysis patients.
    Scandinavian Journal of Urology and Nephrology 02/2012; 46(1):54-7. · 1.01 Impact Factor
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    ABSTRACT: IntroductionRecent studies of the incidence of acute kidney injury (AKI) are largely based on estimated baseline serum creatinine values. The aim of this study was to more accurately determine the incidence of AKI using the RIFLE criteria for intensive care unit (ICU) patients of a whole population. Materials and methodsAll adult patients admitted to the ICUs of Landspitali – The National University Hospital of Iceland in 2007 (n = 1026) were studied with meticulous search for baseline creatinine. The underlying risk factors and contributing causes for AKI were defined, and survival and ratio of end‐stage renal failure evaluated. ResultsA measured baseline creatinine value was found for all but two patients with AKI. The incidence of AKI according to RIFLE criteria was 21.7% [95% confidence interval (CI): 19.0–24.1%], with 7.1% (95 CI: 5.6–8.9%), 6.8% (95 CI: 5.3–8.5%) and 7.8% (95 CI: 6.2–9.6%) in the risk, injury and failure subgroups. Using estimated baseline creatinine overestimated the incidence of AKI by 3.5%. The sensitivity and specificity of the RIFLE criteria using estimated baseline creatinine were 76% and 95%. Renal replacement therapy was required for 17% of the AKI patients. One year survival of AKI patients was 51%, but only 2.5% of patients surviving 90 days required chronic renal replacement therapy. Conclusions The incidence of AKI in the ICU was lower than previously published, perhaps due to overestimation of AKI using estimated baseline creatinine or bias from tertiary referrals. AKI patients have high mortality, but the survivors have a low incidence of end‐stage renal failure.
    Acta Anaesthesiologica Scandinavica 01/2012; 56(10). · 2.36 Impact Factor
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    ABSTRACT: The purpose of the study was to investigate blood pressure (BP) distribution, prevalence of hypertension, and correlation between BP and body mass index (BMI) in 9- to 10-year-old Icelandic children. Two manual and two automated BP measurements were performed in 1071 Icelandic children. Children with elevated BP underwent a second BP screening, and a third screening was performed if the BP was elevated at the second visit. Hypertension was defined as BP ≥95th percentile at all three visits. White-coat hypertension was diagnosed in hypertensive children with normal 24-hour ambulatory BP. Of 970 children with complete data, 489 were girls (50.4%). The mean BP was 111/63 mm Hg in girls and 112/64 mm Hg in boys (P<.001). The prevalence of elevated BP was 13.1%, 6.0%, and 3.1% after the first, second, and third screen, respectively. The prevalence of sustained hypertension was 2.5% and an additional 0.6% had white-coat hypertension. A significant correlation between BMI and BP was observed (r=0.338, P<.001) and 8.6% of the obese children had hypertension. The prevalence of hypertension in 9- to 10-year-old Icelandic children is lower than indicated in recent reports and is associated with obesity.
    Journal of Clinical Hypertension 10/2011; 13(10):774-9. · 2.36 Impact Factor
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    ABSTRACT: The anti-inflammatory or anti-arrhythmic effects of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) may decrease the risk of postoperative atrial fibrillation (POAF), but interventional studies have yielded conflicting results. We examined the association between n-3 LC-PUFA and n-6 LC-PUFA in plasma phospholipids (PL) and POAF in patients undergoing coronary artery bypass grafting (CABG). A total of 125 patients undergoing CABG were enrolled in the study. The levels of fatty acids in PL were measured preoperatively and on the third postoperative day. The endpoint was defined as POAF lasting ≥5 min. The incidence of POAF was compared between quartiles of the level of each fatty acid in plasma PL by univariate and multivariable analysis. The incidence of POAF was 49·6%. By univariate analysis, the incidence of POAF increased significantly with each higher quartile of pre- and postoperative docosahexaenoic acid (DHA) and diminished significantly with each higher quartile of pre- and postoperative arachidonic acid (AA). For postoperative total n-3 LC-PUFA, there was a significant U-curve relationship where the second quartile had the lowest incidence of POAF or 25·8%. In multivariable analysis, this U-curve relationship between n-3 LC-PUFA levels and POAF risk was not significant, whereas the association between POAF and DHA or AA remained statistically significant. This study suggests that n-3 LC-PUFA supplements might prevent POAF in CABG patients with low baseline levels of these fatty acids in plasma PL, but may be harmful in those with high levels. AA may play an important role in electrophysiological processes.
    European Journal of Clinical Investigation 03/2011; 41(9):995-1003. · 3.37 Impact Factor
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    ABSTRACT: Risk factors for bone loss among the elderly are largely unknown. The objective of the study was to examine longitudinal bone loss in the hip in one-hundred and sixty-two 75-year-old women. Bone mineral density (BMD, g/cm(2)) was measured with dual X-ray absorptiometry (DXA) at baseline and after 4 years. The relationship between changes in BMD during follow-up and the following factors; baseline BMD, baseline weight, weight change, baseline lean and fat body mass (measured with DXA), serum values of biochemical markers and hormones, nutritional and lifestyle factors according to a questionnaire was assessed. The annual mean (SD) change in femoral neck BMD was -0.31% (1.38) in total trochanter -0.35% (1.15) and total hip -0.34% (1.10) and did not differ significantly between measurement sites. Bisphosphonate users had a 2.9%, 1.7% and 1.9% mean adjusted increase in femoral neck, total trochanter and total hip BMD respectively, different from none-users (p<0.05). Subjects with more than three weekly physical activity sessions had less femoral neck bone loss than less active women (p<0.05). The proportion of the variance in BMD changes explained by multivariate models (R(2)) was 12-13%. Women gaining weight had less loss of BMD than those losing weight in the trochanter and the total hip (p<0.001), and in the femoral neck (p=0.055). Elderly women should be advised to maintain their body weight and participate in physical activity. Despite the large number of variables examined in this study, bone loss occurring with increased age is not thoroughly explained.
    Maturitas 11/2010; 67(3):256-61. · 2.84 Impact Factor
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    ABSTRACT: Chronic kidney disease (CKD) is a worldwide public health problem that is associated with substantial morbidity and mortality. To search for sequence variants that associate with CKD, we conducted a genome-wide association study (GWAS) that included a total of 3,203 Icelandic cases and 38,782 controls. We observed an association between CKD and a variant with 80% population frequency, rs4293393-T, positioned next to the UMOD gene (GeneID: 7369) on chromosome 16p12 (OR = 1.25, P = 4.1x10(-10)). This gene encodes uromodulin (Tamm-Horsfall protein), the most abundant protein in mammalian urine. The variant also associates significantly with serum creatinine concentration (SCr) in Icelandic subjects (N = 24,635, P = 1.3 x 10(-23)) but not in a smaller set of healthy Dutch controls (N = 1,819, P = 0.39). Our findings validate the association between the UMOD variant and both CKD and SCr recently discovered in a large GWAS. In the Icelandic dataset, we demonstrate that the effect on SCr increases substantially with both age (P = 3.0 x 10(-17)) and number of comorbid diseases (P = 0.008). The association with CKD is also stronger in the older age groups. These results suggest that the UMOD variant may influence the adaptation of the kidney to age-related risk factors of kidney disease such as hypertension and diabetes. The variant also associates with serum urea (P = 1.0 x 10(-6)), uric acid (P = 0.0064), and suggestively with gout. In contrast to CKD, the UMOD variant confers protection against kidney stones when studied in 3,617 Icelandic and Dutch kidney stone cases and 43,201 controls (OR = 0.88, P = 5.7 x 10(-5)).
    PLoS Genetics 07/2010; 6(7):e1001039. · 8.52 Impact Factor

Publication Stats

597 Citations
176.02 Total Impact Points

Institutions

  • 2001–2014
    • National University Hospital of Iceland
      • • Department of Medicine
      • • Childrens hospital
      Reikiavik, Capital Region, Iceland
  • 2002–2013
    • University of Iceland
      • • Faculty of Medicine
      • • School of Health Sciences
      Reykjavík, Capital Region, Iceland
  • 2010
    • deCODE genetics, Inc.
      Reikiavik, Capital Region, Iceland
    • Norwegian University of Science and Technology
      Nidaros, Sør-Trøndelag, Norway