Publications by authors named "Kay-Tee Khaw"

1,045 Publications

  • Page 1 of 1

Fracture Incidence and the Relevance of Dietary and Lifestyle Factors Differ in the United Kingdom and Hong Kong: An International Comparison of Longitudinal Cohort Study Data.

Calcif Tissue Int 2021 Jun 3. Epub 2021 Jun 3.

Department of Epidemiology and Public Health, Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, NR4 7TJ, UK.

Geographic variation in fracture risk may be due to divergent profiles of dietary, lifestyle, and other risk factors between populations. We investigated differences in fracture rates between two older-population cohorts: the European Prospective Investigation into Cancer and Nutrition (EPIC) Norfolk cohort (n = 7732) in the United Kingdom (UK), and the Mr and Ms Os cohort (n = 3956) in Hong Kong (HK). Data were collected by questionnaires, laboratory assessments, and hospital records. Incidence of hip, spine, and wrist fractures in the two cohorts was calculated and multivariable regression was used to explore variables important to fracture risk. Total hip, spine, and wrist fracture incidence was higher in the UK vs HK for women (13.70 vs 8.76 per 1000 person-years; p < 0.001), but not men (5.95 vs 5.37 per 1000 person-years; p = 0.337), and the proportions of different fractures also varied between cohorts (p < 0.001). Hip fracture was the most common UK fracture (accounting for 56.8% fractures in men and 52.6% in women), while wrist fracture was most common in HK (42.9% in men and 57.9% in women). The major contributor to total fracture risk in multivariable regression models of both cohorts and sexes, was age; with BMI also an important contributor to fracture risk HK men and UK women. The distribution of factors relevant to fracture risk, and the rates of different fractures, varied significantly between UK and HK cohorts. However, the importance of each factor in contributing to fracture risk was similar between the cohorts. The differences in fracture rates suggest targeted approaches may be required when developing interventions and public health recommendations to reduce the burden of osteoporosis in these two countries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00223-021-00870-zDOI Listing
June 2021

KLK3 SNP-SNP interactions for prediction of prostate cancer aggressiveness.

Sci Rep 2021 Apr 29;11(1):9264. Epub 2021 Apr 29.

Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, 90015, USA.

Risk classification for prostate cancer (PCa) aggressiveness and underlying mechanisms remain inadequate. Interactions between single nucleotide polymorphisms (SNPs) may provide a solution to fill these gaps. To identify SNP-SNP interactions in the four pathways (the angiogenesis-, mitochondria-, miRNA-, and androgen metabolism-related pathways) associated with PCa aggressiveness, we tested 8587 SNPs for 20,729 cases from the PCa consortium. We identified 3 KLK3 SNPs, and 1083 (P < 3.5 × 10) and 3145 (P < 1 × 10) SNP-SNP interaction pairs significantly associated with PCa aggressiveness. These SNP pairs associated with PCa aggressiveness were more significant than each of their constituent SNP individual effects. The majority (98.6%) of the 3145 pairs involved KLK3. The 3 most common gene-gene interactions were KLK3-COL4A1:COL4A2, KLK3-CDH13, and KLK3-TGFBR3. Predictions from the SNP interaction-based polygenic risk score based on 24 SNP pairs are promising. The prevalence of PCa aggressiveness was 49.8%, 21.9%, and 7.0% for the PCa cases from our cohort with the top 1%, middle 50%, and bottom 1% risk profiles. Potential biological functions of the identified KLK3 SNP-SNP interactions were supported by gene expression and protein-protein interaction results. Our findings suggest KLK3 SNP interactions may play an important role in PCa aggressiveness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-85169-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084951PMC
April 2021

Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies.

Nat Commun 2021 04 22;12(1):2329. Epub 2021 Apr 22.

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-22370-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062567PMC
April 2021

The Relationship Between Cognitive Performance Using Tests Assessing a Range of Cognitive Domains and Future Dementia Diagnosis in a British Cohort: A Ten-Year Prospective Study.

J Alzheimers Dis 2021 ;81(1):123-135

Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

Background: Exploring the domains of cognitive function which are most strongly associated with future dementia may help with understanding risk factors for, and the natural history of dementia.

Objective: To examine the association of performance on a range of cognitive tests (both global and domain specific) with subsequent diagnosis of dementia through health services in a population of relatively healthy men and women and risk of future dementia.

Methods: We examined the association between performance on different cognitive tests as well as a global score and future dementia risk ascertained through health record linkage in a cohort of 8,581 individuals (aged 48-92 years) between 2004-2019 with almost 15 years follow-up (average of 10 years) before and after adjustment for socio-demographic, lifestyle, and health characteristics.

Results: Those with poor performance for global cognition (bottom 10%) were almost four times as likely to receive a dementia diagnosis from health services over the next 15 years than those who performed well HR = 3.51 (95% CI 2.61, 4.71 p < 0.001) after adjustment for socioeconomic, lifestyle, and biological factors and also prevalent disease. Poor cognition performance in multiple tests was associated with 10-fold increased risk compared to those not performing poorly in any test HR = 10.82 (95% CI 6.85, 17.10 p < 0.001).

Conclusion: Deficits across multiple cognitive domains substantially increase risk of future dementia over and above neuropsychological test scores ten years prior to a clinical diagnosis. These findings may help further understanding of the natural history of dementia and how such measures could contribute to strengthening future models of dementia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-210030DOI Listing
January 2021

Plasma metabolites to profile pathways in noncommunicable disease multimorbidity.

Nat Med 2021 03 11;27(3):471-479. Epub 2021 Mar 11.

MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.

Multimorbidity, the simultaneous presence of multiple chronic conditions, is an increasing global health problem and research into its determinants is of high priority. We used baseline untargeted plasma metabolomics profiling covering >1,000 metabolites as a comprehensive readout of human physiology to characterize pathways associated with and across 27 incident noncommunicable diseases (NCDs) assessed using electronic health record hospitalization and cancer registry data from over 11,000 participants (219,415 person years). We identified 420 metabolites shared between at least 2 NCDs, representing 65.5% of all 640 significant metabolite-disease associations. We integrated baseline data on over 50 diverse clinical risk factors and characteristics to identify actionable shared pathways represented by those metabolites. Our study highlights liver and kidney function, lipid and glucose metabolism, low-grade inflammation, surrogates of gut microbial diversity and specific health-related behaviors as antecedents of common NCD multimorbidity with potential for early prevention. We integrated results into an open-access webserver ( https://omicscience.org/apps/mwasdisease/ ) to facilitate future research and meta-analyses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-021-01266-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127079PMC
March 2021

Plasma trimethylamine N-oxide (TMAO) levels predict future risk of coronary artery disease in apparently healthy individuals in the EPIC-Norfolk prospective population study.

Am Heart J 2021 Jun 21;236:80-86. Epub 2021 Feb 21.

Center for Microbiome and Human Health, Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland, OH; Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland, OH.

Background: Recent studies show a mechanistic link between gut microbiota-dependent formation of the atherosclerosis- and thrombosis-promoting metabolite trimethylamine N-oxide (TMAO) and cardiovascular disease (CVD). The clinical utility of TMAO in apparently healthy subjects for predicting incident CVD risks is unclear.

Methods And Results: In the EPIC-Norfolk community-based study, we examined baseline fasting levels of TMAO and two of its nutrient precursors, choline and betaine, in a case:control design study comparing apparently European healthy middle-aged participants who subsequently develop CVD (Cases, n = 908) vs those who did not (Controls, n = 1,273) over an ensuing average follow-up period of 8 years. In participants who developed CVD vs controls, higher plasma TMAO (3.70 [IQR 2.50-6.41]μM vs 3.25 [IQR 2.19-52,1.15]μM; P < .001) and choline levels (9.09 [IQR 7.87-10.53]μM vs 8.89 [IQR 7.66-10.13]μM; P = .001) were observed. Following adjustments for traditional risk factors, elevated TMAO (adjusted odds ratio (OR) 1.58 [95% confidence interval (CI) 1.21-2.06], P < .001) and choline levels (adjusted OR 1.31 [95%CI 1.00-1.72], P < .05) remained predictive of incident CVD development. The clinical prognostic utility of TMAO remained significant and essentially unchanged regardless of the level of cutoff chosen between 1.5 uM (10%ile) to 10.5 uM (90%ile).

Conclusion: In apparently healthy participants of the community-based middle-aged EPIC-Norfolk population, elevated plasma levels of the gut microbe-dependent metabolite TMAO, and its nutrient precursor choline, predict incident risk for CVD development independent of traditional risk factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ahj.2021.01.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085024PMC
June 2021

Polygenic hazard score is associated with prostate cancer in multi-ethnic populations.

Nat Commun 2021 02 23;12(1):1236. Epub 2021 Feb 23.

Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Radiotherapy Related Research, The Christie Hospital NHS Foundation Trust, Manchester, UK.

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS (PHS, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10). Comparing the 80/20 PHS percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-21287-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902617PMC
February 2021

Alcohol Consumption and Incident Cataract Surgery in Two Large UK Cohorts.

Ophthalmology 2021 Jun 8;128(6):837-847. Epub 2021 Feb 8.

NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust & UCL Institute of Ophthalmology, London, United Kingdom; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.

Purpose: To examine the association of alcohol consumption and type of alcoholic beverage with incident cataract surgery in 2 large cohorts.

Design: Longitudinal, observational study.

Participants: We included 469 387 participants of UK Biobank with a mean age of 56 years and 23 162 participants of European Prospective Investigation of Cancer (EPIC)-Norfolk with a mean age of 59 years.

Methods: Self-reported alcohol consumption at baseline was ascertained by a touchscreen questionnaire in UK Biobank and a food-frequency questionnaire in EPIC-Norfolk. Cases were defined as participants undergoing cataract surgery in either eye as ascertained via data linkage to National Health Service procedure statistics. We excluded participants with cataract surgery up to 1 year after the baseline assessment visit or those with self-reported cataract at baseline. Cox proportional hazards models were used to examine the associations of alcohol consumption with incident cataract surgery, adjusted for age, sex, ethnicity, Townsend deprivation index, body mass index (BMI), smoking, and diabetes status.

Main Outcome Measures: Incident cataract surgery.

Results: There were 19 011 (mean cohort follow-up of 95 months) and 4573 (mean cohort follow-up of 193 months) incident cases of cataract surgery in UK Biobank and EPIC-Norfolk, respectively. Compared with nondrinkers, drinkers were less likely to undergo cataract surgery in UK Biobank (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.85-0.93) and EPIC-Norfolk (HR, 0.90; 95% CI, 0.84-0.97) after adjusting for covariables. Among alcohol consumers, greater alcohol consumption was associated with a reduced risk of undergoing cataract surgery in EPIC-Norfolk (P < 0.001), whereas a U-shaped association was observed in the UK Biobank. Compared with nondrinkers, subgroup analysis by type of alcohol beverage showed the strongest protective association with wine consumption; the risk of incident cataract surgery was 23% and 14% lower among those in the highest category of wine consumption in EPIC-Norfolk and UK Biobank, respectively.

Conclusions: Our findings suggest a lower risk of undergoing cataract surgery with low to moderate alcohol consumption. The association was particularly apparent with wine consumption. We cannot exclude the possibility of residual confounding, and further studies are required to determine whether this association is causal in nature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ophtha.2021.02.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162662PMC
June 2021

Effect of Monthly Vitamin D Supplementation on Preventing Exacerbations of Asthma or Chronic Obstructive Pulmonary Disease in Older Adults: Post Hoc Analysis of a Randomized Controlled Trial.

Nutrients 2021 Feb 6;13(2). Epub 2021 Feb 6.

School of Population Health, University of Auckland, Auckland 1142, New Zealand.

Randomized controlled trials have suggested that vitamin D supplementation can prevent asthma and chronic obstructive pulmonary disease (COPD) exacerbations. For COPD, the benefit appears to be limited to individuals with baseline 25-hydroxyvitamin D (25OHD) levels <25 nmol/L. We performed a post hoc analysis of data from a randomized, double-blinded, placebo-controlled trial to investigate the effect that monthly, high-dose vitamin D supplementation (versus placebo) had on older adults with asthma and/or COPD. Specifically, we investigated whether vitamin D supplementation prevented exacerbations of these conditions. Participants were randomly assigned either to an initial oral dose of 200,000 IU vitamin D3 followed by 100,000 IU monthly or to placebo, with an average follow-up period of 3.3 years. Among the 5110 participants, 775 had asthma or COPD at the beginning of the study, and were eligible for inclusion in this analysis. Exacerbations were defined by the prescription of a short-burst of oral corticosteroids. The mean age of the participants was 67 years old, and 56% were male. The mean baseline blood 25OHD level was 63 nmol/L; 2.3% were <25 nmol/L. Overall, we found that vitamin D supplementation did not affect the exacerbation risk (hazard ratio 1.08; 95%CI 0.84-1.39). Among those with baseline 25OHD <25 nmol/L, however, the hazard ratio was 0.11 (95%CI 0.02-0.51); for interaction = 0.001. Although monthly vitamin D supplementation had no overall impact on risk of exacerbations of asthma or COPD, we found evidence of a probable benefit among those with severe vitamin D deficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13020521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915442PMC
February 2021

Correlates of change in accelerometer-assessed total sedentary time and prolonged sedentary bouts among older English adults: results from five-year follow-up in the EPIC-Norfolk cohort.

Aging (Albany NY) 2021 01 11;13(1):134-149. Epub 2021 Jan 11.

MRC Epidemiology Unit, University of Cambridge, School of Clinical Medicine, Cambridge, UK.

Background: Development of effective strategies to reduce sedentary time among older adults necessitates understanding of its determinants but longitudinal studies of this utilising objective measures are scarce.

Methods: Among 1536 older adults (≥60 years) in the EPIC-Norfolk study, sedentary time was assessed for seven days at two time-points using accelerometers. We assessed associations of change in total and prolonged bouts of sedentary time (≥ 30 minutes) with change in demographic and behavioural factors using multi-level regression.

Results: Over follow-up (5.3±1.9 years), greater increases in total sedentary time were associated with older age, being male, higher rate of increase in BMI, lower rate of increase in gardening (0.5 min/day/yr greater sedentary time per hour/week/yr less gardening, 95% CI 0.1, 1.0), a lower rate of increase in walking (0.2 min/day/yr greater sedentary time per hour/week/yr less walking, 95% CI 0.1, 0.3) and a higher rate of increase in television viewing. Correlates of change in prolonged sedentary bouts were similar.

Conclusion: Individuals in specific sub-groups (older, male, higher BMI) and who differentially participate in certain behaviours (less gardening, less walking and more television viewing) but not others increase their sedentary time at a higher rate than others; utilising this information could inform successful intervention content and targeting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835006PMC
January 2021

A cross-platform approach identifies genetic regulators of human metabolism and health.

Nat Genet 2021 01 7;53(1):54-64. Epub 2021 Jan 7.

Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.

In cross-platform analyses of 174 metabolites, we identify 499 associations (P < 4.9 × 10) characterized by pleiotropy, allelic heterogeneity, large and nonlinear effects and enrichment for nonsynonymous variation. We identify a signal at GLP2R (p.Asp470Asn) shared among higher citrulline levels, body mass index, fasting glucose-dependent insulinotropic peptide and type 2 diabetes, with β-arrestin signaling as the underlying mechanism. Genetically higher serine levels are shown to reduce the likelihood (by 95%) and predict development of macular telangiectasia type 2, a rare degenerative retinal disease. Integration of genomic and small molecule data across platforms enables the discovery of regulators of human metabolism and translation into clinical insights.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-020-00751-5DOI Listing
January 2021

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Nat Genet 2021 01 4;53(1):65-75. Epub 2021 Jan 4.

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-020-00748-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148035PMC
January 2021

Calcium intake, calcium supplementation and cardiovascular disease and mortality in the British population: EPIC-norfolk prospective cohort study and meta-analysis.

Eur J Epidemiol 2020 Dec 31. Epub 2020 Dec 31.

Ageing Clinical and Experimental Research (ACER) Team, University of Aberdeen, Aberdeen, UK.

The role of dietary calcium in cardiovascular disease prevention is unclear. We aimed to determine the association between calcium intake and incident cardiovascular disease and mortality. Data were extracted from the European Prospective Investigation of Cancer, Norfolk (EPIC-Norfolk). Multivariable Cox regressions analysed associations between calcium intake (dietary and supplemental) and cardiovascular disease (myocardial infarction, stroke, heart failure, aortic stenosis, peripheral vascular disease) and mortality (cardiovascular and all-cause). The results of this study were pooled with those from published prospective cohort studies in a meta-analsyis, stratifying by average calcium intake using a 700 mg/day threshold. A total of 17,968 participants aged 40-79 years were followed up for a median of 20.36 years (20.32-20.38). Compared to the first quintile of calcium intake (< 770 mg/day), intakes between 771 and 926 mg/day (second quintile) and 1074-1254 mg/day (fourth quintile) were associated with reduced all-cause mortality (HR 0.91 (0.83-0.99) and 0.85 (0.77-0.93), respectively) and cardiovascular mortality [HR 0.95 (0.87-1.04) and 0.93 (0.83-1.04)]. Compared to the first quintile of calcium intake, second, third, fourth, but not fifth quintiles were associated with fewer incident strokes: respective HR 0.84 (0.72-0.97), 0.83 (0.71-0.97), 0.78 (0.66-0.92) and 0.95 (0.78-1.15). The meta-analysis results suggest that high levels of calcium intake were associated with decreased all-cause mortality, but not cardiovascular mortality, regardless of average calcium intake. Calcium supplementation was associated with cardiovascular and all-cause mortality amongst women, but not men. Moderate dietary calcium intake may protect against cardiovascular and all-cause mortality and incident stroke. Calcium supplementation may reduce mortality in women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10654-020-00710-8DOI Listing
December 2020

Long-term effects of gestational diabetes on bone mineral density and fracture risk: Analysis of the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk) population-based study.

Maturitas 2021 Feb 18;144:68-73. Epub 2020 Nov 18.

School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, Scotland, UK. Electronic address:

Objectives: Gestational diabetes mellitus (GDM) is a common pregnancy complication. This study aims to investigate the association between a history of GDM and bone mineral density (BMD), fractures, and falls in later life.

Study Design: We used data from the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk) where BMD at calcaneum was measured at second health check (1997-2000) using broadband ultrasound attenuation (BUA) and velocity of sound (VOS) in 7,515 women. Fractures and falls were documented from hospital admissions data via linkage with ENCORE (East Norfolk Commission Record) and history of GDM from health questionnaires at baseline. We examined the relationship between GDM and BUA/VOS using linear regression. Cox regression was used to estimate hazard ratios (HRs) for incident fractures and falls, controlling for age, BMI, smoking status, physical activity, area deprivation, self-reported stroke, use of diuretics, calcium and vitamin D supplements, social class and education, statin and total blood cholesterol, prevalent diabetes, hormone therapy and menopausal status.

Results: History of GDM (n = 183) was not statistically significantly associated with BUA/VOS in fully adjusted linear regression models with unstandardised beta coefficients (standard error): -0.37 (1.40) and -5.41 (3.48). GDM was significantly (p < 0.05) associated with risk of hip and all fractures, fully adjusted HRs(95 %CI) 2.46(1.54-3.92) and 1.60(1.09-2.35), respectively. Median follow-up from first live birth to date of admission was 53 and 52 years, respectively.

Conclusion: There was an association between history of GDM and risk of any fracture as well as hip fracture specifically. Further research is required to confirm this.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.maturitas.2020.11.005DOI Listing
February 2021

Plasma Sulfur Amino Acids and Risk of Cerebrovascular Diseases: A Nested Case-Control Study in the EPIC-Norfolk Cohort.

Stroke 2021 01 22;52(1):172-180. Epub 2020 Dec 22.

Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, United Kingdom (N.J.W., N.G.F., F.I.).

Background And Purpose: B-vitamin supplements lower circulating concentrations of homocysteine and may reduce stroke incidence. Homocysteine concentrations are associated with the incidence of stroke but other sulfur-containing compounds in the related metabolic pathway have not yet been investigated for an association with incident cerebrovascular diseases.

Methods: Nested within the EPIC (European Prospective Investigation Into Cancer and Nutrition)-Norfolk cohort, we established a case-control study with 480 incident cases of cerebrovascular diseases and 480 controls matched by age, sex, and year of baseline examination (1993-1997). Using baseline plasma samples, we assayed sulfur-containing compounds including methionine, homocysteine, cystathionine, cysteine, glutathione, and taurine with liquid chromatography-tandem mass spectrometry. We examined the association of concentrations of each of the compounds and the ratio of methionine to homocysteine (representing activity of one-carbon metabolism) with risk of incident cerebrovascular diseases, adjusted for potential confounders.

Results: Plasma methionine and the methionine/homocysteine ratio were inversely associated with risk of cerebrovascular diseases, with odds ratios per 1 SD of 0.83 (95% CI, 0.72-0.96) and 0.82 (95% CI, 0.71-0.95), respectively. The association of methionine remained significant after adjustment for homocysteine. None of the other examined compounds was significantly associated with incident cerebrovascular diseases.

Conclusions: These findings suggest that greater availability of methionine, an essential amino acid, may play a role in the prevention of cerebrovascular diseases and explain the previously recognized link between elevated homocysteine and stroke. Further research is needed to determine causation and the potential of circulating methionine as a target in cerebrovascular disease prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.120.029177DOI Listing
January 2021

Cross-sectional and prospective associations between active living environments and accelerometer-assessed physical activity in the EPIC-Norfolk cohort.

Health Place 2021 Jan 13;67:102490. Epub 2020 Dec 13.

Medical Research Council (MRC) Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.

The environments in which young and middle-aged adults live may influence their physical activity (PA) behaviours. These associations are less clear among older adults. We estimated cross-sectional and prospective associations of population density, junction density, and land use mix and perceived active living environments with accelerometer-assessed PA in a cohort of older adults. Adults living in more dense and mixed neighbourhoods had less optimal activity profiles at baseline and less optimal changes in activity. Better perceptions were associated with more overall PA at baseline. Interventions for older adults may wish to target individuals living in more dense and mixed neighbourhoods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.healthplace.2020.102490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883217PMC
January 2021

Anticholinergic medication exposure predicts poor physical capability: Findings from a large prospective cohort study in England.

Maturitas 2020 Dec 25;142:55-63. Epub 2020 Jul 25.

Ageing Clinical & Experimental Research (ACER) Team, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; Department of Medicine for the Elderly, Aberdeen Royal Infirmary, Aberdeen, UK. Electronic address:

Objectives: To examine whether anticholinergic medication exposure in middle and late life is associated with physical capability.

Study Design: We used data from 8477 men and women who had enrolled in the European Prospective Investigation of Cancer-Norfolk study at baseline (1HC; 1993-1997) and who had attended its third health examination (3HC; 2004-2010). Medication history at the 1HC and 3HC was used to score participants according to the Anticholinergic Cognitive Burden (ACB) Scale at baseline and 3HC; participants were categorised as ACB = 0, ACB = 1, ACB>2.

Main Outcome Measure: At 3HC, physical capability was objectively measured by: usual walking speed, maximum grip strength, timed chair stands speed (TCSS) and standing balance. Linear and logistic regression models examined prospective and cross-sectional associations between ACB and physical capability, controlling for co-morbidity, sociodemographic and lifestyle factors.

Results: The analyses included 3386 men and 4110 women who were 56.4 (SD 7.9) and 55.0 (7.7) years old respectively at baseline and 69.4 (8.1) and 67.9 (8.0) years old at follow-up. Significant cross-sectional and prospective relationships were observed for all physical capability measures in women, except grip strength. For example, women with ACB ≥ 2 compared with ACB = 0 at baseline had 0.07 m/s (95 % CI -0.11, -0.03) slower usual walking speed, 2.61 stands/min (-4.17, -1.05) slower TCSS and higher odds of being unable to complete a tandem stand (odds ratio 2.40, 95 % CI 1.53, 3.76). These trends were observed in men but were less consistent in prospective analyses.

Conclusion: Exposure to anticholinergic medication predicts poor physical capability and is a potentially reversible risk factor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.maturitas.2020.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656240PMC
December 2020

A prediction tool for vitamin D deficiency in New Zealand adults.

Arch Osteoporos 2020 10 31;15(1):172. Epub 2020 Oct 31.

Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

Purpose: This study aims to develop a model for predicting vitamin D deficiency in New Zealand adults using easily accessible clinical characteristics.

Methods: Data were derived from the Vitamin D Assessment (ViDA) study dataset. Included participants in the main analysis were aged 50-84 years and resided in Auckland, New Zealand. The dataset was split into a discovery dataset in which the prediction model was developed (n = 2036) and a validation dataset in which it was tested (n = 2037). The prediction model was developed using clinical characteristics in a logistic regression analysis with deseasonalised serum 25OHD (DS-25OHD) as the dependent variable.

Results: DS-25OHD < 40 nmol/L was found in 8.2% of European participants, 18.8% of Māori participants, 23.1% of Pacific participants and 52.2% of South Asian participants. Predictors for DS-25OHD < 40 nmol/L in the European sub-cohort included increasing age, female sex, higher body mass index, current smoking, no alcohol intake, lower self-reported general health status, lower physical activity hours, lower outdoor hours and no use of vitamin D-containing supplementation. The area under the curve in the discovery dataset was 0.73, and in the validation dataset was 0.71. Of those with a prediction score ≥ 10 (total risk score range 0-21.5), the sensitivity and specificity for predicting vitamin D deficiency was 0.90 and 0.41, respectively.

Conclusion: Non-European ethnicity is an important risk factor for vitamin D deficiency. Our vitamin D deficiency prediction model performed well and demonstrates its potential as a tool that can be integrated into clinical practice for the prediction of vitamin D deficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11657-020-00844-yDOI Listing
October 2020

Hypertensive Disorders of Pregnancy (HDP) and the Risk of Common Cancers in Women: Evidence from the European Prospective Investigation into Cancer (EPIC)-Norfolk Prospective Population-Based Study.

Cancers (Basel) 2020 Oct 23;12(11). Epub 2020 Oct 23.

Aberdeen Centre for Women's Health Research, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZL, UK.

Purpose: The purpose was to determine the association between HDP and cancer in a UK cohort.

Methods: Between 1993 and 1997, participants from the EPIC-Norfolk cohort attended baseline health-checks and completed questionnaires, where a history of HDP was collected. Incident cancer cases were identified through NHS record linkage until March 2016. Univariable and multivariable logistic regression analyses were employed to determine the association between HDP and odds of cancer, with adjustment for potential confounders including co-morbidities, sociodemographic, lifestyle and reproductive factors.

Results: 13,562 women were included after excluding prevalent cancer cases and women with no pregnancies. 2919 (21.5%) reported HDP and 2615 incident cancers occurred during mean follow up of 19 years. Median age (IQR) at baseline for incident cancer was 60.8 (±14.8) years. Among incident cancer cases, 578 (22.1%) had HDP. In multivariable analyses, HDP had odds ratio (OR) 1.06; 95% CI 0.95-1.18 for incident cancer. The ORs (95% CIs) for common site-specific cancers including breast, colorectal, lung, ovarian and endometrial cancers were 1.06 (0.88-1.28), 1.15 (0.92-1.45), 0.96 (0.68-1.35), 1.30 (0.93-1.83) and 1.16 (0.80-1.67).

Conclusion: We found no association between HDP and cancer risk. Further studies are required to confirm and account for any underlying genetic factors involved in pregnancy-related exposures and cancer risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12113100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690818PMC
October 2020

Biomarker-estimated flavan-3-ol intake is associated with lower blood pressure in cross-sectional analysis in EPIC Norfolk.

Sci Rep 2020 10 21;10(1):17964. Epub 2020 Oct 21.

Department of Food and Nutritional Sciences, University of Reading, Reading, UK.

Flavan-3-ols are a group of bioactive compounds that have been shown to improve vascular function in intervention studies. They are therefore of great interest for the development of dietary recommendation for the prevention of cardio-vascular diseases. However, there are currently no reliable data from observational studies, as the high variability in the flavan-3-ol content of food makes it difficult to estimate actual intake without nutritional biomarkers. In this study, we investigated cross-sectional associations between biomarker-estimated flavan-3-ol intake and blood pressure and other CVD risk markers, as well as longitudinal associations with CVD risk in 25,618 participants of the European Prospective Investigation into Cancer (EPIC) Norfolk cohort. High flavan-3-ol intake, achievable as part of an habitual diet, was associated with a significantly lower systolic blood pressure (- 1.9 (- 2.7; - 1.1) mmHg in men and - 2.5 (- 3.3; - 1.8) mmHg in women; lowest vs highest decile of biomarker), comparable to adherence to a Mediterranean Diet or moderate salt reduction. Subgroup analyses showed that hypertensive participants had stronger inverse association between flavan-3-ol biomarker and systolic blood pressure when compared to normotensive participants. Flavanol intake could therefore have a role in the maintenance of cardiovascular health on a population scale.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-74863-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578063PMC
October 2020

The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis.

PLoS Med 2020 10 16;17(10):e1003394. Epub 2020 Oct 16.

Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.

Background: Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis.

Methods And Findings: We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]-InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1-standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities.

Conclusions: Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pmed.1003394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567390PMC
October 2020

Genome-wide association study identifies 48 common genetic variants associated with handedness.

Nat Hum Behav 2021 01 28;5(1):59-70. Epub 2020 Sep 28.

Institute of Biological Psychiatry, Mental Health Services of Copenhagen, Copenhagen, Denmark.

Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (r = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41562-020-00956-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116623PMC
January 2021

Sociodemographic and lifestyle predictors of incident hospital admissions with multimorbidity in a general population, 1999-2019: the EPIC-Norfolk cohort.

BMJ Open 2020 09 22;10(9):e042115. Epub 2020 Sep 22.

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.

Background: The ageing population and prevalence of long-term disorders with multimorbidity are a major health challenge worldwide. The associations between comorbid conditions and mortality risk are well established; however, few prospective community-based studies have reported on prior risk factors for incident hospital admissions with multimorbidity. We aimed to explore the independent associations for a range of demographic, lifestyle and physiological determinants and the likelihood of subsequent hospital incident multimorbidity.

Methods: We examined incident hospital admissions with multimorbidity in 25 014 men and women aged 40-79 in a British prospective population-based study recruited in 1993-1997 and followed up until 2019. The determinants of incident multimorbidity, defined as Charlson Comorbidity Index ≥3, were investigated using multivariable logistic regression models for the 10-year period 1999-2009 and repeated with independent measurements in a second 10-year period 2009-2019.

Results: Between 1999 and 2009, 18 179 participants (73% of the population) had a hospital admission. Baseline 5-year and 10-year incident multimorbidities were observed in 6% and 12% of participants, respectively. Age per 10-year increase (OR 2.19, 95% CI 2.06 to 2.33) and male sex (OR 1.32, 95% CI 1.19 to 1.47) predicted incident multimorbidity over 10 years. In the subset free of the most serious diseases at baseline, current smoking (OR 1.86, 95% CI 1.60 to 2.15), body mass index >30 kg/m² (OR 1.48, 95% CI 1.30 to 1.70) and physical inactivity (OR 1.16, 95% CI 1.04 to 1.29) were positively associated and plasma vitamin C (a biomarker of plant food intake) per SD increase (OR 0.86, 95% CI 0.81 to 0.91) inversely associated with incident 10-year multimorbidity after multivariable adjustment for age, sex, social class, education, alcohol consumption, systolic blood pressure and cholesterol. Results were similar when re-examined for a further time period in 2009-2019.

Conclusion: Age, male sex and potentially modifiable lifestyle behaviours including smoking, body mass index, physical inactivity and low fruit and vegetable intake were associated with increased risk of future incident hospital admissions with multimorbidity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-042115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509968PMC
September 2020

Management of Cardiovascular Disease Patients With Confirmed or Suspected COVID-19 in Limited Resource Settings.

Glob Heart 2020 07 1;15(1):44. Epub 2020 Jul 1.

Division of Cardiology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, Cape Town, ZA.

In this paper, we provide recommendations on the management of cardiovascular disease (CVD) among patients with confirmed or suspected coronavirus disease (COVID-19) to facilitate the decision making of healthcare professionals in low resource settings. The emergence of novel coronavirus disease, also known as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), has presented an unprecedented global challenge for the healthcare community. The ability of SARS-CoV-2 to get transmitted during the asymptomatic phase and its high infectivity have led to the rapid transmission of COVID-19 beyond geographic regions, leading to a pandemic. There is concern that COVID-19 is cardiotropic, and it interacts with the cardiovascular system on multiple levels. Individuals with established CVD are more susceptible to severe COVID-19. Through a consensus approach involving an international group this WHF statement summarizes the links between cardiovascular disease and COVID-19 and present some practical recommendations for the management of hypertension and diabetes, acute coronary syndrome, heart failure, rheumatic heart disease, Chagas disease, and myocardial injury for patients with COVID-19 in low-resource settings. This document is not a clinical guideline and it is not intended to replace national clinical guidelines or recommendations. Given the rapidly growing burden posed by COVID-19 illness and the associated severe prognostic implication of CVD involvement, further research is required to understand the potential mechanisms linking COVID-19 and CVD, clinical presentation, and outcomes of various cardiovascular manifestations in COVID-19 patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5334/gh.823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413193PMC
July 2020

A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort.

Sci Rep 2020 09 3;10(1):14541. Epub 2020 Sep 3.

Andalusian School of Public Health (EASP), Granada, Spain.

Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI < 18.5 kg/m) or obese (BMI ≥ 30 kg/m) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-71302-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471961PMC
September 2020

Dietary acid-base load and its association with risk of osteoporotic fractures and low estimated skeletal muscle mass.

Eur J Clin Nutr 2020 08;74(Suppl 1):33-42

Department of Population Health and Primary Care, Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, NR4 7TJ, UK.

Background/objectives: Age-related decline in skeletal muscle mass and strength, loss of bone density, and increased risk of osteoporotic fractures are important public health issues. Systemic acid-base balance is affected by dietary intake and may be relevant to these conditions. We therefore investigated associations of dietary acid-base load with skeletal muscle mass, bone density status, and fracture risk.

Subjects/methods: We analysed the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort of >25,000 individuals, 39-79 years at baseline. Potential renal acid load (PRAL) was calculated from 7-day food diary data. As a proxy for skeletal muscle mass, we estimated fat-free mass from bioelectrical impedance analysis and scaled this for BMI (FFM). Bone density status was assessed by heel-bone broadband ultrasound attenuation (BUA), and fracture rates were obtained from health-care records. Multivariable regression was used to test musculoskeletal outcomes across sex-specific quintiles of PRAL.

Results: PRAL in quintiles was negatively associated with FFM in men (n = 6350, p < 0.001) and women (n = 7989, p < 0.001), with quintile 5 vs 1 differences of -1.5% and -3.2% (both p < 0.001). PRAL was also negatively associated with BUA in women (n = 8312, p = 0.016; quintile 5 vs 1 difference -1.5%, p = 0.024). The combined hazard of hip, wrist and spine fractures (mean ± SD follow-up 17.9 ± 4.9 years) was higher with increasing quintiles of PRAL in men (610 fractures; n = 11,511; p = 0.013) and women (1583 fractures; n = 13,927; p = 0.009), with quintile 5 vs 1 hazard ratios of 1.33 (95% CI: 1.03-1.72, p = 0.029) and 1.21 (95% CI: 1.03-1.42, p = 0.022), but associations were not consistent for all fractures sites and age groups tested.

Conclusions: This study provides strong evidence, albeit observational, for a negative association between PRAL and musculoskeletal health in middle to older age men and women, and thus supports the rationale for a less acidic dietary load.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41430-020-0686-4DOI Listing
August 2020

Lower Dietary and Circulating Vitamin C in Middle- and Older-Aged Men and Women Are Associated with Lower Estimated Skeletal Muscle Mass.

J Nutr 2020 10;150(10):2789-2798

Department of Epidemiology and Public Health, Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom.

Background: Age-related loss of skeletal muscle mass contributes to poor outcomes including sarcopenia, physical disability, frailty, type 2 diabetes, and mortality. Vitamin C has physiological relevance to skeletal muscle and may protect it during aging, but few studies have investigated its importance in older populations.

Objectives: We aimed to investigate cross-sectional associations of dietary and plasma vitamin C with proxy measures of skeletal muscle mass in a large cohort of middle- and older-aged individuals.

Methods: We analyzed data from >13,000 men and women in the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort, aged 42-82 y. Fat-free mass (FFM), as a proxy for skeletal muscle mass, was estimated using bioelectrical impedance analysis and expressed as a percentage of total mass (FFM%) or standardized by BMI (FFMBMI). Dietary vitamin C intakes were calculated from 7-d food diary data, and plasma vitamin C was measured in peripheral blood. Multivariable regression models, including relevant lifestyle, dietary, and biological covariates, were used to determine associations between FFM measures and quintiles of dietary vitamin C or insufficient compared with sufficient plasma vitamin C (<50 μmol/L and ≥50 μmol/L).

Results: Positive trends were found across quintiles of dietary vitamin C and FFM measures for both sexes, with interquintile differences in FFM% and FFMBMI of 1.0% and 2.3% for men and 1.9% and 2.9% for women, respectively (all P < 0.001). Similarly, FFM% and FFMBMI measures were higher in participants with sufficient than with insufficient plasma vitamin C: by 1.6% and 2.0% in men, and 3.4% and 3.9% in women, respectively (all P < 0.001). Associations were also evident in analyses stratified into <65-y and ≥65-y age groups.

Conclusions: Our findings of positive associations, of both dietary and circulating vitamin C with measures of skeletal muscle mass in middle- and older-aged men and women, suggest that dietary vitamin C intake may be useful for reducing age-related muscle loss.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jn/nxaa221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549302PMC
October 2020

Improved cardiovascular risk prediction using targeted plasma proteomics in primary prevention.

Eur Heart J 2020 11;41(41):3998-4007

Department of Vascular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

Aims: In the era of personalized medicine, it is of utmost importance to be able to identify subjects at the highest cardiovascular (CV) risk. To date, single biomarkers have failed to markedly improve the estimation of CV risk. Using novel technology, simultaneous assessment of large numbers of biomarkers may hold promise to improve prediction. In the present study, we compared a protein-based risk model with a model using traditional risk factors in predicting CV events in the primary prevention setting of the European Prospective Investigation (EPIC)-Norfolk study, followed by validation in the Progressione della Lesione Intimale Carotidea (PLIC) cohort.

Methods And Results: Using the proximity extension assay, 368 proteins were measured in a nested case-control sample of 822 individuals from the EPIC-Norfolk prospective cohort study and 702 individuals from the PLIC cohort. Using tree-based ensemble and boosting methods, we constructed a protein-based prediction model, an optimized clinical risk model, and a model combining both. In the derivation cohort (EPIC-Norfolk), we defined a panel of 50 proteins, which outperformed the clinical risk model in the prediction of myocardial infarction [area under the curve (AUC) 0.754 vs. 0.730; P < 0.001] during a median follow-up of 20 years. The clinically more relevant prediction of events occurring within 3 years showed an AUC of 0.732 using the clinical risk model and an AUC of 0.803 for the protein model (P < 0.001). The predictive value of the protein panel was confirmed to be superior to the clinical risk model in the validation cohort (AUC 0.705 vs. 0.609; P < 0.001).

Conclusion: In a primary prevention setting, a proteome-based model outperforms a model comprising clinical risk factors in predicting the risk of CV events. Validation in a large prospective primary prevention cohort is required to address the value for future clinical implementation in CV prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehaa648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672529PMC
November 2020