Kay-Tee Khaw

National Cancer Institute (USA), 베서스다, Maryland, United States

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Publications (698)5288.29 Total impact

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    ABSTRACT: Dietary magnesium could modify the major stroke risk factors, high blood pressure (BP) and cholesterol, but has been understudied in both sexes in a single population. This study aimed to investigate if dietary magnesium intake was associated with BP, total cholesterol (TC) and incident stroke risk in an adult population. We conducted cross-sectional analyses in a case-cohort study of 4443, men and women aged 40-75, representative of 25,639 participants years of the EPIC (European Prospective Investigation into Cancer)-Norfolk cohort. The cohort included 928 stroke cases (42,556.5person years). Dietary data from 7day food diaries were analysed using multivariate regression to assess associations between quintiles or data-derived categories of dietary magnesium intake and BP, TC and stroke risk, adjusted for relevant confounders. We observed differences of -7mmHg systolic BP (P trend≤0.01) and -3.8mmHg diastolic BP (P trend=0.01) between extreme intakes of magnesium in men, a significant inverse association with TC was observed (P trend=0.02 men and 0.04 women). Compared to the bottom 10%, the top 30% of magnesium intake was associated with a 41% relative reduction in stroke risk (HR 0.59; 95% CI 0.38-0.93) in men. Lower dietary magnesium intake was associated with higher BP and stroke risk, which may have implications for primary prevention. Copyright © 2015. Published by Elsevier Ireland Ltd.
    International journal of cardiology 10/2015; 196. DOI:10.1016/j.ijcard.2015.05.166 · 6.18 Impact Factor
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    ABSTRACT: The prevalence of cardiometabolic multimorbidity is increasing. To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689 300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128 843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499 808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). All-cause mortality and estimated reductions in life expectancy. In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
    JAMA The Journal of the American Medical Association 07/2015; 314(1):52-60. DOI:10.1001/jama.2015.7008 · 30.39 Impact Factor
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    ABSTRACT: In our aging population, maintenance of bone health is critical to reduce the risk of osteoporosis and potentially debilitating consequences of fractures in older individuals. Among modifiable lifestyle and dietary factors, dietary magnesium and potassium intakes are postulated to influence bone quality and osteoporosis, principally via calcium-dependent alteration of bone structure and turnover. We investigated the influence of dietary magnesium and potassium intakes, as well as circulating magnesium, on bone density status and fracture risk in an adult population in the United Kingdom. A random subset of 4000 individuals from the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort of 25,639 men and women with baseline data was used for bone density cross-sectional analyses and combined with fracture cases (n = 1502) for fracture case-cohort longitudinal analyses (mean follow-up 13.4 y). Relevant biological, lifestyle, and dietary covariates were used in multivariate regression analyses to determine associations between dietary magnesium and potassium intakes and calcaneal broadband ultrasound attenuation (BUA), as well as in Prentice-weighted Cox regression to determine associated risk of fracture. Separate analyses, excluding dietary covariates, investigated associations of BUA and fractures with serum magnesium concentration. Statistically significant positive trends in calcaneal BUA for women (n = 1360) but not men (n = 968) were apparent across increasing quintiles of magnesium plus potassium (Mg+K) z score intake (P = 0.03) or potassium intake alone (P = 0.04). Reduced hip fracture risk in both men (n = 1958) and women (n = 2755) was evident for individuals in specific Mg+K z score intake quintiles vs. the lowest. Statistically significant trends in fracture risk in men across serum magnesium concentration groups were apparent for spine fractures (P = 0.02) and total hip, spine, and wrist fractures (P = 0.02). None of these individual statistically significant associations remained after adjustment for multiple testing. These findings enhance the limited literature studying the association of magnesium and potassium with bone density and demonstrate that further investigation is warranted into the mechanisms involved and the potential protective role against osteoporosis. © 2015 American Society for Nutrition.
    American Journal of Clinical Nutrition 07/2015; DOI:10.3945/ajcn.114.102723 · 6.92 Impact Factor
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    ABSTRACT: Although it seems biologically plausible for iron to be associated with gastric carcinogenesis, the evidence is insufficient to lead to any conclusions. To further investigate the relationship between body iron status and gastric cancer risk, we conducted a nested case-control study in the multi-centric European Prospective Investigation into Cancer and Nutrition (EPIC) study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured pre-diagnostic serum iron, ferritin, transferrin, and C-reactive protein, and further estimated total iron-binding capacity (TIBC) and transferrin saturation (TS). Odds ratios (OR) and 95% confidence intervals (CI) for the risk of gastric cancer by iron metrics were estimated from multivariable conditional logistic regression models. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and ferritin and TS indices (ORlog2 =0.80, 95% CI=0.72-0.88; and OR10%increment =0.87, 95% CI=0.78-0.97, respectively). These associations seem to be restricted to noncardia gastric cancer (ferritin showed a P for heterogeneity=0.04 and TS had a P for heterogeneity=0.02), and no differences were found by histological type. TIBC increased risk of overall gastric cancer (OR50µg/dl =1.13, 95% CI=1.02-1.2) and also with noncardia gastric cancer (P for heterogeneity=0.04). Additional analysis suggests that time between blood draw and gastric cancer diagnosis could modify these findings. In conclusion, our results showed a decreased risk of gastric cancer related to higher body iron stores as measured by serum iron and ferritin. Further investigation is needed to clarify the role of iron in gastric carcinogenesis. This article is protected by copyright. All rights reserved. © 2015 UICC.
    International Journal of Cancer 07/2015; DOI:10.1002/ijc.29669 · 5.01 Impact Factor
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    Dataset: IJC2015
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    ABSTRACT: The role of amount and type of dietary fat consumption in the aetiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-h diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95%CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV/HCV) status and biomarkers of liver function were assessed separately in a nested case-control subset with available blood samples (HCC=122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g/d, HR=0.80, 95%CI: 0.65-0.99), which was mainly driven by monounsaturated fats (per 5 g/d, HR=0.71, 95%CI: 0.55-0.92) rather than polyunsaturated fats (per 5 g/d, HR=0.92, 95%CI: 0.68-1.25). There was no association between saturated fats (HR=1.08, 95%CI: 0.88-1.34) and HCC risk. The ratio of polyunsaturated/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR=0.86, 95%CI: 0.73-1.01). Restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk. This article is protected by copyright. All rights reserved. © 2015 UICC.
    International Journal of Cancer 06/2015; DOI:10.1002/ijc.29643 · 5.01 Impact Factor
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    ABSTRACT: Previously, a lower risk of colorectal cancer was observed with fruit and vegetable consumption in the European Prospective Investigation into Cancer and Nutrition within a follow-up period of nine years which was not fully supported by a recent meta-analysis. Therefore, we were interested in the relation with extended follow-up, also focusing on single subtypes and variety of intake of fruit and vegetables. Fruit and vegetable consumption was assessed at baseline. After an average of thirteen years of follow-up, 3,370 participants were diagnosed with colon or rectal cancer. Diet diversity scores were constructed to quantify variety in fruit and vegetable consumption. A lower risk of colon cancer was observed with higher self-reported consumption of fruit and vegetable combined (HR Q4 vs. Q1 0.87, 95%CI 0.75-1.01, P for trend 0.02), but no consistent association was observed for separate consumption of fruits and vegetables. No associations with risk of rectal cancer were observed. The few observed associations for some fruit and vegetable subtypes with colon cancer risk may have been due to chance. Variety in consumption of fruits and vegetables was not associated with a lower risk of colon or rectal cancer. Although a lower risk of colon cancer is suggested with high consumption of fruit and vegetables, this study does not support a clear inverse association between fruit and vegetable consumption and colon or rectal cancer beyond a follow-up of more than ten years. Attenuation of the risk estimates from dietary changes over time cannot be excluded, but seems unlikely. This article is protected by copyright. All rights reserved. © 2015 UICC.
    International Journal of Cancer 06/2015; DOI:10.1002/ijc.29640 · 5.01 Impact Factor
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    ABSTRACT: To examine the association between chocolate intake and the risk of future cardiovascular events. We conducted a prospective study using data from the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. Habitual chocolate intake was quantified using the baseline food frequency questionnaire (1993-1997) and cardiovascular end points were ascertained up to March 2008. A systematic review was performed to evaluate chocolate consumption and cardiovascular outcomes. A total of 20 951 men and women were included in EPIC-Norfolk analysis (mean follow-up 11.3±2.8 years, median 11.9 years). The percentage of participants with coronary heart disease (CHD) in the highest and lowest quintile of chocolate consumption was 9.7% and 13.8%, and the respective rates for stroke were 3.1% and 5.4%. The multivariate-adjusted HR for CHD was 0.88 (95% CI 0.77 to 1.01) for those in the top quintile of chocolate consumption (16-99 g/day) versus non-consumers of chocolate intake. The corresponding HR for stroke and cardiovascular disease (cardiovascular disease defined by the sum of CHD and stroke) were 0.77 (95% CI 0.62 to 0.97) and 0.86 (95% CI 0.76 to 0.97). The propensity score matched estimates showed a similar trend. A total of nine studies with 157 809 participants were included in the meta-analysis. Higher compared to lower chocolate consumption was associated with significantly lower CHD risk (five studies; pooled RR 0.71, 95% CI 0.56 to 0.92), stroke (five studies; pooled RR 0.79, 95% CI 0.70 to 0.87), composite cardiovascular adverse outcome (two studies; pooled RR 0.75, 95% CI 0.54 to 1.05), and cardiovascular mortality (three studies; pooled RR 0.55, 95% CI 0.36 to 0.83). Cumulative evidence suggests that higher chocolate intake is associated with a lower risk of future cardiovascular events, although residual confounding cannot be excluded. There does not appear to be any evidence to say that chocolate should be avoided in those who are concerned about cardiovascular risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Heart (British Cardiac Society) 06/2015; DOI:10.1136/heartjnl-2014-307050 · 6.02 Impact Factor
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    ABSTRACT: Genome-wide association studies have identified SNPs near ZNF365 at 10q21.2 that are associated with both breast cancer risk and mammographic density. To identify the most likely causal SNPs, we fine mapped the association signal by genotyping 428 SNPs across the region in 89,050 European and 12,893 Asian case and control subjects from the Breast Cancer Association Consortium. We identified four independent sets of correlated, highly trait-associated variants (iCHAVs), three of which were located within ZNF365. The most strongly risk-associated SNP, rs10995201 in iCHAV1, showed clear evidence of association with both estrogen receptor (ER)-positive (OR = 0.85 [0.82-0.88]) and ER-negative (OR = 0.87 [0.82-0.91]) disease, and was also the SNP most strongly associated with percent mammographic density. iCHAV2 (lead SNP, chr10: 64,258,684:D) and iCHAV3 (lead SNP, rs7922449) were also associated with ER-positive (OR = 0.93 [0.91-0.95] and OR = 1.06 [1.03-1.09]) and ER-negative (OR = 0.95 [0.91-0.98] and OR = 1.08 [1.04-1.13]) disease. There was weaker evidence for iCHAV4, located 5' of ADO, associated only with ER-positive breast cancer (OR = 0.93 [0.90-0.96]). We found 12, 17, 18, and 2 candidate causal SNPs for breast cancer in iCHAVs 1-4, respectively. Chromosome conformation capture analysis showed that iCHAV2 interacts with the ZNF365 and NRBF2 (more than 600 kb away) promoters in normal and cancerous breast epithelial cells. Luciferase assays did not identify SNPs that affect transactivation of ZNF365, but identified a protective haplotype in iCHAV2, associated with silencing of the NRBF2 promoter, implicating this gene in the etiology of breast cancer. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
    The American Journal of Human Genetics 06/2015; 97(1). DOI:10.1016/j.ajhg.2015.05.002 · 10.99 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large scale genotyping and imputation in 25,723 PrCa cases and 26,274 controls of European ancestry.We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, whilst the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed 2 association signals in Europeans that had been previously reported only in East-Asian GWAS.Based on statistical evidence and LD structure we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain approximately 38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same region. © The Author 2015. Published by Oxford University Press.
    Human Molecular Genetics 05/2015; DOI:10.1093/hmg/ddv203 · 6.68 Impact Factor
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    ABSTRACT: Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH <0.45 mIU/L), and subclinical hypothyroidism (TSH ≥4.50-19.99 mIU/L) with normal thyroxine concentrations. The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. Among 70 298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762 401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56 471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25 901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21 722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20 328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk. Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures.
    JAMA The Journal of the American Medical Association 05/2015; 313(20):2055-2065. DOI:10.1001/jama.2015.5161 · 30.39 Impact Factor
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    ABSTRACT: Flavonoids are a group of phenolic secondary plant metabolites that are ubiquitous in plant-based diets. Data from anthropological, observational and intervention studies have shown that many flavonoids are bioactive. For this reason, there is an increasing interest in investigating the potential health effects of these compounds. The translation of these findings into the context of the health of the general public requires detailed information on habitual dietary intake. However, only limited data are currently available for European populations. The objective of this study is to determine the habitual intake and main sources of anthocyanidins, flavanols, flavanones, flavones, flavonols, proanthocyanidins, theaflavins and thearubigins in the European Union. We use food consumption data from the European Food Safety Authority (EFSA) and the FLAVIOLA Food Composition Database to estimate intake of flavonoids. Mean (±SEM) intake of total flavonoids in Europe was 428±49 mg/d, of which 136±14 mg/d were monomeric compounds. Gallated flavan-3-ols (53±12 mg/d) were the main contributor. The lowest flavonoid intake was observed in Mediterranean countries (monomeric compounds: 95±11 mg/d). The distribution of intake was skewed in many countries, especially in Germany (monomeric flavonoids; mean intake: 181 mg/d; median intake: 3 mg/d). The habitual intake of flavonoids in Europe is below the amounts found to have a significant health effect.
    PLoS ONE 05/2015; 10(5):e0128132. DOI:10.1371/journal.pone.0128132 · 3.53 Impact Factor
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    ABSTRACT: Although HDL cholesterol concentrations are strongly and inversely associated with risk of coronary heart disease, interventions that raise HDL cholesterol do not reduce risk of coronary heart disease. HDL cholesterol efflux capacity-a prototypical measure of HDL function-has been associated with coronary heart disease after adjusting for HDL cholesterol, but its effect on incident coronary heart disease risk is uncertain. We measured cholesterol efflux capacity and assessed its relation with vascular risk factors and incident coronary heart disease events in a nested case-control sample from the prospective EPIC-Norfolk study of 25 639 individuals aged 40-79 years, assessed in 1993-97 and followed up to 2009. We quantified cholesterol efflux capacity in 1745 patients with incident coronary heart disease and 1749 control participants free of any cardiovascular disorders by use of a validated ex-vivo radiotracer assay that involved incubation of cholesterol-labelled J774 macrophages with apoB-depleted serum from study participants. Cholesterol efflux capacity was positively correlated with HDL cholesterol concentration (r=0·40; p<0·0001) and apoA-I concentration (r=0·22; p<0·0001). It was also inversely correlated with type 2 diabetes (r=-0·18; p<0·0001) and positively correlated with alcohol consumption (r=0·12; p<0·0001). In analyses comparing the top and bottom tertiles, cholesterol efflux capacity was significantly and inversely associated with incident coronary heart disease events, independent of age, sex, diabetes, hypertension, smoking and alcohol use, waist:hip ratio, BMI, LDL cholesterol concentration, log-triglycerides, and HDL cholesterol or apoA-I concentrations (odds ratio 0·64, 95% CI 0·51-0·80). After a similar multivariable adjustment the risk of incident coronary heart disease was 0·80 (95% CI 0·70-0·90) for a per-SD change in cholesterol efflux capacity. HDL cholesterol efflux capacity might provide an alternative mechanism for therapeutic modulation of the HDL pathway beyond HDL cholesterol concentration to help reduce risk of coronary heart disease. US National Institutes of Health, UK Medical Research Council, Cancer Research UK. Copyright © 2015 Saleheen et al. Open Acess article disrtibuted under the terms of CC BY-NC-ND. Published by Elsevier Ltd.. All rights reserved.
    05/2015; 3(7). DOI:10.1016/S2213-8587(15)00126-6
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    ABSTRACT: Type-2 diabetes is associated with systemic inflammation and higher C-reactive protein (CRP) levels. However, the longitudinal association of CRP and haemoglobin-A1c (HbA1c) has not been described in large prospective studies. Understanding such associations may shed light on the role of inflammation in development of type-2 diabetes and its complications such as cardiovascular diseases. EPIC-Norfolk is a cohort study of men and women aged 40-79 years at time of recruitment (1993-1997). Serum CRP (mg/l) was measured using a high-sensitivity assay at baseline and 13-years follow-up. HbA1c (%) was measured at baseline, 4, and 13 years. Participants were excluded if they were diagnosed with diabetes or were taking diabetes medication. Data on at least one measurement of CRP and HbA1c was available for 14228 participants (55 % of the cohort). In the cross-sectional analysis of baseline data, a 1-SD higher loge-CRP (about three-fold higher CRP) was associated with 0.06 (95 % CI 0.04, 0.08) higher HbA1c (%) adjusted for potential confounders. In longitudinal analysis using multivariable linear mixed models, change in CRP over 13 years was to a similar extent positively associated with increase in HbA1c, such that 1-SD higher longitudinal change in loge-CRP was associated with 0.04 (95 % CI 0.02, 0.05) increase in HbA1c. In this study we found longitudinal observational evidence suggesting that increase in systemic inflammation is associated with an increase in HbA1c and thus systemic inflammation may have a role in development of type-2 diabetes and its complications.
    Cardiovascular Diabetology 05/2015; 14(1):61. DOI:10.1186/s12933-015-0224-1 · 3.71 Impact Factor
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    ABSTRACT: This study aimed to evaluate the association of types of sugar-sweetened beverages (SSB) (soft drinks, sweetened-milk beverages, sweetened tea/coffee), artificially sweetened beverages (ASB) and fruit juice with incident type 2 diabetes and determine the effects of substituting non-SSB for SSB and the population-attributable fraction of type 2 diabetes due to total sweet beverages. Beverage consumption of 25,639 UK-resident adults without diabetes at baseline (1993-1997) in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study was assessed using 7-day food diaries. During 10.8 years of follow-up 847 incident type 2 diabetes cases were verified. In adjusted Cox regression analyses there were positive associations (HR [95% CI] per serving/day]) for soft drinks 1.21 (1.05, 1.39), sweetened-milk beverages 1.22 (1.05, 1.43) and ASB 1.22 (1.11, 1.33), but not for sweetened tea/coffee 0.98 (0.94, 1.02) or fruit juice 1.01 (0.88, 1.15). Further adjustment for adiposity attenuated the association of ASB, HR 1.06 (0.93, 1.20). There was a positive dose-response relationship with total sweet beverages: HR per 5% energy 1.18 (1.11, 1.26). Substituting ASB for any SSB did not reduce the incidence in analyses accounting for energy intake and adiposity. Substituting one serving/day of water or unsweetened tea/coffee for soft drinks and for sweetened-milk beverages reduced the incidence by 14%-25%. If sweet beverage consumers reduced intake to below 2% energy, 15% of incident diabetes might be prevented. The consumption of soft drinks, sweetened-milk beverages and energy from total sweet beverages was associated with higher type 2 diabetes risk independently of adiposity. Water or unsweetened tea/coffee appear to be suitable alternatives to SSB for diabetes prevention. These findings support the implementation of population-based interventions to reduce SSB consumption and increase the consumption of suitable alternatives.
    Diabetologia 05/2015; 58(7). DOI:10.1007/s00125-015-3572-1 · 6.88 Impact Factor
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    ABSTRACT: Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD). To assess the association between differences in thyroid function within the reference range and CHD risk. Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55 412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline. Thyroid function as expressed by serum thyrotropin levels at baseline. Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status. Among 55 412 individuals, 1813 people (3.3%) died of CHD during 643 183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48 875 individuals (9.5%) experienced a first-time CHD event during 533 408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95% CI, 0.90-1.04) for CHD mortality and 1.00 (95% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95% CI, 0.74-1.20]) and CHD events (0.97 [95% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results. Thyrotropin levels within the reference range are not associated with risk of CHD events or CHD mortality. This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit.
    JAMA Internal Medicine 04/2015; 175(6). DOI:10.1001/jamainternmed.2015.0930 · 13.25 Impact Factor
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    ABSTRACT: Mammographic density measures adjusted for age and body mass index (BMI) are heritable predictors of breast cancer risk but few mammographic density-associated genetic variants have been identified. Using data for 10,727 women from two international consortia, we estimated associations between 77 common breast cancer susceptibility variants and absolute dense area, percent dense area and absolute non-dense area adjusted for study, age and BMI using mixed linear modeling. We found strong support for established associations between rs10995190 (in the region of ZNF365), rs2046210 (ESR1) and rs3817198 (LSP1) and adjusted absolute and percent dense areas (all p <10-5). Of 41 recently discovered breast cancer susceptibility variants, associations were found between rs1432679 (EBF1), rs17817449 (MIR1972-2: FTO), rs12710696 (2p24.1), and rs3757318 (ESR1) and adjusted absolute and percent dense areas, respectively. There were associations between rs6001930 (MKL1) and both adjusted absolute dense and non-dense areas, and between rs17356907 (NTN4) and adjusted absolute non-dense area. Trends in all but two associations were consistent with those for breast cancer risk. Results suggested that 18% of breast cancer susceptibility variants were associated with at least one mammographic density measure. Genetic variants at multiple loci were associated with both breast cancer risk and the mammographic density measures. Further understanding of the underlying mechanisms at these loci could help identify etiological pathways implicated in how mammographic density predicts breast cancer risk. Copyright © 2015, American Association for Cancer Research.
    Cancer Research 04/2015; DOI:10.1158/0008-5472.CAN-14-2012 · 9.28 Impact Factor
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    ABSTRACT: To determine the risk of stroke associated with subclinical hypothyroidism. Data Sources and Study Selection Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data (IPD) on thyroid function and stroke outcome. Euthyroidism was defined as thyrotropin (TSH) levels 0.45-4.49 mIU/L, subclinical hypothyroidism as TSH levels 4.5-19.9 mIU/L with normal thyroxin levels. Data Extraction and Synthesis We collected IPD on 47,573 adults (3451 subclinical hypothyroidism) from 17 cohorts, followed-up 1972-2014 (489,192 person-years). Age- and sex-adjusted pooled hazard ratio (HR) for participants with subclinical hypothyroidism compared to euthyroidism was 1.05 (95% CI, 0.91-1.21) for stroke events (combined fatal and non-fatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratified by age, the HR for stroke events was 3.32 (95% CI, 1.25-8.80) for individuals aged 18-49 years. There was an increased risk of fatal stroke in the age groups 18-49 and 50-64 years with a HR of 4.22 (95% CI, 1.08-16.55) and 2.86 (95% CI, 1.31-6.26), respectively (p trend 0.04). We found no increased risk for those 65-79 years (HR 1.00, 95% CI, 0.86-1.18) or ≥80 years (HR 1.31, 95% CI, 0.79-2.18). There was a pattern of increased risk of fatal stroke with higher TSH concentrations. Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed.
    The Journal of Clinical Endocrinology and Metabolism 04/2015; DOI:10.1210/jc.2015-1438 · 6.31 Impact Factor

Publication Stats

26k Citations
5,288.29 Total Impact Points

Institutions

  • 2015
    • National Cancer Institute (USA)
      • Division of Cancer Epidemiology and Genetics
      베서스다, Maryland, United States
  • 1997–2015
    • University of Cambridge
      • • Department of Public Health and Primary Care
      • • Cambridge Institute of Public Health
      Cambridge, England, United Kingdom
  • 2014
    • IDIBELL Bellvitge Biomedical Research Institute
      Barcino, Catalonia, Spain
  • 2006–2014
    • German Institute of Human Nutrition
      • Department of Epidemiology
      Berlín, Berlin, Germany
    • Universitetet i Tromsø
      • Department of Community Medicine
      Tromsø, Troms Fylke, Norway
  • 2005–2014
    • Epic
      Verona, Wisconsin, United States
    • Utrecht University
      Utrecht, Utrecht, Netherlands
  • 2013
    • MRC Mitochondrial Biology Unit
      Cambridge, England, United Kingdom
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2011–2013
    • German Cancer Research Center
      • Division of Cancer Epidemiology
      Heidelberg, Baden-Wuerttemberg, Germany
    • Imperial College London
      • School of Public Health
      London, ENG, United Kingdom
    • University College London
      • Department of Epidemiology and Public Health
      London, ENG, United Kingdom
  • 2007–2013
    • Umeå University
      • • Department of Medical Biosciences
      • • Department of Clinical Sciences
      Umeå, Västerbotten, Sweden
    • University of Naples Federico II
      Napoli, Campania, Italy
  • 2004–2013
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Department of Vascular Medicine
      • • Academic Medical Center
      Amsterdam, North Holland, Netherlands
    • Leiden University
      Leyden, South Holland, Netherlands
  • 2012
    • University of Cologne
      • Heart Center
      Köln, North Rhine-Westphalia, Germany
    • Otto-von-Guericke-Universität Magdeburg
      • Institute for Clinical Chemistry and Pathobiochemistry
      Magdeburg, Saxony-Anhalt, Germany
    • McGill University
      • Department of Epidemiology, Biostatistics and Occupational Health
      Montréal, Quebec, Canada
  • 2010–2012
    • Catalan Institute of Oncology
      • • Nutrition, Environment and Cancer Unit
      • • Cancer Epidemiology Research Programme (PREC)
      Badalona, Catalonia, Spain
    • Icahn School of Medicine at Mount Sinai
      Borough of Manhattan, New York, United States
    • Institut universitaire de cardiologie et de pneumologie de Québec
      Québec, Quebec, Canada
    • Universidade Federal de Ouro Preto
      • Department of Social and Clinical Nutrition(DENCS)
      Ouro Preto, Minas Gerais, Brazil
  • 2010–2011
    • International Agency for Research on Cancer
      Lyons, Rhône-Alpes, France
  • 2008–2011
    • University of East Anglia
      • • Norwich Medical School
      • • Health and Social Sciences Research Institute
      Norwich, England, United Kingdom
    • University of Oxford
      • Cancer Epidemiology Unit
      Oxford, ENG, United Kingdom
    • Medical Research Council (UK)
      Londinium, England, United Kingdom
  • 2009
    • National Institute for Public Health and the Environment (RIVM)
      • Centre for Nutrition and Health
      Utrecht, Utrecht, Netherlands
    • Cambridge Health Alliance
      Cambridge, Massachusetts, United States
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      Milano, Lombardy, Italy
    • Diakonhjemmet Hospital (Norway)
      Kristiania (historical), Oslo County, Norway
  • 2006–2007
    • Institute of Cancer Research
      Londinium, England, United Kingdom
  • 2003
    • Papworth Hospital NHS Foundation Trust
      Papworth, England, United Kingdom