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103. Mutation in APOA1 predicts increased risk of ischaemic heart disease and mortality without low HDL cholesterol

Author

Haase, C.L., Frikke-Schmidt, R., Nordestgaard, B.G., Kateifides, A.K., Kardassis, D., Nielsen, L.B., Johnsen, A.H., Grande, P., Zannis, V.I., Tybjaerg-Hansen, A., Johnsen, Anders Holten, Tybjærg-Hansen, Anne, Haase, C.L., Frikke-Schmidt, R., Nordestgaard, B.G., Kateifides, A.K., Kardassis, D., Nielsen, L.B., Johnsen, A.H., Grande, P., Zannis, V.I., Tybjaerg-Hansen, A., Johnsen, Anders Holten, and Tybjærg-Hansen, Anne

Published
2010

104. The influence of genotype on vascular endothelial growth factor and regulation of myocardial collateral blood flow in patients with acute and chronic coronary heart disease

Author

Ripa, R.S., Jorgensen, E., Baldazzi, F., Frikke-Schmidt, R., Wang, Y., Tybjaerg-Hansen, A., Kastrup, J., Ripa, R.S., Jorgensen, E., Baldazzi, F., Frikke-Schmidt, R., Wang, Y., Tybjaerg-Hansen, A., and Kastrup, J.

Abstract

OBJECTIVE: To test the hypothesis that mutations in the vascular endothelial growth factor (VEGF) gene are associated with plasma concentration of VEGF and subsequently the ability to influence coronary collateral arteries in patients with coronary heart disease (CHD). METHODS: Blood samples from patients with chronic ischemic heart disease (n=53) and acute coronary syndrome (n=61) were analysed. Coronary collaterals were scored from diagnostic biplane coronary angiograms. RESULTS: The plasma concentration of VEGF was increased in patients with acute compared to chronic CHD (p=0.01). The genotype frequencies differed significantly from Hardy-Weinberg equilibrium in three of 15 examined loci. Four new mutations in addition to the already described were identified. The VEGF haplotype did not seem to predict plasma VEGF concentration (p=0.5). There was an association between the genotype in locus VEGF-1154 and coronary collateral size (p=0.03) and a significant association between the VEGF plasma concentration and the collateral size (p=0.03). CONCLUSION: VEGF plasma concentration seems related to coronary collateral function in patients with CHD. The results did not support the hypothesis that polymorphisms in the untranslated region of the VEGF gene were associated with the concentration of circulating VEGF. Increased understanding of VEGF in the regulation of myocardial collateral flow may lead to new therapies in CHD Udgivelsesdato: 2009

Published
2009

105. High-throughput genotyping of copy number variation in glutathione S-transferases M1 and T1 using real-time PCR in 20,687 individuals

Author

Norskov, M.S., Frikke-Schmidt, R., Loft, S., Tybjaerg-Hansen, A., Norskov, M.S., Frikke-Schmidt, R., Loft, S., and Tybjaerg-Hansen, A.

Abstract

OBJECTIVES: Characteristic for the genes encoding glutathione S-transferase (GST) M1 and GSTT1 is a null allele, suggested to increase susceptibility to chronic diseases. We report an optimized method for the determination of copy number variation (CNV) in GST genes. DESIGN AND METHODS: Real-time multiplex PCR reactions were optimized for quantification of GSTM1 and GSTT1 CNV using the DeltaCt method, a fixed volume of diluted DNA, a total volume of 10 microL, 384-well formats, and single determinations of each sample. RESULTS: Consistent genotyping was obtained using DNA in a range of 0.41 ng to 100 ng. In a general population sample of 20,687 individuals the genotype frequencies were concordant with other methods used as standards. Throughput was 4600 genotypes per day at a reagent price of 0.5 euros per sample. CONCLUSIONS: This high-throughput, low cost method accurately determines CNV in the GST genes enabling reliable estimates of disease prediction in large epidemiological samples Udgivelsesdato: 2009/2

Published
2009

106. Elevated plasma YKL-40 predicts increased risk of gastrointestinal cancer and decreased survival after any cancer diagnosis in the general population

Author

Johansen, J.S., Bojesen, S.E., Mylin, A.K., Frikke-Schmidt, R., Price, P.A., Nordestgaard, B.G., Johansen, J.S., Bojesen, S.E., Mylin, A.K., Frikke-Schmidt, R., Price, P.A., and Nordestgaard, B.G.

Abstract

PURPOSE: Elevated plasma YKL-40 is a biomarker of poor prognosis in cancer patients. We tested the hypotheses that elevated plasma YKL-40 predicts risk of cancer as well as survival after a cancer diagnosis in the general population. PATIENTS AND METHODS: A prospective cohort study of 8,899 subjects (20 to 95 years) from the Danish general population, the Copenhagen City Heart Study, observed for 11 years for cancer incidence and 14 years for death: 1,432 participants had a first incident cancer, 968 of these died. Hazard ratios (HRs) for cancer events and death after events according to plasma YKL-40 in sex and 10 years age percentile categories: 0% to 33%, 34% to 66%, 67% to 90%, 91% to 95%, and 96% to 100%. RESULTS: The cumulative incidence of gastrointestinal cancer increased with increasing YKL-40 (trend P < .0001). Multifactorially adjusted HRs for gastrointestinal cancer were 1.0 (95% CI, 0.7 to 1.5) for YKL-40 in category 34% to 66%, 1.5 for 67% to 90% (95% CI, 1.0 to 2.3), 2.4 for 91% to 95%, (95% CI, 1.3 to 4.6), and 3.4 for 96% to 100% (95% CI, 1.9 to 6.1) versus YKL-40 category 0% to 33% (P < .0001). Participants with any cancer event and YKL-40 category 91% to 100% had a median survival time after the diagnosis of 1 year versus 4 years in participants with YKL-40 category 0% to 33% (P < .0001). Corresponding values for gastrointestinal cancer were 6 months versus 1 year (P = .007). Multifactorially adjusted HRs for early death were 1.8 (95% CI, 1.3 to 2.5; P < .0001) after any cancer and 2.4 (95% CI, 1.3 to 4.3; P = .005) after gastrointestinal cancer in participants with YKL-40 category 91% to 100% versus 0% to 33%. CONCLUSION: In the general population, elevated plasma YKL-40 predicts increased risk of gastrointestinal cancer and decreased survival after any cancer diagnosis Udgivelsesdato: 2009/2/1

Published
2009

108. Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease

Author

Frikke-Schmidt, R., Nordestgaard, B.G., Stene, M.C.A., Sethi, A.A., Remaley, A.T., Schnohr, P., Grande, P., Tybjaerg-Hansen, A., Frikke-Schmidt, R., Nordestgaard, B.G., Stene, M.C.A., Sethi, A.A., Remaley, A.T., Schnohr, P., Grande, P., and Tybjaerg-Hansen, A.

Abstract

Context Low levels of high- density lipoprotein ( HDL) cholesterol are inversely related to cardiovascular risk. Whether this is a causal effect is unclear. Objective To determine whether genetically reduced HDL cholesterol due to heterozygosity for 4 loss- of- function mutations in ABCA1 cause increased risk of ischemic heart disease ( IHD). Design, Setting, and Participants Three studies of white individuals from Copenhagen, Denmark, were used: the Copenhagen City Heart Study ( CCHS), a 31-year prospective general population study ( n= 9022; 28 heterozygotes); the Copenhagen General Population Study ( CGPS), a cross- sectional general population study ( n= 31 241; 76 heterozygotes); and the Copenhagen Ischemic Heart Disease Study ( CIHDS), a case- control study ( n= 16 623; 44 heterozygotes). End points in all 3 studies were recorded during the period of January 1, 1976, through July 9, 2007. Main Outcome Measures Levels of HDL cholesterol in the general population, cellular cholesterol efflux, and the association between IHD and HDL cholesterol and genotype. Results Heterozygotes vs noncarriers for 4 ABCA1 mutations ( P1065S, G1216V, N1800H, R2144X) had HDL cholesterol levels of 41 mg/ dL ( interquartile range, 31- 50 mg/ dL) vs 58 mg/ dL ( interquartile range, 46- 73 mg/ dL), corresponding to a reduction in HDL cholesterol of 17 mg/ dL ( P <. 001). A 17- mg/ dL lower HDL cholesterol level in the CCHS was associated with a multifactorially adjusted hazard ratio for IHD of 1.70 ( 95% confidence interval [ CI], 1.57- 1.85). However, for IHD in heterozygotes vs noncarriers, the multifactorially adjusted hazard ratio was 0.67 ( 95% CI, 0.28-1.61; 1741 IHD events) in the CCHS, the multifactorially adjusted odds ratio was 0.82 ( 95% CI, 0.34- 1.96; 2427 IHD events) in the CGPS, and the multifactorially adjusted odds ratio was 0.86 ( 95% CI, 0.32- 2.32; 2498 IHD cases) in the CIHDS. The corresponding odds ratio for IHD in heterozygotes vs noncarriers for the combined

Published
2008

109. Functional promoter variant in zinc finger protein 202 predicts severe atherosclerosis and ischemic heart disease

Author

Frikke-Schmidt, R., Nordestgaard, Børge, Grande, Peer, Tybjærg-Hansen, Anne, Schnohr, Peter, Frikke-Schmidt, R., Nordestgaard, Børge, Grande, Peer, Tybjærg-Hansen, Anne, and Schnohr, Peter

Abstract

Objectives This study was designed to test the hypotheses that single nucleotide polymorphisms ( SNPs), in zinc finger protein 202 ( ZNF202), predict severe atherosclerosis and ischemic heart disease ( IHD). Background ZNF202 is a transcriptional repressor controlling promoter elements in genes involved in vascular maintenance and lipid metabolism. Methods We first determined genotype association for 9 ZNF202 SNPs with severe atherosclerosis ( ankle brachial index >0.7 vs. <= 0.7) in a cross-sectional study of 5,355 individuals from the Danish general population. We then determined genotype association with IHD in 10,431 individuals from the Danish general population, the CCHS ( Copenhagen City Heart Study), including 1,511 incident IHD events during 28 years of follow-up. Results were verified in 2 independent case-control studies including, respectively, 942 and 1,549 cases with IHD and 8,998 controls. Finally, we determined whether g. -660A>G altered transcriptional activity of the ZNF202 promoter in vitro. Results Cross-sectionally, ZNF202 g. -660 GG versus AA homozygosity predicted an odds ratio for severe atherosclerosis of 2.01 ( 95% confidence interval [CI]: 1.34 to 3.01). Prospectively, GG versus AA homozygosity predicted a hazard ratio for IHD of 1.21 ( 95% CI: 1.02 to 1.43). In the 2 case-control studies, the equivalent odds ratios for IHD were 1.29 ( 95% CI: 1.02 to 1.62) and 1.60 ( 95% CI: 1.34 to 1.92), confirming the results from the prospective study. Only 2 other SNPs, which were highly correlated with g. -660A>G, also predicted risk of severe atherosclerosis and IHD. Finally, ZNF202 g. -660G versus g. -660A was associated with a 60% reduction in transcriptional activity in vitro, whereas none of the 2 correlated SNPs were predicted to be functional. Conclusions Homozygosity for a common functional promoter variant in ZNF202 predicts severe atherosclerosis and an increased risk of IHD Udgivelsesdato: 2008/7/29

Published
2008

110. A genome-wide association analysis of high-density lipoprotein cholesterol in the population-based KORA study sheds new light on intergenic regions

Author

Heid, I.M., Boes, E., Mueller, M., Kollerits, B., Lamina, C., Coassin, S., Gieger, C., Doering, A., Klopp, N., Frikke-Schmidt, R., Tybjaerg-Hansen, A., Brandstaetter, A., Luchner, A., Meitinger, T., Wichmann, H.R., Kronenberg, F., Heid, I.M., Boes, E., Mueller, M., Kollerits, B., Lamina, C., Coassin, S., Gieger, C., Doering, A., Klopp, N., Frikke-Schmidt, R., Tybjaerg-Hansen, A., Brandstaetter, A., Luchner, A., Meitinger, T., Wichmann, H.R., and Kronenberg, F.

Abstract

Udgivelsesdato: 2008

Published
2008

111. Levels of apolipoprotein M are not associated with the risk of coronary heart disease in two independent case-control studies

Author

Ahnstrom, J., Axler, O., Jauhiainen, M., Salomaa, V., Havulinna, A.S., Ehnholm, C., Frikke-Schmidt, R., Tybjaerg-Hansen, A., Dahlback, B., Ahnstrom, J., Axler, O., Jauhiainen, M., Salomaa, V., Havulinna, A.S., Ehnholm, C., Frikke-Schmidt, R., Tybjaerg-Hansen, A., and Dahlback, B.

Abstract

Apolipoprotein M (apoM), a 25 kDa plasma protein belonging to the lipocalin protein family, is predominantly associated with HDL. Studies in mice have suggested apoM to be important for the formation of pre-beta-HDL and to increase cholesterol efflux from macrophage foam cells. Overexpression of human apoM in LDL receptor-deficient mice reduced the atherogenic effect of a cholesterol-rich diet. The aim of the present study was to investigate whether the apoM levels in man predict the risk for coronary heart disease (CHD). ApoM was measured in samples from two separate case-control studies. FINRISK '92 consisted of 255 individuals, of whom 80 developed CHD during follow-up and 175 were controls. The Copenhagen City Heart Study included 1,865 individuals, of whom 921 developed CHD during follow-up and 944 were controls. Correlation studies of apoM concentration with several analytes showed a marked positive correlation with HDL and total cholesterol as well as with apoA-I and apoB. There was no significant difference in mean apoM level between CHD and control subjects in either study. In conditional logistic regression analyses, apoM was not a predictor of CHD events, [odds ratio (95% CI) 0.97 (0.74-1.27) and 0.92 (0.84-1.02), respectively]. In conclusion, no association between apoM and CHD could be found in this study Udgivelsesdato: 2008/9

Published
2008

121. Mutation inAPOA1predicts increased risk of ischaemic heart disease and total mortality without low HDL cholesterol levels

Author

Haase, C. L., primary, Frikke-Schmidt, R., additional, Nordestgaard, B. G., additional, Kateifides, A. K., additional, Kardassis, D., additional, Nielsen, L. B., additional, Andersen, C. B., additional, Køber, L., additional, Johnsen, A. H., additional, Grande, P., additional, Zannis, V. I., additional, and Tybjaerg-Hansen, A., additional

Published
2011
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135. ABC transporter genes and risk of type 2 diabetes: a study of 40,000 individuals from the general population.

Author

Schou J, Tybjærg-Hansen A, Møller HJ, Nordestgaard BG, Frikke-Schmidt R, Schou, Jesper, Tybjærg-Hansen, Anne, Møller, Holger J, Nordestgaard, Børge G, and Frikke-Schmidt, Ruth

Abstract

Objective: Alterations of pancreatic β-cell cholesterol content may contribute to β-cell dysfunction. Two important determinants of intracellular cholesterol content are the ATP-binding cassette (ABC) transporters A1 (ABCA1) and -G1 (ABCG1). Whether genetic variation in ABCA1 and ABCG1 predicts risk of type 2 diabetes in the general population is unknown.Research Design and Methods: We tested whether genetic variation in the promoter and coding regions of ABCA1 and ABCG1 predicted risk of type 2 diabetes in the general population. Twenty-seven variants, identified by previous resequencing of both genes, were genotyped in the Copenhagen City Heart Study (CCHS) (n = 10,185). Two loss-of-function mutations (ABCA1 N1800H and ABCG1 g.-376C>T) (n = 322) and a common variant (ABCG1 g.-530A>G) were further genotyped in the Copenhagen General Population Study (CGPS) (n = 30,415).Results: Only one of the variants examined, ABCG1 g.-530A>G, predicted a decreased risk of type 2 diabetes in the CCHS (P for trend = 0.05). Furthermore, when validated in the CGPS or in the CCHS and CGPS combined (n = 40,600), neither the two loss-of-function mutations (ABCA1 N1800H, ABCG1 g.-376C>T) nor ABCG1 g.-530A>G were associated with type 2 diabetes (P values >0.57 and >0.30, respectively).Conclusions: Genetic variations in ABCA1 and ABCG1 were not associated with increased risk of type 2 diabetes in the general population. These data were obtained in general population samples harboring the largest number of heterozygotes for loss-of-function mutations in ABCA1 and ABCG1. [ABSTRACT FROM AUTHOR]

Published
2012
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136. Copy number variation in glutathione-S-transferase T1 and M1 predicts incidence and 5-year survival from prostate and bladder cancer, and incidence of corpus uteri cancer in the general population.

Author

Nørskov, M S, Frikke-Schmidt, R, Bojesen, S E, Nordestgaard, B G, Loft, S, and Tybjærg-Hansen, A

Subjects
*DIAGNOSIS, *PROSTATE cancer, *UTERINE cancer, *GLUTATHIONE, *TRANSFERASES, *BLADDER cancer, *HUMAN genetic variation, *POPULATION, CANCER susceptibility
Abstract

Glutathione-S-transferase T1 (GSTT1) and GSTM1 detoxify carcinogens and thus potentially contribute to inter-individual susceptibility to cancer. We determined the ability of GST copy number variation (CNV) to predict the risk of cancer in the general population. Exact copy numbers of GSTT1 and GSTM1 were measured by real-time PCR in 10 247 individuals, of whom 2090 had cancer. In men, the cumulative incidence of prostate cancer increased and the cumulative 5-year survival decreased with decreasing GSTT1 copy numbers (trends=0.02). The hazard ratios (HRs) (95% CIs) for prostate cancer and for death after prostate cancer diagnosis were, respectively, 1.2 (0.8-1.8) and 1.2 (0.6-2.1) for GSTT1*1/0, and 1.8 (1.1-3.0) and 2.2 (1.1-4.4) for GSTT1*0/0 versus GSTT1*1/1. In women, the cumulative incidence of corpus uteri cancer increased with decreasing GSTT1 copy numbers (trend=0.04). The HRs for corpus uteri cancer were, respectively, 1.8 (1.0-3.2) and 2.2 (1.0-4.6) for GSTT1*1/0 and GSTT1*0/0 versus GSTT1*1/1. Finally, the cumulative incidence of bladder cancer increased, and the cumulative 5-year survival decreased, with decreasing GSTM1 copy numbers (P=0.03-0.05). The HRs for bladder cancer were, respectively, 1.5 (0.7-3.2) and 2.0 (0.9-4.3) for GSTM1*1/0 and GSTM1*0/0 versus GSTM1*1/1. The HR for death after bladder cancer diagnosis was 1.9 (1.0-3.7) for GSTM1*0/0 versus GSTM1*1/0. In conclusion, exact CNV in GSTT1 and GSTM1 predict incidence and 5-year survival from prostate and bladder cancer, and incidence of corpus uteri cancer. [ABSTRACT FROM AUTHOR]

Published
2011
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139. Context-dependent and invariant associations between APOE genotype and levels of lipoproteins and risk of ischemic heart disease: a review.

Author

Frikke-Schmidt, R.

Subjects
*APOLIPOPROTEIN E, *LIPOPROTEINS, *LIGANDS (Biochemistry), *HYPERGLYCEMIA, *CORONARY disease
Abstract

Apolipoprotein E (APOE) plays a pivotal role in the catabolism of triglyceride-rich lipoproteins by serving as a ligand for lipoprotein receptors. The common three-allele (ε2/ε3/ε4) variation in the APOE gene is the most studied susceptibility polymorphism to date, identified in more than 50 different populations worldwide. Differences in the associations between APOE genotype and lipids, lipoproteins, and risk of ischemic heart disease between and within studies have raised the possibility that this gene is expressed in a context-dependent rather than invariant manner. The objective of this review was to focus on studies that in particular yield information about such context-dependent associations of the APOE polymorphism. The well-documented pattern of increasing cholesterol levels from ε2 to ε3 to ε4 seems invariant across different populations; however, the magnitude of this association appears to be modifiable by gender, exogenous estrogens, diet and perhaps by body size. The less pronounced associations between the APOE polymorphism and high-density lipoprotein (HDL) cholesterol and triglycerides appear to differ by gender, to be enhanced by hyperglycemia and alcohol consumption, and abolished by exogenous estrogens in women, thus suggesting strong context dependency. The APOE polymorphism explains more of the variation in levels of cholesterol and apolipoprotein B (APOB) in women than in men, whereas a larger fraction of the variation in triglycerides is explained by the APOE polymorphism in men than in women. Finally, relative to ε33 individuals, ε32 women may be protected while ε43 and ε44 men may be particularly susceptible to ischemic heart disease. In conclusion, differences in magnitude or presence of APOE gene associations across studies or across subgroups within studies appear to be due to the influence of gender, exogenous estrogens, diet, hyperglycemia, alcohol consumption and perhaps body size. Consequently, these contexts should be considered when APOE polymorphism is studied. [ABSTRACT FROM AUTHOR]

Published
2000
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140. THE ASTRUP COMPETITION.

Author

Frikke-Schmidt, R., Noderstgaard, B. G., Schnohr, P., Jensen, G., Steffensen, R., Meinertz, H., Anderholm-Larsen, B., Wittrup, H. H., Tybæg-Hansen, A., Björnsson, B., Blom, Anna M., Villoutreix, B.O., Foltyn-Zadua, A., Berggård, A., Webb, J., Lindahl, G., Dahlback, B., Wan-Ming Zhang, Finne, Patrik, and Leinonen, Jari

Subjects
*APOLIPOPROTEIN E, *GENETICS, *HYDROPHOBIC surfaces
Abstract

Presents summaries of the Astrup Competition in Scandinavia. Effects of apolipoprotein E Genotype; Treatment of hydrophobic membranes with cationic detergents; Regulation of the human complement system through a cluster of charged amino acids.

Published
2000

141. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies

Author

Triglyceride Coronary Disease Genetics Consortium, Emerging Risk Factors Collaboration, Sarwar, N, Sandhu, Ms, Ricketts, Sl, Butterworth, As, Di Angelantonio, E, Boekholdt, Sm, Ouwehand, W, Watkins, H, Samani, Nj, Saleheen, D, Lawlor, D, Reilly, Mp, Hingorani, Ad, Talmud, Pj, Collaborators: Braund PS, Danesh J., Hall, As, Thompson, J, März, W, Sivapalaratnam, S, Soranzo, N, Trip, M, Lawlor, Da, Casas, Jp, Ebrahim, S, Arsenault, Bj, Khaw, Kt, Wareham, Nj, Grallert, H, Illig, T, Humphries, Se, Talmud, T, Rader, Dj, He, J, Clarke, R, Hamsten, A, Hopewell, Jc, Frossard, P, Deloukas, P, Danesh, J, Ye, S, Simpson, Ia, Onat, A, Kömürcü Bayrak, E, Martinelli, Nicola, Olivieri, Oliviero, Girelli, Domenico, Kivimäki, M, Kumari, M, Aouizerat, Be, Baum, L, Campos, H, Chaaba, R, Chen, Bs, Cho, Ey, Evans, D, Hill, J, Hsu, La, Hubacek, Ja, Lai, Cq, Lee, Jh, Klos, K, Liu, H, Masana, L, Melegh, B, Nabika, T, Ribalta, J, Ruiz Narvaez, E, Thomas, Gn, Tomlinson, B, Szalai, C, Vaverkova, H, Yamada, Y, Yang, Y, Tipping, Rw, Ford, Ce, Pressel, Sl, Ballantyne, C, Brautbar, A, Knuiman, M, Whincup, Ph, Wannamethee, Sg, Morris, Rw, Kiechl, S, Willeit, J, Santer, P, Mayr, A, Wald, N, Yarnell, Jw, Gallacher, J, Casiglia, E, Tikhonoff, V, Cushman, M, Psaty, Bm, Tracy, Rp, Tybjaerg Hansen, A, Nordestgaard, Bg, Benn, M, Frikke Schmidt, R, Giampaoli, S, Palmieri, L, Panico, S, Vanuzzo, D, Pilotto, L, de la Cámara AG, Gómez Gerique JA, Simons, L, Mccallum, J, Friedlander, Y, Fowkes, Fg, Lee, Aj, Taylor, J, Guralnik, Jm, Phillips, Cl, Wallace, R, Blazer, Dg, Brenner, H, Raum, E, Müller, H, Rothenbacher, D, Jansson, Jh, Wennberg, P, Nissinen, A, Donfrancesco, C, Salomaa, V, Harald, K, Jousilahti, P, Vartiainen, E, D'Agostino, Rb, Vasan, Rs, Pencina, Mj, Bladbjerg, Em, Jørgensen, T, Møller, L, Jespersen, J, Dankner, R, Chetrit, A, Lubin, F, Björkelund, C, Lissner, L, Bengtsson, C, Cremer, P, Nagel, D, Rodriguez, B, Dekker, Jm, Nijpels, G, Stehouwer, Cd, Sato, S, Iso, H, Kitamura, A, Noda, H, Salonen, Jt, Nyyssönen, K, Tuomainen, Tp, Voutilainen, S, Meade, Tw, Cooper, Ja, Kuller, Lh, Grandits, G, Gillum, R, Mussolino, M, Rimm, E, Hankinson, S, Manson, Ja, Pai, Jk, Bauer, Ka, Naito, Y, Amouyel, P, Arveiler, D, Evans, A, Ferrières, J, Schulte, H, Assmann, G, Packard, Cj, Sattar, N, Westendorp, Rg, Buckley, Bm, Cantin, B, Lamarche, B, Després, Jp, Dagenais, Gr, Barrett Connor, E, Wingard, Dl, Bettencourt, R, Gudnason, V, Aspelund, T, Sigurdsson, G, Thorsson, B, Trevisan, M, Tunstall Pedoe, H, Tavendale, R, Lowe, Gd, Woodward, M, Howard, Bv, Zhang, Y, Best, L, Umans, J, Ben Shlomo, Y, Davey Smith, G, Njølstad, I, Mathiesen, Eb, Løchen, Ml, Wilsgaard, T, Ingelsson, E, Lind, L, Giedraitis, V, Michaëlsson, K, Brunner, E, Shipley, M, Ridker, P, Buring, J, Shepherd, J, Cobbe, Sm, Ford, I, Robertson, M, Ibañez, Am, Feskens, Ej, Kromhout, D, Walker, M, Watson, S, Collins, R, Kaptoge, S, Perry, Pl, Thompson, A, Thompson, Sg, White, Ir, Wood, Am, Danesh, J., ACS - Amsterdam Cardiovascular Sciences, Cardiology, Vascular Medicine, Interne Geneeskunde, MUMC+: MA Interne Geneeskunde (3), RS: CARIM School for Cardiovascular Diseases, Sarwar, N, Sandhu, M, Ricketts, Sl, Butterworth, A, Braund, P, Hall, A, Samani, Nj, Thompson, J, März, W, Ouwehand, W, Sivapalaratnam, S, Soranzo, N, Trip, M, Lawlor, Da, Casas, Jp, Ebrahim, S, Arsenault, Bj, Boekholdt, Sm, Khaw, Kt, Wareham, Nj, Grallert, H, Illig, T, Humphries, Se, Talmud, T, Rader, Dj, He, J, Reilly, Mp, Clarke, R, Hamsten, A, Hopewell, Jc, Watkins, H, Saleheen, D, Frossard, P, Deloukas, P, Danesh, J, Ye, S, Simpson, Ia, Onat, A, Kömürcü Bayrak, E, Martinelli, N, Olivieri, O, Girelli, D, Hingorani, Ad, Kivimäki, M, Kumari, M, Aouizerat, Be, Baum, L, Campos, H, Chaaba, R, Chen, B, Cho, Ey, Evans, D, Hill, J, Hsu, La, Hubacek, Ja, Lai, Cq, Lee, Jh, Klos, K, Liu, H, Masana, L, Melegh, B, Nabika, T, Ribalta, J, Ruiz Narvaez, E, Thomas, Gn, Tomlinson, B, Szalai, C, Vaverkova, H, Yamada, Y, Yang, Y, Kastelein, Jj, Tipping, Rw, Ford, Ce, Pressel, Sl, Ballantyne, C, Brautbar, A, Knuiman, M, Whincup, Ph, Wannamethee, Sg, Morris, Rw, Kiechl, S, Willeit, J, Santer, P, Mayr, A, Wald, N, Yarnell, Jw, Gallacher, J, Casiglia, E, Tikhonoff, V, Cushman, M, Psaty, Bm, Tracy, Rp, Tybjaerg Hansen, A, Nordestgaard, Bg, Benn, M, Frikke Schmidt, R, Giampaoli, S, Palmieri, L, Panico, Salvatore, Vanuzzo, D, Pilotto, L, de la Cámara, Ag, Gómez Gerique, Ja, Simons, L, Mccallum, J, Friedlander, Y, Fowkes, Fg, Lee, Aj, Taylor, J, Guralnik, Jm, Phillips, Cl, Wallace, R, Blazer, Dg, Brenner, H, Raum, E, Müller, H, Rothenbacher, D, Jansson, Jh, Wennberg, P, Nissinen, A, Donfrancesco, C, Salomaa, V, Harald, K, Jousilahti, P, Vartiainen, E, D'Agostino, Rb, Vasan, R, Pencina, Mj, Bladbjerg, Em, Jørgensen, T, Møller, L, Jespersen, J, Dankner, R, Chetrit, A, Lubin, F, Björkelund, C, Lissner, L, Bengtsson, C, Cremer, P, Nagel, D, Rodriguez, B, Dekker, Jm, Nijpels, G, Stehouwer, Cd, Sato, S, Iso, H, Kitamura, A, Noda, H, Salonen, Jt, Nyyssönen, K, Tuomainen, Tp, Voutilainen, S, Meade, Tw, Cooper, Ja, Kuller, Lh, Grandits, G, Gillum, R, Mussolino, M, Rimm, E, Hankinson, S, Manson, Ja, Pai, Jk, Bauer, Ka, Naito, Y, Amouyel, P, Arveiler, D, Evans, A, Ferrières, J, Schulte, H, Assmann, G, Packard, Cj, Sattar, N, Westendorp, Rg, Buckley, Bm, Cantin, B, Lamarche, B, Després, Jp, Dagenais, Gr, Barrett Connor, E, Wingard, Dl, Bettencourt, R, Gudnason, V, Aspelund, T, Sigurdsson, G, Thorsson, B, Trevisan, M, Tunstall Pedoe, H, Tavendale, R, Lowe, Gd, Woodward, M, Howard, Bv, Zhang, Y, Best, L, Umans, J, Ben Shlomo, Y, Davey Smith, G, Njølstad, I, Mathiesen, Eb, Løchen, Ml, Wilsgaard, T, Ingelsson, E, Lind, L, Giedraitis, V, Michaëlsson, K, Brunner, E, Shipley, M, Ridker, P, Buring, J, Shepherd, J, Cobbe, Sm, Ford, I, Robertson, M, Ibañez, Am, Feskens, Ej, Kromhout, D, Walker, M, Watson, S, Collins, R, Di Angelantonio, E, Kaptoge, S, Perry, Pl, Thompson, A, Thompson, Sg, White, Ir, Wood, Am, Lawlor, D, Talmud, Pj, Danesh, J., Epidemiology and Data Science, General practice, and EMGO - Lifestyle, overweight and diabetes

Subjects
Very low-density lipoprotein, Nutrition and Disease, Heart disease, Coronary Disease, Lipoproteins, VLDL, 030204 cardiovascular system & hematology, low-density-lipoprotein apolipoprotein-a-v transfer protein heart-disease myocardial-infarction metabolic syndrome rich lipoproteins risk dyslipidemia association, Bioinformatics, chemistry.chemical_compound, 0302 clinical medicine, triglyceride, APOA5 gene polymorphysm, coronary heart disease, Gene Frequency, Risk Factors, Voeding en Ziekte, Medicine, Myocardial infarction, Promoter Regions, Genetic, risk, 0303 health sciences, Men, Mendelian Randomization Analysis, Articles, General Medicine, Lipids, myocardial-infarction, 3. Good health, Lipoproteins, LDL, Low-density lipoprotein, Lipoproteins, HDL, apolipoprotein-a-v, Receptor, medicine.medical_specialty, Genotype, transfer protein, Snp, Polymorphism, Single Nucleotide, metabolic syndrome, 03 medical and health sciences, Internal medicine, Humans, Particle Size, Apolipoproteins A, Triglycerides, VLAG, 030304 developmental biology, low-density-lipoprotein, Triglyceride, business.industry, dyslipidemia, association, rich lipoproteins, medicine.disease, heart-disease, Apolipoproteins, Endocrinology, chemistry, Apolipoprotein A-V, Metabolic syndrome, business, Dyslipidemia
Abstract

Udgivelsesdato: May-8 BACKGROUND: Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality. METHODS: We assessed the -1131T>C (rs662799) promoter polymorphism of the apolipoprotein A5 (APOA5) gene in relation to triglyceride concentration, several other risk factors, and risk of coronary heart disease. We compared disease risk for genetically-raised triglyceride concentration (20,842 patients with coronary heart disease, 35,206 controls) with that recorded for equivalent differences in circulating triglyceride concentration in prospective studies (302 430 participants with no history of cardiovascular disease; 12,785 incident cases of coronary heart disease during 2.79 million person-years at risk). We analysed -1131T>C in 1795 people without a history of cardiovascular disease who had information about lipoprotein concentration and diameter obtained by nuclear magnetic resonance spectroscopy. FINDINGS: The minor allele frequency of -1131T>C was 8% (95% CI 7-9). -1131T>C was not significantly associated with several non-lipid risk factors or LDL cholesterol, and it was modestly associated with lower HDL cholesterol (mean difference per C allele 3.5% [95% CI 2.6-4.6]; 0.053 mmol/L [0.039-0.068]), lower apolipoprotein AI (1.3% [0.3-2.3]; 0.023 g/L [0.005-0.041]), and higher apolipoprotein B (3.2% [1.3-5.1]; 0.027 g/L [0.011-0.043]). By contrast, for every C allele inherited, mean triglyceride concentration was 16.0% (95% CI 12.9-18.7), or 0.25 mmol/L (0.20-0.29), higher (p=4.4x10(-24)). The odds ratio for coronary heart disease was 1.18 (95% CI 1.11-1.26; p=2.6x10(-7)) per C allele, which was concordant with the hazard ratio of 1.10 (95% CI 1.08-1.12) per 16% higher triglyceride concentration recorded in prospective studies. -1131T>C was significantly associated with higher VLDL particle concentration (mean difference per C allele 12.2 nmol/L [95% CI 7.7-16.7]; p=9.3x10(-8)) and smaller HDL particle size (0.14 nm [0.08-0.20]; p=7.0x10(-5)), factors that could mediate the effects of triglyceride. INTERPRETATION: These data are consistent with a causal association between triglyceride-mediated pathways and coronary heart disease. FUNDING: British Heart Foundation, UK Medical Research Council, Novartis.

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145. APOEgenotype predicts AD and other dementia but not ischemic cerebrovascular disease

Author

Frikke–Schmidt, R., Nordestgaard, B.G., Thudium, D., Moes Grønholdt, M.-L., and Tybjærg–Hansen, A.

Abstract

The APOEpolymorphism is an important modulator of plasma lipoproteins and a risk factor for AD. The hypothesis that APOEgenotype, through its effect on lipoproteins, is a common risk factor for ischemic cerebrovascular disease (ICVD), AD, and other dementia (OD) was tested.

Published
2001

146. Context-dependent and invariant associations between lipids, lipoproteins, and apolipoproteins and apolipoprotein E genotype.

Author

Frikke-Schmidt, R, Nordestgaard, B G, Agerholm-Larsen, B, Schnohr, P, and Tybjaerg-Hansen, A

Abstract

Variation in apolipoprotein (apo)E genotypes predicts variation in plasma cholesterol and apoB; however, the context-dependent associations between high density lipoprotein (HDL) cholesterol, apoA-I, triglycerides, and lipoprotein[a] (Lp[a]) and this polymorphism remain unsettled. We genotyped 5,025 women and 4,035 men sampled to represent a white general population in the age range 20 to 80+ years (mean ages 58 and 57 years for women and men, respectively). The relative frequencies of the varepsilon22, varepsilon32, varepsilon42, varepsilon33, varepsilon43, and varepsilon44 genotypes were 0.005, 0.127, 0.027, 0.564, 0.251, and 0. 027, respectively. Variations in apoE genotype (in the order listed above) predicted stepwise increases in cholesterol and apoB in both genders (all ANOVAs: P < 0.001), and stepwise decreases in HDL cholesterol and apoA-I in women (both ANOVAs: P < 0.001), but not in men. In both genders varepsilon33 individuals had the lowest levels of nonfasting triglycerides, whereas the highest levels were found in individuals with varepsilon22 and varepsilon44 genotypes (both ANOVAs: P < 0.001). Finally, a stepwise increase in Lp[a] was seen in women (ANOVA: P < 0.001), but not in men. In women, the association between variation in nonfasting triglycerides and Lp[a], and variation in apoE genotypes was mainly seen in those with the highest alcohol consumption, similar to the consumption of most men. Variations in apoE genotype predicted 5% and 11% in women, and 2% and 6% in men, of the total variation in plasma cholesterol and apoB, respectively. Variation in levels of plasma lipoproteins is associated with variation in apoE genotypes in the population at large, with the most pronounced association in women, except for nonfasting triglycerides, for which the association is most pronounced in men.Whereas the associations between variation in plasma cholesterol and apoB and the variation in apoE genotypes seem invariant, the associations with variation in plasma HDL cholesterol, apoA-I, nonfasting triglycerides, and Lp[a] seem context dependent.

Published
2000

148. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies

Author

Emerging Risk Factors Collaboration, Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD, Lewington S, Pennells L, Thompson A, Sattar N, White IR, Ray KK, Danesh J. Tipping RW, Ford CE, Pressel SL, Folsom AR, Chambless LE, Wagenknecht LE, Panagiotakos DB, Pitsavos C, Chrysohoou C, Stefanadis C, Knuiman M, Whincup PH, Wannamethee SG, Morris RW, Kiechl S, Willeit J, Oberhollenzer F, Mayr A, Wald N, Ebrahim S, Yarnell JW, Gallacher J, Casiglia E, Tikhonoff V, Nietert PJ, Sutherland SE, Bachman DL, Keil JE, de Boer IH, Kizer JR, Mukamal KJ, Tybjaerg Hansen A, Nordestgaard BG, Benn M, Frikke Schmidt R, Palmieri L, Vanuzzo D, Pilotto L, de la Cámara AG, Rubio MA, Simons L, McCallum J, Friedlander Y, Fowkes FG, Lee AJ, Taylor J, Guralnik JM, Phillips CL, Wallace R, Blazer DG, Khaw KT, Brenner H, Raum E, Müller H, Rothenbacher D, Jansson JH, Wennberg P, Nissinen A, Donfrancesco C, Giampaoli S, Salomaa V, Harald K, Jousilahti P, Vartiainen E, Woodward M, D'Agostino RB, Vasan RS, Fox CS, Pencina MJ, Bladbjerg E, Jørgensen T, Møller L, Jespersen J, Dankner R, Chetrit A, Lubin F, Wilhelmsen L, Eriksson H, Svärdsudd K, Welin L, Rosengren A, Lappas G, Björkelund C, Lissner L, Bengtsson C, Cremer P, Nagel D, Strandberg TE, Tilvis RS, Miettinen TA, Kiyohara Y, Arima H, Doi Y, Ninomiya T, Rodriguez B, Dekker JM, Nijpels G, Rimm E, Pai JK, Sato S, Iso H, Kitamura A, Noda H, Goldbourt U, Nyyssönen K, Tuomainen TP, Salonen JT, Deeg D, Poppelaars JL, Meade TW, Cooper JA, Hedblad B, Berglund G, Engström G, Verschuren WM, Blokstra A, Cushman M, Psaty BM, Shea S, Döring A, Koenig W, Meisinger C, Mraz W, Bueno de Mesquita HB, Fletcher A, Kuller LH, Grandits G, Selmer R, Tverdal A, Nystad W, Gillum R, Mussolino M, Hankinson S, Manson JE, Bauer KA, Davidson KW, Kirkland S, Shaffer J, Korin MR, Holme I, Ducimetiere P, Jouven X, Bakker SJ, Gansevoort RT, Hillege HL, Crespo CJ, Garcia Palmieri MR, Amouyel P, Arveiler D, Evans A, Ferrières J, Schulte H, Assmann G, Westendorp RG, Buckley BM, Packard CJ, Cantin B, Lamarche B, Després JP, Dagenais GR, Barrett Connor E, Wingard DL, Bettencourt R, Gudnason V, Aspelund T, Sigurdsson G, Thorsson B, Trevisan M, Witteman J, Kardys I, Breteler M, Hofman A, Tunstall Pedoe H, Tavendale R, Lowe GD, Howard BV, Zhang Y, Best L, Umans J, Ben Shlomo Y, Davey Smith G, Onat A, Hergenç G, Can G, Njølstad I, Mathiesen EB, Løchen ML, Wilsgaard T, Zethelius B, Risérus U, Berne C, Gaziano JM, Ridker P, Ulmer H, Diem G, Concin H, Tosetto A, Rodeghiero F, Tinker L, Liu S, Marmot IM, Clarke R, Collins R, Brunner E, Shipley M, Buring J, Shepherd J, Cobbe SM, Ford I, Robertson M, Ibañez AM, Feskens EJ, Kromhout D, Walker M, Watson S, Alexander M, Erqou S, Haycock P, Perry PL, Thompson SG, Wood AM, Wormser D, Danesh J., PANICO, SALVATORE, Interne Geneeskunde, RS: NUTRIM - R1 - Metabolic Syndrome, RS: CARIM School for Cardiovascular Diseases, Emerging Risk Factors, Collaboration, Sarwar, N, Gao, P, Seshasai, Sr, Gobin, R, Kaptoge, S, Di Angelantonio, E, Ingelsson, E, Lawlor, Da, Selvin, E, Stampfer, M, Stehouwer, Cd, Lewington, S, Pennells, L, Thompson, A, Sattar, N, White, Ir, Ray, Kk, Danesh J., Tipping RW, Ford, Ce, Pressel, Sl, Folsom, Ar, Chambless, Le, Wagenknecht, Le, Panagiotakos, Db, Pitsavos, C, Chrysohoou, C, Stefanadis, C, Knuiman, M, Whincup, Ph, Wannamethee, Sg, Morris, Rw, Kiechl, S, Willeit, J, Oberhollenzer, F, Mayr, A, Wald, N, Ebrahim, S, Yarnell, Jw, Gallacher, J, Casiglia, E, Tikhonoff, V, Nietert, Pj, Sutherland, Se, Bachman, Dl, Keil, Je, de Boer, Ih, Kizer, Jr, Mukamal, Kj, Tybjaerg Hansen, A, Nordestgaard, Bg, Benn, M, Frikke Schmidt, R, Palmieri, L, Panico, Salvatore, Vanuzzo, D, Pilotto, L, de la Cámara, Ag, Rubio, Ma, Simons, L, Mccallum, J, Friedlander, Y, Fowkes, Fg, Lee, Aj, Taylor, J, Guralnik, Jm, Phillips, Cl, Wallace, R, Blazer, Dg, Khaw, Kt, Brenner, H, Raum, E, Müller, H, Rothenbacher, D, Jansson, Jh, Wennberg, P, Nissinen, A, Donfrancesco, C, Giampaoli, S, Salomaa, V, Harald, K, Jousilahti, P, Vartiainen, E, Woodward, M, D'Agostino, Rb, Vasan, R, Fox, C, Pencina, Mj, Bladbjerg, E, Jørgensen, T, Møller, L, Jespersen, J, Dankner, R, Chetrit, A, Lubin, F, Wilhelmsen, L, Eriksson, H, Svärdsudd, K, Welin, L, Rosengren, A, Lappas, G, Björkelund, C, Lissner, L, Bengtsson, C, Cremer, P, Nagel, D, Strandberg, Te, Tilvis, R, Miettinen, Ta, Kiyohara, Y, Arima, H, Doi, Y, Ninomiya, T, Rodriguez, B, Dekker, Jm, Nijpels, G, Rimm, E, Pai, Jk, Sato, S, Iso, H, Kitamura, A, Noda, H, Goldbourt, U, Nyyssönen, K, Tuomainen, Tp, Salonen, Jt, Deeg, D, Poppelaars, Jl, Meade, Tw, Cooper, Ja, Hedblad, B, Berglund, G, Engström, G, Verschuren, Wm, Blokstra, A, Cushman, M, Psaty, Bm, Shea, S, Döring, A, Koenig, W, Meisinger, C, Mraz, W, Bueno de Mesquita, Hb, Fletcher, A, Kuller, Lh, Grandits, G, Selmer, R, Tverdal, A, Nystad, W, Gillum, R, Mussolino, M, Hankinson, S, Manson, Je, Bauer, Ka, Davidson, Kw, Kirkland, S, Shaffer, J, Korin, Mr, Holme, I, Ducimetiere, P, Jouven, X, Bakker, Sj, Gansevoort, Rt, Hillege, Hl, Crespo, Cj, Garcia Palmieri, Mr, Amouyel, P, Arveiler, D, Evans, A, Ferrières, J, Schulte, H, Assmann, G, Westendorp, Rg, Buckley, Bm, Packard, Cj, Cantin, B, Lamarche, B, Després, Jp, Dagenais, Gr, Barrett Connor, E, Wingard, Dl, Bettencourt, R, Gudnason, V, Aspelund, T, Sigurdsson, G, Thorsson, B, Trevisan, M, Witteman, J, Kardys, I, Breteler, M, Hofman, A, Tunstall Pedoe, H, Tavendale, R, Lowe, Gd, Howard, Bv, Zhang, Y, Best, L, Umans, J, Ben Shlomo, Y, Davey Smith, G, Onat, A, Hergenç, G, Can, G, Njølstad, I, Mathiesen, Eb, Løchen, Ml, Wilsgaard, T, Zethelius, B, Risérus, U, Berne, C, Gaziano, Jm, Ridker, P, Ulmer, H, Diem, G, Concin, H, Tosetto, A, Rodeghiero, F, Tinker, L, Liu, S, Marmot, Im, Clarke, R, Collins, R, Brunner, E, Shipley, M, Buring, J, Shepherd, J, Cobbe, Sm, Ford, I, Robertson, M, Ibañez, Am, Feskens, Ej, Kromhout, D, Walker, M, Watson, S, Alexander, M, Erqou, S, Haycock, P, Perry, Pl, Thompson, Sg, Wood, Am, Wormser, D, Danesh, J., and University of Groningen

Subjects
Adult, Blood Glucose, Male, medicine.medical_specialty, PATHOPHYSIOLOGY, 030209 endocrinology & metabolism, Coronary Disease, Disease, 030204 cardiovascular system & hematology, THERAPY, Diabetes Complications, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Diabetes mellitus, Internal medicine, General & Internal Medicine, medicine, Diabetes Mellitus, Humans, CORONARY-HEART-DISEASE, Prospective cohort study, Stroke, Aged, Glucose Metabolism Disorders, business.industry, Vascular disease, MORTALITY, Absolute risk reduction, ASIA-PACIFIC REGION, WOMEN, General Medicine, Fasting, 11 Medical And Health Sciences, Articles, Middle Aged, medicine.disease, Impaired fasting glucose, 3. Good health, Endocrinology, Blood pressure, ATHEROSCLEROSIS, Cardiovascular Diseases, CARDIOVASCULAR-DISEASES, Female, coronary-heart-disease asia-pacific region cardiovascular-diseases task-force pathophysiology atherosclerosis mortality therapy women, business, TASK-FORCE
Abstract

Summary Background Uncertainties persist about the magnitude of associations of diabetes mellitus and fasting glucose concentration with risk of coronary heart disease and major stroke subtypes. We aimed to quantify these associations for a wide range of circumstances. Methods We undertook a meta-analysis of individual records of diabetes, fasting blood glucose concentration, and other risk factors in people without initial vascular disease from studies in the Emerging Risk Factors Collaboration. We combined within-study regressions that were adjusted for age, sex, smoking, systolic blood pressure, and body-mass index to calculate hazard ratios (HRs) for vascular disease. Findings Analyses included data for 698 782 people (52 765 non-fatal or fatal vascular outcomes; 8·49 million person-years at risk) from 102 prospective studies. Adjusted HRs with diabetes were: 2·00 (95% CI 1·83–2·19) for coronary heart disease; 2·27 (1·95–2·65) for ischaemic stroke; 1·56 (1·19–2·05) for haemorrhagic stroke; 1·84 (1·59–2·13) for unclassified stroke; and 1·73 (1·51–1·98) for the aggregate of other vascular deaths. HRs did not change appreciably after further adjustment for lipid, inflammatory, or renal markers. HRs for coronary heart disease were higher in women than in men, at 40–59 years than at 70 years and older, and with fatal than with non-fatal disease. At an adult population-wide prevalence of 10%, diabetes was estimated to account for 11% (10–12%) of vascular deaths. Fasting blood glucose concentration was non-linearly related to vascular risk, with no significant associations between 3·90 mmol/L and 5·59 mmol/L. Compared with fasting blood glucose concentrations of 3·90–5·59 mmol/L, HRs for coronary heart disease were: 1·07 (0·97–1·18) for lower than 3·90 mmol/L; 1·11 (1·04–1·18) for 5·60–6·09 mmol/L; and 1·17 (1·08–1·26) for 6·10–6·99 mmol/L. In people without a history of diabetes, information about fasting blood glucose concentration or impaired fasting glucose status did not significantly improve metrics of vascular disease prediction when added to information about several conventional risk factors. Interpretation Diabetes confers about a two-fold excess risk for a wide range of vascular diseases, independently from other conventional risk factors. In people without diabetes, fasting blood glucose concentration is modestly and non-linearly associated with risk of vascular disease. Funding British Heart Foundation, UK Medical Research Council, and Pfizer.

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