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

Long-term interleukin-6 levels and subsequent risk of coronary heart disease: Two new prospective studies and a systematic review

Background The relevance to coronary heart disease (CHD) of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6), may be underestimated because such mediators are short acting and prone to fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined as nonfatal myocardial infarction [MI] or fatal CHD) in two population-based cohorts, involving serial measurements to enable correction for within-person variability. We updated a systematic review to put the new findings in context. Methods and Findings Measurements were made in samples obtained at baseline from 2,138 patients who had a first-ever nonfatal MI or died of CHD during follow-up, and from 4,267 controls in two cohorts comprising 24,230 participants. Correction for within-person variability was made using data from repeat measurements taken several years apart in several hundred participants. The year-to-year variability of IL-6 values within individuals was relatively high (regression dilution ratios of 0.41, 95% confidence interval [CI] 0.28-0.53, over 4 y, and 0.35, 95% CI 0.23-0.48, over 12 y). Ignoring this variability, we found an odds ratio for CHD, adjusted for several established risk factors, of 1.46 (95% CI 1.29-1.65) per 2 standard deviation (SD) increase of baseline IL-6 values, similar to that for baseline C-reactive protein. After correction for within-person variability, the odds ratio for CHD was 2.14 (95% CI 1.45-3.15) with long-term average ("usual'') IL-6, similar to those for some established risk factors. Increasing IL-6 levels were associated with progressively increasing CHD risk. An updated systematic review of electronic databases and other sources identified 15 relevant previous population-based prospective studies of IL-6 and clinical coronary outcomes (i.e., MI or coronary death). Including the two current studies, the 17 available prospective studies gave a combined odds ratio of 1.61 (95% CI 1.42-1.83) per 2 SD increase in baseline IL-6 (corresponding to an odds ratio of 3.34 [95% CI 2.45-4.56] per 2 SD increase in usual [long-term average] IL-6 levels). Conclusions Long-term IL-6 levels are associated with CHD risk about as strongly as are some major established risk factors, but causality remains uncertain. These findings highlight the potential relevance of IL-6-mediated pathways to CH

Incidence and prevalence of total joint replacements due to osteoarthritis in the elderly: risk factors and factors associated with late life prevalence in the AGES-Reykjavik Study.

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.Total joint replacements (TJRs) should be considered as one of few definite endpoints in osteoarthritis research. We analyzed factors associated with late-life prevalence and risk factors for incidence of TJRs due to osteoarthritis in a population based cohort.After exclusion of inflammatory arthritis and fractures as causes of TJR, 5170 participants in the AGES-Reykjavik Study (mean age (SD) 76.4(6), 58 % females) were included for osteoarthritis studies. Three thousand one hundred thirty-three of them had a follow-up visit 5 years later.The prevalence of having at least one joint replacement operation due to OA was 13.6 % and the yearly incidence was 1.4 %/year during the five-year follow-up. Factors positively associated with late life prevalence of TJR included BMI, hand OA severity, female gender, finger length ratio and spine BMD. Risk factors for TJRs in the incidence group were symptoms at initial visit, prior TJR in the contralateral joint and BMI. Much stronger associations were seen for TKR than for THR with discriminatory analysis showing an AUC 0.71 for late life prevalence and 0.84 for the incidence.This study illustrates the importance of the different information expressed by late life prevalence vs. incidence on the factors associated with severe osteoarthritis of the knee and hip. The observation that prior TJR is a risk factor for subsequent TJR in the contralateral joint has not been described previously. The high power predictions for TKR suggest that a predictive model may be feasible, particularly if it can be extended by the addition of further predictive variables, perhaps through genetic, biomarker or imaging data.NIH N01-AG-12100 NIA Intramural Research Program Hjartavernd (the Icelandic Heart Association) Althingi (the Icelandic Parliament) Icelandic Osteoarthritis Fund University of Iceland Research Fun

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

Type 3 finger length pattern is associated with total knee replacements due to osteoarthritis but not with hip replacements or hand osteoarthritis in the elderly: the AGES-Reykjavik study.

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.Recent case-control studies have shown an association between type 3 finger length pattern (longer ring finger than index finger) and knee osteoarthritis. This large cross-sectional study tests the hypothesis that the type 3 pattern is associated with total joint replacements due to osteoarthritis in a large population based study.Finger length ratios were assessed visually on 5170 hand photographs (2975 females, 2195 males, mean age 76). In this population-based multidisciplinary study of aging in Reykjavik, Iceland, the prevalence of osteoarthritis associated total knee replacements was 223(4.3%) and total hip replacements 316(6.1%). We then performed a binary logistic regression analysis for total knee replacements and total hip replacements, including finger length patterns, osteoarthritis at other sites and other variables with possible association to osteoarthritis such as age, BMI and bone mineral density of the spine.The prevalence of the type 3 pattern was 50% (43% in females, 58% in males). The regression analysis revealed an odds ratio for total knee replacements of 1.65 (1.24-2.2) p = 0.0007, in the type 3 finger pattern group, similar in both genders. This association was independent of the associations we have previously reported between total knee replacements and BMI and the presence of hand osteoarthritis. No association was seen between finger length patterns and total hip replacements.Finger length patterns read from digital photographs in this large study confirm previous radiographic observations with significant associations between the type 3 pattern and total knee replacements but not total hip replacements in both genders in this elderly group.NIH N01-AG-12100 NIA Intramural Research Program Hjartavernd (the Icelandic Heart Association) Althingi (the Icelandic Parliament) Icelandic Osteoarthritis Fund University of Iceland Research Fun

Glycemic status and brain injury in older individuals: 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: To examine the association of glycemic status to magnetic resonance imaging indicators of brain pathological changes. RESEARCH DESIGN AND METHODS: This was a cross-sectional, population-based study of 4,415 men and women without dementia (mean age 76 years) participating in the Age Gene/Environment Susceptibility-Reykjavik Study. Glycemic status groups included the following: type 2 diabetes (self-report of diabetes, use of diabetes medications, or fasting blood glucose > or =7.0 mmol/l [11.1%]); impaired fasting glucose (IFG) (fasting blood glucose 5.6-6.9 mmol/l [36.2%]); and normoglycemic (52.7%). Outcomes were total brain volume, white and gray matter volume, white matter lesion (WML) volume, and presence of cerebral infarcts. RESULTS: After adjustment for demographic and cardiovascular risk factors, participants with type 2 diabetes had significantly lower total brain volume (72.2 vs. 71.5%; P < 0.001) and lower gray and white matter volumes (45.1 vs. 44.9%, P < 0.01 and 25.7 vs. 25.3%, P < 0.001, respectively) and were more likely to have single (odds ratio 1.45 [95% CI 1.14-1.85]) or multiple (2.27 [1.60-3.23]) cerebral infarcts compared with normoglycemic participants. Longer duration of type 2 diabetes was associated with lower total brain volume and gray and white matter volume, higher WML volume (all P(trend) < 0.05), and a greater likelihood of single and multiple cerebral infarcts (all P(trend) < 0.01). CONCLUSIONS: Type 2 diabetic participants have more pronounced brain atrophy and are more likely to have cerebral infarcts. Duration of type 2 diabetes is associated with brain changes, suggesting that type 2 diabetes has a cumulative effect on the brain

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

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

Worksite Physical Activity Interventions and their effect on employees' sickness absence: a literature review

Masteroppgave - Norges idrettshøgskole, 2016Objective: To investigate the effect of physical exercise interventions, done in the workplace, on sickness absence. The review was done with special interest in progress in the intervention effect and design the last 5 years. Method: The literature was identified by search in three scientific databases, PubMed, Sport Discus and Web of Science. The search identified 660 studies that were screened and then excluded if: 1.They were not in English. 2. Full text was not available. 3. The intervention was not implemented at the workplace or in relation with the workplace. 4. Sickness absence was not reported. 5. The study was not experimental design. 6. Intervention did not comprise physical exercise or aim to increase physical exercise. In total 10 studies were included in the review.Results: Two of the ten included studies showed significant decrease in sickness absence, revealing the effect of increased physical exercise on sickness absence. The positive effect in those two studies were shown with physical exercise during work hours and focused on high intensity exercise. In terms of intervention strategies, three studies targeted consultation and lifestyle coaching to increase physical activity and the other seven studies had active physical exercise intervention. The intervention design varied between studies both of intensity and type of exercise. All of the studies had the aim to decrease sickness absence. Conclusion: Based on the results of this review, a fair conclusion seems that out of the amount of exercise interventions or interventions that promote physical activity to reduce sickness absence that has been conducted, only a small minority have shown evidence of effect. In this review studies comprising different kind of interventions were included in terms of intervention content, strategies as well as physical activity intensity.Seksjon for coaching og psykologi / Department of Coaching and Psycholog