Hemostatic factors and risk of coronary heart disease in general populations: new prospective study and updated meta-analyses

<p>Background: Activation of blood coagulation and fibrinolysis may be associated with increased risk of coronary heart disease. We aimed to assess associations of circulating tissue plasminogen activator (t-PA) antigen, D-dimer and von Willebrand factor (VWF) with coronary heart disease risk.</p> <p>Design: Prospective case-control study, systematic review and meta-analyses.</p> <p>Methods: Measurements were made in 1925 people who had a first-ever nonfatal myocardial infarction or died of coronary heart disease during follow-up (median 19.4 years) and in 3616 controls nested within the prospective population-based Reykjavik Study.</p> <p>Results: Age and sex-adjusted odds ratios for coronary heart disease per 1 standard deviation higher baseline level were 1.25 (1.18, 1.33) for t-PA antigen, 1.01 (0.95, 1.07) for D-dimer and 1.11 (1.05, 1.18) for VWF. After additional adjustment for conventional cardiovascular risk factors, corresponding odds ratios were 1.07 (0.99, 1.14) for t-PA antigen, 1.06 (1.00, 1.13) for D-dimer and 1.08 (1.02, 1.15) for VWF. When combined with the results from previous prospective studies in a random-effects meta-analysis, overall adjusted odds ratios were 1.13 (1.06, 1.21) for t-PA antigen (13 studies, 5494 cases), 1.23 (1.16, 1.32) with D-dimer (18 studies, 6799 cases) and 1.16 (1.10, 1.22) with VWF (15 studies, 6556 cases).</p> <p>Conclusions: Concentrations of t-PA antigen, D-dimer and VWF may be more modestly associated with first-ever CHD events than previously reported. More detailed analysis is required to clarify whether these markers are causal risk factors or simply correlates of coronary heart disease.</p&gt

The interaction of adiposity with the CRP gene affects CRP levels: age, gene/environment susceptibilty-Reykjavik study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: Common diseases often have an inflammatory component reflected by associated markers such as serum C-reactive protein (CRP) levels. Circulating CRP levels have also been associated with adipose tissue as well as with specific CRP genotypes. We examined the interaction between measures of body mass index (BMI), waist circumference and fat percent (total fat measured by bioimpedance) with genotypes of the CRP gene in the determination of CRP levels. METHODS: The first 2296 participants (mean age 76+/-6 years, 42% men) in the Age, Gene/Environment Susceptibility-Reykjavik Study, a multidisciplinary epidemiological study to determine risk factors in aging, were genotyped for 10 single nucleotide polymorphisms (SNPs) in the CRP gene. General linear models with age and terms for interaction of CRP genotypes with BMI, waist circumference and percent fat were used to evaluate the association of genotypes to CRP levels (high-sensitivity method, range 0-10 mg l(-1)) in men and women separately. RESULTS: We focused on the SNP rs1205 that represents the allele that captures the strongest effects of the gene on CRP levels. Carriers of the rs1205 G allele had significantly higher CRP levels than noncarriers in a dose-dependent manner. Compared to the AA genotype, the slope of the increase in CRP with increasing BMI (P=0.045) and waist circumference (P=0.014) was different for the G allele carriers and of similar magnitude in both men and women. The rs1205 interactions were not significant for fat mass percent, suggesting a possible association with fat localization. CONCLUSIONS: This study further illuminates the known association between measures of adiposity and CRP levels and is shown to be dependent on variation in the rs1205 SNP of the CRP gene. The correlated increase in CRP levels with adiposity is accentuated by presence of the G allele

Trichomonas vaginalis is Rare Among Women in Iceland

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesLandspitali University Hospital Orebro County Council Research Committee Foundation for Medical Research at Orebro University Hospital, Orebro, Swede

Retinopathy in old persons with and without diabetes mellitus: the Age, Gene/Environment Susceptibility--Reykjavik Study (AGES-R).

To access full text version of this article. Please click on the hyperlink "View/open" at the bottom of this pageWe aimed to describe the prevalence of retinopathy in an aged cohort of Icelanders with and without diabetes mellitus. The study population consisted of 4,994 persons aged ≥ 67 years, who participated in the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-R). Type 2 diabetes mellitus was defined as HbA(1c) ≥ 6.5% (>48 mmol/mol). Retinopathy was assessed by grading fundus photographs using the modified Airlie House adaptation of the Early Treatment Diabetic Retinopathy Study protocol. Associations between retinopathy and risk factors were estimated using odds ratios obtained from multivariate analyses. The overall prevalence of retinopathy in AGES-R was 12.4%. Diabetes mellitus was present in 516 persons (10.3%), for 512 of whom gradable fundus photos were available, including 138 persons (27.0%, 95% CI 23.2, 31.0) with any retinopathy. Five persons (1.0%, 95% CI 0.3, 2.3) had proliferative retinopathy. Clinically significant macular oedema was present in five persons (1.0%, 95% CI 0.3, 2.3). Independent risk factors for retinopathy in diabetic patients in a multivariate model included HbA(1c), insulin use and use of oral hypoglycaemic agents, the last two being indicators of longer disease duration. In 4478 participants without diabetes mellitus, gradable fundus photos were available for 4,453 participants, with retinopathy present in 476 (10.7%, 95% CI 9.8, 11.6) and clinically significant macular oedema in three persons. Independent risk factors included increasing age and microalbuminuria. Over three-quarters (78%) of retinopathy cases were found in persons without diabetes and a strong association between microalbuminuria and non-diabetic retinopathy was found. These results may have implications for patient management of the aged.NIH N01-AG-12100 NIH/NIA, National Eye Institute (NEI) of the NIH ZIAEY000401, Hjartavernd (the Icelandic Heart Association), Althingi (the Icelandic Parliament), University of Iceland

Retinal and cerebral microvascular signs and diabetes: the age, gene/environment susceptibility-Reykjavik study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: Diabetes increases the risk for microvascular disease. The retina and the brain both have intricate microvascular systems that are developmentally similar. We sought to examine whether microvascular lesions in the retina and in the brain are associated and whether this association differs among people with and without diabetes. RESEARCH DESIGN AND METHODS: The analysis included 4,218 participants of the Icelandic population-based Age, Gene/Environment Susceptibility-Reykjavik Study who were born in 1907-1935 and who were previously followed as a part of the Reykjavik Study. Retinal focal arteriolar narrowing, arteriovenous (AV) nicking, and microaneurysms/hemorrhages were evaluated on digital retinal images of both eyes. Cerebral microbleeds (CMBs) were evaluated from magnetic resonance images. Data were analyzed with logistic and multinomial logistic regression models controlling for demographics, major cardiovascular risk factors, cerebral infarcts, and white matter lesions. RESULTS: Evidence of brain microbleeds was found in 485 (11.5%) people, including 192 with multiple (>or=2) microbleeds. Subjects with signs of retinal microvascular lesions were at a significantly increased likelihood for having multiple CMBs. People with diabetes in combination with the presence of either retinal AV nicking (odds ratio [OR] 2.47 [95% CI 1.42-4.31]) or retinal microaneurysms/hemorrhages (2.28 [1.24-4.18]) were significantly more likely to have multiple CMBs. CONCLUSIONS: Retinal microvascular abnormalities and brain microbleeds may occur together in older adults. People with both diabetes and signs of retinal microvascular lesions (AV nicking and microaneurysms/hemorrhages) are more likely to have multiple microbleeds in the brain. Microvascular disease in diabetes extends to the brain

Non-skeletal health effects of vitamin D supplementation: a systematic review on findings from meta-analyses summarizing trial data

Background A large number of observational studies have reported harmful effects of low 25-hydroxyvitamin D (25OHD) levels on non-skeletal outcomes. We performed a systematic quantitative review on characteristics of randomized clinical trials (RCTs) included in meta-analyses (MAs) on non-skeletal effects of vitamin D supplementation. Methods and findings We identified systematic reviews (SR) reporting summary data in terms of MAs of RCTs on selected non-skeletal outcomes. For each outcome, we summarized the results from available SRs and scrutinized included RCTs for a number of predefined characteristics. We identified 54 SRs including data from 210 RCTs. Most MAs as well as the individual RCTs reported null-findings on risk of cardiovascular diseases, type 2 diabetes, weight-loss, and malignant diseases. Beneficial effects of vitamin D supplementation was reported in 1 of 4 MAs on depression, 2 of 9 MAs on blood pressure, 3 of 7 MAs on respiratory tract infections, and 8 of 12 MAs on mortality. Most RCTs have primarily been performed to determine skeletal outcomes, whereas non-skeletal effects have been assessed as secondary outcomes. Only one-third of the RCTs had low level of 25OHD as a criterion for inclusion and a mean baseline 25OHD level below 50 nmol/L was only present in less than half of the analyses. Conclusions Published RCTs have mostly been performed in populations without low 25OHD levels. The fact that most MAs on results from RCTs did not show a beneficial effect does not disprove the hypothesis suggested by observational findings on adverse health outcomes of low 25OHD levels

Three-dimensional cometary dust coma modelling in the collisionless regime: strengths and weaknesses

Inverse coma and tail modelling of comets based on the method developed by Finson & Probstein is commonly used to analyse cometary coma images. Models of this type often contain a large number of assumptions that may not be constrained unless wide temporal or spectral coverage is available and the comets are bright and at relatively small geocentric distance. They are used to predict physical parameters, such as the mass distribution of the dust, but rarely give assessments of the accuracy of the estimate. A three-dimensional cometary dust coma model in the collisionless regime has been developed to allow the effectiveness of such models to constrain dust coma properties to be tested. The model is capable of simulating the coma morphology for the following input parameters: the comet nucleus shape, size, rotation, emission function (including active fraction and jets), grain velocity distribution (and dispersion), size distribution, dust production rate, grain material and light scattering from the cometary dust. Characterization of the model demonstrates that the mass distribution cannot be well constrained as is often assumed; the cumulative mass distribution index ? can only be constrained to within ±0.15. The model is highly sensitive to the input grain terminal velocity distribution so model input can be tested with a large degree of confidence. Complex secondary parameters such as jets, rotation and grain composition all have an effect on the structure of the coma in similar ways, so unique solutions for these parameters cannot be derived from a single optical image alone. Multiple images at a variety of geometries close in time can help constrain these effects. The model has been applied to photometric observations of comets 126P/IRAS and 46P/Wirtanen to constrain a number of physical properties including the dust production rate and mass distribution index. The derived dust production rate (Qdust) for 46P/Wirtanen was 3+7/1.5 kg s1 at a pre-perihelion heliocentric distance of 1.8 au, and for P/IRAS was 50+100/20 kg s1 at a pre-perihelion heliocentric distance of 1.7 au; both comets exhibited a mass distribution index ? = 0.8 ± 0.15

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events

Similar decline in mortality rate of older persons with and without type 2 diabetes between 1993 and 2004 the Icelandic population-based Reykjavik and AGES-Reykjavik cohort studies.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.A decline in mortality rates due to cardiovascular diseases and all-cause mortality has led to increased life expectancy in the Western world in recent decades. At the same time, the prevalence of type 2 diabetes, a disease associated with a twofold excess risk of cardiovascular disease and mortality, has been increasing. The objective of this study was to estimate the secular trend of cardiovascular and all-cause mortality rates in two population-based cohorts of older persons, with and without type 2 diabetes, examined 11 years apart.1506 participants (42% men) from the population-based Reykjavik Study, examined during 1991-1996 (median 1993), mean age 75.0 years, and 4814 participants (43% men) from the AGES-Reykjavik Study, examined during 2002-2006 (median 2004), mean age 77.2 years, age range in both cohorts 70-87 years. The main outcome measures were age-specific mortality rates due to cardiovascular disease and all causes, over two consecutive 5.7- and 5.3-year follow-up periods.A 32% decline in cardiovascular mortality rate and a 19% decline in all-cause mortality rate were observed between 1993 and 2004. The decline was greater in those with type 2 diabetes, as illustrated by the decline in the adjusted hazard ratio of cardiovascular mortality in individuals with diabetes compared to those without diabetes, from 1.88 (95% CI 1.24-2.85) in 1993 to 1.46 (95% CI 1.11-1.91) in 2004. We also observed a concurrent decrease in major cardiovascular risk factors in both those with and without diabetes. A higher proportion of persons with diabetes received glucose-lowering, hypertensive and lipid-lowering medication in 2004.A decline in cardiovascular and all-cause mortality rates was observed in older persons during the period 1993-2004, in both those with and without type 2 diabetes. This decline may be partly explained by improvements in cardiovascular risk factors and medical treatment over the period studied. However, type 2 diabetes still persists as an independent risk factor for cardiovascular mortality.National Institute of Health/N01-AG-1-2100 NIA Intramural Research Program Icelandic Heart Association (Hjartavernd) Icelandic Parliament (Althingi