Biomedical subjects

Vilmundur Gudnason

Publications and source records attributed to Vilmundur Gudnason.

At least 19 recordsLinked to original sources

PubMed2026

Large-Scale Proteomic Profiling of Incident Heart Failure and Its Subtypes in Older Adults.

BACKGROUND: Heart failure (HF) and its main subtypes, heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF), impose an enormous health burden on elders. Assessment of the circulating proteome to illuminate pathogenesis could open new opportunities for treatment. METHODS: We conducted a plasma proteomics screen of incident HF and its subtypes in 2 older population-based cohorts, the CHS (Cardiovascular Health Study) and the AGES-RS (Aging, Gene/Environment Susceptibility-Reykjavik Study). The 2 studies used SomaLogic platforms, with 4404 aptamers in common. Multivariable Cox models were fit to evaluate individual-protein associations with HF, HFpEF, and HFrEF separately in each cohort, and study-specific associations were combined by fixed-effects meta-analysis. Replication was performed in the ARIC (Atherosclerosis Risk in Communities) cohort. Two-sample Mendelian randomization of HF and its subtypes, along with colocalization analysis, was performed to support causal inference. RESULTS: Among 8599 participants, 1590 experienced incident HF (536 HFpEF, 471 HFrEF). There were 119 proteins associated with HF, 15 proteins with HFpEF, and 11 proteins with HFrEF, at Bonferroni-corrected significance. Among these, 9 have never previously been identified for cardiovascular diseases, and another 61 represent new associations with incident HF or its subtypes. Of these 70 proteins, 55 of the 66 available replicated externally. Mendelian randomization analysis revealed 7 proteins genetically associated with HF at nominal significance; 2 were separately associated with HFpEF, and another 2 with HFrEF. Seven of these 9 proteins (NPDC1 [neural proliferation differentiation and control protein 1], APOF [apolipoprotein F], LMAN2 [lectin, mannose-binding 2], ADIPOQ [adiponectin], CD14 [cluster of differentiation 14], ARHGAP1 [Rho GTPase-activating protein 1], C9 [complement 9]) showed new, possibly causal associations, although we did not detect evidence for colocalization. CONCLUSIONS: In this large-scale proteomic study involving 3 longitudinal cohorts of older adults, we identified and replicated 55 novel protein markers of HF or its subtypes, and 7 new, possibly causal proteins. These proteins may enhance risk prediction, improve understanding of pathobiology, and help prioritize targets for therapeutic development of these foremost disorders in elders.

Humans↗

PubMed2025

Cardiac Troponins and Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis.

BACKGROUND: The extent to which high-sensitivity cardiac troponin can predict cardiovascular disease (CVD) is uncertain. OBJECTIVES: We aimed to quantify the potential advantage of adding information on cardiac troponins to conventional risk factors in the prevention of CVD. METHODS: We meta-analyzed individual-participant data from 15 cohorts, comprising 62,150 participants without prior CVD. We calculated HRs, measures of risk discrimination, and reclassification after adding cardiac troponin T (cTnT) or I (cTnI) to conventional risk factors. The primary outcome was first-onset CVD (ie, coronary heart disease or stroke). We then modeled the implications of initiating statin therapy using incidence rates from 2.1 million individuals from the United Kingdom. RESULTS: Among participants with cTnT or cTnI measurements, 8,133 and 3,749 incident CVD events occurred during a median follow-up of 11.8 and 9.8 years, respectively. HRs for CVD per 1-SD higher concentration were 1.31 (95% CI: 1.25-1.37) for cTnT and 1.26 (95% CI: 1.19-1.33) for cTnI. Addition of cTnT or cTnI to conventional risk factors was associated with C-index increases of 0.015 (95% CI: 0.012-0.018) and 0.012 (95% CI: 0.009-0.015) and continuous net reclassification improvements of 6% and 5% in cases and 22% and 17% in noncases. One additional CVD event would be prevented for every 408 and 473 individuals screened based on statin therapy in those whose CVD risk is reclassified from intermediate to high risk after cTnT or cTnI measurement, respectively. CONCLUSIONS: Measurement of cardiac troponin results in a modest improvement in the prediction of first-onset CVD that may translate into population health benefits if used at scale.

Humans↗

PubMed2006

Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies.

BACKGROUND: Many epidemiological studies have reported on associations between serum triglyceride concentrations and the risk of coronary heart disease, but this association has not been reliably quantified. In the present study, we report 2 separate nested case-control comparisons in 2 different prospective, population-based cohorts, plus an updated meta-analysis of 27 additional prospective studies in general Western populations. METHODS AND RESULTS: Measurements were made in a total of 3582 incident cases of fatal and nonfatal coronary heart disease and 6175 controls selected from among the 44,237 men and women screened in the Reykjavik and the European Prospective Investigation of Cancer (EPIC)-Norfolk studies. Repeat measurements were obtained an average of 4 years apart in 1933 participants in the EPIC-Norfolk Study and an average of 12 years apart in 379 participants in the Reykjavik study. The long-term stability of log-triglyceride values (within-person correlation coefficients of 0.64 [95% CI, 0.60 to 0.68] over 4 years and 0.63 [95% CI, 0.57 to 0.70] over 12 years) was similar to those of blood pressure and total serum cholesterol. After adjustment for baseline values of several established risk factors, the strength of the association was substantially attenuated, and the adjusted odds ratio for coronary heart disease was 1.76 (95% CI, 1.39 to 2.21) in the Reykjavik study and 1.57 (95% CI, 1.10 to 2.24) in the EPIC-Norfolk study in a comparison of individuals in the top third with those in the bottom third of usual log-triglyceride values. Similar overall findings (adjusted odds ratio, 1.72; 95% CI, 1.56 to 1.90) were observed in an updated meta-analysis involving a total of 10,158 incident coronary heart disease cases from 262,525 participants in 29 studies. CONCLUSIONS: Available prospective studies in Western populations consistently indicate moderate and highly significant associations between triglyceride values and coronary heart disease risk. Because these associations depend considerably on levels of established risk factors, however, further studies are needed to help assess the nature of any independent associations.

Case-Control Studies↗

PubMed2006

Increasing sex difference in bone strength in old age: The Age, Gene/Environment Susceptibility-Reykjavik study (AGES-REYKJAVIK).

INTRODUCTION: It is important to identify possible pathological mechanisms that underlie the known sexual dimorphism in bone fragility in old age. In this cross-sectional population-based study, we use data from three different skeletal sites to examine sex differences in volumetric bone density, geometry and strength indices and determine whether sex differences in these bone strength measures continue to increase into very old age. MATERIALS AND METHODS: A total of 1715 elderly individuals (807 men and 908 women) age 67-93 years, participants in a population-based study, the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-REYKJAVIK) and not taking medications affecting bone metabolism, were studied. Quantitative computed tomography (QCT) was performed in the lumbar spine, hip and mid-femoral shaft to estimate volumetric trabecular, cortical and integral BMD, bone geometry and bone strength indices. Regression models were used to assess the effects of age and gender-adjustment for standing midlife height and current weight. RESULTS: At age 67-69 years, men had 24.9-31.7% larger cross-sectional bone size at measured sites than women. At all bone sites, women had two- to fivefold diminution in net bone mass with age compared to men but had comparable increments in bone size (1.8-6.0% per 10 years). This was reflected in significantly worse (more than twofold) bone strength measures with age in women, including compressive strength indices at the spine, femoral neck and trochanter and bending strength indices at the femoral neck. CONCLUSION: With the limitations of a cross-sectional study, our data support the hypothesis that sex differences in bone strength continue into old age. These sex differences appear to be due to greater net bone loss in women rather than due to greater bone gain in men.

Age Distribution↗

PubMed2006

Apolipoprotein E genotype and statins affect CRP levels through independent and different mechanisms: AGES-Reykjavik Study.

OBJECTIVE: C-reactive protein (CRP), an inflammatory marker, was linked to coronary heart disease (CHD) in the Reykjavik study cohort. Recent genetic studies have shown that the apolipoprotein E (APOE) epsilon4 allele is associated with lower CRP levels. Statin treatment has also been shown to lower CRP levels. In the Age Gene/Environment Susceptibility (AGES)-Reykjavik Study, we examined the association of APOE genotypes with CRP accounting for the effect of statin treatment, previous CHD and a mid-life measurement of erythrocyte sedimentation rate (ESR), an inflammatory marker associated with risk in this cohort. METHODS AND RESULTS: The first 2296 participants (mean age 76+/-6 years, 42% men) in the AGES-Reykjavik Study were genotyped for APOE CRP concentration was measured with a high sensitivity method. A general linear model was used to evaluate the association of APOE genotype to CRP levels. The frequencies of the APOE alleles are epsilon2=0.06, epsilon3=0.78 and epsilon4=0.16. CRP levels ranged from 0.2 to 56.6 mg/L, median 1.9 mg/L. Participants carrying one or two epsilon4 alleles have significantly lower CRP levels than non-carriers and this effect was observed in a dose-dependent manner. This trend is the same in users and non-users of statin treatment. CONCLUSIONS: This study suggests that the contribution of the epsilon4 allele towards lowering CRP levels is independent and may be by a different mechanism than how statins affect inflammation.

Aged↗

PubMed2006

Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes.

We have previously reported suggestive linkage of type 2 diabetes mellitus to chromosome 10q. We genotyped 228 microsatellite markers in Icelandic individuals with type 2 diabetes and controls throughout a 10.5-Mb interval on 10q. A microsatellite, DG10S478, within intron 3 of the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4) was associated with type 2 diabetes (P = 2.1 x 10(-9)). This was replicated in a Danish cohort (P = 4.8 x 10(-3)) and in a US cohort (P = 3.3 x 10(-9)). Compared with non-carriers, heterozygous and homozygous carriers of the at-risk alleles (38% and 7% of the population, respectively) have relative risks of 1.45 and 2.41. This corresponds to a population attributable risk of 21%. The TCF7L2 gene product is a high mobility group box-containing transcription factor previously implicated in blood glucose homeostasis. It is thought to act through regulation of proglucagon gene expression in enteroendocrine cells via the Wnt signaling pathway.

Chromosome Mapping↗

PubMed2006

[The health risk associated with smoking has been seriously underestimated. The Reykjavik Study].

OBJECTIVE: To assess the risk for coronary heart disease, myocardial infarction, cancer deaths, and all deaths associated with different smoking categories as determined by smoking status at a baseline examination only and at a baseline with reexamination 15-19 years later (persistent smokers). MATERIAL AND METHODS: The participants were a random sample of 2930 men and 3084 women aged 34-61 years (when selected in 1967) invited for various standardized examinations under two periods, 1967-1972 and 1979-1991 and followed-up until the end of year 2001. The main outcome measures were clinical coronary heart disease, myocardial infarction, cancer deaths, and all deaths. Risk was calculated for each smoking category as determined by two assessments of smoking habits and also compared with the risk as determined by one baseline examination only. RESULTS: Mean follow-up for men was 26 years (SD 9 years). For women the mean follow-up was 28 years (SD 7 years). There were substantial differences in hazard ratios (HR) and median lifetime in smoking groups as determined by one or two examinations. In men the greatest difference in hazard ratios was for cancer deaths (one examination: 2.80, two: 3.83) in women for total deaths (3.02 vs. 3.7). Loss of median lifetime was greatest in "heavy" cigarette smoking men (one examination: eight years; two examinations: 13 years), in women the corresponding figures were nine and 10 years, in "light" cigarette smokers, the figures for men were four and nine years, and for women four and six years. CONCLUSIONS: Middle-aged men smoking one or more packets of cigarettes per day shorten their life expectancy by 13 years and middle-aged women by 10 years. Only one baseline determination of smoking status with subsequent follow-up underestimates the health risk associated with smoking by 15-40% at least in populations where smoking prevalence is declining.

Adult↗

PubMed2005

Examination of genetic effects of polymorphisms in the MCP-1 and CCR2 genes on MI in the Icelandic population.

Monocyte chemotactic protein-1 (MCP-1) and its receptor CCR2 may play a role in mediating atherosclerosis. The polymorphisms MCP-1 -2518A>G and CCR2 190G>A have been reported to be associated with increased risk for developing atherosclerosis. The aim of this study was to investigate the effect of these polymorphisms and the MCP-1 -2076A>T polymorphism on the development of myocardial infarction (MI) in an Icelandic cohort. Four hundred and sixty MI survivors and 1842 disease free controls were genotyped. No significant difference in the frequencies of any of the polymorphisms between the cases and the controls was found, with OR=0.87 (95% CI 0.71-1.08) for MCP-1 -2518G, OR=1.05 (95% CI 0.84-1.33) for MCP-1 -2076T and OR=0.93 (95% CI 0.71-1.23) for CCR2 190A. An effect of an OR for MI of 1.4 for the MCP-1 -2518G, MCP-1 -2076T and CCR2 190A alleles could be detected in a cohort of the size of this study with power=0.8 and alpha=0.05. In our cohort we were unable to demonstrate a significant association of the MCP-1 -2518A>G, MCP-1 -2076A>T or CCR2 190G>A polymorphisms with MI. These results do not support the extent of risk associated with developing MI previously reported for the CCR2 190 and MCP-1 -2518 polymorphisms.

Aged↗

PubMed2005

A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction.

Variants of the gene ALOX5AP (also known as FLAP) encoding arachidonate 5-lipoxygenase activating protein are known to be associated with risk of myocardial infarction. Here we show that a haplotype (HapK) spanning the LTA4H gene encoding leukotriene A4 hydrolase, a protein in the same biochemical pathway as ALOX5AP, confers modest risk of myocardial infarction in an Icelandic cohort. Measurements of leukotriene B4 (LTB4) production suggest that this risk is mediated through upregulation of the leukotriene pathway. Three cohorts from the United States also show that HapK confers a modest relative risk (1.16) in European Americans, but it confers a threefold larger risk in African Americans. About 27% of the European American controls carried at least one copy of HapK, as compared with only 6% of African American controls. Our analyses indicate that HapK is very rare in Africa and that its occurrence in African Americans is due to European admixture. Interactions with other genetic or environmental risk factors that are more common in African Americans are likely to account for the greater relative risk conferred by HapK in this group.

Black or African American↗

PubMed2005

Prevalence of chronic kidney disease based on estimated glomerular filtration rate and proteinuria in Icelandic adults.

BACKGROUND: The purpose of this study was to compare three different equations to calculate estimated glomerular filtration rate (eGFR) based on serum creatinine (SCr) and to estimate the prevalence of chronic kidney disease (CKD) in the Icelandic population. METHODS: This was a cross-sectional study using data from the Reykjavik Heart Study. GFR was estimated with three equations: Equation I was based on 1/SCr; Equation II based on the Cockcroft-Gault equation; and Equation III was the modified MDRD equation. The eGFR calculated with Equation III and proteinuria were used to estimate the prevalence of CKD. The prevalence was age-standardized to the truncated world population. We used chi-square and ANCOVA to compare the group with low eGFR to age-matched controls. RESULTS: The subjects consisted of 9229 males and 10,027 females, aged 33-85 years. The equations performed very differently. Equation I showed women with higher eGFR than men and little change with age. Equation II showed men with higher eGFR than women and marked decline in eGFR with age. Equation III was similar to Equation II but the decline in eGFR with age was not as great. Regardless of the equation used, most subjects (63.7-80.7%) had an eGFR in the range of 60-89 ml/min/1.73 m2. Using Equation III, age-standardized prevalence of low eGFR for the population aged 35-80+ years was estimated to be 4.7 and 11.6% for men and women, respectively. The proportion of subjects with eGFR <60 ml/min/1.73 m2 increased with advancing age. An additional 2.39% of men and 0.89% of women had proteinuria. The prevalence of renal and cardiovascular risk factors including proteinuria, hypertension, lipid abnormalities and markers of inflammation was higher among those with low eGFR than age-matched controls. CONCLUSIONS: GFR estimates and the prevalence of CKD are dependent on the equation used to calculate eGFR. Unexpectedly, a low proportion of the Icelandic population had normal kidney function according to the eGFR regardless of the equation used. These equations may not be useful in epidemiological research.

Adult↗

PubMed2005

Serum uric acid and coronary heart disease in 9,458 incident cases and 155,084 controls: prospective study and meta-analysis.

BACKGROUND: It has been suggested throughout the past fifty years that serum uric acid concentrations can help predict the future risk of coronary heart disease (CHD), but the epidemiological evidence is uncertain. METHODS AND FINDINGS: We report a "nested" case-control comparison within a prospective study in Reykjavik, Iceland, using baseline values of serum uric acid in 2,456 incident CHD cases and in 3,962 age- and sex-matched controls, plus paired serum uric acid measurements taken at baseline and, on average, 12 y later in 379 participants. In addition, we conducted a meta-analysis of 15 other prospective studies in eight countries conducted in essentially general populations. Compared with individuals in the bottom third of baseline measurements of serum uric acid in the Reykjavik study, those in the top third had an age- and sex-adjusted odds ratio for CHD of 1.39 (95% confidence interval [CI], 1.23-1.58) which fell to 1.12 (CI, 0.97-1.30) after adjustment for smoking and other established risk factors. Overall, in a combined analysis of 9,458 cases and 155,084 controls in all 16 relevant prospective studies, the odds ratio was 1.13 (CI, 1.07-1.20), but it was only 1.02 (CI, 0.91-1.14) in the eight studies with more complete adjustment for possible confounders. CONCLUSIONS: Measurement of serum uric acid levels is unlikely to enhance usefully the prediction of CHD, and this factor is unlikely to be a major determinant of the disease in general populations.

Age Factors↗

PubMed2005

Short hospital stay augmented with education and home-based rehabilitation improves function and quality of life after hip replacement: randomized study of 50 patients with 6 months of follow-up.

BACKGROUND: Because of current cost restrictions, we studied the effect of a shorter hospital stay on function, pain and quality of life (QOL) after total hip replacement (THR). PATIENTS AND METHODS: 50 patients from two hospitals were randomized into a study group (SG) of 27 patients receiving preoperative and postoperative education programs, as well as home visits from an outpatient team, and a control group (CG) of 23 patients receiving "conventional" rehabilitation often augmented by a stay at a rehabilitation center. RESULTS: Mean hospital stay was shorter for the SG than for the CG (6.4 days and 10 days, respectively; p < 0.001). During the 6-month study period, there were 9 non-fatal complications in the SG and 12 in the CG (p = 0.3). The difference in Oxford Hip Score between the groups was not statistically significant before the operation, but was better for the SG at 2 months (p = 0.03) and this difference remained more or less constant throughout the study. The overall score from the Nottingham Health Profile indicated a better QOL in the SG. INTERPRETATION: Our preoperative education program, followed by postoperative home-based rehabilitation, appears to be safer and more effective in improving function and QOL after THR than conventional treatment.

Adult↗

PubMed2005

Glucose abnormalities and heart failure predict poor prognosis in the population-based Reykjavík Study.

BACKGROUND: The risk of cardiovascular disease increases progressively with increasing blood glucose from levels well below the diabetic threshold. In the Reykjavík Study the relationship between heart failure and abnormal glucose regulation was already apparent at the level of impaired glucose tolerance. The aim of this study was to determine the prognosis of participants with any glucose abnormality and heart failure and to test whether the combination of these conditions may adversely affect the subsequent prognosis. DESIGN: A prospective population-based study. METHODS: Data from the first visit of 19 381 participants were used. Participants were divided into groups according to their glycaemic and heart failure level, and comparisons were made between the groups and disease-free participants serving as a reference group. The risk of mortality and morbidity was calculated with adjustments for main cardiovascular risk factors and ischaemic heart disease. RESULTS: Participants in the reference group were younger, had lower body mass indices and more seldom a history of myocardial infarction compared with diseased groups. Mortality was lowest in the reference group (P<0.0001) increasing to a maximum in participants with the combination of glucose abnormality and heart failure. Prognostically, the mortality risk associated with abnormal glucose regulation was increased but was lower than the risk of diabetes. The risk of a new myocardial infarction was highest in participants with diabetes [hazard ratio (HR) 1.6; 95% confidence interval (CI) 1.3-2.0] or diabetes in combination with heart failure (HR 1.8; CI 1.1-2.7). CONCLUSIONS: Heart failure or glucose abnormalities are related to increased morbidity and mortality. The combination of glucose abnormality and heart failure did, however, not add further to the unfavourable prognosis in the presence of ischaemic heart disease.

Adolescent↗

PubMed2005

The association between glucose abnormalities and heart failure in the population-based Reykjavik study.

OBJECTIVE: Diabetes is an independent risk factor for heart failure, whereas the relation between heart failure and abnormal glucose regulation (AGR) needs further evaluation. We studied this combination in the Reykjavik Study. RESEARCH DESIGN AND METHODS: The Reykjavik Study, a population-based cohort study during 1967-1997, recruited 19,381 participants aged 33-84 years who were followed until 2002. Oral glucose tolerance tests and chest X-rays were obtained from all participants. Cases were defined in accordance with World Health Organization criteria for type 2 diabetes or AGR (impaired glucose tolerance or impaired fasting glucose) and European Society of Cardiology guidelines for heart failure. RESULTS: The overall prevalence of type 2 diabetes and heart failure was 0.5% in men and 0.4% in women, while AGR and heart failure were found in 0.7% of men and 0.6% of women. Among participants with normal glucose regulation, heart failure was diagnosed in 3.2% compared with 6.0 and 11.8% among those with AGR and type 2 diabetes, respectively. The prevalence of type 2 diabetes in the age-group 45-65 years increased in both sexes during the period (P for trend = 0.007). The odds ratio was 2.8 (95% CI 2.2-3.6) for the association between type 2 diabetes and heart failure and 1.7 (1.4-2.1) between AGR and heart failure. CONCLUSIONS: There is a strong association between any form of glucometabolic perturbation and heart failure. Future studies in this field should focus on all types of glucose abnormalities rather than previously diagnosed diabetes only.

Adult↗

PubMed2005

[Trends in overweight and obesity in 45-64 year old men and women in Reykjavík 1975-1994. 2001].

OBJECTIVE: The aim of this study was to assess possible changes in the prevalence of overweight and obesity in Iceland during the last decades. Furthermore, the possible effect of dietary changes on the observed trend in obesity prevalence was evaluated. MATERIAL AND METHODS: Participants came from stages III-V in the Reykjavik Health Study and the Reykjavik part of the MONICA studies from the period 1975-1994. The age groups 45-54 years and 55-64 years were examined. Only the information from the first visit of each person was included. The body mass index (BMI) for the participants was calculated and the percentage of those subjects considered overweight and obese according to WHO standards evaluated, using 25= or >BMI<30 kg/m2 as the cut-off point for overweight and BMI= or >30 kg/m2 as the cut-off point for obesity. Also, the observed trend in obesity prevalence is compared to changes in diet that have occurred in the same period. RESULTS: The results show that the mean weight and height of both men and women have been increasing during the study period. However, weight has increased more than can be accounted for by increased height, resulting in increased BMI. At the same time, the prevalence of overweight and obesity have increased, the relative increase in obesity far exceeding the relative increase in overweight. The prevalence of obesity more than doubled in both age groups of women during the study period, according to trend analyses. At the end of the period, almost 15% (95% confidence interval (CI), 9-22%) in the younger group of women and 25% (95% CI, 17-34%) in the older group were classified as obese. In the younger group of men, the prevalence of obesity almost doubled, while the observed increase in the older group was not statistically significant, according to trend analyses. The prevalence of obesity in the final period was about 19% (95% CI, 13-27%) and 17% (95% CI, 11-25%) in the younger and older groups of men, respectively. According to the food supply statistics there have been insignificant changes in the consumption of energy nutrients during the period. CONCLUSIONS: Overweight and obesity are becoming more common among middle-aged men and women in Reykjavik, during the period 1975-1994 and the rate of increase being comparable to that observed in many Western countries. It is urgent to respond to this problem by promoting a healthier lifestyle, both with respect to diet and physical activity.

Body Mass Index↗

PubMed2005

[Latent autoimmune diabetes in adults in Iceland: prevalence, phenotype and relatedness].

INTRODUCTION: Ninety percent of diabetic individuals in Iceland suffer from type 2 diabetes mellitus. Antibodies against ss-cell components characterise type 1 diabetes, but these antibodies are also found in type 2 diabetic individuals, defined as latent autoimmune diabetes in adults or LADA. The purpose of this investigation was to estimate the prevalence of LADA in Iceland and to describe the phenotype and relatedness of these individuals. MATERIAL AND METHODS: A list of individuals diagnosed with type 2 diabetes was generated from outpatient clinic lists and the Reykjavik Study of the Icelandic Heart Association. A genealogy database (Book of Icelanders; deCODE Genetics) was used to identify all individuals related to these index cases within six meioses. This method identified 950 type 2 diabetic individuals during the years 1998-2000. We analyzed their phenotype and measured glutamic acid decarboxylase antibody (GAD). Kinship coefficient was used to compare the relatedness of those with antibodies to GAD to the relatedness of all type 2 diabetic individuals in the study. RESULTS: 10.1% of men and 9.3% women had measurable antibodies against GAD (non-significant difference). The mean age of GAD positive and GAD negative individuals was comparable (67.1 +/- 10.7 and 68.0 +/- 11.3; years +/- SD). Body mass index was significantly lower (p=0,02) for the GAD positive individuals or 28.2 kg/m(2) (27.2-29.2; 95% CI) vs. 29.7 (29.3-30.1). Of the GAD positive individuals, 47% +/- 9% (95% CI) had the metabolic syndrome as defined by WHO compared with 60 +/- 4% of the GAD negative individuals (p=0.02). The kinship coefficient for GAD positive individuals (n=94) was 6.00x10(-4) compared with 3.93x10(-4) +/- 8.3x10(-5) for 500 random samples (each of 94 individuals) of the whole cohort (p=0.008). CONCLUSION: About 10% of Icelandic type 2 diabetic individuals have antibodies against GAD, which is comparable to the results of other investigators. Icelandic GAD positive type 2 diabetic individuals have less frequently the metabolic syndrome than other type 2 diabetic individuals and GAD positive individuals are significantly more related to each other than type 2 diabetic individuals in general.

Adult↗

PubMed2004

Mannan binding lectin as an adjunct to risk assessment for myocardial infarction in individuals with enhanced risk.

Inflammation can predispose to myocardial infarction (MI), and mannan binding lectin (MBL) promotes phagocytic clearance of inflammatory agents, but the predictive value of MBL levels for MI is not known. MBL was analyzed in subgroups of the population-based Reykjavik study, a cohort of 19,381 participants recruited from 1967. MBL levels were very stable over time (self correlation: 0.86). In a cross-sectional group from the original cohort (n = 987), high MBL (>1,000 microg/L) was associated with a greatly lowered odds ratio for MI (0.64, P < 0.001). To verify this finding, a nested case control sample (n = 1,309) was randomly selected from the cohort. High MBL at recruitment was also associated with decreased MI risk in this follow-up group, but to a lesser extent and not significant for the whole group, smokers, or hypertensive individuals. However, high MBL was as in the cross-sectional group, associated with greatly decreased MI risk in diabetic (P = 0.02) or hypercholesterolemic individuals (P = 0.004). This also applied to raised erythrocyte sedimentation rate (P = 0.007). Diabetic patients with high MBL did not have a higher MI risk than nondiabetic individuals. Our findings indicate that high MBL may predict decreased likelihood of MI, particularly in diabetics, and are consistent with the possibility that MBL may promote clearance of atherogenic agents.

Aged↗

PubMed2004

Familial risk of lung carcinoma in the Icelandic population.

CONTEXT: The dominant role of tobacco smoke as a causative factor in lung carcinoma is well established; however, an inherited predisposition may also be an important factor in the susceptibility to lung carcinoma. OBJECTIVE: To investigate the contribution of genetic factors to the risk of developing lung carcinoma in the Icelandic population. DESIGN, SETTING, AND PARTICIPANTS: Risk ratios (RRs) of lung carcinoma for first-, second-, and third-degree relatives of patients with lung carcinoma were estimated by linking records from the Icelandic Cancer Registry (ICR) of all 2756 patients diagnosed with lung carcinoma within the Icelandic population from January 1, 1955, to February 28, 2002, with an extensive genealogical database containing all living Icelanders and most of their ancestors since the settlement of Iceland. The RR for smoking was similarly estimated using a random population-based cohort of 10,541 smokers from the Reykjavik Heart Study who had smoked for more than 10 years. Of these smokers, 562 developed lung cancer based on the patients with lung cancer list from the ICR. MAIN OUTCOME MEASURES: Estimation of RRs of close and distant relatives of patients with lung carcinoma and comparison with RRs for close and distant relatives of smokers. RESULTS: A familial factor for lung carcinoma was shown to extend beyond the nuclear family, as evidenced by significantly increased RR for first-degree relatives (for parents: RR, 2.69; 95% confidence interval [CI], 2.20-3.23; for siblings: RR, 2.02; 95% CI, 1.77-2.23; and for children: RR, 1.96; 95% CI, 1.53-2.39), second-degree relatives (for uncles/aunts: RR, 1.34; 95% CI, 1.15-1.49; and for nephews/nieces: RR, 1.28; 95% CI, 1.10-1.43), and third-degree relatives (for cousins: RR, 1.14; 95% CI, 1.05-1.22) of patients with lung carcinoma. This effect was stronger for relatives of patients with early-onset disease (age at onset < or =60 years) (for parents: RR, 3.48; 95% CI, 1.83-8.21; for siblings: RR, 3.30; 95% CI, 2.19-4.58; and for children: RR, 2.84; 95% CI, 1.34-7.21). The hypothesis that this increased risk is solely due to the effects of smoking was rejected for all relationships, except cousins and spouses, with a single-sided test of the RRs for lung carcinoma vs RRs for smoking. CONCLUSIONS: These results underscore the importance of genetic predisposition in the development of lung carcinoma, with its strongest effect in patients with early-onset disease. However, tobacco smoke plays a dominant role in the pathogenesis of this disease, even among those individuals who are genetically predisposed to lung carcinoma.

Adenocarcinoma↗