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

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 μg/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

Body size at birth and age-related macular degeneration in old age

Purpose To study associations between body size at birth and age-related macular degeneration (AMD) in old age. Methods The study sample consists of 1497 community-dwelling individuals (56.1% women) aged 67-89 years with birth data and retinal data collected twice in old age 5 years apart. Birth data (weight, length, birth order) were extracted from original birth records. Digital retinal photographs were graded to determine AMD status. Data on covariates were collected at the baseline physical examination in old age. Multivariable regression analyses were used to study the association between birth data and AMD adjusting for known confounding factors, including birth year cohort effects. Results The prevalence and 5-year incidence of any AMD were 33.1% and 17.0%, respectively. Men and women born in 1930-1936 were significantly leaner and slightly longer at birth compared to those in earlier birth cohorts. There were no consistent associations between weight, length or ponderal index (PI) at birth and AMD in old age even when stratified by birth cohort. Age-related macular degeneration (AMD) prevalence (39.8%) and 5-year incidence (28.6%) were highest in individuals who were in the highest quartile of PI at birth and who were obese in old age. Conclusion Body size at birth was not consistently associated with AMD in old age, suggesting that intrauterine growth might have little direct importance in the development of AMD in old age. It is possible that some yet unknown factors related to larger size at birth and obesity in old age may explain differences in the prevalence and incidence of AMD in the ageing population.Peer reviewe

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

Effects of statin medication on mortality risk associated with type 2 diabetes in older persons: the population-based AGES-Reykjavik Study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.OBJECTIVE: To examine if the beneficial effect of statin medication on mortality seen in randomised clinical trials of type 2 diabetes applies equally to observational studies in the general population of older people. DESIGN: A prospective, population-based cohort study. SETTING: Reykjavik, Iceland. PARTICIPANTS: 5152 men and women from the Age, Gene/Environment Susceptibility-Reykjavik Study, mean age 77 years, range of 66-96 years. MAIN OUTCOME MEASURE: Cardiovascular and all-cause mortalities and the RR of dying according to statin use and history of coronary heart disease (CHD) in persons with type 2 diabetes and those without diabetes with a median follow-up time of 5.3 years, until end of 2009. RESULTS: The prevalence of type 2 diabetes was 12.4% of which 35% used statins. Statin use was associated with a 50% (95% CI 8% to 72%) lower cardiovascular mortality and 53% (29% to 68%) lower all-cause mortalities in persons with diabetes. For those without diabetes, statin use was associated with a 16% (-24% to 43%) lower cardiovascular and 30% (11% to 46%) lower all-cause mortalities. Persons with diabetes using statins had a comparable risk of cardiovascular and all-cause mortality to that of the general population without diabetes. The effect was independent of the level of glycaemic control. CONCLUSION: This observational study lends important support to existing data from randomised clinical trials. These data suggest that in the general population of older people with diabetes, statin medication markedly reduces the excess cardiovascular and all-cause mortality risk, irrespective of the presence or absence of coronary heart disease or glucose-lowering medication

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

Personalized Epigenomic Signatures That Are Stable Over Time and Covary with Body Mass Index

International audienc

Hyperuricemia is associated with intermittent hand joint pain in a cross sectional study of elderly females: 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 DownloadBACKGROUND: The debate whether "asymptomatic hyperuricemia" should be treated is still ongoing. The objective of this cross-sectional study was to analyze whether hyperuricema in the elderly is associated with joint pain. METHODS AND FINDINGS: Participants in the population-based AGES-Reykjavik Study (males 2195, females 2975, mean age 76(6)) answered standardized questions about joint pain. In addition they recorded intermittent hand joint pain by marking a diagram of the hand. In males, no association was found between hyperuricemia and pain. Females however, showed a positive association between hyperuricemia and joint pain at many sites. After adjustment for age, BMI and hand osteoarthritis however, only intermittent hand joint pain (OR 1.30(1.07-1.58), p = 0.008) and intermittent pain in ≥10 hand joints (OR 1.75(1.32-2.31), p<0.001) remained significant. The best model for describing the relationship between serum uric acid levels (SUA) and intermittent hand joint pain in ≥10 joints was non-linear with a cut-off at 372 μmol/L. The attributable surplus number of symptomatic females with SUA ≥372 μmol/L was approximately 2.0% of the study population for those reporting pain in ≥10 hand joints. Next after having severe hand osteoarthritis, SUA ≥372 was an independent predictive factor of intermittent pain in ≥10 hand joints. Intermittent hand joint pain was also an independent risk factor for worse general health description. CONCLUSION: Results from this population based study indicate that hyperuricemia in elderly females may be a rather frequent cause of intermittent hand joint pain, often in many joints. The most likely explanation relates to low-grade urate crystal induced inflammation. Our data do not allow for assessment of the severity of symptoms or whether they merit specific treatment, but intermittent hand joint pain was an independent predictor of worse general health. These findings may be an important contribution to the debate on whether hyperuricemia should be treated.United States Department of Health & Human Services National Institutes of Health (NIH) - USA United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Aging (NIA) Althingi (the Icelandic Parliament) Icelandic Osteoarthritis Fund University of Iceland Research Fund Hjartavernd (the Icelandic Heart Association

Population distribution of traditional and the emerging cardiovascular risk factors carotid plaque and IMT: the REFINE-Reykjavik study with comparison with the Tromsø 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 FilesOBJECTIVES: Population statistics for carotid plaque and cardiovascular risk factors reported in scientific journals are usually presented as averages for the population or age and sex adjusted, rather than sex and age groups. Important population differences about atherosclerosis and cardiovascular risk factors may thus be missed. We compare the distribution of cardiovascular risk factors, carotids plaque and carotid intima-media thickness (CIMT) in two population-based studies. METHODS: Carotid artery atherosclerotic plaque prevalence and risk factors levels for cardiovascular disease by sex in 5-year age groups from the Risk Evaluation For Infarct Estimates Reykjavik study (REFINE-Reykjavik study) were compared with data from the Tromsø 6 study. RESULTS: The threshold of carotid plaque presence in the Tromsø 6 study fell between minimal and moderate plaque defined in the REFINE-Reykjavik study reflecting carotid plaque prevalence. The prevalence of minimal carotid plaque in the REFINE-Reykjavik study was 47% in men (40-69 years old) and 38% in women and 11% in men and 7% in women of moderate plaque. The prevalence of any plaque in the Tromsø 6 study was 35% in men and 27% in women. The mean (CIMT) was similar in the studies. In the Tromsø 6 study mean systolic blood pressure was 8 mm Hg higher in men and 10 mm Hg higher in women, mean low-density lipoprotein was 0.5 mmol/L higher in men and 0.3 mmol/L higher in women and the prevalence of smoking was 4% higher in men and 9% higher in women. However, body mass index was 0.8 kg/m2 higher in men and 0.9 kg/m2 in women in the REFINE-Reykjavik study. CONCLUSION: Comparison between Iceland and Norway revealed differences in the prevalence of carotid plaque, which was assumed to be due to different definition of plaque. However, clinically significant differences in conventional cardiovascular risk factors were seen. This underscores the importance of detailed comparison of population data across different populations.RANNIS (The Icelandic Centre for Research) Hjartavernd (Icelandic Heart Association