Epidemiology Resource Center

Southampton, United Kingdom

Epidemiology Resource Center

Southampton, United Kingdom

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Abrahamsen B.,University of Southern Denmark | Masud T.,University of Nottingham | Avenell A.,University of Aberdeen | Anderson F.,University of Southampton | And 14 more authors.
BMJ (Online) | Year: 2010

Objectives: To identify participants' characteristics that influence the anti-fracture efficacy of vitamin D or vitamin D plus calcium with respect to any fracture, hip fracture, and clinical vertebral fracture and to assess the influence of dosing regimens and co-administration of calcium. Design: Individual patient data analysis using pooled data from randomised trials. Data sources: Seven major randomised trials of vitamin D with calcium or vitamin D alone, yielding a total of 68 517 participants (mean age 69.9 years, range 47-107 years, 14.7% men). Study selection: Studies included were randomised studies with at least one intervention arm in which vitamin D was given, fracture as an outcome, and at least 1000 participants. Data synthesis: Logistic regression analysis was used to identify significant interaction terms, followed by Cox's proportional hazards models incorporating age, sex, fracture history, and hormone therapy and bisphosphonate use. Results: Trials using vitamin D with calcium showed a reduced overall risk of fracture (hazard ratio 0.92, 95% confidence interval 0.86 to 0.99, P=0.025) and hip fracture (all studies: 0.84, 0.70 to 1.01, P=0.07; studies using 10 μg of vitamin D given with calcium: 0.74, 0.60 to 0.91, P=0.005). For vitamin D alone in daily doses of 10 μg or 20 μg, no significant effects were found. No interaction was found between fracture history and treatment response, nor any interaction with age, sex, or hormone replacement therapy. Conclusion: This individual patient data analysis indicates that vitamin D given alone in doses of 10-20 μg is not effective in preventing fractures. By contrast, calcium and vitamin D given together reduce hip fractures and total fractures, and probably vertebral fractures, irrespective of age, sex, or previous fractures.


Lakshmy R.,All India Institute of Medical Sciences | Fall C.H.D.,Epidemiology Resource Center | Sachdev H.S.,Sitaram Bhartia Institute of Science and Research | Osmond C.,Epidemiology Resource Center | And 7 more authors.
International Journal of Epidemiology | Year: 2011

Objective Weight gain and growth in early life may influence adult proinflammatory and pro-thrombotic cardiovascular risk factors. Methods: Follow-up of a birth cohort in New Delhi, India, whose weight and height were measured every 6 months until age 21 years. Body mass index (BMI) at birth, during infancy (2 years), childhood (11 years) and adulthood (26-32 years) and BMI gain between these ages were analysed in 886 men and 640 women with respect to adult fibrinogen, high-sensitivity C-reactive protein (hsCRP) and plasminogen activator inhibitor-1 (PAI-1) concentrations. Results: All the pro-inflammatory/pro-thrombotic risk factors were higher in participants with higher adiposity. In women, BMI at birth and age 2 years was inversely related to fibrinogen (P=0.002 and 0.05) and, after adjusting for adult adiposity, to hsCRP (P=0.02 and 0.009). After adjusting for adult adiposity, BMI at 2 years was inversely related to hsCRP and PAI-1 concentrations (P<0.001 and 0.02) in men. BMI gain between 2 and 11 years and/or 11 years to adulthood was positively associated with fibrinogen and hsCRP in women and with hsCRP and PAI-1 in men. Conclusions: Thinness at birth or during infancy, and accelerated BMI gain during childhood/adolescence are associated with a pro-inflammatory/pro-thrombotic state in adult life. An altered inflammatory state could be one link between small newborn/infant size and adult cardiovascular disease. Associations between pro-inflammatory markers and childhood/adolescent BMI gain are probably mediated through adult adiposity. © The Author 2010. Published by Oxford University Press on behalf of the International Epidemiological Association. All rights reserved.


Evangelou E.,University of Ioannina | Valdes A.M.,King's College London | Kerkhof H.J.M.,Erasmus Medical Center | Kerkhof H.J.M.,The Netherlands Genomics Initiative Sponsored Netherlands Consortium for Healthy Aging | And 86 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Objectives: Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods: A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results: With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p=9.2×10-9), thereby confirming its role as a susceptibility locus for OA. Conclusion: The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, β), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.


Valdes A.M.,King's College London | Arden N.K.,University of Oxford | Arden N.K.,Arthritis Research Institute of America | Vaughn F.L.,University of Nottingham | And 14 more authors.
Arthritis Care and Research | Year: 2011

Objective. To assess the genetic association of pain in patients with knee osteoarthritis (OA) and those with multiple regional pain with the R1150W variant in the α-subunit of the voltage-gated sodium channel Na V1.7. Methods. Knee OA patients from 2 UK cohorts (1,411 from the Genetics of Osteoarthritis and Lifestyle study and 267 from the Hertfordshire Cohort Study; 74% with symptomatic OA) with Western Ontario and McMaster Universities OA Index (WOMAC) pain scores were genotyped for rs6746030 (encoding the R1150W change). One hundred seventy-six knee OA patients (53% symptomatic) from the Clearwater Osteoarthritis Study were also tested. A total of 4,295 samples (both affected and unaffected OA) from all 3 studies with data on multiple regional pain were tested. Fixed-effects meta-analyses were carried out with the WOMAC, symptomatic OA (adjusting for radiographic severity), and multiple regional pain as outcomes. Results. No association with the WOMAC was seen in the UK cohorts. Overall, the meta-analysis of WOMAC yielded a summary statistic of β = 0.47 (95% confidence interval [95% CI] 0.04, 0.89; P = 0.030) for the variant allele. The meta-analysis of symptomatic versus asymptomatic OA did not demonstrate an association with rs6746030 (odds ratio [OR] 0.90 [95% CI 0.71, 1.15], P = 0.38). The meta-analysis of multiple regional pain resulted in a significant OR of 1.40 (95% CI 1.08, 1.80; P = 0.0085). No interstudy heterogeneity was seen for any of the analyses. Conclusion. We find evidence that the R1150W amino acid change in the Na V1.7 α-chain is associated with multiple regional pain. This variant is confirmed to be involved in genetic susceptibility to pain, but it does not appear to have a major role in OA-specific pain. © 2011, American College of Rheumatology.


Salonen M.K.,National Public Health Institute | Salonen M.K.,University of Helsinki | Kajantie E.,National Public Health Institute | Osmond C.,Epidemiology Resource Center | And 10 more authors.
European Journal of Public Health | Year: 2011

Background: Physical activity plays an important role in prevention of chronic diseases. Animal studies have suggested that lifestyle and exercise habits may have a prenatal origin. Our aim was to assess the role of early growth on leisure time physical activity (LTPA) in later life among 57-70-years-old men and women. Methods: We examined 2003 individuals born in Helsinki, Finland between 1934 and 1944. Of them, 1967 individuals with adequate information on their LTPA in adult life were included in this study. LTPA was assessed by a validated exercise questionnaire (KIHD Study 12 month physical activity history). Subjects' birth and serial growth measurements were obtained from birth, child welfare and school health records. Results: Participants with higher engagement in LTPA showed a more favourable adult anthropometric and body composition profile than those who were less active. LTPA was positively associated with adult social class. Higher weight and length at birth, and weight at 2 years after adult BMI adjustment, predicted higher intensity of total LTPA (P=0.04, P=0.01 and P=0.03), respectively. Higher height at 2, 7 and 11 years predicted higher intensity of conditioning LTPA (P=0.01, P=0.04 and P=0.004). Higher weight and height at 2, 7 and 11 years predicted higher energy expenditure (EE) of total LTPA (P-values being from 0.01 to 0.03). Furthermore, higher height at 2 and 11 years predicted higher EE of conditioning LTPA (P=0.02 and P=0.03). Conclusion: People who as children were taller and weighed more engage more in leisure time physical activity in late adulthood. The Author 2010. Published by Oxford University Press on behalf of the European Public Health Association.


Salonen M.K.,Finnish National Institute for Health and Welfare | Salonen M.K.,University of Helsinki | Kajantie E.,Finnish National Institute for Health and Welfare | Osmond C.,Epidemiology Resource Center | And 10 more authors.
PLoS ONE | Year: 2011

Background: Cardiorespiratory fitness (CRF) is a major factor influencing health and disease outcomes including all-cause mortality and cardiovascular disease. Importantly CRF is also modifiable and could therefore have a major public health impact. Early life exposures play a major role in chronic disease development. Our aim was to explore the potential prenatal and childhood origins of CRF in later life. Methods/Principal Findings: This sub-study of the HBCS (Helsinki Birth Cohort Study) includes 606 men and women who underwent a thorough clinical examination and participated in the UKK 2-km walk test, which has been validated against a maximal exercise stress test as a measure of CRF in population studies. Data on body size at birth and growth during infancy and childhood were obtained from hospital, child welfare and school health records. Body size at birth was not associated with adult CRF. A 1 cm increase in height at 2 and 7 years was associated with 0.21 ml/kg/min (95% CI 0.02 to 0.40) and 0.16 ml/kg/min (95% CI 0.03 to 0.28) higher VO 2max, respectively. Adjustment for adult lean body mass strengthened these findings. Weight at 2 and 7 years and height at 11 years became positively associated with CRF after adult lean body mass adjustment. However, a 1 kg/m 2 higher BMI at 11 years was associated with -0.57 ml/kg/min (95% CI -0.91 to -0.24) lower adult VO 2max, and remained so after adjustment for adult lean body mass. Conclusion/Significance: We did not observe any significant associations between body size at birth and CRF in later life. However, childhood growth was associated with CRF in adulthood. These findings suggest, importantly from a public point of view, that early growth may play a role in predicting adult CRF. © 2011 Salonen et al.


Feldt K.,University of Helsinki | Raikkonen K.,University of Helsinki | Pyhala R.,University of Helsinki | Jones A.,Epidemiology Resource Center | And 10 more authors.
Journal of Human Hypertension | Year: 2011

Cardiovascular (CV) response to mental stress, a predictor of CV disease risk, may be determined already in utero. However, the underlying mechanisms remain unclear, and previous studies have used adult subjects and neglected CV recovery. We investigated 147 girls and 136 boys aged 8 years who underwent the Trier Social Stress Test for children to determine whether body size at birth is associated with CV activity. Blood pressure (BP), electrocardiogram and impedance-derived indices were recorded and analyzed from continuous measurements using Vasotrac APM205A and Biopac MP150 systems. Among girls, lower birth weight was associated with lower baseline systolic BP (SBP) and diastolic BP (DBP) values (1.9 mm Hg and 1.5 mm Hg per 1 s.d. birth weight for gestational age, respectively), higher SBP and DBP response to mental stress (1.6 mm Hg and 1.1 mm Hg per 1 s.d. birth weight for gestational age, respectively), slower BP recovery and overall higher cardiac sympathetic activity. In contrast, among boys lower birth weight was associated with higher baseline levels of SBP (2.1 mm Hg per 1 s.d. birth weight for gestational age) and total peripheral resistance (TPR), overall lower cardiac sympathetic activity, lower TPR response to mental stress and a more rapid BP and cardiac sympathetic recovery. In boys, the associations with baseline levels and cardiac sympathetic activity became significant only after adjusting for current body size. These sex-specific results suggest that individual differences in childhood CV response to and recovery from mental stress may have prenatal origins. This phenomenon may be important in linking smaller body size at birth to adult CV disease. © 2011 Macmillan Publishers Limited All rights reserved.


Godfrey K.M.,University of Southampton | Godfrey K.M.,NIHR Biomedical Research Unit in Nutrition | Godfrey K.M.,Epidemiology Resource Center | Gluckman P.D.,University of Auckland | And 3 more authors.
Trends in Endocrinology and Metabolism | Year: 2010

Recent evidence demonstrates important maternal effects on an offspring's risk of developing metabolic disease. These effects extend across the full range of maternal environments and partly involve epigenetic mechanisms. The maternal effects can be explained in evolutionary terms, and there is some evidence for their transmission into succeeding generations. Unbalanced maternal diet or body composition, ranging from poor to rich environments, adversely influences the offspring's response to later challenges such as an obesogenic diet or physical inactivity, increasing the risk of disease. Adopting a life course approach that takes into account intergenerational effects has important implications for prevention of non-communicable diseases, particularly in populations undergoing rapid economic transition. © 2010.

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