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Joep Perk,
Guy De Backer,
Helmut Gohlke,
Ian Graham,
Zeljko Reiner,
W M Monique Verschuren,
Christian Albus,
Pascale Benlian,
Gudrun Boysen,
Renata Cifkova, [......],
Alessandro Mezzani,
Eva Prescott,
Lars Ryden,
Martin Scherer,
Mikko Syvanne,
Wilma J M Scholte Op Reimer,
Christiaan Vrints,
David Wood,
Jose Luis Zamorano,
Faiez Zannad
Giornale italiano di cardiologia (2006) 05/2013; 14(5):328-92.
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Tauseef A Khan,
Tina Shah,
David Prieto,
Weili Zhang,
Jackie Price,
Gerald R Fowkes,
Jackie Cooper,
Philippa J Talmud,
Steve E Humphries,
Johan Sundstrom, [......],
Meena Kumari,
Liam Smeeth,
Kay-Tee Khaw,
Michael Nalls,
James Meschia,
Kai Sun,
Rutai Hui,
Ian Day,
Aroon D Hingorani,
Juan P Casas
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ABSTRACT: BACKGROUND: At the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less clear. We evaluated the association of APOE genotype with risk of ischaemic stroke and assessed whether the observed effect was consistent with the effects of APOE genotype on LDL-C or other lipids and biomarkers of cardiovascular risk. METHODS: We conducted a systematic review of published and unpublished studies reporting on APOE genotype and ischaemic stroke. We pooled 41 studies (with a total of 9027 cases and 61 730 controls) using a Bayesian meta-analysis to calculate the odds ratios (ORs) for ischaemic stroke with APOE genotype. To better evaluate potential mechanisms for any observed effect, we also conducted a pooled analysis of primary data using 16 studies (up to 60 883 individuals) of European ancestry. We evaluated the association of APOE genotype with lipids, other circulating biomarkers of cardiovascular risk and carotid intima-media thickness (C-IMT). RESULTS: The ORs for association of APOE genotypes with ischaemic stroke were: 1.09 (95% credible intervals (CrI): 0.84-1.43) for ε2/ε2; 0.85 (95% CrI: 0.78-0.92) for ε2/ε3; 1.05 (95% CrI: 0.89-1.24) for ε2/ε4; 1.05 (95% CrI: 0.99-1.12) for ε3/ε4; and 1.12 (95% CrI: 0.94-1.33) for ε4/ε4 using the ε3/ε3 genotype as the reference group. A regression analysis that investigated the effect of LDL-C (using APOE as the instrument) on ischaemic stroke showed a positive dose-response association with an OR of 1.33 (95% CrI: 1.17, 1.52) per 1 mmol/l increase in LDL-C. In the separate pooled analysis, APOE genotype was linearly and positively associated with levels of LDL-C (P-trend: 2 × 10(-152)), apolipoprotein B (P-trend: 8.7 × 10(-06)) and C-IMT (P-trend: 0.001), and negatively and linearly associated with apolipoprotein E (P-trend: 6 × 10(-26)) and HDL-C (P-trend: 1.6 × 10(-12)). Associations with lipoprotein(a), C-reactive protein and triglycerides were non-linear. CONCLUSIONS: In people of European ancestry, APOE genotype showed a positive dose-response association with LDL-C, C-IMT and ischaemic stroke. However, the association of APOE ε2/ε2 genotype with ischaemic stroke requires further investigation. This cross-domain concordance supports a causal role of LDL-C on ischaemic stroke.
International Journal of Epidemiology 04/2013; 42(2):475-492. · 6.41 Impact Factor
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ABSTRACT: BACKGROUND: the evaluation of the determinants of change over time in health-related quality of life (HR-QoL) in older people is limited. This study aims to identify patterns of change in HR-QoL over 7 years and their determinants using data from the British Women's Heart and Health Study, a representative sample of older women (n = 4286). METHODS: longitudinal latent class analysis was used to identify subpopulations of women with similar HR-QoL trajectories from 1999-2000 to 2007. HR-QoL was measured using the EQ-5D. Multivariate multinomial logistic regression was used to model the association of identified trajectories with baseline predictors after multiple imputation of missing data. RESULTS: four distinct EQ-5D trajectories were suggested: high (19% of women), high decline (22%), intermediate (42%) and low decline (16%). Prevalent arthritis (OR = 13.4; 95% CI: 8.8, 20.5), diabetes (OR = 4.6; 95% CI: 1.5, 14.2) and obesity (OR = 3.9; 95% CI: 2.5, 6.0) were the strongest predicting health conditions of adverse changes in HR-QoL and physical activity the strongest predicting lifestyle factor (OR = 2.8; 95% CI: 2.0, 3.9). CONCLUSIONS: findings suggest that older women without obesity or pre-existing health conditions who undertake more physical activity are more likely to experience high HR-QoL, reinforcing the importance of these factors for healthy ageing.
Age and Ageing 03/2013; · 3.09 Impact Factor
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ABSTRACT: BACKGROUND: Creatinine based formulae for estimating renal function developed in white populations may be less valid in other ethnic groups. We assessed the performance of various estimating formulae in an Indian population. METHODS: 917 subjects were recruited from the Hyderabad arm of the Indian Migration Study. Data were collected on comorbidity, serum creatinine and body composition from DXA scans. Renal function was compared using the modified Cockcroft-Gault, MDRD and CKD-EPI formulae. 24-hour creatinine production was derived from each estimate and the agreement with measured muscle mass examined. 24-hour creatinine production estimates were compared to that derived from a formula by Rule incorporating DXA measured muscle mass. Potential systematic biases were examined by age and eGFR. We assessed the association of renal function by each formula with hypertension and self-reported measures of vascular disease. RESULTS: Mean modified Cockcroft-Gault eCCl was 98.8 ml/min/1.73 m2, MDRD eGFR 91.2 ml/min/1.73 m2 and CKD-EPI eGFR 96.3 ml/min/1.73 m2. MDRD derived 24-hour creatinine production showed the least age-related underestimation compared to the Rule formula. CKD-EPI showed a marked bias at higher eGFRs. All formulae showed similar strength associations with vascular disease and hypertension. CONCLUSIONS: Our analyses support the use of MDRD for estimating renal function in Indian populations. Further work is required to assess the predictive value of formulae for incident disease and complications of CKD.
BMC Nephrology 02/2013; 14(1):30. · 2.18 Impact Factor
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ABSTRACT: Shah Ebrahim and colleagues argue that more research on non-communicable diseases (NCDs) in both high-income countries and low- and middle-income countries can result in mutual benefits and will help better address the growing burden of NCDs.
PLoS Medicine 01/2013; 10(1):e1001377. · 16.27 Impact Factor
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Vipin Gupta,
Donipadi Guru Vinay,
Ulla Sovio,
Sajjad Rafiq,
Madamchetty Venkata Kranthi Kumar,
Charles Spurgeon Janipalli,
David Evans,
Kulathu Radha Mani,
Madana Narasimha Sandeep,
Amy Taylor, [......],
Ruth Sullivan,
Liza Bowen,
Nicholas Timpson,
George Davey Smith,
Frank Dudbridge,
Dorairaj Prabhakaran,
Yoav Ben-Shlomo,
Kolli Srinath Reddy, Shah Ebrahim,
Giriraj Ratan Chandak
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ABSTRACT: Obesity is an established risk factor for type 2 diabetes (T2D) and they are metabolically related through the mechanism of insulin resistance. In order to explore how common genetic variants associated with T2D correlate with body mass index (BMI), we examined the influence of 25 T2D associated loci on obesity risk. We used 5056 individuals (2528 sib-pairs) recruited in Indian Migration Study and conducted within sib-pair analysis for six obesity phenotypes. We found associations of variants in CXCR4 (rs932206) and HHEX (rs5015480) with higher body mass index (BMI) (β = 0.13, p = 0.001) and (β = 0.09, p = 0.002), respectively and weight (β = 0.13, p = 0.001) and (β = 0.09, p = 0.001), respectively. CXCR4 variant was also strongly associated with body fat (β = 0.10, p = 0.0004). In addition, we demonstrated associations of CXCR4 and HHEX with overweight/obesity (OR = 1.6, p = 0.003) and (OR = 1.4, p = 0.002), respectively, in 1333 sib-pairs (2666 individuals). We observed marginal evidence of associations between variants at six loci (TCF7L2, NGN3, FOXA2, LOC646279, FLJ3970 and THADA) and waist hip ratio (WHR), BMI and/or overweight which needs to be validated in larger set of samples. All the above findings were independent of daily energy consumption and physical activity level. The risk score estimates based on eight significant loci (including nominal associations) showed associations with WHR and body fat which were independent of BMI. In summary, we establish the role of T2D associated loci in influencing the measures of obesity in Indian population, suggesting common underlying pathophysiology across populations.
PLoS ONE 01/2013; 8(1):e53944. · 4.09 Impact Factor
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ABSTRACT: The nutritional aetiology of obesity remains unclear, especially with regard to the role of dairy products in developing countries.
To examine whether milk/milk product consumption is associated with obesity and high waist circumference among adult Indians.
Information on plain milk, tea, curd and buttermilk/lassi consumption assessed using a Food Frequency Questionnaire was obtained from the cross-sectional sib-pair designed Indian Migration Study (3698 men and 2659 women), conducted at four factory locations across north, central and south India. The anthropometric measures included were Body Mass Index (BMI) and Waist Circumference (WC). Mixed-effect logistic regression models were conducted to accommodate sib-pair design and adjust for potential confounders.
After controlling for potential confounders, the risk of being obese (BMI≥25 kg/m(2)) was lower among women (OR = 0.57;95%CI:0.43-0.76;p≤0.0001) and men (OR = 0.67;95%CI: 0.51-0.87;p = 0.005), and the risk of a high WC (men: >90 cm; women: >80 cm) was lower among men (OR = 0.71;95%CI:0.54-0.93;p = 0.005) and women (OR = 0.79;95%CI:0.59-1.05;p>0.05) who consume ≥1 portions of plain milk daily than those who do not consume any milk. The inverse association between daily plain milk consumption and obesity was also confirmed in sibling-pair analyses. Daily tea consumption of ≥1 portion was associated with obesity (OR = 1.51;95%CI:1.00-2.25;p>0.050) and high WC (OR = 1.65;95%CI:1.08-2.51;p>0.019) among men but not among women but there was no strong evidence of association of curd and buttermilk/lassi consumption with obesity and high waist circumference among both men and women.
The independent, inverse association of daily plain milk consumption with the risk of being obese suggests that high plain milk intake may lower the risk of obesity in adult Indians. However, this is an observational finding and uncontrolled confounding cannot be excluded as an explanation for the association. Therefore, confirmatory studies are needed to clarify this relationship.
PLoS ONE 01/2013; 8(4):e60739. · 4.09 Impact Factor
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ABSTRACT: PURPOSE: This study investigates the effect of changes in moderate or vigorous physical activity (MVPA) on trajectories in health-related quality of life (HR-QoL) over 7 years in British elderly women. METHODS: A total of 1,926 women from the British Women's Heart and Health Study with information on MVPA and HR-QoL [measured using Euro quality of life 5 dimension (EQ-5D)] at baseline and at 7 years of follow-up were included in the analysis. Baseline and 7-year follow-up MVPA values were categorised into 3 groups, generating 9 categories of change in MVPA. Logistic regression was used to obtain odds ratios (ORs) of maintaining or improving HR-QoL according to different patterns of change in MVPA level. RESULTS: Women who remained inactive over the 7 years of follow-up had the largest reduction in their EQ-5D scores. Compared to these women, women that increased their MPVA level from "inactive" to "low" or to "moderate-high" were more likely to maintain or improve their HR-QoL over 7 years (ORs 1.65 or 2.70, respectively, p value for trend <0.001). After adjustment for baseline EQ-5D score and a wide range of potential confounders, results remained largely unchanged, though precision of the estimates generally decreased. CONCLUSIONS: Our findings suggest that relatively regular MVPA, even taken up later in life, can help older women prevent a decline in HR-QoL and even improve their enjoyment of life.
Quality of Life Research 12/2012; · 2.30 Impact Factor
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ABSTRACT: AIM: IL-18 is hypothesized to destabilise atherosclerotic plaques, leading to thrombotic events and epidemiologic studies suggest that IL-18 may increase risk of CHD or CVD. We examined prospective associations between levels of serum IL-18 and new CHD and stroke events in older men and women from a general population. METHODS: A case-control study was nested within a prospective cohort of men and women aged 60-79years recruited from general practices in 25 British towns in 1998-2000 and followed-up for 7.5years for fatal and non-fatal MI and stroke. Baseline IL-18 was measured in stored serum samples of incident cases of MI (n=364) or stroke (n=300) and two controls per case. RESULTS: Geometric mean IL-18 levels were higher among the 364 MI cases than the 706 controls; 417.84pg/mL (IQR 316.25, 537.44) compared to 386.90pg/mL (IQR 296.54, 482.33), p(difference)=0.002. IL-18 was positively associated with adverse lipid and inflammatory profiles. Men and women in the top third of baseline IL-18 levels had an age and sex-adjusted odds ratio (OR) for MI of 1.31 (95%CI 0.92, 1.85) compared with those in the lowest third; this attenuated to 1.05 (95%CI 0.72, 1.53) after additional adjustment for established vascular and inflammatory risk factors. Each doubling of IL-18 level was associated with an increased OR for MI 1.34 (95%CI 1.04, 1.72), which was attenuated on adjustment for established vascular and inflammatory risk factors; 1.09 (95%CI 0.83, 1.44). Geometric mean IL-18 levels did not differ between stroke cases and controls. The OR for stroke associated with the highest compared to the lowest tertile of IL-18 was 1.24 (95%CI 0.84, 1.84). Results for MI and stroke did not differ by presence of pre-existing CVD, gender or age. CONCLUSIONS: Circulating IL-18 levels were strongly associated with a range of established and novel risk factors but were not independently associated with risk of MI or stroke in our study.
Cytokine 11/2012; · 3.02 Impact Factor
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Sajjad Rafiq,
Kranthi Kumar Venkata,
Vipin Gupta,
Vinay D Guru,
Charles J Spurgeon,
Smitha Parameshwaran,
Sandeep N Madana,
Sanjay Kinra,
Liza Bowen,
Nicholas J Timpson,
George Davey Smith,
Frank Dudbridge,
Dorairaj Prabhakaran,
Yoav Ben-Shlomo,
K Srinath Reddy, Shah Ebrahim,
Giriraj R Chandak
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ABSTRACT: BACKGROUND: Genome wide association studies (GWAS), mostly in Europeans have identified several common variants as associated with key lipid traits. Replication of these genetic effects in South Asian populations is important since it would suggest wider relevance for these findings. Given the rising prevalence of metabolic disorders and heart disease in the Indian sub-continent, these studies could be of future clinical relevance. METHODS: We studied seven common variants associated with a variety of lipid traits in previous GWASs. The study sample comprised of 3178 sib-pairs recruited as participants for the Indian Migration Study (IMS). Associations with various lipid parameters and quantitative traits were analyzed using the Fulker genetic association model. RESULTS: We replicated five of the 7 main effect associations with p-values ranging from 0.03 to 1.97x10-7. We identified particularly strong association signals at rs662799 in APOA5 (beta=0.18 s.d, p=1.97 x 10-7), rs10503669 in LPL (beta =-0.18 s.d, p=1.0 x 10-4) and rs780094 in GCKR (beta=0.11 s.d, p=0.001) loci in relation to triglycerides. In addition, the GCKR variant was also associated with total cholesterol (beta=0.11 s.d, p=3.9x10-4). We also replicated the association of rs562338 in APOB (p=0.03) and rs4775041 in LIPC (p=0.007) with LDL-cholesterol and HDL-cholesterol respectively. CONCLUSIONS: We report associations of five loci with various lipid traits with the effect size consistent with the same reported in Europeans. These results indicate an overlap of genetic effects pertaining to lipid traits across the European and Indian populations.
Lipids in Health and Disease 11/2012; 11(1):155. · 2.17 Impact Factor
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Joep Perk,
Guy De Backer,
Helmut Gohlke,
Ian Graham,
Zeljko Reiner,
W M Monique Verschuren,
Christian Albus,
Pascale Benlian,
Gudrun Boysen,
Renata Cifkova, [......],
Alessandro Mezzani,
Eva Prescott,
Lars Ryden,
Martin Scherer,
Mikko Syvänne,
Wilma J M Scholte Op Reimer,
Christiaan Vrints,
David Wood,
Jose Luis Zamorano,
Faiez Zannad
International Journal of Behavioral Medicine 10/2012; · 2.63 Impact Factor
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Sonia Shah,
Juan P Casas,
Tom R Gaunt,
Jackie Cooper,
Fotios Drenos,
Delilah Zabaneh,
Daniel I Swerdlow,
Tina Shah,
Reecha Sofat,
Jutta Palmen,
Meena Kumari,
Mika Kivimaki, Shah Ebrahim,
George Davey Smith,
Debbie A Lawlor,
Philippa J Talmud,
John Whittaker,
Ian N M Day,
Aroon D Hingorani,
Steve E Humphries
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ABSTRACT: AimsThe aim of this study was to quantify the collective effect of common lipid-associated single nucleotide polymorphisms (SNPs) on blood lipid levels, cardiovascular risk, use of lipid-lowering medication, and risk of coronary heart disease (CHD) events.Methods and resultsAnalysis was performed in two prospective cohorts: Whitehall II (WHII; N = 5059) and the British Women's Heart and Health Study (BWHHS; N = 3414). For each participant, scores were calculated based on the cumulative effect of multiple genetic variants influencing total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Compared with the bottom quintile, individuals in the top quintile of the LDL-C genetic score distribution had higher LDL-C {mean difference of 0.85 [95% confidence interval, (CI) = 0.76-0.94] and 0.63 [95% CI = 0.50-0.76] mmol/l in WHII and BWHHS, respectively}. They also tended to have greater odds of having 'high-risk' status (Framingham 10-year cardiovascular disease risk >20%) [WHII: odds ratio (OR) = 1.36 (0.93-1.98), BWHHS: OR = 1.49 (1.14-1.94)]; receiving lipid-lowering treatment [WHII: OR = 2.38 (1.57-3.59), BWHHS: OR = 2.24 (1.52-3.29)]; and CHD events [WHII: OR = 1.43 (1.02-2.00), BWHHS: OR = 1.31 (0.99-1.72)]. Similar associations were observed for the TC score in both studies. The TG score was associated with high-risk status and medication use in both studies. Neither HDL nor TG scores were associated with the risk of coronary events. The genetic scores did not improve discrimination over the Framingham risk score.Conclusion
At the population level, common SNPs associated with LDL-C and TC contribute to blood lipid variation, cardiovascular risk, use of lipid-lowering medications and coronary events. However, their effects are too small to discriminate future lipid-lowering medication requirements or coronary events.
European Heart Journal 09/2012; · 10.48 Impact Factor
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Jessica Tyrrell,
Ville Huikari,
Jennifer T Christie,
Alana Cavadino,
Rachel Bakker,
Marie-Jo A Brion,
Frank Geller,
Lavinia Paternoster,
Ronny Myhre,
Catherine Potter, [......],
Thorkild I A Sørensen,
Jeffrey C Murray,
Debbie A Lawlor,
Craig E Pennell,
Vincent W V Jaddoe,
Elina Hypponen,
William L Lowe,
Marjo-Riitta Jarvelin,
George Davey Smith,
Rachel M Freathy
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ABSTRACT: Maternal smoking during pregnancy is associated with low birth weight. Common variation at rs1051730 is robustly associated with smoking quantity and was recently shown to influence smoking cessation during pregnancy, but its influence on birth weight is not clear. We aimed to investigate the association between this variant and birth weight of term, singleton offspring in a well-powered meta-analysis. We stratified 26 241 European origin study participants by smoking status (women who smoked during pregnancy versus women who did not smoke during pregnancy) and, in each stratum, analysed the association between maternal rs1051730 genotype and offspring birth weight. There was evidence of interaction between genotype and smoking (P = 0.007). In women who smoked during pregnancy, each additional smoking-related T-allele was associated with a 20 g [95% confidence interval (95% CI): 4-36 g] lower birth weight (P = 0.014). However, in women who did not smoke during pregnancy, the effect size estimate was 5 g per T-allele (95% CI: -4 to 14 g; P = 0.268). To conclude, smoking status during pregnancy modifies the association between maternal rs1051730 genotype and offspring birth weight. This strengthens the evidence that smoking during pregnancy is causally related to lower offspring birth weight and suggests that population interventions that effectively reduce smoking in pregnant women would result in a reduced prevalence of low birth weight.
Human Molecular Genetics 09/2012; · 7.64 Impact Factor
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Joep Perk,
Guy De Backer,
Helmut Gohlke,
Ian Graham,
Zeljko Reiner,
Wm Monique Verschuren,
Christian Albus,
Pascale Benlian,
Gudrun Boysen,
Renata Cifkova, [......],
Alessandro Mezzani,
Eva Prescott,
Lars Ryden,
Martin Scherer,
Mikko Syvänne,
Wilma Jm Scholte Op Reimer,
Christiaan Vrints,
David Wood,
Jose Luis Zamorano,
Faiez Zannad
European journal of preventive cardiology. 07/2012;
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07/2012; EPPI-Centre, Social Science Research Unit, Institute of ducation, University of London.
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Archives of internal medicine 06/2012; 172(12):919-20. · 11.46 Impact Factor
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ABSTRACT: This study investigated associations between chronic inflammation and coagulation and incident locomotor disability using prospective data from the British Women's Heart and Health Study. Locomotor disability was assessed using self-reported questionnaires in 1999/2000, and 3 and 7 years later. Scores for inflammation and coagulation were obtained from summation of quartile categories of all available biomarkers from blood samples taken at baseline. 534 women developed locomotor disability after 3 years, 260 women after 7 years, while 871 women remained free of locomotor disability over the whole study period. After adjustment for demographic characteristics, lifestyle factors and health conditions, we found associations between inflammation and incident locomotor disability after three (OR per unit increase in score = 1.08, 95 % confidence interval (CI): 1.03, 1.13) and 7 years (OR = 1.10, 95 % CI: 1.03, 1.18) and between coagulation and incident locomotor disability after 3 (OR = 1.06, 95 % CI: 0.98, 1.14) and 7 years (OR = 1.09, 95 % CI: 1.00, 1.18). This corresponds to ORs between 1.8 and 2.4 comparing women with highest to lowest inflammation or coagulation scores. These results support the role of inflammation and coagulation in the development of locomotor disability in elderly women irrespective of their lifestyle factors and underlying age-related chronic diseases.
European Journal of Epidemiology 06/2012; 27(8):633-45. · 4.71 Impact Factor
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Michael P Gardner,
Stafford Lightman,
Avan Aihie Sayer,
Cyrus Cooper,
Rachel Cooper,
Dorly Deeg, Shah Ebrahim,
John Gallacher,
Mika Kivimaki,
Meena Kumari,
Diana Kuh,
Richard M Martin,
Geeske Peeters,
Yoav Ben-Shlomo
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ABSTRACT: The association between functioning of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages remains poorly understood. We carried out meta-analyses to test the hypothesis that dysregulation of the HPA axis, as indexed by patterns of diurnal cortisol release, is associated with worse physical performance. Data from six adult cohorts (ages 50-92 years) were included in a two stage meta-analysis of individual participant data. We analysed each study separately using linear and logistic regression models and then used meta-analytic methods to pool the results. Physical performance outcome measures were walking speed, balance time, chair rise time and grip strength. Exposure measures were morning (serum and salivary) and evening (salivary) cortisol. Total sample sizes in meta-analyses ranged from n=2146 for associations between morning Cortisol Awakening Response and balance to n=8448 for associations between morning cortisol and walking speed. A larger diurnal drop was associated with faster walking speed (standardised coefficient per SD increase 0.052, 95% confidence interval (CI) 0.029, 0.076, p<0.001; age and gender adjusted) and a quicker chair rise time (standardised coefficient per SD increase -0.075, 95% CI -0.116, -0.034, p<0.001; age and gender adjusted). There was little evidence of associations with balance or grip strength. Greater diurnal decline of the HPA axis is associated with better physical performance in later life. This may reflect a causal effect of the HPA axis on performance or that other ageing-related factors are associated with both reduced HPA reactivity and performance.
Psychoneuroendocrinology 05/2012; · 5.81 Impact Factor
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ABSTRACT: Previous studies suggest that physical activity may be protective for dementia and cognitive impairment. We report findings comparing leisure-time and work-related physical activity from the Caerphilly Prospective study (CaPS) with dementia and cognitive impairment not dementia (CIND) after around 16 years of follow-up. We synthesized our results with a meta-analysis specifically testing if length of follow-up was associated with the size of any association. Age-adjusted models found no real association with dementia, and if anything increased risk for CIND (odds ratio (OR) highest versus lowest tertile 2.61, 95% CI 1.58 to 4.31), though this was attenuated after adjustment for other confounders (OR highest versus lowest tertile 1.38, 95% CI 0.78 to 2.44). There was no evidence that this differed by type (vascular versus non-vascular) of cognitive disease. Meta-analysis of other published effect estimates showed a protective effect of physical activity on cognitive impairment (OR 0.66, 95% CI 0.52 to 0.85) but with significant heterogeneity which was partially explained by length of follow up (p = 0.03). A protective association was also seen for dementia (OR 0.78, 95% CI 0.65, 0.94), which did not appear to be related to follow-up length but there was evidence of small study bias (p = 0.002) suggesting an absence of small null studies. The apparent protective effects of physical activity on cognitive health may partially reflect reverse causation and current estimates may be overly optimistic in terms of cognitive benefits.
Journal of Alzheimer's disease: JAD 05/2012; 31(3):569-80. · 3.74 Impact Factor
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The Lancet 05/2012; 380(9841):545-7. · 38.28 Impact Factor
