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51. Consumption of Meat, Fish, Dairy Products, and Eggs and Risk of Ischemic Heart Disease: A Prospective Study of 7198 Incident Cases among 409 885 Participants in the Pan-European EPIC Cohort

Author: Key, T.J. Appleby, P.N. Bradbury, K.E. Sweeting, M. Wood, A. Johansson, I. Kühn, T. Steur, M. Weiderpass, E. Wennberg, M. Lund Würtz, A.M. Agudo, A. Andersson, J. Arriola, L. Boeing, H. Boer, J.M.A. Bonnet, F. Boutron-Ruault, M.-C. Cross, A.J. Ericson, U. Fagherazzi, G. Ferrari, P. Gunter, M. Huerta, J.M. Katzke, V. Khaw, K.-T. Krogh, V. La Vecchia, C. Matullo, G. Moreno-Iribas, C. Naska, A. Nilsson, L.M. Olsen, A. Overvad, K. Palli, D. Panico, S. Molina-Portillo, E. Quirós, J.R. Skeie, G. Sluijs, I. Sonestedt, E. Stepien, M. Tjønneland, A. Trichopoulou, A. Tumino, R. Tzoulaki, I. Van Der Schouw, Y.T. Verschuren, W.M.M. Di Angelantonio, E. Langenberg, C. Forouhi, N. Wareham, N. Butterworth, A. Riboli, E. Danesh, J.
Abstract: Background: There is uncertainty about the relevance of animal foods to the pathogenesis of ischemic heart disease (IHD). We examined meat, fish, dairy products, and eggs and risk for IHD in the pan-European EPIC cohort (European Prospective Investigation Into Cancer and Nutrition). Methods: In this prospective study of 409 885 men and women in 9 European countries, diet was assessed with validated questionnaires and calibrated with 24-hour recalls. Lipids and blood pressure were measured in a subsample. During a mean of 12.6 years of follow-up, 7198 participants had a myocardial infarction or died of IHD. The relationships of animal foods with risk were examined with Cox regression with adjustment for other animal foods and relevant covariates. Results: The hazard ratio (HR) for IHD was 1.19 (95% CI, 1.06-1.33) for a 100-g/d increment in intake of red and processed meat, and this remained significant after exclusion of the first 4 years of follow-up (HR, 1.25 [95% CI, 1.09-1.42]). Risk was inversely associated with intakes of yogurt (HR, 0.93 [95% CI, 0.89-0.98] per 100-g/d increment), cheese (HR, 0.92 [95% CI, 0.86-0.98] per 30-g/d increment), and eggs (HR, 0.93 [95% CI, 0.88-0.99] per 20-g/d increment); the associations with yogurt and eggs were attenuated and nonsignificant after exclusion of the first 4 years of follow-up. Risk was not significantly associated with intakes of poultry, fish, or milk. In analyses modeling dietary substitutions, replacement of 100 kcal/d from red and processed meat with 100 kcal/d from fatty fish, yogurt, cheese, or eggs was associated with ≈20% lower risk of IHD. Consumption of red and processed meat was positively associated with serum non-high-density lipoprotein cholesterol concentration and systolic blood pressure, and consumption of cheese was inversely associated with serum non-high-density lipoprotein cholesterol. Conclusions: Risk for IHD was positively associated with consumption of red and processed meat and inversely associated with consumption of yogurt, cheese, and eggs, although the associations with yogurt and eggs may be influenced by reverse causation bias. It is not clear whether the associations with red and processed meat and cheese reflect causality, but they were consistent with the associations of these foods with plasma non-high-density lipoprotein cholesterol and for red and processed meat with systolic blood pressure, which could mediate such effects. © 2018 American Heart Association, Inc.
Published: 2019

52. A protective role of a cholesteryl ester transfer protein gene variant towards ischaemic stroke in Sardinians

Author: Quarta, G., Stanzione, R., Evangelista, A., Zanda, B., Sciarretta, S., Di Angelantonio, E., Marchitti, S., Di Murro, D., Volpe, M., and Rubattu, S.
Published: 2007

53. Percutaneous coronary intervention in HIV infected patients: immediate results and long term prognosis

Author: Boccara, F, Teiger, E, Cohen, A, Ederhy, S, Janower, S, Odi, G, Di Angelantonio, E, Barbarini, G, and Barbaro, G
Published: 2006

54. Prognostic significance of admission levels of troponin I in patients with acute ischaemic stroke

Author: Di Angelantonio, E, Fiorelli, M, Toni, D, Sacchetti, M L, Lorenzano, S, Falcou, A, Ciarla, M V, Suppa, M, Bonanni, L, Bertazzoni, G, Aguglia, F, and Argentino, C
Published: 2005

55. Lipoprotein signatures of cholesteryl ester transfer protein and HMG-CoA reductase inhibition

Author: Kettunen, J. (Johannes), Holmes, M. V. (Michael V.), Allara, E. (Elias), Anufrieva, O. (Olga), Ohukainen, P. (Pauli), Oliver-Williams, C. (Clare), Wang, Q. (Qin), Tillin, T. (Therese), Hughes, A. D. (Alun D.), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Viikari, J. (Jorma), Raitakari, O. T. (Olli T.), Salomaa, V. (Veikko), Järvelin, M.-R. (Marjo-Riitta), Perola, M. (Markus), Smith, G. D. (George Davey), Chaturvedi, N. (Nish), Danesh, J. (John), Di Angelantonio, E. (Emanuele), Butterworth, A. S. (Adam S.), Ala-Korpela, M. (Mika), Kettunen, J. (Johannes), Holmes, M. V. (Michael V.), Allara, E. (Elias), Anufrieva, O. (Olga), Ohukainen, P. (Pauli), Oliver-Williams, C. (Clare), Wang, Q. (Qin), Tillin, T. (Therese), Hughes, A. D. (Alun D.), Kähönen, M. (Mika), Lehtimäki, T. (Terho), Viikari, J. (Jorma), Raitakari, O. T. (Olli T.), Salomaa, V. (Veikko), Järvelin, M.-R. (Marjo-Riitta), Perola, M. (Markus), Smith, G. D. (George Davey), Chaturvedi, N. (Nish), Danesh, J. (John), Di Angelantonio, E. (Emanuele), Butterworth, A. S. (Adam S.), and Ala-Korpela, M. (Mika)
Abstract: Cholesteryl ester transfer protein (CETP) inhibition reduces vascular event risk, but confusion surrounds its effects on low-density lipoprotein (LDL) cholesterol. Here, we clarify associations of genetic inhibition of CETP on detailed lipoprotein measures and compare those to genetic inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). We used an allele associated with lower CETP expression (rs247617) to mimic CETP inhibition and an allele associated with lower HMGCR expression (rs12916) to mimic the well-known effects of statins for comparison. The study consists of 65,427 participants of European ancestries with detailed lipoprotein subclass profiling from nuclear magnetic resonance spectroscopy. Genetic associations were scaled to 10% reduction in relative risk of coronary heart disease (CHD). We also examined observational associations of the lipoprotein subclass measures with risk of incident CHD in 3 population-based cohorts totalling 616 incident cases and 13,564 controls during 8-year follow-up. Genetic inhibition of CETP and HMGCR resulted in near-identical associations with LDL cholesterol concentration estimated by the Friedewald equation. Inhibition of HMGCR had relatively consistent associations on lower cholesterol concentrations across all apolipoprotein B-containing lipoproteins. In contrast, the associations of the inhibition of CETP were stronger on lower remnant and very-low-density lipoprotein (VLDL) cholesterol, but there were no associations on cholesterol concentrations in LDL defined by particle size (diameter 18–26 nm) (−0.02 SD LDL defined by particle size; 95% CI: −0.10 to 0.05 for CETP versus −0.24 SD, 95% CI −0.30 to −0.18 for HMGCR). Inhibition of CETP was strongly associated with lower proportion of triglycerides in all high-density lipoprotein (HDL) particles. In observational analyses, a higher triglyceride composition within HDL subclasses was associated with higher risk of CHD, independently of total cho
Published: 2019

56. World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions

Author: Di Angelantonio, E, Kaptoge, S, Pennells, L, De Bacquer, D, Cooney, MT, Kavousi, Maryam, Di Angelantonio, E, Kaptoge, S, Pennells, L, De Bacquer, D, Cooney, MT, and Kavousi, Maryam
Published: 2019

57. Cardiovascular Risk Factors Associated With Venous Thromboembolism

Author: Gregson, J, Kaptoge, S, Bolton, T, Pennells, L, Willeit, P, Burgess, S, Kavousi, Maryam, Di Angelantonio, E, Meade, T, Gregson, J, Kaptoge, S, Bolton, T, Pennells, L, Willeit, P, Burgess, S, Kavousi, Maryam, Di Angelantonio, E, and Meade, T
Published: 2019

58. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 26, 2018)

Author: Turcot, V, Lu, Y, Highland, HM, Schurmann, C, Justice, AE, Fine, RS, Bradfield, JP, Esko, T, Giri, A, Graff, M, Guo, X, Hendricks, AE, Karaderi, T, Lempradl, A, Locke, AE, Mahajan, A, Marouli, E, Sivapalaratnam, S, Young, KL, Alfred, T, Feitosa, MF, Masca, NGD, Manning, AK, Medina-Gomez, C, Mudgal, P, Ng, MCY, Reiner, AP, Vedantam, S, Willems, SM, Winkler, TW, Abecasis, G, Aben, KK, Alam, DS, Alharthi, SE, Allison, M, Amouyel, P, Asselbergs, FW, Auer, PL, Balkau, B, Bang, LE, Barroso, I, Bastarache, L, Benn, M, Bergmann, S, Bielak, LF, Bluher, M, Boehnke, M, Boeing, H, Boerwinkle, E, Boger, CA, Bork-Jensen, J, Bots, ML, Bottinger, EP, Bowden, DW, Brandslund, I, Breen, G, Brilliant, MH, Broer, L, Brumat, M, Burt, AA, Butterworth, AS, Campbell, PT, Cappellani, S, Carey, DJ, Catamo, E, Caulfield, MJ, Chambers, JC, Chasman, DI, Chen, Y-DI, Chowdhury, R, Christensen, C, Chu, AY, Cocca, M, Collins, FS, Cook, JP, Corley, J, Galbany, JC, Cox, AJ, Crosslin, DS, Cuellar-Partida, G, D'Eustacchio, A, Danesh, J, Davies, G, Bakker, PIW, Groot, MCH, Mutsert, R, Deary, IJ, Dedoussis, G, Demerath, EW, Heijer, M, Hollander, AI, Ruijter, HM, Dennis, JG, Denny, JC, Di Angelantonio, E, Drenos, F, Du, M, Dube, M-P, Dunning, AM, Easton, DF, Edwards, TL, Ellinghaus, D, Ellinor, PT, Elliott, P, Evangelou, E, Farmaki, A-E, Farooqi, IS, Faul, JD, Fauser, S, Feng, S, Ferrannini, E, Ferrieres, J, Florez, JC, Ford, I, Fornage, M, Franco, OH, Franke, A, Franks, PW, Friedrich, N, Frikke-Schmidt, R, Galesloot, TE, Gan, W, Gandin, I, Gasparini, P, Gibson, J, Giedraitis, V, Gjesing, AP, Gordon-Larsen, P, Gorski, M, Grabe, H-J, Grant, SFA, Grarup, N, Griffiths, HL, Grove, ML, Gudnason, V, Gustafsson, S, Haessler, J, Hakonarson, H, Hammerschlag, AR, Hansen, T, Harris, KM, Harris, TB, Hattersley, AT, Have, CT, Hayward, C, He, L, Heard-Costa, NL, Heath, AC, Heid, IM, Helgeland, O, Hernesniemi, J, Hewitt, AW, Holmen, OL, Hovingh, GK, Howson, JMM, Hu, Y, Huang, PL, Huffman, JE, Ikram, MA, Ingelsson, E, Jackson, AU, Jansson, J-H, Jarvik, GP, Jensen, GB, Jia, Y, Johansson, S, Jorgensen, ME, Jorgensen, T, Jukema, JW, Kahali, B, Kahn, RS, Kahonen, M, Kamstrup, PR, Kanoni, S, Kaprio, J, Karaleftheri, M, Kardia, SLR, Karpe, F, Kathiresan, S, Kee, F, Kiemeney, LA, Kim, E, Kitajima, H, Komulainen, P, Kooner, JS, Kooperberg, C, Korhonen, T, Kovacs, P, Kuivaniemi, H, Kutalik, Z, Kuulasmaa, K, Kuusisto, J, Laakso, M, Lakka, TA, Lamparter, D, Lange, EM, Lange, LA, Langenberg, C, Larson, EB, Lee, NR, Lehtimaki, T, Lewis, CE, Li, H, Li, J, Li-Gao, R, Lin, H, Lin, K-H, Lin, L-A, Lin, X, Lind, L, Lindstrom, J, Linneberg, A, Liu, C-T, Liu, DJ, Liu, Y, Lo, KS, Lophatananon, A, Lotery, AJ, Loukola, A, Luan, J, Lubitz, SA, Lyytikainen, L-P, Mannisto, S, Marenne, G, Mazul, AL, McCarthy, MI, McKean-Cowdin, R, Medland, SE, Meidtner, K, Milani, L, Mistry, V, Mitchell, P, Mohlke, KL, Moilanen, L, Moitry, M, Montgomery, GW, Mook-Kanamori, DO, Moore, C, Mori, TA, Morris, AD, Morris, AP, Mueller-Nurasyid, M, Munroe, PB, Nalls, MA, Narisu, N, Nelson, CP, Neville, M, Nielsen, SF, Nikus, K, Njolstad, PR, Nordestgaard, BG, Nyholt, DR, O'Connel, JR, O'Donoghue, ML, Loohuis, LMO, Ophoff, RA, Owen, KR, Packard, CJ, Padmanabhan, S, Palmer, CNA, Palmer, ND, Pasterkamp, G, Patel, AP, Pattie, A, Pedersen, O, Peissig, PL, Peloso, GM, Pennell, CE, Perola, M, Perry, JA, Perry, JRB, Pers, TH, Person, TN, Peters, A, Petersen, ERB, Peyser, PA, Pirie, A, Polasek, O, Polderman, TJ, Puolijoki, H, Raitakari, OT, Rasheed, A, Rauramaa, R, Reilly, DF, Renstrom, F, Rheinberger, M, Ridker, PM, Rioux, JD, Rivas, MA, Roberts, DJ, Robertson, NR, Robino, A, Rolandsson, O, Rudan, I, Ruth, KS, Saleheen, D, Salomaa, V, Samani, NJ, Sapkota, Y, Sattar, N, Schoen, RE, Schreiner, PJ, Schulze, MB, Scott, RA, Segura-Lepe, MP, Shah, SH, Sheu, WH-H, Sim, X, Slater, AJ, Small, KS, Smith, AV, Southam, L, Spector, TD, Speliotes, EK, Starr, JM, Stefansson, K, Steinthorsdottir, V, Stirrups, KE, Strauch, K, Stringham, HM, Stumvoll, M, Sun, L, Surendran, P, Swift, AJ, Tada, H, Tansey, KE, Tardif, J-C, Taylor, KD, Teumer, A, Thompson, DJ, Thorleifsson, G, Thorsteinsdottir, U, Thuesen, BH, Tonjes, A, Tromp, G, Trompet, S, Tsafantakis, E, Tuomilehto, J, Tybjaerg-Hansen, A, Tyrer, JP, Uher, R, Uitterlinden, AG, Uusitupa, M, Laan, SW, Duijn, CM, Leeuwen, N, van Setten, J, Vanhala, M, Varbo, A, Varga, TV, Varma, R, Edwards, DRV, Vermeulen, SH, Veronesi, G, Vestergaard, H, Vitart, V, Vogt, TF, Volker, U, Vuckovic, D, Wagenknecht, LE, Walker, M, Wallentin, L, Wang, F, Wang, CA, Wang, S, Wang, Y, Ware, EB, Wareham, NJ, Warren, HR, Waterworth, DM, Wessel, J, White, HD, Willer, CJ, Wilson, JG, Witte, DR, Wood, AR, Wu, Y, Yaghootkar, H, Yao, J, Yao, P, Yerges-Armstrong, LM, Young, R, Zeggini, E, Zhan, X, Zhang, W, Zhao, JH, Zhao, W, Zhou, W, Zondervan, KT, Consortium, GG, Rotter, JI, Pospisilik, JA, Rivadeneira, F, Borecki, IB, Deloukas, P, Frayling, TM, Lettre, G, North, KE, Lindgren, CM, Hirschhorn, JN, Loos, RJF, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, and Amsterdam Cardiovascular Sciences
Published: 2018

59. Mid- and Long-Term Health Risks in Living Kidney Donors: A Systematic Review and Meta-analysis

Author: Di Angelantonio, E, Willeit, Peter, Ramond, Anna, Oliver-Williams, Clare, O'Keeffe, Linda, Evans, Jonathan, Di Angelantonio, Emanuele [0000-0001-8776-6719], Ramond, Anna [0000-0002-9958-3693], Oliver-Williams, Clare [0000-0002-3573-2426], and Apollo - University of Cambridge Repository
Subjects: Kidney Disease, Prevention, Renal and urogenital, 32 Biomedical and Clinical Sciences, 3 Good Health and Well Being, Cardiovascular, Kidney, Kidney Transplantation, Postoperative Complications, Clinical Research, Risk Factors, Hypertension, Living Donors, Tissue and Organ Harvesting, Humans, Patient Safety, 3202 Clinical Sciences
Abstract: Background: Long-term health risks for adults who donate kidneys are unclear. Purpose: To summarize evidence about mid- and long-term health risks associated with living kidney donation in adults. Data Sources: PubMed, Embase, Scopus, and PsycINFO without language restriction from April 1964 to July 2017. Study Selection: Observational studies with at least 1 year of follow-up that compared health outcomes in adult living kidney donors versus nondonor populations. Data Extraction: Two investigators independently extracted study data and assessed study quality. Data Synthesis: 52 studies, comprising 118 426 living kidney donors and 117 656 nondonors, were included. Average follow-up was 1 to 24 years. No evidence suggested higher risk for all-cause mortality, cardiovascular disease, hypertension, type 2 diabetes, or adverse psychosocial health outcomes in living kidney donors than in nondonor populations. Donors had higher diastolic blood pressure, lower estimated glomerular filtration rates, and higher risk for end-stage renal disease (ESRD) (relative risk [RR], 8.83 [95% CI, 1.02 to 20.93]) and preeclampsia in female donors (RR, 2.12 [CI, 1.06 to 4.27]). Despite the increased RR, donors had low absolute risk for ESRD (incidence rate, 0.5 event [CI, 0.1 to 4.9 events] per 1000 person-years) and preeclampsia (incidence rate, 5.9 events [CI, 2.9 to 8.9 events] per 100 pregnancies). Limitation: Generalizability was limited by selected control populations, few studies reported pregnancy-related outcomes, and few studies were from low- and middle-income countries. Conclusion: Although living kidney donation is associated with higher RRs for ESRD and preeclampsia, the absolute risk for these outcomes remains low. Compared with nondonor populations, living kidney donors have no increased risk for other major chronic diseases, such as type 2 diabetes, or for adverse psychosocial outcomes.
Published: 2018
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60. Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies

Author: Wood, A.M. Kaptoge, S. Butterworth, A.S. Willeit, P. Warnakula, S. Bolton, T. Paige, E. Paul, D.S. Sweeting, M. Burgess, S. Bell, S. Astle, W. Stevens, D. Koulman, A. Selmer, R.M. Verschuren, W.M.M. Sato, S. Njølstad, I. Woodward, M. Salomaa, V. Nordestgaard, B.G. Yeap, B.B. Fletcher, A. Melander, O. Kuller, L.H. Balkau, B. Marmot, M. Koenig, W. Casiglia, E. Cooper, C. Arndt, V. Franco, O.H. Wennberg, P. Gallacher, J. de la Cámara, A.G. Völzke, H. Dahm, C.C. Dale, C.E. Bergmann, M.M. Crespo, C.J. van der Schouw, Y.T. Kaaks, R. Simons, L.A. Lagiou, P. Schoufour, J.D. Boer, J.M.A. Key, T.J. Rodriguez, B. Moreno-Iribas, C. Davidson, K.W. Taylor, J.O. Sacerdote, C. Wallace, R.B. Quiros, J.R. Tumino, R. Blazer, D.G., II Linneberg, A. Daimon, M. Panico, S. Howard, B. Skeie, G. Strandberg, T. Weiderpass, E. Psaty, B.M. Kromhout, D. Salamanca-Fernandez, E. Kiechl, S. Krumholz, H.M. Grioni, S. Palli, D. Huerta, J.M. Price, J. Sundström, J. Arriola, L. Arima, H. Travis, R.C. Panagiotakos, D.B. Karakatsani, A. Trichopoulou, A. Kühn, T. Grobbee, D.E. Barrett-Connor, E. van Schoor, N. Boeing, H. Overvad, K. Kauhanen, J. Wareham, N. Langenberg, C. Forouhi, N. Wennberg, M. Després, J.-P. Cushman, M. Cooper, J.A. Rodriguez, C.J. Sakurai, M. Shaw, J.E. Knuiman, M. Voortman, T. Meisinger, C. Tjønneland, A. Brenner, H. Palmieri, L. Dallongeville, J. Brunner, E.J. Assmann, G. Trevisan, M. Gillum, R.F. Ford, I.F. Sattar, N. Lazo, M. Thompson, S.G. Ferrari, P. Leon, D.A. Davey Smith, G. Peto, R. Jackson, R. Banks, E. Di Angelantonio, E. Danesh, J. Veikko, S. Gómez de la Cámara, A. Rimm, E.B. Dallongeville, J.-P. Gillumn, R.F. Thompson, S. Emerging Risk Factors Collaboration/EPIC-CVD/UK Biobank Alcohol Study Group
Abstract: Background: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. Methods: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose–response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th–95th percentile 1·04–13·5]) from 71 011 participants from 37 studies. Findings: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10–1·17), coronary disease excluding myocardial infarction (1·06, 1·00–1·11), heart failure (1·09, 1·03–1·15), fatal hypertensive disease (1·24, 1·15–1·33); and fatal aortic aneurysm (1·15, 1·03–1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91–0·97). In comparison to those who reported drinking >0–≤100 g per week, those who reported drinking >100–≤200 g per week, >200–≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1–2 years, or 4–5 years, respectively. Interpretation: In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines. Funding: UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council. © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
Published: 2018

61. Comorbidities to restless legs syndrome - results from the Danish blood donor study

Author: Didriksen, Maria, Hansen, T., Rigas, A.S., Allen, R., Burchell, B., Thørner, Lise Wegner, Nielsen, K, Di Angelantonio, E., Nielsen, M, Jennum, Poul, Werge, Thomas, Erikstrup, Christian, Pedersen, O., Paarup, Helene M., Hjalgrim, Henrik, Bruun, Mie Topholm, Burgdorf, Kristoffer S, Sørensen, E., and Ullum, Henrik
Published: 2017

62. Major lipids, apolipoproteins, and risk of vascular disease

Author: Emerging Risk Factors Collaboration, Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, Wood AM, Lewington S, Sattar N, Packard CJ, Collins R, Thompson SG, Tipping RW, Ford CE, Pressel SL, Walldius G, Jungner I, Folsom AR, Chambless LE, Panagiotakos DB, Pitsavos C, Chrysohoou C, Stefanadis C, Knuiman M, Goldbourt U, Benderly M, Tanne D, Whincup PH, Wannamethee SG, Morris RW, Kiechl S, Willeit J, Santer P, Mayr A, Wald N, Ebrahim S, Lawlor DA, Yarnell JW, Gallacher J, Casiglia E, Tikhonoff V, Nietert PJ, Sutherland SE, Bachman DL, Keil JE, Cushman M, Psaty BM, Tracy RP, Tybjaerg Hansen A, Nordestgaard BG, Benn M, Frikke Schmidt R, Giampaoli S, Palmieri L, Vanuzzo D, Pilotto L, Gómez de la Cámara A, Gómez Gerique JA, Simons L, McCallum J, Friedlander Y, Fowkes FG, Lee AJ, Smith FB, Taylor J, Guralnik JM, Phillips CL, Wallace R, Guralnik J, Blazer DG, Khaw KT, Brenner H, Raum E, Müller H, Rothenbacher D, Jansson JH, Wennberg P, Nissinen A, Donfrancesco C, Salomaa V, Harald K, Jousilahti P, Vartiainen E, Woodward M, D'Agostino RB, Wolf PA, Vasan RS, Pencina MJ, Bladbjerg EM, Jørgensen T, Møller L, Jespersen J, Dankner R, Chetrit A, Lubin F, Rosengren A, Wilhelmsen L, Lappas G, Eriksson H, Björkelund C, Lissner L, Bengtsson C, Cremer P, Nagel D, Tilvis RS, Strandberg TE, Rodriguez B, Dekker JM, Nijpels G, Stehouwer CD, Rimm E, Pai JK, Sato S, Iso H, Kitamura A, Noda H, Salonen JT, Nyyssönen K, Tuomainen TP, Deeg DJ, Poppelaars JL, Meade TW, Cooper JA, Hedblad B, Berglund G, Engstrom G, Verschuren WM, Blokstra A, Döring A, Koenig W, Meisinger C, Mraz W, Verschure WM, Bas Bueno de Mesquita H, Kuller LH, Grandits G, Selmer R, Tverdal A, Nystad W, Gillum R, Mussolino M, Hankinson S, Manson J, Knottenbelt C, Bauer KA, Naito Y, Holme I, Nakagawa H, Miura K, Ducimetiere P, Jouven X, Crespo CJ, Garcia Palmieri MR, Amouyel P, Arveiler D, Evans A, Ferrieres J, Schulte H, Assmann G, Shepherd J, Ford I, 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, Njølstad I, Mathiesen EB, Løchen ML, Wilsgaard T, Ingelsson E, Lind L, Giedraitis V, Lannfelt L, Gaziano JM, Stampfer M, Ridker P, Ulmer H, Diem G, Concin H, Tosetto A, Rodeghiero F, Marmot M, Clarke R, Fletcher A, Brunner E, Shipley M, Buring J, Cobbe SM, Robertson M, He Y, Marin Ibañez A, Feskens EJ, Kromhout D, Walker M, Watson S, Erqou S, Orfei L, Pennells L, Perry PL, Alexander M, Wensley F, White IR, Danesh J., PANICO, SALVATORE, Developmental Genetics, EMGO+ - Lifestyle, Overweight and Diabetes, Epidemiology and Data Science, General practice, Psychiatry, EMGO - Lifestyle, overweight and diabetes, Emerging Risk Factors, Collaboration, Di Angelantonio, E, Sarwar, N, Perry, P, Kaptoge, S, Ray, Kk, Thompson, A, Wood, Am, Lewington, S, Sattar, N, Packard, Cj, Collins, R, Thompson, Sg, Tipping, Rw, Ford, Ce, Pressel, Sl, Walldius, G, Jungner, I, Folsom, Ar, Chambless, Le, Panagiotakos, Db, Pitsavos, C, Chrysohoou, C, Stefanadis, C, Knuiman, M, Goldbourt, U, Benderly, M, Tanne, D, Whincup, Ph, Wannamethee, Sg, Morris, Rw, Kiechl, S, Willeit, J, Santer, P, Mayr, A, Wald, N, Ebrahim, S, Lawlor, Da, Yarnell, Jw, Gallacher, J, Casiglia, E, Tikhonoff, V, Nietert, Pj, Sutherland, Se, Bachman, Dl, Keil, Je, 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, Gómez de la Cámara, A, Gómez Gerique, Ja, Simons, L, Mccallum, J, Friedlander, Y, Fowkes, Fg, Lee, Aj, Smith, Fb, Taylor, J, Guralnik, Jm, Phillips, Cl, Wallace, R, Guralnik, J, Blazer, Dg, Khaw, Kt, Brenner, H, Raum, E, Müller, H, Rothenbacher, D, Jansson, Jh, Wennberg, P, Nissinen, A, Donfrancesco, C, Salomaa, V, Harald, K, Jousilahti, P, Vartiainen, E, Woodward, M, D'Agostino, Rb, Wolf, Pa, Vasan, R, Pencina, Mj, Bladbjerg, Em, Jørgensen, T, Møller, L, Jespersen, J, Dankner, R, Chetrit, A, Lubin, F, Rosengren, A, Wilhelmsen, L, Lappas, G, Eriksson, H, Björkelund, C, Lissner, L, Bengtsson, C, Cremer, P, Nagel, D, Tilvis, R, Strandberg, Te, Rodriguez, B, Dekker, Jm, Nijpels, G, Stehouwer, Cd, Rimm, E, Pai, Jk, Sato, S, Iso, H, Kitamura, A, Noda, H, Salonen, Jt, Nyyssönen, K, Tuomainen, Tp, Deeg, Dj, Poppelaars, Jl, Meade, Tw, Cooper, Ja, Hedblad, B, Berglund, G, Engstrom, G, Verschuren, Wm, Blokstra, A, Döring, A, Koenig, W, Meisinger, C, Mraz, W, Verschure, Wm, Bas Bueno de Mesquita, H, Kuller, Lh, Grandits, G, Selmer, R, Tverdal, A, Nystad, W, Gillum, R, Mussolino, M, Hankinson, S, Manson, J, Knottenbelt, C, Bauer, Ka, Naito, Y, Holme, I, Nakagawa, H, Miura, K, Ducimetiere, P, Jouven, X, Crespo, Cj, Garcia Palmieri, Mr, Amouyel, P, Arveiler, D, Evans, A, Ferrieres, J, Schulte, H, Assmann, G, Shepherd, J, Ford, I, 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, Njølstad, I, Mathiesen, Eb, Løchen, Ml, Wilsgaard, T, Ingelsson, E, Lind, L, Giedraitis, V, Lannfelt, L, Gaziano, Jm, Stampfer, M, Ridker, P, Ulmer, H, Diem, G, Concin, H, Tosetto, A, Rodeghiero, F, Marmot, M, Clarke, R, Fletcher, A, Brunner, E, Shipley, M, Buring, J, Cobbe, Sm, Robertson, M, He, Y, Marin Ibañez, A, Feskens, Ej, Kromhout, D, Walker, M, Watson, S, Erqou, S, Orfei, L, Pennells, L, Perry, Pl, Alexander, M, Wensley, F, White, Ir, and Danesh, J.
Subjects: medicine.medical_specialty, Apolipoprotein B, biology, Triglyceride, business.industry, Vascular disease, Cholesterol, Proportional hazards model, Hazard ratio, Context (language use), General Medicine, 11 Medical And Health Sciences, medicine.disease, Gastroenterology, Article, chemistry.chemical_compound, Endocrinology, chemistry, Internal medicine, General & Internal Medicine, biology.protein, Medicine, lipids (amino acids, peptides, and proteins), Myocardial infarction, business
Abstract: Udgivelsesdato: 2009-Nov-11 CONTEXT: Associations of major lipids and apolipoproteins with the risk of vascular disease have not been reliably quantified. OBJECTIVE: To assess major lipids and apolipoproteins in vascular risk. DESIGN, SETTING, AND PARTICIPANTS: Individual records were supplied on 302,430 people without initial vascular disease from 68 long-term prospective studies, mostly in Europe and North America. During 2.79 million person-years of follow-up, there were 8857 nonfatal myocardial infarctions, 3928 coronary heart disease [CHD] deaths, 2534 ischemic strokes, 513 hemorrhagic strokes, and 2536 unclassified strokes. MAIN OUTCOME MEASURES: Hazard ratios (HRs), adjusted for several conventional factors, were calculated for 1-SD higher values: 0.52 log(e) triglyceride, 15 mg/dL high-density lipoprotein cholesterol (HDL-C), 43 mg/dL non-HDL-C, 29 mg/dL apolipoprotein AI, 29 mg/dL apolipoprotein B, and 33 mg/dL directly measured low-density lipoprotein cholesterol (LDL-C). Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. RESULTS: The rates of CHD per 1000 person-years in the bottom and top thirds of baseline lipid distributions, respectively, were 2.6 and 6.2 with triglyceride, 6.4 and 2.4 with HDL-C, and 2.3 and 6.7 with non-HDL-C. Adjusted HRs for CHD were 0.99 (95% CI, 0.94-1.05) with triglyceride, 0.78 (95% CI, 0.74-0.82) with HDL-C, and 1.50 (95% CI, 1.39-1.61) with non-HDL-C. Hazard ratios were at least as strong in participants who did not fast as in those who did. The HR for CHD was 0.35 (95% CI, 0.30-0.42) with a combination of 80 mg/dL lower non-HDL-C and 15 mg/dL higher HDL-C. For the subset with apolipoproteins or directly measured LDL-C, HRs were 1.50 (95% CI, 1.38-1.62) with the ratio non-HDL-C/HDL-C, 1.49 (95% CI, 1.39-1.60) with the ratio apo B/apo AI, 1.42 (95% CI, 1.06-1.91) with non-HDL-C, and 1.38 (95% CI, 1.09-1.73) with directly measured LDL-C. Hazard ratios for ischemic stroke were 1.02 (95% CI, 0.94-1.11) with triglyceride, 0.93 (95% CI, 0.84-1.02) with HDL-C, and 1.12 (95% CI, 1.04-1.20) with non-HDL-C. CONCLUSION: Lipid assessment in vascular disease can be simplified by measurement of either total and HDL cholesterol levels or apolipoproteins without the need to fast and without regard to triglyceride.
Published: 2016

63. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease

Author: Zanoni, P., Khetarpal, S.A., Larach, D.B., Hancock-Cerutti, W.F., Millar, J.S., Cuchel, M., Derohannessian, S.L., Kontush, A., Surendran, P., Saleheen, D., Trompet, S., Jukema, J.W., de Craen, A.J., Deloukas, P., Sattar, N., Ford, I., Packard, C., Al Shafi Majumder, A., Alam, D.S., di Angelantonio, E., Abecasis, G., Chowdhury, R., Erdmann, J., Nørdestgaard, B.G., Nielsen, S.F., Tybjærg-Hansen, A., Schmidt, R.F., Kuulasmaa, K., Liu, D.J., Perola, M., Blankenberg, S., Salomaa, V., Männistö, S., Amouyel, P., Arveiler, D., Ferrieres, J., Müller-Nurasyid, M., Ferrario, M., Kee, F., Willer, C.J., Samani, N., Schunkert, H., Butterworth, A.S., Howson, J.M.M., Peloso, G.M., Stitziel, N.O., Danesh, J., Kathiresan, S., Rader, D.J., CHD Exome Consortium (), CARDIoGRAM Exome Consortium (), Global Lipids Genetics Consortium (), CHD Exome+ Consortium, CARDIoGRAM Exome Consortium, Global Lipids Genetics Consortium, Watson, S., Schmidt, E.M., Sengupta, S., Gustafsson, S., Kanoni, S., Ganna, A., Chen, J., Buchkovich, M.L., Mora, S., Beckmann, J.S., Bragg-Gresham, J.L., Chang, H.Y., Demirkan, A., Den Hertog, H.M., Do, R., Donnelly, L.A., Ehret, G.B., Esko, T., Feitosa, M.F., Ferreira, T., Fischer, K., Fontanillas, P., Fraser, R.M., Freitag, D.F., Gurdasani, D., Heikkilä, K., Hyppönen, E., Isaacs, A., Jackson, A.U., Johansson, Å., Johnson, T., Kaakinen, M., Kettunen, J., Kleber, M.E., Li, X., Luan, J., Lyytikäinen, L.P., Magnusson, P.K., Mangino, M., Mihailov, E., Montasser, M.E., Nolte, I.M., O'Connell, J.R., Palmer, C.D., Petersen, A.K., Sanna, S., Saxena, R., Service, S.K., Shah, S., Shungin, D., Sidore, C., Song, C., Strawbridge, R.J., Surakka, I., Tanaka, T., Teslovich, T.M., Thorleifsson, G., Van den Herik, E.G., Voight, B.F., Volcik, K.A., Waite, L.L., Wong, A., Wu, Y., Zhang, W., Absher, D., Asiki, G., Barroso, I., Been, L.F., Bolton, J.L., Bonnycastle, L.L., Brambilla, P., Burnett, M.S., Cesana, G., Dimitriou, M., Doney, A.S., Döring, A., Elliott, P., Epstein, S.E., Eyjolfsson, G.I., Gigante, B., Goodarzi, M.O., Grallert, H., Gravito, M.L., Groves, C.J., Hallmans, G., Hartikainen, A.L., Hayward, C., Hernandez, D., Hicks, A.A., Holm, H., Hung, Y.J., Illig, T., Jones, M.R., Kaleebu, P., Kastelein, J.J., Khaw, K.T., Kim, E., Klopp, N., Komulainen, P., Kumari, M., Langenberg, C., Lehtimäki, T., Lin, S.Y., Lindström, J., Loos, R.J., Mach, F., McArdle, W.L., Meisinger, C., Mitchell, B.D., Müller, G., Nagaraja, R., Narisu, N., Nieminen, T.V., Nsubuga, R.N., Olafsson, I., Ong, K.K., Palotie, A., Papamarkou, T., Pomilla, C., Pouta, A., Reilly, M.P., Ridker, P.M., Rivadeneira, F., Rudan, I., Ruokonen, A., Scharnagl, H., Seeley, J., Silander, K., Stancáková, A., Stirrups, K., Swift, A.J., Tiret, L., Uitterlinden, A.G., van Pelt, L.J., Vedantam, S., Wainwright, N., Wijmenga, C., Wild, S.H., Willemsen, G., Wilsgaard, T., Wilson, J.F., Young, E.H., Zhao, J.H., Adair, L.S., Arveiler, D., Assimes, T.L., Bandinelli, S., Bennett, F., Bochud, M., Boehm, B.O., Boomsma, D.I., Borecki, I.B., Bornstein, S.R., Bovet, P., Burnier, M., Campbell, H., Chakravarti, A., Chambers, J.C., Chen, Y.D., Collins, F.S., Cooper, R.S., Dedoussis, G., de Faire, U., Feranil, A.B., Ferrucci, L., Freimer, N.B., Gieger, C., Groop, L.C., Gudnason, V., Gyllensten, U., Hamsten, A., Harris, T.B., Hingorani, A., Hirschhorn, J.N., Hofman, A., Hovingh, G.K., Hsiung, C.A., Humphries, S.E., Hunt, S.C., Hveem, K., Iribarren, C., Järvelin, M.R., Jula, A., Kähönen, M., Kaprio, J., Kesäniemi, A., Kivimaki, M., Kooner, J.S., Koudstaal, P.J., Krauss, R.M., Kuh, D., Kuusisto, J., Kyvik, K.O., Laakso, M., Lakka, T.A., Lind, L., Lindgren, C.M., Martin, N.G., März, W., McCarthy, M.I., McKenzie, C.A., Meneton, P., Metspalu, A., Moilanen, L., Morris, A.D., Munroe, P.B., Njølstad, I., Pedersen, N.L., Power, C., Pramstaller, P.P., Price, J.F., Psaty, B.M., Quertermous, T., Rauramaa, R., Salomaa, V., Sanghera, D.K., Saramies, J., Schwarz, P.E., Sheu, W.H., Shuldiner, A.R., Siegbahn, A., Spector, T.D., Stefansson, K., Strachan, D.P., Tayo, B.O., Tremoli, E., Tuomilehto, J., Uusitupa, M., van Duijn, C.M., Vollenweider, P., Wallentin, L., Wareham, N.J., Whitfield, J.B., Wolffenbuttel, B.H., Ordovas, J.M., Boerwinkle, E., Palmer, C.N., Thorsteinsdottir, U., Chasman, D.I., Rotter, J.I., Franks, P.W., Riatti, S., Cupples, L.A., Sandhu, M.S., Rich, S.S., Boehnke, M., Deloukas, P., Mohlke, K.L., Ingelsson, E., Gu, D., Roberts, R., Watkins, H., Blankenberg, S., Clarke, R., Collins, R., Kim, B.J., McPherson, R., Nieminen, M.S., O'Donnell, C., Schreiber, S., Zalloua, P.A., Zanoni, P, Khetarpal, SA, Larach, DB, Hancock-Cerutti, WF, Rader, DJ, Hypponen, Elina, Biological Psychology, Khetarpal, S, Larach, D, Hancock Cerutti, W, Millar, J, Cuchel, M, Derohannessian, S, Kontush, A, Surendran, P, Saleheen, D, Trompet, S, Wouter Jukema, J, De Craen, A, Deloukas, P, Sattar, N, Ford, I, Packard, C, Majumder, A, Alam, D, Di Angelantonio, E, Abecasis, G, Chowdhury, R, Erdmann, J, Nordestgaard, B, Nielsen, S, Tybjærg Hansen, A, Ruth Frikke Schmidt, N, Kuulasmaa, K, Liu, D, Perola, M, Blankenberg, S, Salomaa, V, Männistö, S, Amouyel, P, Arveiler, D, Ferrieres, J, Möller Nurasyid, M, Ferrario, M, Kee, F, Willer, C, Samani, N, Schunkert, H, Butterworth, A, Howson, J, Peloso, G, Stitziel, N, Danesh, J, Kathiresan, S, Rader, D, Brambilla, P, ACS - Amsterdam Cardiovascular Sciences, and Vascular Medicine
Subjects: Netherlands Twin Register (NTR), 0301 basic medicine, Male, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Scavenger Receptors, DNA Mutational Analysis, Coronary Disease, 030204 cardiovascular system & hematology, scavenger receptor, chemistry.chemical_compound, Mice, 0302 clinical medicine, High-density lipoprotein, Receptor, increased atherosclerosis, levels of plasma, Multidisciplinary, Medicine (all), Homozygote, Scavenger Receptors, Class B, Middle Aged, 3. Good health, Cholesterol, Knockout mouse, Female, lipids (amino acids, peptides, and proteins), Human, Risk, medicine.medical_specialty, Heterozygote, HDL, Proline, Aged, Amino Acid Substitution, Animals, Cholesterol, HDL, Genetic Variation, Humans, Leucine, Protein Processing, Post-Translational, Article, DNA Mutational Analysi, Cholesterol, HDL/blood, Coronary Disease/blood, Coronary Disease/genetics, Leucine/genetics, Proline/genetics, Scavenger Receptors, Class B/genetics, Scavenger Receptors, Class B/metabolism, 03 medical and health sciences, Internal medicine, medicine, Scavenger receptor, Protein Processing, Animal, business.industry, Post-Translational, Heterozygote advantage, SCARB1, 030104 developmental biology, Endocrinology, chemistry, Class B, business, Lipoprotein
Abstract: Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a lossof-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant). Zanoni P, Khetarpal SA, Larach DB, Hancock-Cerutti WF, Millar JS, Cuchel M, DerOhannessian S, Kontush A, Surendran P, Saleheen D, Trompet S, Jukema JW, De Craen A, Deloukas P, Sattar N, Ford I, Packard C, Majumder Aa, Alam DS, Di Angelantonio E, Science (New York, N.Y.), 2016, vol. 351, no. 6278, pp. 1166-1171, 2016 Refereed/Peer-reviewed
Published: 2016

64. Genomic Risk Prediction of Coronary Artery Disease in 480,000 Adults Implications for Primary Prevention

Author: Inouye, M, Abraham, G, Nelson, CP, Wood, AM, Sweeting, MJ, Dudbridge, F, Lai, FY, Kaptoge, S, Brozynska, M, Wang, T, Ye, S, Webb, TR, Rutter, MK, Tzoulaki, I, Patel, RS, Loos, RJF, Keavney, B, Hemingway, H, Thompson, J, Watkins, H, Deloukas, P, Di Angelantonio, E, Butterworth, AS, Danesh, J, Samani, NJ, Inouye, M, Abraham, G, Nelson, CP, Wood, AM, Sweeting, MJ, Dudbridge, F, Lai, FY, Kaptoge, S, Brozynska, M, Wang, T, Ye, S, Webb, TR, Rutter, MK, Tzoulaki, I, Patel, RS, Loos, RJF, Keavney, B, Hemingway, H, Thompson, J, Watkins, H, Deloukas, P, Di Angelantonio, E, Butterworth, AS, Danesh, J, and Samani, NJ
Abstract: BACKGROUND: Coronary artery disease (CAD) has substantial heritability and a polygenic architecture. However, the potential of genomic risk scores to help predict CAD outcomes has not been evaluated comprehensively, because available studies have involved limited genomic scope and limited sample sizes. OBJECTIVES: This study sought to construct a genomic risk score for CAD and to estimate its potential as a screening tool for primary prevention. METHODS: Using a meta-analytic approach to combine large-scale, genome-wide, and targeted genetic association data, we developed a new genomic risk score for CAD (metaGRS) consisting of 1.7 million genetic variants. We externally tested metaGRS, both by itself and in combination with available data on conventional risk factors, in 22,242 CAD cases and 460,387 noncases from the UK Biobank. RESULTS: The hazard ratio (HR) for CAD was 1.71 (95% confidence interval [CI]: 1.68 to 1.73) per SD increase in metaGRS, an association larger than any other externally tested genetic risk score previously published. The metaGRS stratified individuals into significantly different life course trajectories of CAD risk, with those in the top 20% of metaGRS distribution having an HR of 4.17 (95% CI: 3.97 to 4.38) compared with those in the bottom 20%. The corresponding HR was 2.83 (95% CI: 2.61 to 3.07) among individuals on lipid-lowering or antihypertensive medications. The metaGRS had a higher C-index (C = 0.623; 95% CI: 0.615 to 0.631) for incident CAD than any of 6 conventional factors (smoking, diabetes, hypertension, body mass index, self-reported high cholesterol, and family history). For men in the top 20% of metaGRS with >2 conventional factors, 10% cumulative risk of CAD was reached by 48 years of age. CONCLUSIONS: The genomic score developed and evaluated here substantially advances the concept of using genomic information to stratify individuals with different trajectories of CAD risk and highlights the potential for genomic screeni
Published: 2018

65. Risk thresholds for alcohol consumption:combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies

Author: Wood, A. M. (Angela M.), Kaptoge, S. (Stephen), Butterworth, A. S. (Adam S.), Willeit, P. (Peter), Warnakula, S. (Samantha), Bolton, T. (Thomas), Paige, E. (Ellie), Paul, D. S. (Dirk S.), Sweeting, M. (Michael), Burgess, S. (Stephen), Bell, S. (Steven), Astle, W. (William), Stevens, D. (David), Koulman, A. (Albert), Selmer, R. M. (Randi M.), Verschuren, W. M. (W. M. Monique), Sato, S. (Shinichi), Njolstad, I. (Inger), Woodward, M. (Mark), Salomaa, V. (Veikko), Nordestgaard, B. G. (Borge G.), Yeap, B. B. (Bu B.), Fletcher, A. (Astrid), Melander, O. (Olle), Kuller, L. H. (Lewis H.), Balkau, B. (Beverley), Marmot, M. (Michael), Koenig, W. (Wolfgang), Casiglia, E. (Edoardo), Cooper, C. (Cyrus), Arndt, V. (Volker), Franco, O. H. (Oscar H.), Wennberg, P. (Patrik), Gallacher, J. (John), de la Camara, A. G. (Agustin Gomez), Volzke, H. (Henry), Dahm, C. C. (Christina C.), Dale, C. E. (Caroline E.), Bergmann, M. M. (Manuela M.), Crespo, C. J. (Carlos J.), van der Schouw, Y. T. (Yvonne T.), Kaaks, R. (Rudolf), Simons, L. A. (Leon A.), Lagiou, P. (Pagona), Schoufour, J. D. (Josje D.), Boer, J. M. (Jolanda M. A.), Key, T. J. (Timothy J.), Rodriguez, B. (Beatriz), Moreno-Iribas, C. (Conchi), Davidson, K. W. (Karina W.), Taylor, J. O. (James O.), Sacerdote, C. (Carlotta), Wallace, R. B. (Robert B.), Quiros, J. R. (J. Ramon), Tumino, R. (Rosario), Blazer, D. G. (Dan G., II), Linneberg, A. (Allan), Daimon, M. (Makoto), Panico, S. (Salvatore), Howard, B. (Barbara), Skeie, G. (Guri), Strandberg, T. (Timo), Weiderpass, E. (Elisabete), Nietert, P. J. (Paul J.), Psaty, B. M. (Bruce M.), Kromhout, D. (Daan), Salamanca-Fernandez, E. (Elena), Kiechl, S. (Stefan), Krumholz, H. M. (Harlan M.), Grioni, S. (Sara), Palli, D. (Domenico), Huerta, J. M. (Jose M.), Price, J. (Jackie), Sundstrom, J. (Johan), Arriola, L. (Larraitz), Arima, H. (Hisatomi), Travis, R. C. (Ruth C.), Panagiotakos, D. B. (Demosthenes B.), Karakatsani, A. (Anna), Trichopoulou, A. (Antonia), Kuhn, T. (Tilman), Grobbee, D. E. (Diederick E.), Barrett-Connor, E. (Elizabeth), van Schoor, N. (Natasja), Boeing, H. (Heiner), Overvad, K. (Kim), Kauhanen, J. (Jussi), Wareham, N. (Nick), Langenberg, C. (Claudia), Forouhi, N. (Nita), Wennberg, M. (Maria), Despres, J.-P. (Jean-Pierre), Cushman, M. (Mary), Cooper, J. A. (Jackie A.), Rodriguez, C. J. (Carlos J.), Sakurai, M. (Masaru), Shaw, J. E. (Jonathan E.), Knuiman, M. (Matthew), Voortman, T. (Trudy), Meisinger, C. (Christa), Tjonneland, A. (Anne), Brenner, H. (Hermann), Palmieri, L. (Luigi), Dallongeville, J. (Jean), Brunner, E. J. (Eric J.), Assmann, G. (Gerd), Trevisan, M. (Maurizio), Gillum, R. F. (Richard F.), Ford, I. (Ian), Sattar, N. (Naveed), Lazo, M. (Mariana), Thompson, S. G. (Simon G.), Ferrari, P. (Pietro), Leon, D. A. (David A.), Smith, G. D. (George Davey), Peto, R. (Richard), Jackson, R. (Rod), Banks, E. (Emily), Di Angelantonio, E. (Emanuele), Danesh, J. (John), Wood, A. M. (Angela M.), Kaptoge, S. (Stephen), Butterworth, A. S. (Adam S.), Willeit, P. (Peter), Warnakula, S. (Samantha), Bolton, T. (Thomas), Paige, E. (Ellie), Paul, D. S. (Dirk S.), Sweeting, M. (Michael), Burgess, S. (Stephen), Bell, S. (Steven), Astle, W. (William), Stevens, D. (David), Koulman, A. (Albert), Selmer, R. M. (Randi M.), Verschuren, W. M. (W. M. Monique), Sato, S. (Shinichi), Njolstad, I. (Inger), Woodward, M. (Mark), Salomaa, V. (Veikko), Nordestgaard, B. G. (Borge G.), Yeap, B. B. (Bu B.), Fletcher, A. (Astrid), Melander, O. (Olle), Kuller, L. H. (Lewis H.), Balkau, B. (Beverley), Marmot, M. (Michael), Koenig, W. (Wolfgang), Casiglia, E. (Edoardo), Cooper, C. (Cyrus), Arndt, V. (Volker), Franco, O. H. (Oscar H.), Wennberg, P. (Patrik), Gallacher, J. (John), de la Camara, A. G. (Agustin Gomez), Volzke, H. (Henry), Dahm, C. C. (Christina C.), Dale, C. E. (Caroline E.), Bergmann, M. M. (Manuela M.), Crespo, C. J. (Carlos J.), van der Schouw, Y. T. (Yvonne T.), Kaaks, R. (Rudolf), Simons, L. A. (Leon A.), Lagiou, P. (Pagona), Schoufour, J. D. (Josje D.), Boer, J. M. (Jolanda M. A.), Key, T. J. (Timothy J.), Rodriguez, B. (Beatriz), Moreno-Iribas, C. (Conchi), Davidson, K. W. (Karina W.), Taylor, J. O. (James O.), Sacerdote, C. (Carlotta), Wallace, R. B. (Robert B.), Quiros, J. R. (J. Ramon), Tumino, R. (Rosario), Blazer, D. G. (Dan G., II), Linneberg, A. (Allan), Daimon, M. (Makoto), Panico, S. (Salvatore), Howard, B. (Barbara), Skeie, G. (Guri), Strandberg, T. (Timo), Weiderpass, E. (Elisabete), Nietert, P. J. (Paul J.), Psaty, B. M. (Bruce M.), Kromhout, D. (Daan), Salamanca-Fernandez, E. (Elena), Kiechl, S. (Stefan), Krumholz, H. M. (Harlan M.), Grioni, S. (Sara), Palli, D. (Domenico), Huerta, J. M. (Jose M.), Price, J. (Jackie), Sundstrom, J. (Johan), Arriola, L. (Larraitz), Arima, H. (Hisatomi), Travis, R. C. (Ruth C.), Panagiotakos, D. B. (Demosthenes B.), Karakatsani, A. (Anna), Trichopoulou, A. (Antonia), Kuhn, T. (Tilman), Grobbee, D. E. (Diederick E.), Barrett-Connor, E. (Elizabeth), van Schoor, N. (Natasja), Boeing, H. (Heiner), Overvad, K. (Kim), Kauhanen, J. (Jussi), Wareham, N. (Nick), Langenberg, C. (Claudia), Forouhi, N. (Nita), Wennberg, M. (Maria), Despres, J.-P. (Jean-Pierre), Cushman, M. (Mary), Cooper, J. A. (Jackie A.), Rodriguez, C. J. (Carlos J.), Sakurai, M. (Masaru), Shaw, J. E. (Jonathan E.), Knuiman, M. (Matthew), Voortman, T. (Trudy), Meisinger, C. (Christa), Tjonneland, A. (Anne), Brenner, H. (Hermann), Palmieri, L. (Luigi), Dallongeville, J. (Jean), Brunner, E. J. (Eric J.), Assmann, G. (Gerd), Trevisan, M. (Maurizio), Gillum, R. F. (Richard F.), Ford, I. (Ian), Sattar, N. (Naveed), Lazo, M. (Mariana), Thompson, S. G. (Simon G.), Ferrari, P. (Pietro), Leon, D. A. (David A.), Smith, G. D. (George Davey), Peto, R. (Richard), Jackson, R. (Rod), Banks, E. (Emily), Di Angelantonio, E. (Emanuele), and Danesh, J. (John)
Abstract: Background: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. Methods: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose–response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th–95th percentile 1·04–13·5]) from 71 011 participants from 37 studies. Findings: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality ris
Published: 2018

66. Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: A comparative risk assessment

Author: Danaei, G, Lu, Y, Singh, Gm, Carnahan, E, Stevens, Ga, Cowan, Mj, Farzadfar, F, Lin, Jk, Finucane, Mm, Rao, M, Khang, Yh, Riley, Lm, Mozaffarian, D, Lim, Ss, Ezzati, M, Aamodt, G, Abdeen, Z, Abdella, Na, Rahim, Hf, Addo, J, Aekplakorn, W, Afifi, Mm, Agabiti Rosei, E, Salinas, Ca, Agyemang, C, Ali, Mk, Ali, Mm, Al Nsour, M, Al Nuaim AR, Ambady, R, Di Angelantonio, E, Aro, P, Azizi, F, Babu, Bv, Bahalim, An, Barbagallo, Cm, Barbieri, Ma, Barceló, A, Barreto, Sm, Barros, H, Bautista, Le, Benetos, A, Bjerregaard, P, Björkelund, C, Bo, S, Bobak, M, Bonora, Enzo, Botana, Ma, Bovet, P, Breckenkamp, J, Breteler, Mm, Broda, G, Brown, Ij, Bursztyn, M, de León AC, Campos, H, Cappuccio, Fp, Capuano, V, Casiglia, E, Castellano, M, Castetbon, K, Cea, L, Chang, Cj, Chaouki, N, Chatterji, S, Chen, Cj, Chen, Z, Choi, Js, Chua, L, Cífková, R, Cobiac, Lj, Cooper, Rs, Corsi, Am, Costanza, Mc, Craig, Cl, Dankner, Rs, Dastgiri, S, Delgado, E, Dinc, G, Doi, Y, Dong, Gh, Dorsi, E, Dragano, N, Drewnowski, A, Eggertsen, R, Elliott, P, Engeland, A, Erem, C, Esteghamati, A, Fall, Ch, Fan, Jg, Ferreccio, C, Fezeu, L, Firmo, Jo, Florez, Hj, Fornés, Ns, Fowkes, Fg, Franceschini, G, Frisk, F, Fuchs, Fd, Fuller, El, Getz, L, Giampaoli, S, Gómez, Lf, Gomez Zumaquero JM, Graff Iversen, S, Grant, Jf, Carvajal, Rg, Gulliford, Mc, Gupta, R, Gupta, Pc, Gureje, O, Gutierrez, Hr, Hansen, Tw, Hata, J, He, J, Heim, N, Heinrich, J, Hemmingsson, T, Hennis, A, Herman, Wh, Herrera, Vm, Ho, S, Holdsworth, M, Frisman, Gh, Hopman, Wm, Hussain, A, Husseini, A, Ibrahim, Mm, Ikeda, N, Jacobsen, Bk, Jaddou, Hy, Jafar, Th, Janghorbani, M, Jasienska, G, Joffres, Mr, Jonas, Jb, Kadiki, Oa, Kalter Leibovici, O, Kamadjeu, Rm, Kaptoge, S, Karalis, I, Kastarinen, Mj, Katz, J, Keinan Boker, L, Kelly, P, Khalilzadeh, O, Kiechl, S, Kim, Kw, Kiyohara, Y, Kobayashi, J, Krause, Mp, Kubínová, R, Kurjata, P, Kusuma, Ys, Lam, Th, Langhammer, A, Lawes, Cm, Le, C, Lee, J, Lévy Marchal, C, Lewington, S, Li, Y, Lim, To, 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JK, Finucane MM, Rao M, Khang Y-H, Riley LM, Mozaffarian D, Lim SS, Ezzati M, Aamodt G, Abdeen Z, Abdella NA, Abdul Rahim HF, Addo J, Aekplakorn W, Afi fi MM, Agabiti-Rosei E, Aguilar Salinas CA, Agyemang C, Ali MK, Ali MM, Al-Nsour M, Al-Nuaim AR, Ambady R, Di Angelantonio E, Aro P, Azizi F, Babu BV, Bahalim AN, Barbagallo CM, Barbieri MA, Barcelo A, Barreto SM, Barros H, Bautista LE, Benetos A, Bjerregaard P, Bjorkelund C, Bo S, Bobak M, Bonora E, Botana MA, Bovet P, Breckenkamp J, Breteler MM, Broda G, Brown IJ, Bursztyn M, Cabrera de Leon A, Campos H, Cappuccio FP, Capuano V, Casiglia E, Castellano M, Castetbon K, Cea L, Chang C-J, Chaouki N, Chatterji S, Chen C-J, Chen Z, Choi J-S, Chua L, Cifkova R, Cobiac LJ, Cooper RS, Corsi AM, Costanza MC, Craig CL, Dankner RS, Dastgiri S, Delgado E, Dinc G, Doi Y, Dong G-H, Dorsi E, Dragano N, Drewnowski A, Eggertsen R, Elliott P, Anders Engeland, Erem C, Esteghamati A, Fall CHD, Fan J-G, Ferreccio C, Fezeu L, Firmo JO, Florez HF, Fornes NF, Fowkes FGR, Franceschini G, Frisk F, Fuchs FD, Fuller EL, Getz L, Giampaoli S, Gomez LF, Gomez-Zumaquero JM, Graff –Iversen S, Grant JF, Guerrero Carvajal R, Gulliford MC, Gupta R, Gupta PC, Gureje O, Gutierrez HR, Hansen TW, Hata J, He J, Heim N, Heinrich J, Hemmingsson T, Hennis A, Herman WH, Herrera VM, Ho S, Holdsworth M, Hollman Frisman G, Hopman WM, Hussain A, Husseini A, Ibrahim MM, Ikeda N, Jacobsen BK, Jaddou HY, Jafar TH, Janghorbani M, Jasienska G, Joffres MR, Jonas JB, Kadiki OA, Kalter-Leibovici O, Kamadjeu RM, Kaptoge S, Karalis I, Kastarinen MJ, Katz J, Keinan-Boker L, Kelly P, Khalilzadeh O, Kiechl S, Woong Kim KW, Kiyohara Y, Kobayashi J, Krause MP, Kubinova R, Kurjata P, Kusuma YS, Lam TH, Langhammer A, Lawes CMM, Le C, Lee J, Levy-Marchal C, Lewington S, Li Y, Lim TO, Lin X, Lin C-C, Lin H-H, Lind L, Lissner L, Liu X, Lopez-Jaramillo P, Lorbeer R, Ma G, Ma S, Macia F, MacLean DR, Maggi S, Magliano DJ, Makdisse M, Mancia G, Mannami T, Marques-Vidal P, Mbanya JCN, McFarlane-Anderson N, Miccoli R, Miettola J, Minh HV, Miquel JF, J Miranda JJ, Mohamed MK, Mohan V, Mohanna S, Mokdad A, Mollentze WF, Morales DD, Morgan K, Muiesan LM, Muntoni S, Nabipour I, Nakagami T, Nangia V, Nemesure B, Neovius M, Nerhus KA, Nervi F, Neuhauser H, Nguyen M, Ninomiya T, Noale M, Oh SW, Ohkubo T, Olivieri O, Onal AE, Onat A, Orostegui M, Ouedraogo H, Pan W-A, Panagiotakos DB, Panza F, Park Y, Passos VMA, Pednekar MS, Pelizzari PM, Peres MA, Perez C, Perez-Fernandez R, Pichardo R, Hwee Pin Phua, Francesco Pistelli, Plans P, Polakowska M, Poulter N, Prabhakaran D, Qiao Q, Rafiei M, Raitakari OT, Ramos LR, Rampal S, Rampal L, Rasmussen F, Reddy KKR, Josep Redon J, Revilla L, Reyes-GarciaV, Roaeid RB, Robinson CA, Rodriguez-Artalejo F, Rojas-Martinez R, Ronkainen K, Rosero-Bixby L, Roth GA, Sachdev HS, Sanchez JR, Sanisoglu SY, Sans S, Sarraf-Zadegan N, Scazufca M, Schaan BD, Schapochnik N, Schelleman H, Schneider IJC, Schooling CM, Schwarz B, Sekuri C, Sereday MS, Serra-Majem L, Shaw J, Shera AS, Shi Z, Shiri R, Shu XO, Santos Silva DA, Silva E, Simons LA, Smith M, Soderberg S, Soebardi S, Solfrizzi V, Sonestedt E, Soysal A, StattinP, Stein AD, Stergiou GS, Stessman J, Sudo A, Suka M, Sundh V, Sundquist K, Sundstrom J, Swai AB, Tai ES, Tambs K, Tesfaye F, Thomas GN, Thorogood M, Tilvis RS, Tobias M, Torheim LE, Trenkwalder P, Tuomilehto JO, Tur JA, Tzourio C, Uhernik A, Ukoli FA, Unwin N, Vander Hoorn S, Vanderpump MP, Varo JJ, Veierod MB, Velasquez-Melendez G, Verschuren M, Viet L, Villalpando S, Vioque J, Vollenweider P, Volpato S, Wang N, Wang YX, Ward M, Waspadji S, Welin LX, Whitlock G, Wilhelmsen L, Willeit J, Woodward M, Wormser D, Xavier AJ, Xu F, Xu L, Yamamoto A, Yang G, Yang X, Yeh L-C, Yoon J-S, You Q, Yu Z, Zhang J, Zhang L, Zheng W, Zhou M, Danaei, G, Lu, Y, Singh, G, Carnahan, E, Stevens, G, Cowan, M, Farzadfar, F, Lin, J, Finucane, M, Rao, M, Khang, Y, Riley, L, Arian, D, Lim, S, Ezzati, M, Aamodt, G, Abdeen, Z, Abdella, N, Rahim, H, Addo, J, Aekplakorn, W, Afifi, M, Agabiti-Rosei, E, Salinas, C, Agyemang, C, Ali, M, Al-Nsour, M, Al-Nuaim, A, Ambady, R, Angelantonio, E, Aro, P, Azizi, F, Babu, B, Bahalim, A, Barbagallo, C, Barbieri, M, Barceló, A, Barreto, S, Barros, H, Bautista, L, Benetos, A, Bjerregaard, P, Björkelund, C, Bo, S, Bobak, M, Bonora, E, Botana, M, Bovet, P, Breckenkamp, J, Breteler, M, Broda, G, Brown, I, Bursztyn, M, de León, A, Campos, H, Cappuccio, F, Capuano, V, Casiglia, E, Castellano, M, Castetbon, K, Cea, L, Chang, C, Chaouki, N, Chatterji, S, Chen, C, Chen, Z, Choi, J, Chua, L, Cífková, R, Cobiac, L, Cooper, R, Corsi, A, Costanza, M, Craig, C, Dankner, R, Dastgiri, S, Delgado, E, Dinc, G, Doi, Y, Dong, G, Dorsi, E, Dragano, N, Drewnowski, A, Eggertsen, R, Elliott, P, Engeland, A, Erem, C, Esteghamati, A, Fall, C, Fan, J, Ferreccio, C, Fezeu, L, Firmo, J, Florez, H, Fornés, N, Fowkes, F, Franceschini, G, Frisk, F, Fuchs, F, Fuller, E, Getz, L, Giampaoli, S, Gómez, L, Gomez-Zumaquero, J, Iversen, S, Grant, J, Carvajal, R, Gulliford, M, Gupta, R, Gupta, P, Gureje, O, Gutierrez, H, Hansen, T, Hata, J, He, J, Heim, N, Heinrich, J, Hemmingsson, T, Hennis, A, Herman, W, Herrera, V, Ho, S, Holdsworth, M, Frisman, G, Hopman, W, Hussain, A, Husseini, A, Ibrahim, M, Ikeda, N, Jacobsen, B, Jaddou, H, Jafar, T, Janghorbani, M, Jasienska, G, Joffres, M, Jonas, J, Kadiki, O, Kalter-Leibovici, O, Kamadjeu, R, Kaptoge, S, Karalis, I, Kastarinen, M, Katz, J, Keinan-Boker, L, Kelly, P, Khalilzadeh, O, Kiechl, S, Kim, K, Kiyohara, Y, Kobayashi, J, Krause, M, Kubínová, R, Kurjata, P, Kusuma, Y, Lam, T, Langhammer, A, Lawes, C, Le, C, Lee, J, Lévy-Marchal, C, Lewington, S, Li, Y, Lim, T, Lin, X, Lin, C, Lin, H, Lind, L, Lissner, L, Liu, X, Lopez-Jaramillo, P, Lorbeer, R, Ma, G, Ma, S, Macià, F, Maclean, D, Maggi, S, Magliano, D, Makdisse, M, Mancia, G, Mannami, T, Marques-Vidal, P, Mbanya, J, McFarlane-Anderson, N, Miccoli, R, Miettola, J, Minh, H, Miquel, J, Miranda, J, Mohamed, M, Mohan, V, Mohanna, S, Mokdad, A, Mollentze, W, Morales, D, Morgan, K, Lorenza M Muiesan, N, Muntoni, S, Nabipour, I, Nakagami, T, Nangia, V, Nemesure, B, Neovius, M, Nerhus, K, Nervi, F, Neuhauser, H, Nguyen, M, Ninomiya, T, Noale, M, Oh, S, Ohkubo, T, Olivieri, O, Önal, A, Onat, A, Oróstegui, M, Ouedraogo, H, Pan, W, Panagiotakos, D, Panza, F, Park, Y, Passos, V, Pednekar, M, Pelizzari, P, Peres, M, Cynthia Pérez, N, Pérez-Fernández, R, Pichardo, R, Phua, H, Pistelli, F, Plans, P, Polakowska, M, Poulter, N, Prabhakaran, D, Qiao, Q, Rafiei, M, Raitakari, O, Ramos, L, Rampal, S, Rampal, L, Rasmussen, F, Reddy, K, Redon, J, Revilla, L, Reyes-García, V, Roaeid, R, Robinson, C, Rodriguez-Artalejo, F, Rojas-Martinez, R, Ronkainen, K, Rosero-Bixby, L, Roth, G, Sachdev, H, Sánchez, J, Sanisoglu, S, Sans, S, Sarraf-Zadegan, N, Scazufca, M, Schaan, B, Schapochnik, N, Schelleman, H, Schneider, I, Schooling, C, Schwarz, B, Sekuri, C, Sereday, M, Serra-Majem, L, Shaw, J, Shera, A, Shi, Z, Shiri, R, Shu, X, Silva, D, Silva, E, Simons, L, Smith, M, Söderberg, S, Soebardi, S, Solfrizzi, V, Sonestedt, E, Soysal, A, Stattin, P, Stein, A, Stergiou, G, Stessman, J, Sudo, A, Suka, M, Sundh, V, Sundquist, K, Sundström, J, Swai, A, Tai, E, Tambs, K, Tesfaye, F, Thomas, G, Thorogood, M, Tilvis, R, Tobias, M, Torheim, L, Trenkwalder, P, Tuomilehto, J, Tur, J, Tzourio, C, Uhernik, A, Ukoli, F, Unwin, N, Hoorn, S, Vanderpump, M, Varo, J, Veierød, M, Velásquez-Meléndez, G, Verschuren, M, Viet, L, Villalpando, S, Vioque, J, Vollenweider, P, Volpato, S, Wang, N, Wang, Y, Ward, M, Waspadji, S, Lennart X Welin, N, Whitlock, G, Wilhelmsen, L, Willeit, J, Woodward, M, Wormser, D, André J Xavier, N, Xu, F, Xu, L, Yamamoto, A, Yang, G, Yang, X, Yeh, L, Yoon, J, You, Q, Yu, Z, Zhang, J, Zhang, L, Zheng, W, and Zhou, M
Subjects: Male, Settore MED/09 - Medicina Interna, kidney disease, Endocrinology, Diabetes and Metabolism, humanos, coste de las enfermedades, Disease, Global Health, Cohort Studies, Endocrinology, Cost of Illness, cardiovascular disease, Health Transition, Risk Factors, transición sanitaria, estudios prospectivos, Renal Insufficiency, Chronic -- complications -- epidemiology -- mortality, evaluación de riesgos, Renal Insufficiency, Prospective Studies, Chronic, estudios de cohortes, Metabolic Syndrome, education.field_of_study, diabetes, Mortality rate, Age Factors, Cardiovascular Diseases, Diabetes Complications, Female, Health Surveys, Humans, Metabolic Syndrome X, Renal Insufficiency, Chronic, Risk Assessment, Sex Factors, Spatio-Temporal Analysis, Internal Medicine, Cardiovascular Diseases -- complications -- epidemiology -- mortality, Cardiovascular disease,Diabetes Mellitus, chronic kidney disease, Diabetes Complications -- epidemiology -- mortality, Sciences bio-médicales et agricoles, Diabetes and Metabolism, encuestas de salud, análisis temporoespacial, Risk assessment, complicaciones de la diabetes, insuficiencia renal, medicine.medical_specialty, Cardiovascular disease, diabetes mortality, Population, enfermedades cardiovasculares, Metabolic Syndrome X -- complications -- epidemiology -- mortality, Article, chronic kidney disease, mortality, Internal medicine, Environmental health, Diabetes mellitus, medicine, factores de riesgo, Risk factor, education, business.industry, medicine.disease, Relative risk, Cardiovascular Diseases/complications, Cardiovascular Diseases/epidemiology, Cardiovascular Diseases/mortality, Diabetes Complications/epidemiology, Diabetes Complications/mortality, Metabolic Syndrome X/complications, Metabolic Syndrome X/epidemiology, Metabolic Syndrome X/mortality, Renal Insufficiency, Chronic/complications, Renal Insufficiency, Chronic/epidemiology, Renal Insufficiency, Chronic/mortality, business, Kidney disease
Abstract: High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010., 0, info:eu-repo/semantics/published
Published: 2014

67. Efficiency and safety of varying the frequency of whole blood donation: randomised trial of 45,000 donors

Author: Di Angelantonio, E, Thompson, SG, Kaptoge, S, Moore, C, Walker, M, Danesh, J, Ouwehand, W, Di Angelantonio, Emanuele [0000-0001-8776-6719], Kaptoge, Stephen [0000-0002-1155-4872], Moore, Carmel [0000-0002-2386-7200], and Apollo - University of Cambridge Repository
Subjects: Adult, Male, Time Factors, Anemia, Iron-Deficiency, Age Factors, Blood Donors, Efficiency, Middle Aged, Risk Assessment, United Kingdom, Young Adult, Sex Factors, Ferritins, Humans, Female, Patient Safety
Abstract: Background Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter -donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings 45263 whole blood donors (22466 men, 22797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p
Published: 2017

68. Prevalence of restless legs syndrome and associated factors in an otherwise healthy population: results from the Danish Blood Donor Study

Author: Didriksen, M, Rigas, AS, Allen, RP, Burchell, BJ, Di Angelantonio, E, Nielsen, MH, Jennum, P, Werge, T, Erikstrup, C, Pedersen, OB, Bruun, MT, Burgdorf, KS, Sørensen, E, Ullum, H, Burchell, Brendan [0000-0002-8243-937X], Di Angelantonio, Emanuele [0000-0001-8776-6719], and Apollo - University of Cambridge Repository
Subjects: The Danish Blood Donor, Willise-Ekbom disease, environmental factors, mental disorders, restless legs syndrome, blood donation, sleep disorders
Abstract: $\textit{Objective}$ Restless legs syndrome (RLS) is a neurological sensorimotor disorder characterized by uncomfortable sensations in the legs. RLS often occurs as a comorbid condition. Besides an increased risk of iron deficiency, blood donors are considered to be generally healthy. Blood donors are therefore an ideal population for studying factors associated with RLS occurrence, herein the role of iron. It is suggested that RLS is linked to sex, age, low socioeconomic status, unhealthy lifestyle, and iron deficiency. The objective of this study is therefore to estimate the RLS prevalence and identify associated biological, sociodemographic, economic, and lifestyle factors in a population of blood donors. $\textit{Methods}$ A total of 13,448 blood donors enrolled in the Danish Blood Donor Study from May 2015 to May 2016. RLS cases were identified using the validated Cambridge–Hopkins RLS-questionnaire. Logistic regression models were applied to assess the relationship between RLS and data on socially related factors collected using questionnaires and population registers. $\textit{Results}$ In this study, 7.2% women and 4.5% men were classified with RLS. RLS was associated with: female sex, high age, smoking, frequent alcohol consumption, and low education. RLS-related symptoms were associated with obesity, parity and donation intensity 3 years prior to inclusion among women. RLS was not related to: reduced plasma ferritin, employment status, and income. $\textit{Conclusions}$ RLS is a frequent disorder in otherwise healthy individuals. The associations discovered in this study can be utilized in preventing or reducing RLS symptoms.
Published: 2017
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69. Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Author: Howson, JMM, Zhao, W, Barnes, DR, Ho, W-K, Young, R, Paul, DS, Waite, LL, Freitag, DF, Fauman, EB, Salfati, EL, Sun, BB, Eicher, JD, Johnson, AD, Sheu, WHH, Nielsen, SF, Lin, W-Y, Surendran, P, Malarstig, A, Wilk, JB, Tybjærg-Hansen, A, Rasmussen, KL, Kamstrup, PR, Deloukas, P, Erdmann, J, Kathiresan, S, Samani, NJ, Schunkert, H, Watkins, H, CARDIoGRAMplusC4D, Do, R, Rader, DJ, Johnson, JA, Hazen, SL, Quyyumi, AA, Spertus, JA, Pepine, CJ, Franceschini, N, Justice, A, Reiner, AP, Buyske, S, Hindorff, LA, Carty, CL, North, KE, Kooperberg, C, Boerwinkle, E, Young, K, Graff, M, Peters, U, Absher, D, Hsiung, CA, Lee, W-J, Taylor, KD, Chen, Y-H, Lee, I-T, Guo, X, Chung, R-H, Hung, Y-J, Rotter, JI, Juang, J-MJ, Quertermous, T, Wang, T-D, Rasheed, A, Frossard, P, Alam, DS, Majumder, AAS, Di Angelantonio, E, Chowdhury, R, EPIC-CVD, Chen, Y-DI, Nordestgaard, BG, Assimes, TL, Danesh, J, Butterworth, AS, Saleheen, D, Howson, Joanna [0000-0001-7618-0050], Barnes, Daniel [0000-0002-3781-7570], Paul, Dirk [0000-0002-8230-0116], Sun, Ben [0000-0001-6347-2281], Surendran, Praveen [0000-0002-4911-6077], Di Angelantonio, Emanuele [0000-0001-8776-6719], Chowdhury, Rajiv [0000-0003-4881-5690], Danesh, John [0000-0003-1158-6791], Butterworth, Adam [0000-0002-6915-9015], and Apollo - University of Cambridge Repository
Subjects: Male, Genotype, Quantitative Trait Loci, Coronary Artery Disease, Cardiovascular, Medical and Health Sciences, Risk Factors, Vascular, Cell Adhesion, Genetics, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Polymorphism, Aetiology, EPIC-CVD, Heart Disease - Coronary Heart Disease, screening and diagnosis, Chemotaxis, Human Genome, Arteries, Single Nucleotide, Leukocyte, Biological Sciences, Atherosclerosis, cardiovascular diseases, Histone Code, Detection, Heart Disease, genome-wide association studies, Muscle, Female, Smooth, Energy Metabolism, CARDIoGRAMplusC4D, Genome-Wide Association Study, Biotechnology, 4.2 Evaluation of markers and technologies, Developmental Biology
Abstract: Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms.
Published: 2017

70. Rare and low-frequency coding variants alter human adult height

Author: Stirrups, KE, Butterworth, AS, Chowdhury, R, Danesh, J, Di Angelantonio, E, Howson, JMM, Surendran, P, Young, R, Dennis, JG, Easton, DF, Thompson, DJ, Dunning, AM, Pirie, A, Tyrer, JP, Langenberg, C, Luan, J, Scott, RA, Wareham, NJ, Willems, SM, Zhao, JH, Sivapalaratnam, S, Johnson, Kathleen [0000-0002-6823-3252], Butterworth, Adam [0000-0002-6915-9015], Chowdhury, Rajiv [0000-0003-4881-5690], Danesh, John [0000-0003-1158-6791], Di Angelantonio, Emanuele [0000-0001-8776-6719], Howson, Joanna [0000-0001-7618-0050], Surendran, Praveen [0000-0002-4911-6077], Dennis, Joe [0000-0003-4591-1214], Easton, Douglas [0000-0003-2444-3247], Thompson, Deborah [0000-0003-1465-5799], Dunning, Alison [0000-0001-6651-7166], Tyrer, Jonathan [0000-0003-3724-4757], Langenberg, Claudia [0000-0002-5017-7344], Luan, Jian'an [0000-0003-3137-6337], Wareham, Nicholas [0000-0003-1422-2993], Zhao, Jing Hua [0000-0003-4930-3582], and Apollo - University of Cambridge Repository
Subjects: genetic association study, development
Abstract: Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome-wide association studies. Here, we report 83 new height-associated coding variants with lower minor allele frequencies (range of 0.1-4.8%) and effects of up to 2 cm/allele (e.g. in IHH, STC2, AR and CRISPLD2), >10 times the average effect of common variants. In functional follow-up studies, rare height-increasing variants of STC2 (+1-2 cm/allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates (e.g. ADAMTS3, IL11RA, NOX4) and pathways (e.g. proteoglycan/glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate to large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
Published: 2017
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71. Prevalence, associated factors and detrimental links to restless legs syndrome in danish blood donors

Author: Didriksen, M., Stribolt Rigas, A., Allen, R., Burchell, B., Thørner, L. Wegner, Nielsen, K., Di Angelantonio, E., Nielsen, M., Jennum, P., Werge, T., Erikstrup, C., Pedersen, O., Bruun, M. Topholm, Burgdorf, K., Sørensen, E., and Ullum, H.
Published: 2017

72. Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis

Author: Schormair, B., Zhao, C., Bell, S., Tilch, E., Salminen, A., Pütz, B., Dauvilliers, Y., Stefani, A., Hoegl, B., Poewe, W., Kemlink, D., Sonka, K., Bachmann, C., Paulus, W., Trenkwalder, C., Oertel, W., Hornyak, M., Teder-Laving, M., Metspalu, A., Hadjigeorgiou, G., Polo, O., Fietze, I., Ross, O., Wszolek, Z., Butterworth, A., Soranzo, N., Ouwehand, W., Roberts, D., Danesh, J., Allen, R., Earley, C., Ondo, W., Xiong, L., Montplaisir, J., Gan-Or, Z., Perola, M., Vodicka, P., Dina, C., Franke, A., Tittmann, L., Stewart, A., Shah, S., Gieger, C., Peters, A., Rouleau, G., Berger, K., Oexle, K., Di Angelantonio, E., Hinds, D., Müller-Myhsok, B., and Winkelmann, J.
Abstract: Background Restless legs syndrome is a prevalent chronic neurological disorder with potentially severe mental and physical health consequences. Clearer understanding of the underlying pathophysiology is needed to improve treatment options. We did a meta-analysis of genome-wide association studies (GWASs) to identify potential molecular targets. Methods In the discovery stage, we combined three GWAS datasets (EU-RLS GENE, INTERVAL, and 23andMe) with diagnosis data collected from 2003 to 2017, in face-to-face interviews or via questionnaires, and involving 15126 cases and 95 725 controls of European ancestry. We identified common variants by fixed-effect inverse-variance meta-analysis. Significant genome-wide signals (p
Published: 2017

73. Identification of novel risk loci for restless legs syndrome: A meta-analysis of genome-wide association studies in individuals of European ancestry: A meta-analysis

Author: Schormair, B., Zhao, C., Bell, S., Tilch, E., Salminen, A.V., Pütz, B., Dauvilliers, Y., Stefani, A., Högl, B., Poewe, W., Kemlink, D., Sonka, K., Bachmann, C.G., Paulus, W., Trenkwalder, C., Oertel, W.H., Hornyak, M., Teder-Laving, M., Metspalu, A., Hadjigeorgiou, G.M., Polo, O., Fietze, I., Ross, O.A., Wszolek, Z., Butterworth, A.S., Soranzo, N., Ouwehand, W.H., Roberts, D.J., Danesh, J., Allen, R.P., Earley, C.J., Ondo, W.G., Xiong, L., Montplaisir, J., Gan-Or, Z., Perola, M., Vodicka, P., Dina, C., Franke, A., Tittmann, L., Stewart, A.F.R., Shah, S.H., Gieger, C., Peters, A., Rouleau, G.A., Berger, K., Oexle, K., di Angelantonio, E., Hinds, D.A., Müller-Myhsok, B., and Winkelmann, J.
Abstract: Background Restless legs syndrome is a prevalent chronic neurological disorder with potentially severe mental and physical health consequences. Clearer understanding of the underlying pathophysiology is needed to improve treatment options. We did a meta-analysis of genome-wide association studies (GWASs) to identify potential molecular targets. Methods In the discovery stage, we combined three GWAS datasets (EU-RLS GENE, INTERVAL, and 23andMe) with diagnosis data collected from 2003 to 2017, in face-to-face interviews or via questionnaires, and involving 15 126 cases and 95 725 controls of European ancestry. We identified common variants by fixed-effect inverse-variance meta-analysis. Significant genome-wide signals (p≤5 × 10−8) were tested for replication in an independent GWAS of 30 770 cases and 286 913 controls, followed by a joint analysis of the discovery and replication stages. We did gene annotation, pathway, and gene-set-enrichment analyses and studied the genetic correlations between restless legs syndrome and traits of interest. Findings We identified and replicated 13 new risk loci for restless legs syndrome and confirmed the previously identified six risk loci. MEIS1 was confirmed as the strongest genetic risk factor for restless legs syndrome (odds ratio 1·92, 95% CI 1·85–1·99). Gene prioritisation, enrichment, and genetic correlation analyses showed that identified pathways were related to neurodevelopment and highlighted genes linked to axon guidance (associated with SEMA6D), synapse formation (NTNG1), and neuronal specification (HOXB cluster family and MYT1). Interpretation Identification of new candidate genes and associated pathways will inform future functional research. Advances in understanding of the molecular mechanisms that underlie restless legs syndrome could lead to new treatment options. We focused on common variants; thus, additional studies are needed to dissect the roles of rare and structural variations. &nbsp
Published: 2017

74. LPA variants, risk of coronary disease, and estimated clinical benefit of lipoprotein(a) lowering therapies: A mendelian randomization analysis

Author: Ference, B.A., primary, Burgess, S., additional, Staley, J.R., additional, Freitag, D.F., additional, Mason, A.M., additional, Nielsen, S.F., additional, Willeit, P., additional, Young, R., additional, Surendran, P., additional, Karthikeyan, S., additional, Bolton, T.R., additional, Peters, J.E., additional, Kamstrup, P.R., additional, Tybjærg-Hansen, A., additional, Benn, M., additional, Langsted, A., additional, Schnohr, P., additional, Vedel-Krogh, S., additional, Kobylecki, C.J., additional, Ford, I., additional, Packard, C., additional, Trompet, S., additional, Jukema, J.W., additional, Sattar, N., additional, Di Angelantonio, E., additional, Saleheen, D., additional, Howson for the CHD Exome+ Consor, J.M.M., additional, Nordestgaard, B.G., additional, Butterworth for the EPIC-CVD Consorti, A., additional, and Danesh, J., additional
Published: 2018
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75. Comorbidities to restless legs syndrome – results from the Danish blood donor study

Author: Didriksen, M., primary, Hansen, T., additional, Rigas, A., additional, Allen, R., additional, Burchell, B., additional, Thørner, L., additional, Nielsen, K., additional, Di Angelantonio, E., additional, Nielsen, M., additional, Jennum, P., additional, Werge, T., additional, Erikstrup, C., additional, Pedersen, O., additional, Paarup, H., additional, Hjalgrim, H., additional, Bruun, M., additional, Burgdorf, K., additional, Sørensen, E., additional, and Ullum, H., additional
Published: 2017
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76. Comorbidities to restless legs syndrome – results from the Danish blood donor study

Author: Didriksen, M., Hansen, T., Rigas, A., Allen, R., Burchell, B., Thørner, L., Nielsen, K., Di Angelantonio, E., Nielsen, M., Jennum, P., Werge, T., Erikstrup, C., Pedersen, O., Paarup, H., Hjalgrim, H., Bruun, M., Burgdorf, K., Sørensen, E., Ullum, H., Didriksen, M., Hansen, T., Rigas, A., Allen, R., Burchell, B., Thørner, L., Nielsen, K., Di Angelantonio, E., Nielsen, M., Jennum, P., Werge, T., Erikstrup, C., Pedersen, O., Paarup, H., Hjalgrim, H., Bruun, M., Burgdorf, K., Sørensen, E., and Ullum, H.
Published: 2017

77. Use of Repeated Blood Pressure and Cholesterol Measurements to Improve Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis

Author: Paige, E, Barrett, J, Pennells, L, Sweeting, M, Willeit, P, Di Angelantonio, E, Gudnason, V, Nordestgaard, BG, Psaty, BM, Goldbourt, U, Best, LG, Assmann, G, Salonen, JT, Nietert, PJ, Verschuren, WMM, Brunner, EJ, Kronmal, RA, Salomaa, V, Bakker, SJL, Dagenais, GR, Sato, S, Jansson, JH, Willeit, J, Onat, A, de la Camara, AG, Roussel, R, Volzke, H, Dankner, R, Tipping, RW, Meade, TW, Donfrancesco, C, Kuller, LH, Peters, A, Gallacher, J, Kromhout, D, Iso, H, Knuiman, M, Casiglia, E, Kavousi, Maryam, Palmieri, L, Sundstrom, J, Davis, BR, Njolstad, I, Couper, D, Danesh, J, Thompson, SG, Wood, A, Paige, E, Barrett, J, Pennells, L, Sweeting, M, Willeit, P, Di Angelantonio, E, Gudnason, V, Nordestgaard, BG, Psaty, BM, Goldbourt, U, Best, LG, Assmann, G, Salonen, JT, Nietert, PJ, Verschuren, WMM, Brunner, EJ, Kronmal, RA, Salomaa, V, Bakker, SJL, Dagenais, GR, Sato, S, Jansson, JH, Willeit, J, Onat, A, de la Camara, AG, Roussel, R, Volzke, H, Dankner, R, Tipping, RW, Meade, TW, Donfrancesco, C, Kuller, LH, Peters, A, Gallacher, J, Kromhout, D, Iso, H, Knuiman, M, Casiglia, E, Kavousi, Maryam, Palmieri, L, Sundstrom, J, Davis, BR, Njolstad, I, Couper, D, Danesh, J, Thompson, SG, and Wood, A
Published: 2017

78. Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits

Author: Tachmazidou, I, Suveges, D, Min, JL, Ritchie, GRS, Steinberg, J, Walter, K, Iotchkova, V, Schwartzentruber, J, Huang, J, Memari, Y, McCarthy, S, Crawford, AA, Bombieri, C, Cocca, M, Farmaki, AE, Gaunt, TR, Jousilahti, P, Kooijman, Marjolein, Lehne, B, Malerba, G, Mannisto, S, Matchan, A, Medina Gomez, Maria, Metrustry, SJ, Nag, A, Ntalla, I, Paternoster, L, Rayner, NW, Sala, C, Scott, WR, Shihab, HA, Southam, L, St Pourcain, B, Traglia, M, Trajanoska, Katerina, Zaza, G, Zhang, WH, Artigas, MS, Bansal, N, Benn, M, Chen, ZS, Danecek, P, Lin, WY, Locke, A, Luan, JA, Manning, AK, Mulas, A, Sidore, C, Tybjaerg-Hansen, A, Varbo, A, Zoledziewska, M, Finan, C, Hatzikotoulas, K, Hendricks, AE, Kemp, JP, Moayyeri, A, Panoutsopoulou, K, Szpak, M, Wilson, SG, Boehnke, M, Cucca, F, Di Angelantonio, E, Langenberg, C, Lindgren, C, McCarthy, MI, Morris, AP, Nordestgaard, BG, Scott, RA, Tobin, MD, Wareham, NJ, Burton, P, Chambers, JC, Smith, GD, Dedoussis, G, Felix, Janine, Franco Duran, OH, Gambaro, G, Gasparini, P, Hammond, CJ, Hofman, Bert, Jaddoe, Vincent, Kleber, M, Kooner, JS, Perola, M, Relton, C, Ring, SM, Rivadeneira, Fernando, Salomaa, V, Spector, TD, Stegle, O, Toniolo, D, Uitterlinden, André, Barroso, I, Greenwood, CMT, Perry, JRB, Walker, BR, Butterworth, AS, Xue, YL, Durbin, R, Small, KS, Soranzo, N, Timpson, NJ, Zeggini, E, Tachmazidou, I, Suveges, D, Min, JL, Ritchie, GRS, Steinberg, J, Walter, K, Iotchkova, V, Schwartzentruber, J, Huang, J, Memari, Y, McCarthy, S, Crawford, AA, Bombieri, C, Cocca, M, Farmaki, AE, Gaunt, TR, Jousilahti, P, Kooijman, Marjolein, Lehne, B, Malerba, G, Mannisto, S, Matchan, A, Medina Gomez, Maria, Metrustry, SJ, Nag, A, Ntalla, I, Paternoster, L, Rayner, NW, Sala, C, Scott, WR, Shihab, HA, Southam, L, St Pourcain, B, Traglia, M, Trajanoska, Katerina, Zaza, G, Zhang, WH, Artigas, MS, Bansal, N, Benn, M, Chen, ZS, Danecek, P, Lin, WY, Locke, A, Luan, JA, Manning, AK, Mulas, A, Sidore, C, Tybjaerg-Hansen, A, Varbo, A, Zoledziewska, M, Finan, C, Hatzikotoulas, K, Hendricks, AE, Kemp, JP, Moayyeri, A, Panoutsopoulou, K, Szpak, M, Wilson, SG, Boehnke, M, Cucca, F, Di Angelantonio, E, Langenberg, C, Lindgren, C, McCarthy, MI, Morris, AP, Nordestgaard, BG, Scott, RA, Tobin, MD, Wareham, NJ, Burton, P, Chambers, JC, Smith, GD, Dedoussis, G, Felix, Janine, Franco Duran, OH, Gambaro, G, Gasparini, P, Hammond, CJ, Hofman, Bert, Jaddoe, Vincent, Kleber, M, Kooner, JS, Perola, M, Relton, C, Ring, SM, Rivadeneira, Fernando, Salomaa, V, Spector, TD, Stegle, O, Toniolo, D, Uitterlinden, André, Barroso, I, Greenwood, CMT, Perry, JRB, Walker, BR, Butterworth, AS, Xue, YL, Durbin, R, Small, KS, Soranzo, N, Timpson, NJ, and Zeggini, E
Published: 2017

79. Body-mass index and all-1 cause mortality: Individual-participant-data meta-analysis of 239 prospective studies in four continents

Author: Di Angelantonio, E, Woodward, M, Cairns, B, Lewington, S, Collins, R, Green, J, Halsey, J, Reeves, G, Yang, L, Beral, V, Chen, Z, and Peto, R
Abstract: Background: Overweight and obesity are increasing worldwide. To help assess their relevance to mortality in different populations we conducted individual-participant-data meta-analyses of the prospective studies of body mass index (BMI), limiting confounding and reverse causality by restricting analyses to never-smokers and excluding prior disease and the first 5 years of follow- up. Methods: Of 10,625,411 participants in Asia, Australia/New Zealand, Europe, and North America from 239 prospective studies (median follow-up 13·7 [IQR: 11·4-14·7] years), 3,951,455 in 189 studies were never-smokers without specific chronic diseases at recruitment who survived 5 years, of whom 385,879 died. The primary analyses are of these deaths, using age and sex-adjusted hazard ratios (HRs). Findings: All-cause mortality was minimal (HR=1) at BMI (kg/m2) 20-25, and increased significantly both just below this range (BMI 18·5-25, mortality increased approximately log-linearly with BMI; HR per 5 units higher BMI was 1·31 (1·29-1·33) in all regions; 1·39 (1·35-1·43) in Europe; 1·29 (1·26-1·32) in North America, 1·39 (1·34-1·44) in East Asia, and 1.31 (1.27, 1.35) in Australia/New Zealand. This HR per 5 units higher BMI (for BMI>25) was greater in younger than older people (1.52 at 35–49 years vs 1·21 at 70-89 years; PheterogeneityInterpretation: The associations of both overweight and obesity with higher all-cause mortality were broadly consistent in four continents. This supports strategies to combat the entire spectrum of excess adiposity in many populations.
Published: 2016

80. Glycated hemoglobin measurement and prediction of cardiovascular disease

Author: Emerging Risk Factors Collaboration, Di Angelantonio E, Gao P, Khan H, Butterworth AS, Wormser D, Kaptoge S, Kondapally Seshasai SR, Thompson A, Sarwar N, Willeit P, Ridker PM, Barr EL, Khaw KT, Psaty BM, Brenner H, Balkau B, Dekker JM, Lawlor DA, Daimon M, Willeit J, Njølstad I, Nissinen A, Brunner EJ, Kuller LH, Price JF, Sundström J, Knuiman MW, Feskens EJ, Verschuren WM, Wald N, Bakker SJ, Whincup PH, Ford I, Goldbourt U, Gómez de la Cámara A, Gallacher J, Simons LA, Rosengren A, Sutherland SE, Björkelund C, Blazer DG, Wassertheil Smoller S, Onat A, Marín Ibañez A, Casiglia E, Jukema JW, Simpson LM, Giampaoli S, Nordestgaard BG, Selmer R, Wennberg P, Kauhanen J, Salonen JT, Dankner R, Barrett Connor E, Kavousi M, Gudnason V, Evans D, Wallace RB, Cushman M, D'Agostino RB Sr, Umans JG, Kiyohara Y, Nakagawa H, Sato S, Gillum RF, Folsom AR, van der Schouw YT, Moons KG, Griffin SJ, Sattar N, Wareham NJ, Selvin E, Thompson SG, Danesh J. Collaborators Simpson LM, Coresh J, Wagenknecht L, Shaw JE, Zimmet PZ, Magliano D, Wannamethee SG, Morris RW, Kiechl S, Santer P, Bonora E, Casas JP, Ebrahim S, Ben Shlomo Y, Yarnell JW, Elwood P, Bachman DL, Nietert PJ, Håheim LL, Søgaard AJ, Tybjaerg Hansen A, Frikke Schmidt R, Benn M, Palmieri L, Vanuzzo D, Bonnet F, Copin N, Roussel R, Gómez Gerique JA, Rubio Herrera MA, Gutiérrez Fuentes JA, Friedlander Y, McCallum J, Simons J, Lee AJ, McLachlan S, Taylor JO, Guralnik JM, Phillips CL, Evans DA, Kohout F, Cohen H, George L, Fillenbaum G, McGloin JM, Khaw K., Schöttker B, Müller H, Rothenbacher D, Jansson J., Hallmans G, Tuomilehto J, Donfrancesco C, Woodward M, Oizumi T, Kayama T, Kato T, Danker R, Chetrit A, Wilhelmsen L, Eriksson H, Lappas G, Bengtsson C, Lissner L, Skoog I, Cremer P, Arima H, Ninomiya T, Hata J, Nijpels G, Stehouwer CD, Tuomainen T., Voutilainen S, Kurl S, de Boer IH, Bertoni AG, Veschuren WM, Dullaart RP, Lambers Heerspink HJ, Hilege HL, Trompet S, Stott DJ, Dagenais GR, Cantin B, Dehghan D, Hofman A, Franco OH, Tunstall Pedoe H, Lee E, Best L, Howard BV, Can G, Ademoğlu E, Sakurai M, Nakamura K, Morikawa Y, Løchen M., Mathiesen EB, Wilsgaard T, Byberg L, Cederholm T, Olsson E, Pradhan AD, Cook NR, Kromhout D, Walker M, Watson S, Burgess S, Gregson J, Harshfield E, Pennells L, Spackman S, Warnakula S, Wood AM, Danesh J., PANICO, SALVATORE, Emerging Risk Factors, Collaboration, Di Angelantonio, E, Gao, P, Khan, H, Butterworth, A, Wormser, D, Kaptoge, S, Kondapally Seshasai, Sr, Thompson, A, Sarwar, N, Willeit, P, Ridker, Pm, Barr, El, Khaw, Kt, Psaty, Bm, Brenner, H, Balkau, B, Dekker, Jm, Lawlor, Da, Daimon, M, Willeit, J, Njølstad, I, Nissinen, A, Brunner, Ej, Kuller, Lh, Price, Jf, Sundström, J, Knuiman, Mw, Feskens, Ej, Verschuren, Wm, Wald, N, Bakker, Sj, Whincup, Ph, Ford, I, Goldbourt, U, Gómez de la Cámara, A, Gallacher, J, Simons, La, Rosengren, A, Sutherland, Se, Björkelund, C, Blazer, Dg, Wassertheil Smoller, S, Onat, A, Marín Ibañez, A, Casiglia, E, Jukema, Jw, Simpson, Lm, Giampaoli, S, Nordestgaard, Bg, Selmer, R, Wennberg, P, Kauhanen, J, Salonen, Jt, Dankner, R, Barrett Connor, E, Kavousi, M, Gudnason, V, Evans, D, Wallace, Rb, Cushman, M, D'Agostino RB, Sr, Umans, Jg, Kiyohara, Y, Nakagawa, H, Sato, S, Gillum, Rf, Folsom, Ar, van der Schouw, Yt, Moons, Kg, Griffin, Sj, Sattar, N, Wareham, Nj, Selvin, E, Thompson, Sg, Danesh J., Collaborators Simpson LM, Coresh, J, Wagenknecht, L, Shaw, Je, Zimmet, Pz, Magliano, D, Wannamethee, Sg, Morris, Rw, Kiechl, S, Santer, P, Bonora, E, Casas, Jp, Ebrahim, S, Ben Shlomo, Y, Yarnell, Jw, Elwood, P, Bachman, Dl, Nietert, Pj, Håheim, Ll, Søgaard, Aj, Tybjaerg Hansen, A, Frikke Schmidt, R, Benn, M, Palmieri, L, Vanuzzo, D, Panico, Salvatore, Bonnet, F, Copin, N, Roussel, R, Gómez Gerique, Ja, Rubio Herrera, Ma, Gutiérrez Fuentes, Ja, Friedlander, Y, Mccallum, J, Simons, J, Lee, Aj, Mclachlan, S, Taylor, Jo, Guralnik, Jm, Phillips, Cl, Evans, Da, Kohout, F, Cohen, H, George, L, Fillenbaum, G, Mcgloin, Jm, Khaw, K., Schöttker, B, Müller, H, Rothenbacher, D, Jansson, J., Hallmans, G, Tuomilehto, J, Donfrancesco, C, Woodward, M, Oizumi, T, Kayama, T, Kato, T, Danker, R, Chetrit, A, Wilhelmsen, L, Eriksson, H, Lappas, G, Bengtsson, C, Lissner, L, Skoog, I, Cremer, P, Arima, H, Ninomiya, T, Hata, J, Nijpels, G, Stehouwer, Cd, Tuomainen, T., Voutilainen, S, Kurl, S, de Boer, Ih, Bertoni, Ag, Veschuren, Wm, Dullaart, Rp, Lambers Heerspink, Hj, Hilege, Hl, Trompet, S, Stott, Dj, Dagenais, Gr, Cantin, B, Dehghan, D, Hofman, A, Franco, Oh, Tunstall Pedoe, H, Lee, E, Best, L, Howard, Bv, Can, G, Ademoğlu, E, Sakurai, M, Nakamura, K, Morikawa, Y, Løchen, M., Mathiesen, Eb, Wilsgaard, T, Byberg, L, Cederholm, T, Olsson, E, Pradhan, Ad, Cook, Nr, Kromhout, D, Walker, M, Watson, S, Burgess, S, Gregson, J, Harshfield, E, Pennells, L, Spackman, S, Warnakula, S, Wood, Am, and Danesh, J.
Published: 2014

81. Collaborative pooled analysis of data on C-reactive protein gene variants and coronary disease: judging causality by Mendelian randomisation

Author: Danesh, J, Collaborat, CRPCHDG, Hingorani, A, Wensley, F, Casas, JP, Smeeth, L, Samani, NJ, Hall, A, Whincup, P, Morris, R, Lawlor, DA, Smith, GD, Timpson, N, Ebrahim, S, Brown, M, Sandhu, M, Reiner, A, Psaty, B, Lange, L, Cushman, M, Tracy, R, Nordestgaard, BG, Tybjaerg-Hansen, A, Zacho, J, Hung, J, Thompson, P, Beilby, J, Palmer, LJ, Fowkes, G, Lowe, G, Tzoulaki, I, Kumari, M, Overvad, K, Khaw, KT, Benjamin, EJ, Larson, MG, Yamamoto, JF, Chiodini, B, Franzosi, M, Norman, PE, Hankey, GJ, Jamrozik, K, Palmer, L, Rimm, E, Pai, J, Heckbert, S, Bis, J, Yusuf, S, Anand, S, Engert, J, Collins, R, Melander, O, Berglund, G, Ladenvall, P, Johansson, L, Jansson, JH, Hallmans, G, Humphries, S, Manson, J, Saleheen, D, Frossard, P, Sattar, N, Robertson, M, Shepherd, J, Schaefer, E, Hofman, A, Witteman, JCM, Kardys, I, de Faire, U, Bennet, A, O'Reilly, D, McMahon, A, Packard, C, Clarke, R, Greenland, P, Bowden, J, Di Angelantonio, E, Shah, T, Verzilli, C, Walker, M, and Wittaker, J
Subjects: Research design, Pathology, medicine.medical_specialty, Heart disease, Epidemiology, Coronary Disease, Bioinformatics, medicine, Humans, Cooperative Behavior, Prospective cohort study, Inflammation, Polymorphism, Genetic, biology, business.industry, C-reactive protein, Haplotype, Case-control study, medicine.disease, Causality, C-Reactive Protein, Haplotypes, Research Design, Case-Control Studies, biology.protein, Cell activation, business
Abstract: Many prospective studies have reported associations between circulating C-reactive protein (CRP) levels and risk of coronary heart disease (CHD), but causality remains uncertain. Studies of CHD are being conducted that involve measurement of common polymorphisms of the CRP gene known to be associated with circulating concentrations, thereby utilising these variants as proxies for circulating CRP levels. By analysing data from several studies examining the association between relevant CRP polymorphisms and CHD risk, the present collaboration will undertake a Mendelian randomisation analysis to help assess the likelihood of any causal relevance of CRP levels to CHD risk. A central database is being established containing individual data on CRP polymorphisms, circulating CRP levels, and major coronary outcomes as well as age, sex and other relevant characteristics. Associations between CRP polymorphisms or haplotypes and CHD will be evaluated under different circumstances. This collaboration comprises, at present, about 37,000 CHD outcomes and about 120,000 controls, which should yield suitably precise findings to help judge causality. This work should advance understanding of the relevance of low-grade inflammation to CHD and indicate whether or not CRP itself is involved in long-term pathogenesis.
Published: 2008

82. 2014 European Conference on Donor Health and Management

Author: Ramond, A, Di Angelantonio, E, Ramond, Anna [0000-0002-9958-3693], Di Angelantonio, Emanuele [0000-0001-8776-6719], and Apollo - University of Cambridge Repository
Subjects: Male, Motivation, donor health, Anemia, Iron-Deficiency, Health Status, Blood Donors, Donor Selection, Hematopoiesis, Europe, Bone Density, Ferritins, Blood Component Removal, Ethnicity, Tissue and Organ Harvesting, Blood Banks, Humans, Female, donor management, conference
Abstract: The first European Conference on Donor Health and Management was held in the Hague from 3th- 5th September 2014 and hosted by Sanquin, the Dutch national blood donation organization. This is the first international conference with a focus on “donor health”, including donors of blood, organs, and other substances of human origin. The conference covered 5 main themes: Donor Health, Donor Base Management, Donor Recruitment, Donor Retention and Donor Blood Collection. This overview presents selected research topics for each of the five themes.
Published: 2015

83. The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease

Author: Astle, W.J., Elding, H., Jiang, T., Allen, D., Ruklisa, D., Mann, A.L., Mead, D., Bouman, H., Riveros-Mckay, F., Kostadima, M.A., Lambourne, J.J., Sivapalaratnam, S., Downes, K., Kundu, K., Bomba, L., Berentsen, K., Bradley, J.R., Daugherty, L.C., Delaneau, O., Freson, K., Garner, S.F., Grassi, L., Guerrero, J., Haimel, M., Janssen-Megens, E.M., Kaan, A., Kamat, M., Kim, B., Mandoli, A., Marchini, J., Martens, J.H.A., Meacham, S., Megy, K., O'Connell, J., Petersen, R., Sharifi, N., Sheard, S.M., Staley, J.R., Tuna, S., Ent, M. van der, Walter, K., Wang, S., Wheeler, E., Wilder, S.P., Iotchkova, V., Moore, C., Sambrook, J., Stunnenberg, H.G., Di Angelantonio, E., Kaptoge, S., Kuijpers, T.W., Carrillo-de-Santa-Pau, E., Juan, D., Rico, D., Valencia, A., Chen, L, Ge, B., Vasquez, L., Kwan, T., Garrido-Martin, D., Watt, S., Yang, Y., Guigo, R., Beck, S., Paul, D.S., Pastinen, T., Bujold, D., Bourque, G., Frontini, M., Danesh, J., Roberts, D.J., Ouwehand, W.H., Butterworth, A.S., Soranzo, N., Astle, W.J., Elding, H., Jiang, T., Allen, D., Ruklisa, D., Mann, A.L., Mead, D., Bouman, H., Riveros-Mckay, F., Kostadima, M.A., Lambourne, J.J., Sivapalaratnam, S., Downes, K., Kundu, K., Bomba, L., Berentsen, K., Bradley, J.R., Daugherty, L.C., Delaneau, O., Freson, K., Garner, S.F., Grassi, L., Guerrero, J., Haimel, M., Janssen-Megens, E.M., Kaan, A., Kamat, M., Kim, B., Mandoli, A., Marchini, J., Martens, J.H.A., Meacham, S., Megy, K., O'Connell, J., Petersen, R., Sharifi, N., Sheard, S.M., Staley, J.R., Tuna, S., Ent, M. van der, Walter, K., Wang, S., Wheeler, E., Wilder, S.P., Iotchkova, V., Moore, C., Sambrook, J., Stunnenberg, H.G., Di Angelantonio, E., Kaptoge, S., Kuijpers, T.W., Carrillo-de-Santa-Pau, E., Juan, D., Rico, D., Valencia, A., Chen, L, Ge, B., Vasquez, L., Kwan, T., Garrido-Martin, D., Watt, S., Yang, Y., Guigo, R., Beck, S., Paul, D.S., Pastinen, T., Bujold, D., Bourque, G., Frontini, M., Danesh, J., Roberts, D.J., Ouwehand, W.H., Butterworth, A.S., and Soranzo, N.
Abstract: Contains fulltext : 163344.pdf (Publisher’s version ) (Open Access)
Published: 2016

84. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents

Author: Di Angelantonio, E., Bhupathiraju, S. N., Wormser, D., Gao, P., Kaptoge, S., de Gonzalez, A. B., Cairns, B. J., Huxley, R., Jackson, C. L., Joshy, G., Lewington, S., Manson, J. A. E., Murphy, N., Patel, A. V., Samet, J. M., Woodward, M., Zheng, W., Zhou, M., Bansal, N., Barricarte, A., Carter, B., Cerhan, J. R., Collins, R., Smith, G. D., Fang, X., Franco, O. H., Green, J., Halsey, J., Hildebrand, J. S., Ji Jung, K., Korda, R. J., McLerran, D. F., Moore, S. C., O'Keeffe, L. M., Paige, E., Ramond, A., Reeves, G. K., Rolland, B., Sacerdote, C., Sattar, N., Anopoulou, E. S., Stevens, J., Thun, M., Ueshima, H., Yang, L., Duk Yun, Y., Willeit, P., Banks, E., Beral, V., Chen, Z., Gapstur, S. M., Gunter, M. J., Hartge, P., Jee, S. H., Lam, T. H., Peto, R., Potter, J. D., Willett, W. C., Thompson, S. G., Danesh, J., Hu, F. B., Di Angelantonio, E., Bhupathiraju, S. N., Wormser, D., Gao, P., Kaptoge, S., de Gonzalez, A. B., Cairns, B. J., Huxley, R., Jackson, C. L., Joshy, G., Lewington, S., Manson, J. A. E., Murphy, N., Patel, A. V., Samet, J. M., Woodward, M., Zheng, W., Zhou, M., Bansal, N., Barricarte, A., Carter, B., Cerhan, J. R., Collins, R., Smith, G. D., Fang, X., Franco, O. H., Green, J., Halsey, J., Hildebrand, J. S., Ji Jung, K., Korda, R. J., McLerran, D. F., Moore, S. C., O'Keeffe, L. M., Paige, E., Ramond, A., Reeves, G. K., Rolland, B., Sacerdote, C., Sattar, N., Anopoulou, E. S., Stevens, J., Thun, M., Ueshima, H., Yang, L., Duk Yun, Y., Willeit, P., Banks, E., Beral, V., Chen, Z., Gapstur, S. M., Gunter, M. J., Hartge, P., Jee, S. H., Lam, T. H., Peto, R., Potter, J. D., Willett, W. C., Thompson, S. G., Danesh, J., and Hu, F. B.
Abstract: © 2016 The Author(s). This is an Open Access article under the CC-BY license Background Overweight and obesity are increasing worldwide. To help assess their relevance to mortality in different populations we conducted individual-participant data meta-analyses of prospective studies of body-mass index (BMI), limiting confounding and reverse causality by restricting analyses to never-smokers and excluding pre-existing disease and the first 5 years of follow-up. Methods Of 10 625 411 participants in Asia, Australia and New Zealand, Europe, and North America from 239 prospective studies (median follow-up 13·7 years, IQR 11·4–14·7), 3 951 455 people in 189 studies were never-smokers without chronic diseases at recruitment who survived 5 years, of whom 385 879 died. The primary analyses are of these deaths, and study, age, and sex adjusted hazard ratios (HRs), relative to BMI 22·5–<25·0 kg/m 2 . Findings All-cause mortality was minimal at 20·0–25·0 kg/m 2 (HR 1·00, 95% CI 0·98–1·02 for BMI 20·0–<22·5 kg/m 2 ; 1·00, 0·99–1·01 for BMI 22·5–<25·0 kg/m 2 ), and increased significantly both just below this range (1·13, 1·09–1·17 for BMI 18·5–<20·0 kg/m 2 ; 1·51, 1·43–1·59 for BMI 15·0–<18·5) and throughout the overweight range (1·07, 1·07–1·08 for BMI 25·0–<27·5 kg/m 2 ; 1·20, 1·18–1·22 for BMI 27·5–<30·0 kg/m 2 ). The HR for obesity grade 1 (BMI 30·0–<35·0 kg/m 2 ) was 1·45, 95% CI 1·41–1·48; the HR for obesity grade 2 (35·0–<40·0 kg/m 2 ) was 1·94, 1·87–2·01; and the HR for obesity grade 3 (40·0&ndash
Published: 2016

85. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease

Author: Zanoni, P, Khetarpal, S, Larach, D, Hancock Cerutti, W, Millar, J, Cuchel, M, Derohannessian, S, Kontush, A, Surendran, P, Saleheen, D, Trompet, S, Wouter Jukema, J, De Craen, A, Deloukas, P, Sattar, N, Ford, I, Packard, C, Majumder, A, Alam, D, Di Angelantonio, E, Abecasis, G, Chowdhury, R, Erdmann, J, Nordestgaard, B, Nielsen, S, Tybjærg Hansen, A, Ruth Frikke Schmidt, N, Kuulasmaa, K, Liu, D, Perola, M, Blankenberg, S, Salomaa, V, Männistö, S, Amouyel, P, Arveiler, D, Ferrieres, J, Möller Nurasyid, M, Ferrario, M, Kee, F, Willer, C, Samani, N, Schunkert, H, Butterworth, A, Howson, J, Peloso, G, Stitziel, N, Danesh, J, Kathiresan, S, Rader, D, Brambilla, P, BRAMBILLA, PAOLO, Zanoni, P, Khetarpal, S, Larach, D, Hancock Cerutti, W, Millar, J, Cuchel, M, Derohannessian, S, Kontush, A, Surendran, P, Saleheen, D, Trompet, S, Wouter Jukema, J, De Craen, A, Deloukas, P, Sattar, N, Ford, I, Packard, C, Majumder, A, Alam, D, Di Angelantonio, E, Abecasis, G, Chowdhury, R, Erdmann, J, Nordestgaard, B, Nielsen, S, Tybjærg Hansen, A, Ruth Frikke Schmidt, N, Kuulasmaa, K, Liu, D, Perola, M, Blankenberg, S, Salomaa, V, Männistö, S, Amouyel, P, Arveiler, D, Ferrieres, J, Möller Nurasyid, M, Ferrario, M, Kee, F, Willer, C, Samani, N, Schunkert, H, Butterworth, A, Howson, J, Peloso, G, Stitziel, N, Danesh, J, Kathiresan, S, Rader, D, Brambilla, P, and BRAMBILLA, PAOLO
Abstract: Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a lossof-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant).
Published: 2016

86. Separate and combined associations of body-mass index andabdominal adiposity with cardiovascular disease: collaborative analysis of 58prospective studies

Author: Emerging Risk Factors Collaboration, Wormser D, Kaptoge S, Di Angelantonio E, Wood AM, Pennells L, Thompson A, Sarwar N, Kizer JR, Lawlor DA, Nordestgaard BG, Ridker P, Salomaa V, Stevens J, Woodward M, Sattar N, Collins R, Thompson SG, Whitlock G, Danesh J., PANICO, SALVATORE, Emerging Risk Factors, Collaboration, Wormser, D, Kaptoge, S, Di Angelantonio, E, Wood, Am, Pennells, L, Thompson, A, Sarwar, N, Kizer, Jr, Lawlor, Da, Nordestgaard, Bg, Ridker, P, Salomaa, V, Stevens, J, Woodward, M, Sattar, N, Collins, R, Thompson, Sg, Whitlock, G, Danesh, J., and Panico, Salvatore
Published: 2011

87. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis

Author: Emerging Risk Factors Collaboration, Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG, Collins R, Danesh JTipping RW, Ford CE, Pressel SL, Walldius G, Jungner I, Folsom AR, Chambless L, Ballantyne CM, Panagiotakos D, Pitsavos C, Chrysohoou C, Stefanadis C, Knuiman MW, Goldbourt U, Benderly M, Tanne D, Whincup P, Wannamethee SG, Morris RW, Kiechl S, Willeit J, Mayr A, Schett G, Wald N, Ebrahim S, Lawlor D, Yarnell J, Gallacher J, Casiglia E, Tikhonoff V, Nietert PJ, Sutherland SE, Bachman DL, Keil JE, Cushman M, Psaty BM, Tracy R, Tybjaerg Hansen A, Nordestgaard BG, Zacho J, Frikke Schmidt R, Giampaoli S, Palmieri L, Vanuzzo D, Pilotto L, de la Cámara AG, Gerique JA, Simons L, McCallum J, Friedlander Y, Fowkes FG, Lee A, Taylor J, Guralnik JM, Phillips CL, Wallace RB, Blazer DG, Khaw KT, Brenner H, Raum E, Müller H, Rothenbacher D, Jansson JH, Wennberg P, Nissinen A, Donfrancesco C, Salomaa V, Harald K, Jousilahti P, Vartiainen E, Woodward M, D'Agostino RB, Wolf PA, Vasan RS, Benjamin EJ, Bladbjerg EM, Jørgensen T, Møller L, Jespersen J, Dankner R, Chetrit A, Lubin F, Rosengren A, Wilhelmsen L, Lappas G, Eriksson H, Björkelund C, Lissner L, Bengtsson C, Cremer P, Nagel D, Tilvis RS, Strandberg TE, Kiyohara Y, Arima H, Doi Y, Ninomiya T, Rodriguez B, Dekker J, Nijpels G, Stehouwer CD, Rimm E, Pai JK, Sato S, Iso H, Kitamura A, Noda H, Salonen JT, Nyyssönen K, Tuomainen TP, Laukkanen JA, Deeg DJ, Bremmer MA, Meade TW, Cooper JA, Hedblad B, Berglund G, Engström G, Verschuren WM, Blokstra A, Shea S, Döring A, Koenig W, Meisinger C, Bueno de Mesquita HB, Kuller LH, Grandits G, Selmer R, Tverdal A, Nystad W, Gillum RF, Mussolino M, Hankinson S, Manson JE, Knottenbelt C, Bauer KA, Davidson K, Kirkland S, Shaffer J, Korin MR, Naito Y, Holme I, Nakagawa H, Miura K, Ducimetiere P, Jouven X, Luc G, Crespo CJ, Garcia Palmieri MR, Amouyel P, Arveiler D, Evans A, Ferrieres 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 RR, Gudnason V, Aspelund T, Sigurdsson G, Thorsson B, Trevisan M, Witteman J, Kardys I, Breteler MM, Hofman A, Tunstall Pedoe H, Tavendale R, Howard BV, Zhang Y, Best L, Umans J, Ben Shlomo Y, Davey Smith G, Onat A, Njølstad I, Mathiesen EB, Løchen ML, Wilsgaard T, Ingelsson E, Basu S, Cederholm T, Byberg L, Gaziano JM, Stampfer M, Ridker PM, Ulmer H, Diem G, Concin H, Tosetto A, Rodeghiero F, Wassertheil Smoller S, Marmot IM, Clarke R, Fletcher A, Brunner E, Shipley M, Buring J, Shepherd J, Cobbe S, Ford I, Robertson M, He Y, Ibañez AM, Feskens EJ, Walker M, Watson S, Erqou S, Lewington S, Pennells L, Perry PL, Ray KK, Sarwar N, Alexander M, Thompson A, White IR, Wood AM, Danesh J., PANICO, SALVATORE, Interne Geneeskunde, MUMC+: MA Interne Geneeskunde (3), RS: CARIM School for Cardiovascular Diseases, General practice, EMGO - Lifestyle, overweight and diabetes, Psychiatry, EMGO - Mental health, Emerging Risk Factors, Collaboration, Kaptoge, S, Di Angelantonio, E, Lowe, G, Pepys, Mb, Thompson, Sg, Collins, R, Danesh JTipping, Rw, Ford, Ce, Pressel, Sl, Walldius, G, Jungner, I, Folsom, Ar, Chambless, L, Ballantyne, Cm, Panagiotakos, D, Pitsavos, C, Chrysohoou, C, Stefanadis, C, Knuiman, Mw, Goldbourt, U, Benderly, M, Tanne, D, Whincup, P, Wannamethee, Sg, Morris, Rw, Kiechl, S, Willeit, J, Mayr, A, Schett, G, Wald, N, Ebrahim, S, Lawlor, D, Yarnell, J, Gallacher, J, Casiglia, E, Tikhonoff, V, Nietert, Pj, Sutherland, Se, Bachman, Dl, Keil, Je, Cushman, M, Psaty, Bm, Tracy, R, Tybjaerg Hansen, A, Nordestgaard, Bg, Zacho, J, Frikke Schmidt, R, Giampaoli, S, Palmieri, L, Panico, Salvatore, Vanuzzo, D, Pilotto, L, de la Cámara, Ag, Gerique, Ja, Simons, L, Mccallum, J, Friedlander, Y, Fowkes, Fg, Lee, A, Taylor, J, Guralnik, Jm, Phillips, Cl, Wallace, Rb, Blazer, Dg, Khaw, Kt, Brenner, H, Raum, E, Müller, H, Rothenbacher, D, Jansson, Jh, Wennberg, P, Nissinen, A, Donfrancesco, C, Salomaa, V, Harald, K, Jousilahti, P, Vartiainen, E, Woodward, M, D'Agostino, Rb, Wolf, Pa, Vasan, R, Benjamin, Ej, Bladbjerg, Em, Jørgensen, T, Møller, L, Jespersen, J, Dankner, R, Chetrit, A, Lubin, F, Rosengren, A, Wilhelmsen, L, Lappas, G, Eriksson, H, Björkelund, C, Lissner, L, Bengtsson, C, Cremer, P, Nagel, D, Tilvis, R, Strandberg, Te, Kiyohara, Y, Arima, H, Doi, Y, Ninomiya, T, Rodriguez, B, Dekker, J, Nijpels, G, Stehouwer, Cd, Rimm, E, Pai, Jk, Sato, S, Iso, H, Kitamura, A, Noda, H, Salonen, Jt, Nyyssönen, K, Tuomainen, Tp, Laukkanen, Ja, Deeg, Dj, Bremmer, Ma, Meade, Tw, Cooper, Ja, Hedblad, B, Berglund, G, Engström, G, Verschuren, Wm, Blokstra, A, Shea, S, Döring, A, Koenig, W, Meisinger, C, Bueno de Mesquita, Hb, Kuller, Lh, Grandits, G, Selmer, R, Tverdal, A, Nystad, W, Gillum, Rf, Mussolino, M, Hankinson, S, Manson, Je, Knottenbelt, C, Bauer, Ka, Davidson, K, Kirkland, S, Shaffer, J, Korin, Mr, Naito, Y, Holme, I, Nakagawa, H, Miura, K, Ducimetiere, P, Jouven, X, Luc, G, Crespo, Cj, Garcia Palmieri, Mr, Amouyel, P, Arveiler, D, Evans, A, Ferrieres, 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, Rr, Gudnason, V, Aspelund, T, Sigurdsson, G, Thorsson, B, Trevisan, M, Witteman, J, Kardys, I, Breteler, Mm, Hofman, A, Tunstall Pedoe, H, Tavendale, R, Howard, Bv, Zhang, Y, Best, L, Umans, J, Ben Shlomo, Y, Davey Smith, G, Onat, A, Njølstad, I, Mathiesen, Eb, Løchen, Ml, Wilsgaard, T, Ingelsson, E, Basu, S, Cederholm, T, Byberg, L, Gaziano, Jm, Stampfer, M, Ridker, Pm, Ulmer, H, Diem, G, Concin, H, Tosetto, A, Rodeghiero, F, Wassertheil Smoller, S, Marmot, Im, Clarke, R, Fletcher, A, Brunner, E, Shipley, M, Buring, J, Shepherd, J, Cobbe, S, Ford, I, Robertson, M, He, Y, Ibañez, Am, Feskens, Ej, Walker, M, Watson, S, Erqou, S, Lewington, S, Pennells, L, Perry, Pl, Ray, Kk, Sarwar, N, Alexander, M, Thompson, A, White, Ir, Wood, Am, and Danesh, J.
Subjects: Lung Diseases, Male, Databases, Factual, Plasma-fibrinogen, Blood Pressure, Coronary Disease, 030204 cardiovascular system & hematology, Associations, Body Mass Index, Low-density-lipoprotein, Leukocyte Count, 0302 clinical medicine, Risk Factors, Neoplasms, 030212 general & internal medicine, Stroke, Framingham Risk Score, biology, Smoking, 11 Medical And Health Sciences, General Medicine, Articles, Middle Aged, 3. Good health, C-Reactive Protein, Cholesterol, Regression Analysis, low-density lipoprotein cardiovascular-disease nonvascular mortality regression dilution plasma-fibrinogen mendelian randomization independent predictor prospective cohorts vascular-disease inflammation, Female, Risk assessment, medicine.medical_specialty, Alcohol Drinking, Regression dilution, Motor Activity, Risk Assessment, 03 medical and health sciences, Sex Factors, Cardiovascular-disease, General & Internal Medicine, Internal medicine, Diabetes Mellitus, medicine, Humans, Women, Risk factor, Serum Albumin, Triglycerides, Inflammation, Markers, Independent predictor, Interleukin-6, business.industry, Vascular disease, C-reactive protein, Fibrinogen, medicine.disease, Surgery, Relative risk, biology.protein, Nonvascular mortality, business, Biomarkers
Abstract: Udgivelsesdato: 2010-Jan-9 BACKGROUND: Associations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people. We assessed the associations of CRP concentration with risk of vascular and non-vascular outcomes under different circumstances. METHODS: We meta-analysed individual records of 160 309 people without a history of vascular disease (ie, 1.31 million person-years at risk, 27 769 fatal or non-fatal disease outcomes) from 54 long-term prospective studies. Within-study regression analyses were adjusted for within-person variation in risk factor levels. RESULTS: Log(e) CRP concentration was linearly associated with several conventional risk factors and inflammatory markers, and nearly log-linearly with the risk of ischaemic vascular disease and non-vascular mortality. Risk ratios (RRs) for coronary heart disease per 1-SD higher log(e) CRP concentration (three-fold higher) were 1.63 (95% CI 1.51-1.76) when initially adjusted for age and sex only, and 1.37 (1.27-1.48) when adjusted further for conventional risk factors; 1.44 (1.32-1.57) and 1.27 (1.15-1.40) for ischaemic stroke; 1.71 (1.53-1.91) and 1.55 (1.37-1.76) for vascular mortality; and 1.55 (1.41-1.69) and 1.54 (1.40-1.68) for non-vascular mortality. RRs were largely unchanged after exclusion of smokers or initial follow-up. After further adjustment for fibrinogen, the corresponding RRs were 1.23 (1.07-1.42) for coronary heart disease; 1.32 (1.18-1.49) for ischaemic stroke; 1.34 (1.18-1.52) for vascular mortality; and 1.34 (1.20-1.50) for non-vascular mortality. INTERPRETATION: CRP concentration has continuous associations with the risk of coronary heart disease, ischaemic stroke, vascular mortality, and death from several cancers and lung disease that are each of broadly similar size. The relevance of CRP to such a range of disorders is unclear. Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation. FUNDING: British Heart Foundation, UK Medical Research Council, BUPA Foundation, and GlaxoSmithKline.
Published: 2010

88. Emerging Risk Factors Collaboration. Statistical methods for the time-to-event analysis of individual participant data from multiple epidemiological studies

Author: hompson S, Kaptoge S, White I, Wood A, Thompson SG, White IR, Wood AM, Perry PL, Danesh J, Tipping RW, Ford CE, Simpson LM, Walldius G, Jungner I, Chambless LE, Panagiotakos DB, Pitsavos C, Chrysohoou C, Stefanadis C, Knuiman M, Goldbourt U, Benderly M, Tanne D, Whincup PH, Wannamethee SG, Morris RW, Willeit J, Kiechl S, Santer P, Mayr A, Lawlor DA, Yarnell JW, Gallacher J, Casiglia E, Tikhonoff V, Nietert PJ, Sutherland SE, Bachman DL, Keil JE, Cushman M, Tracy RP, Tybjærg Hansen A, Nordestgaard BG, Benn M, Frikke Schmidt R, Giampaoli S, Palmieri L, Vanuzzo D, Gómez de la Cámara A, Gómez Gerique JA, Simons L, McCallum J, Friedlander Y, Fowkes FG, Lee AJ, Taylor J, Guralnik JM, Wallace R, Guralnik J, Blazer DG, Khaw KT, Brenner H, Raum E, Müller H, Rothenbacher D, Jansson JH, Wennberg P, Nissinen A, Donfrancesco C, Salomaa V, Harald K, Jousilahti P, Vartiainen E, Woodward M, D'Agostino RB, Vasan RS, Pencina MJ, Bladbjerg EM, Jørgensen T, Møller L, Jespersen J, Dankner R, Chetrit A, Lubin F, Rosengren A, Lappas G, Björkelund C, Lissner L, Bengtsson C, Cremer P, Nagel D, Tilvis RS, Strandberg TE, Kiyohara Y, Arima H, Doi Y, Ninomiya T, Rodriguez B, Dekker JM, Nijpels G, Stehouwer CD, Rimm E, Pai JK, Sato S, Iso H, Kitamura A, Noda H, Salonen JT, Tuomainen TP, Deeg DJ, Poppelaars JL, Meade TW, Cooper JA, Hedblad B, Berglund G, Engstrom G, Verschuren WM, Blokstra A, Shea S, Döring A, Koenig W, Meisinger C, Mraz W, Bas Bueno de Mesquita H, Kuller LH, Grandits G, Selmer R, Tverdal A, Nystad W, Gillum R, Mussolino M, Hankinson S, Manson JE, Knottenbelt C, Bauer KA, Naito Y, Holme I, Nakagawa H, Miura K, Ducimetiere P, Jouven X, Crespo CJ, Garcia MR, Amouyel P, Arveiler D, Evans A, Ferrieres J, Schulte H, Assmann G, Shepherd J, Packard CJ, Sattar N, Ford I, Cantin 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, Ben Shlomo Y, Davey Smith G, Howard BV, Zhang Y, Umans J, Onat A, Wilsgaard T, Ingelsson E, Lind L, Giedraitis V, Lannfelt L, Gaziano JM, Ridker P, Ulmer H, Diem G, Concin H, Tosetto A, Rodeghiero F, Wassertheil Smoller S, Marmot M, Clarke R, Collins R, Brunner E, Shipley M, Buring J, Cobbe SM, Robertson M, He Y, Marín Ibañez A, Feskens EJ, Kromhout D, Di Angelantonio E, Erqou S, Lewington S, Orfei L, Pennells L, Ray KK, Sarwar N, Alexander M, Thompson A, Walker M, Watson S, Wensley F, Perry P, Danesh J., PANICO, SALVATORE, Hompson, S, Kaptoge, S, White, I, Wood, A, Thompson, Sg, White, Ir, Wood, Am, Perry, Pl, Danesh, J, Tipping, Rw, Ford, Ce, Simpson, Lm, Walldius, G, Jungner, I, Chambless, Le, Panagiotakos, Db, Pitsavos, C, Chrysohoou, C, Stefanadis, C, Knuiman, M, Goldbourt, U, Benderly, M, Tanne, D, Whincup, Ph, Wannamethee, Sg, Morris, Rw, Willeit, J, Kiechl, S, Santer, P, Mayr, A, Lawlor, Da, Yarnell, Jw, Gallacher, J, Casiglia, E, Tikhonoff, V, Nietert, Pj, Sutherland, Se, Bachman, Dl, Keil, Je, Cushman, M, Tracy, Rp, Tybjærg Hansen, A, Nordestgaard, Bg, Benn, M, Frikke Schmidt, R, Giampaoli, S, Palmieri, L, Panico, Salvatore, Vanuzzo, D, Gómez de la Cámara, A, Gómez Gerique, Ja, Simons, L, Mccallum, J, Friedlander, Y, Fowkes, Fg, Lee, Aj, Taylor, J, Guralnik, Jm, Wallace, R, Guralnik, J, Blazer, Dg, Khaw, Kt, Brenner, H, Raum, E, Müller, H, Rothenbacher, D, Jansson, Jh, Wennberg, P, Nissinen, A, Donfrancesco, C, Salomaa, V, Harald, K, Jousilahti, P, Vartiainen, E, Woodward, M, D'Agostino, Rb, Vasan, R, Pencina, Mj, Bladbjerg, Em, Jørgensen, T, Møller, L, Jespersen, J, Dankner, R, Chetrit, A, Lubin, F, Rosengren, A, Lappas, G, Björkelund, C, Lissner, L, Bengtsson, C, Cremer, P, Nagel, D, Tilvis, R, Strandberg, Te, Kiyohara, Y, Arima, H, Doi, Y, Ninomiya, T, Rodriguez, B, Dekker, Jm, Nijpels, G, Stehouwer, Cd, Rimm, E, Pai, Jk, Sato, S, Iso, H, Kitamura, A, Noda, H, Salonen, Jt, Tuomainen, Tp, Deeg, Dj, Poppelaars, Jl, Meade, Tw, Cooper, Ja, Hedblad, B, Berglund, G, Engstrom, G, Verschuren, Wm, Blokstra, A, Shea, S, Döring, A, Koenig, W, Meisinger, C, Mraz, W, Bas Bueno de Mesquita, H, Kuller, Lh, Grandits, G, Selmer, R, Tverdal, A, Nystad, W, Gillum, R, Mussolino, M, Hankinson, S, Manson, Je, Knottenbelt, C, Bauer, Ka, Naito, Y, Holme, I, Nakagawa, H, Miura, K, Ducimetiere, P, Jouven, X, Crespo, Cj, Garcia, Mr, Amouyel, P, Arveiler, D, Evans, A, Ferrieres, J, Schulte, H, Assmann, G, Shepherd, J, Packard, Cj, Sattar, N, Ford, I, Cantin, 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, Ben Shlomo, Y, Davey Smith, G, Howard, Bv, Zhang, Y, Umans, J, Onat, A, Wilsgaard, T, Ingelsson, E, Lind, L, Giedraitis, V, Lannfelt, L, Gaziano, Jm, Ridker, P, Ulmer, H, Diem, G, Concin, H, Tosetto, A, Rodeghiero, F, Wassertheil Smoller, S, Marmot, M, Clarke, R, Collins, R, Brunner, E, Shipley, M, Buring, J, Cobbe, Sm, Robertson, M, He, Y, Marín Ibañez, A, Feskens, Ej, Kromhout, D, Di Angelantonio, E, Erqou, S, Lewington, S, Orfei, L, Pennells, L, Ray, Kk, Sarwar, N, Alexander, M, Thompson, A, Walker, M, Watson, S, Wensley, F, Perry, P, and Danesh, J.
Published: 2010

89. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality

Author: Emerging Risk Factors Collaboration, Erqou S, Kaptoge S, Perry PL, Di Angelantonio E, Thompson A, White IR, Marcovina SM, Collins R, Thompson SG, Tipping RW, Ford CE, Simpson LM, Walldius G, Jungner I, Folsom AR, Chambless L, Panagiotakos D, Pitsavos C, Chrysohoou C, Stefanadis C, Goldbourt U, Benderly M, Tanne D, Whincup P, Wannamethee SG, Morris RW, Kiechl S, Willeit J, Santer P, Mayr A, Wald N, Ebrahim S, Lawlor D, Yarnell J, Gallacher J, Casiglia E, Tikhonoff V, Nietert PJ, Sutherland SE, Bachman DL, Cushman M, Psaty BM, Tracy R, Tybjaerg Hansen A, Nordestgaard BG, Frikke Schmidt R, Kamstrup PR, Giampaoli S, Palmieri L, Vanuzzo D, Pilotto L, Gómez de la Cámara A, Gómez Gerique JA, Simons L, McCallum J, Friedlander Y, Fowkes FG, Lee A, Smith FB, Taylor J, Guralnik JM, Phillips CL, Wallace RB, 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, Woodward M, D'Agostino RB, Wolf PA, Vasan RS, Pencina MJ, Bladbjerg EM, Jørgensen T, Møller L, Jespersen J, Dankner R, Chetrit A, Lubin F, Rosengren A, Wilhelmsen L, Lappas G, Eriksson H, Björkelund C, Lissner L, Bengtsson C, Cremer P, Nagel D, Tilvis RS, Strandberg TE, Rodriguez B, Dekker J, Nijpels G, Stehouwer CD, Rimm E, Pai JK, Sato S, Iso H, Kitamura A, Noda H, Salonen JT, Nyyssönen K, Tuomainen TP, Deeg DJ, Poppelaars JL, Hedblad B, Berglund G, Engström G, Verschuren WM, Blokstra A, Döring A, Koenig W, Meisinger C, Mraz W, Bueno de Mesquita HB, Kuller LH, Grandits G, Selmer R, Tverdal A, Nystad W, Gillum RF, Mussolino M, Hankinson S, Manson JE, Cooper JA, Bauer KA, Naito Y, Holme I, Nakagawa H, Miura K, Ducimetiere P, Jouven X, Luc G, Crespo CJ, Garcia Palmieri MR, Amouyel P, Arveiler D, Evans A, Ferrieres J, Schulte H, Assmann G, Shepherd J, Packard CJ, Sattar N, Ford I, Cantin B, Lamarche B, Després JP, Dagenais GR, Barrett Connor E, Daniels LB, Laughlin GA, Gudnason V, Aspelund T, Sigurdsson G, Thorsson B, Trevisan M, Witteman J, Kardys I, Breteler MM, Hofman A, Tunstall Pedoe H, Tavendale R, Lowe G, Ben Shlomo Y, Davey Smith G, Howard BV, Zhang Y, Best L, Umans J, Onat A, Njølstad I, Mathiesen EB, Løchen ML, Wilsgaard T, Ingelsson E, Sundström J, Lind L, Lannfelt L, Gaziano JM, Stampfer M, Ridker PM, Ulmer H, Diem G, Concin H, Tosetto A, Rodeghiero F, Marmot M, Clarke R, Fletcher A, Brunner E, Shipley M, Buring J, Cobbe S, Robertson M, He Y, Marin Ibanñez A, Feskens E, Kromhout D, Walker M, Watson S, Lewington S, Orfei L, Pennells L, Ray KK, Sarwar N, Alexander M, Wensley F, Wood AM, Danesh J., PANICO, SALVATORE, Developmental Genetics, EMGO+ - Lifestyle, Overweight and Diabetes, Emerging Risk Factors, Collaboration, Erqou, S, Kaptoge, S, Perry, Pl, Di Angelantonio, E, Thompson, A, White, Ir, Marcovina, Sm, Collins, R, Thompson, Sg, Tipping, Rw, Ford, Ce, Simpson, Lm, Walldius, G, Jungner, I, Folsom, Ar, Chambless, L, Panagiotakos, D, Pitsavos, C, Chrysohoou, C, Stefanadis, C, Goldbourt, U, Benderly, M, Tanne, D, Whincup, P, Wannamethee, Sg, Morris, Rw, Kiechl, S, Willeit, J, Santer, P, Mayr, A, Wald, N, Ebrahim, S, Lawlor, D, Yarnell, J, Gallacher, J, Casiglia, E, Tikhonoff, V, Nietert, Pj, Sutherland, Se, Bachman, Dl, Cushman, M, Psaty, Bm, Tracy, R, Tybjaerg Hansen, A, Nordestgaard, Bg, Frikke Schmidt, R, Kamstrup, Pr, Giampaoli, S, Palmieri, L, Panico, Salvatore, Vanuzzo, D, Pilotto, L, Gómez de la Cámara, A, Gómez Gerique, Ja, Simons, L, Mccallum, J, Friedlander, Y, Fowkes, Fg, Lee, A, Smith, Fb, Taylor, J, Guralnik, Jm, Phillips, Cl, Wallace, Rb, 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, Woodward, M, D'Agostino, Rb, Wolf, Pa, Vasan, R, Pencina, Mj, Bladbjerg, Em, Jørgensen, T, Møller, L, Jespersen, J, Dankner, R, Chetrit, A, Lubin, F, Rosengren, A, Wilhelmsen, L, Lappas, G, Eriksson, H, Björkelund, C, Lissner, L, Bengtsson, C, Cremer, P, Nagel, D, Tilvis, R, Strandberg, Te, Rodriguez, B, Dekker, J, Nijpels, G, Stehouwer, Cd, Rimm, E, Pai, Jk, Sato, S, Iso, H, Kitamura, A, Noda, H, Salonen, Jt, Nyyssönen, K, Tuomainen, Tp, Deeg, Dj, Poppelaars, Jl, Hedblad, B, Berglund, G, Engström, G, Verschuren, Wm, Blokstra, A, Döring, A, Koenig, W, Meisinger, C, Mraz, W, Bueno de Mesquita, Hb, Kuller, Lh, Grandits, G, Selmer, R, Tverdal, A, Nystad, W, Gillum, Rf, Mussolino, M, Hankinson, S, Manson, Je, Cooper, Ja, Bauer, Ka, Naito, Y, Holme, I, Nakagawa, H, Miura, K, Ducimetiere, P, Jouven, X, Luc, G, Crespo, Cj, Garcia Palmieri, Mr, Amouyel, P, Arveiler, D, Evans, A, Ferrieres, J, Schulte, H, Assmann, G, Shepherd, J, Packard, Cj, Sattar, N, Ford, I, Cantin, B, Lamarche, B, Després, Jp, Dagenais, Gr, Barrett Connor, E, Daniels, Lb, Laughlin, Ga, Gudnason, V, Aspelund, T, Sigurdsson, G, Thorsson, B, Trevisan, M, Witteman, J, Kardys, I, Breteler, Mm, Hofman, A, Tunstall Pedoe, H, Tavendale, R, Lowe, G, Ben Shlomo, Y, Davey Smith, G, Howard, Bv, Zhang, Y, Best, L, Umans, J, Onat, A, Njølstad, I, Mathiesen, Eb, Løchen, Ml, Wilsgaard, T, Ingelsson, E, Sundström, J, Lind, L, Lannfelt, L, Gaziano, Jm, Stampfer, M, Ridker, Pm, Ulmer, H, Diem, G, Concin, H, Tosetto, A, Rodeghiero, F, Marmot, M, Clarke, R, Fletcher, A, Brunner, E, Shipley, M, Buring, J, Cobbe, S, Robertson, M, He, Y, Marin Ibanñez, A, Feskens, E, Kromhout, D, Walker, M, Watson, S, Lewington, S, Orfei, L, Pennells, L, Ray, Kk, Sarwar, N, Alexander, M, Wensley, F, Wood, Am, and Danesh, J.
Subjects: medicine.medical_specialty, Context (language use), Coronary Disease, Article, Risk Factors, General & Internal Medicine, Internal medicine, Cause of Death, medicine, Humans, Myocardial infarction, Prospective cohort study, Stroke, biology, business.industry, 11 Medical And Health Sciences, General Medicine, Lipoprotein(a), medicine.disease, Surgery, Relative risk, Nested case-control study, biology.protein, business, Cohort study
Abstract: Udgivelsesdato: 2009-Jul-22 CONTEXT: Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein-like particle, may be associated with risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationship of Lp(a) concentration with risk of major vascular and nonvascular outcomes. STUDY SELECTION: Long-term prospective studies that recorded Lp(a) concentration and subsequent major vascular morbidity and/or cause-specific mortality published between January 1970 and March 2009 were identified through electronic searches of MEDLINE and other databases, manual searches of reference lists, and discussion with collaborators. DATA EXTRACTION: Individual records were provided for each of 126,634 participants in 36 prospective studies. During 1.3 million person-years of follow-up, 22,076 first-ever fatal or nonfatal vascular disease outcomes or nonvascular deaths were recorded, including 9336 CHD outcomes, 1903 ischemic strokes, 338 hemorrhagic strokes, 751 unclassified strokes, 1091 other vascular deaths, 8114 nonvascular deaths, and 242 deaths of unknown cause. Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. Analyses excluded participants with known preexisting CHD or stroke at baseline. DATA SYNTHESIS: Lipoprotein(a) concentration was weakly correlated with several conventional vascular risk factors and it was highly consistent within individuals over several years. Associations of Lp(a) with CHD risk were broadly continuous in shape. In the 24 cohort studies, the rates of CHD in the top and bottom thirds of baseline Lp(a) distributions, respectively, were 5.6 (95% confidence interval [CI], 5.4-5.9) per 1000 person-years and 4.4 (95% CI, 4.2-4.6) per 1000 person-years. The risk ratio for CHD, adjusted for age and sex only, was 1.16 (95% CI, 1.11-1.22) per 3.5-fold higher usual Lp(a) concentration (ie, per 1 SD), and it was 1.13 (95% CI, 1.09-1.18) following further adjustment for lipids and other conventional risk factors. The corresponding adjusted risk ratios were 1.10 (95% CI, 1.02-1.18) for ischemic stroke, 1.01 (95% CI, 0.98-1.05) for the aggregate of nonvascular mortality, 1.00 (95% CI, 0.97-1.04) for cancer deaths, and 1.00 (95% CI, 0.95-1.06) for nonvascular deaths other than cancer. CONCLUSION: Under a wide range of circumstances, there are continuous, independent, and modest associations of Lp(a) concentration with risk of CHD and stroke that appear exclusive to vascular outcomes.
Published: 2009

90. The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases

Author: Danesh, J, Erqou, S, Walker, M, Thompson, Sg, Tipping, R, Ford, C, Pressel, S, Walldius, G, Jungner, I, Folsom, Ar, Chambless, Le, Knuiman, M, Whincup, Ph, Wannamethee, Sg, Morris, Rw, Willeit, J, Kiechl, S, Santer, P, Mayr, A, Wald, N, Ebrahim, S, Lawlor, Da, Yarnell, Jw, Gallacher, J, Casiglia, Edoardo, Tikhonoff, Valerie, Nietert, Pj, Sutherland, Se, Bachman, Dl, Keil, Je, Cushman, M, Psaty, Bm, Tracy, Rp, Tybjaerg Hansen, A, Nordestgaard, Bg, Frikke Schmidt, R, Giampaoli, S, Palmieri, L, Panico, S, Vanuzzo, D, Pilotto, L, Simons, L, Mccallum, J, Friedlander, Y, Fowkes, Fg, Lee, Aj, Smith, Fb, Taylor, J, Guralnik, J, Phillips, C, Wallace, R, Blazer, D, Khaw, Kt, Jansson, Jh, Donfrancesco, C, Salomaa, V, Harald, K, Jousilahti, P, Vartiainen, E, Woodward, M, D'Agostino, Rb, Wolf, Pa, Vasan, Rs, Pencina, Mj, Bladbjerg, Em, Jorgensen, T, Moller, L, Jespersen, J, Dankner, R, Chetrit, A, Lubin, F, Rosengren, A, Wilhelmsen, L, Lappas, G, Eriksson, H, Bjorkelund, C, Cremer, P, Nagel, D, Tilvis, R, Strandberg, T, Rodriguez, B, Bouter, Lm, Heine, Rj, Dekker, Jm, Nijpels, G, Stehouwer, Cd, Rimm, E, Pai, J, Sato, S, Iso, H, Kitamura, A, Noda, H, Goldbourt, U, Salonen, Jt, Nyyssönen, K, Tuomainen, Tp, Deeg, D, Poppelaars, Jl, Meade, T, Cooper, J, Hedblad, B, Berglund, G, Engstrom, G, Döring, A, Koenig, W, Meisinger, C, Mraz, W, Kuller, L, Selmer, R, Tverdal, A, Nystad, W, Gillum, R, Mussolino, M, Hankinson, S, Manson, J, De Stavola, B, Knottenbelt, C, Cooper, Ja, Bauer, Ka, Rosenberg, Rd, Naito, Y, Holme, I, Nakagawa, H, Miura, H, Ducimetiere, P, Jouven, X, Crespo, C, Garcia Palmieri, M, Amouyel, P, Arveiler, D, Evans, A, Ferrieres, J, Schulte, H, Assmann, G, Shepherd, J, Packard, C, Sattar, N, Cantin, B, Lamarche, B, Després, Jp, Dagenais, Gr, Barrett Connor, E, Wingard, D, 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, Ben Shlomo, Y, Howard, Bv, Zhang, Y, Best, L, Umans, J, Onat, A, Meade, Tw, Njolstad, I, Mathiesen, E, Lochen, Ml, Wilsgaard, T, Gaziano, Jm, Stampfer, M, Ridker, P, Ulmer, H, Diem, G, Concin, H, Rodeghiero, F, Tosetto, A, Brunner, E, Shipley, M, Buring, J, Cobbe, Sm, Ford, I, Robertson, M, He, Y, Ibanez, Am, Feskens, Ej, Kromhout, D, Collins, R, Di Angelantonio, E, Kaptoge, S, Lewington, S, Orfei, L, Pennells, L, Perry, P, Ray, K, Sarwar, N, Scherman, M, Thompson, A, Watson, S, Wensley, F, White, Ir, Wood, Am, Emerging Risk Factors Collaboration, Interne Geneeskunde, RS: NUTRIM School of Nutrition and Translational Research in Metabolism, RS: CARIM School for Cardiovascular Diseases, Movement Behavior, Executive board Vrije Universiteit, Clinical Child and Family Studies, Sociology and Social Gerontology, Earth and Climate, Environmental Policy Analysis, Developmental Genetics, Danesh, J, Erqou, S, Walker, M, Thompson, Sg, Tipping, R, Ford, C, Pressel, S, Walldius, G, Jungner, I, Folsom, Ar, Chambless, Le, Knuiman, M, Whincup, Ph, Wannamethee, Sg, Morris, Rw, Willeit, J, Kiechl, S, Santer, P, Mayr, A, Wald, N, Ebrahim, S, Lawlor, Da, Yarnell, Jw, Gallacher, J, Casiglia, E, Tikhonoff, V, Nietert, Pj, Sutherland, Se, Bachman, Dl, Keil, Je, Cushman, M, Psaty, Bm, Tracy, Rp, Tybjaerg Hansen, A, Nordestgaard, Bg, Frikke Schmidt, R, Giampaoli, S, Palmieri, L, Panico, Salvatore, Vanuzzo, D, Pilotto, L, Simons, L, Mccallum, J, Friedlander, Y, Fowkes, Fg, Lee, Aj, Smith, Fb, Taylor, J, Guralnik, J, Phillips, C, Wallace, R, Blazer, D, Khaw, Kt, Jansson, Jh, Donfrancesco, C, Salomaa, V, Harald, K, Jousilahti, P, Vartiainen, E, Woodward, M, D'Agostino, Rb, Wolf, Pa, Vasan, R, Pencina, Mj, Bladbjerg, Em, Jorgensen, T, Moller, L, Jespersen, J, Dankner, R, Chetrit, A, Lubin, F, Rosengren, A, Wilhelmsen, L, Lappas, G, Eriksson, H, Bjorkelund, C, Cremer, P, Nagel, D, Tilvis, R, Strandberg, T, Rodriguez, B, Bouter, Lm, Heine, Rj, Dekker, Jm, Nijpels, G, Stehouwer, Cd, Rimm, E, Pai, J, Sato, S, Iso, H, Kitamura, A, Noda, H, Goldbourt, U, Salonen, Jt, Nyyssönen, K, Tuomainen, Tp, Deeg, D, Poppelaars, Jl, Meade, T, Cooper, J, Hedblad, B, Berglund, G, Engstrom, G, Döring, A, Koenig, W, Meisinger, C, Mraz, W, Kuller, L, Selmer, R, Tverdal, A, Nystad, W, Gillum, R, Mussolino, M, Hankinson, S, Manson, J, De Stavola, B, Knottenbelt, C, Cooper, Ja, Bauer, Ka, Rosenberg, Rd, Naito, Y, Holme, I, Nakagawa, H, Miura, H, Ducimetiere, P, Jouven, X, Crespo, C, Garcia Palmieri, M, Amouyel, P, Arveiler, D, Evans, A, Ferrieres, J, Schulte, H, Assmann, G, Shepherd, J, Packard, C, Sattar, N, Cantin, B, Lamarche, B, Després, Jp, Dagenais, Gr, Barrett Connor, E, Wingard, D, 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, Ben Shlomo, Y, Howard, Bv, Zhang, Y, Best, L, Umans, J, Onat, A, Meade, Tw, Njolstad, I, Mathiesen, E, Lochen, Ml, Wilsgaard, T, Gaziano, Jm, Stampfer, M, Ridker, P, Ulmer, H, Diem, G, Concin, H, Rodeghiero, F, Tosetto, A, Brunner, E, Shipley, M, Buring, J, Cobbe, Sm, Ford, I, Robertson, M, He, Y, Ibanez, Am, Feskens, Ej, Kromhout, D, Collins, R, Di Angelantonio, E, Kaptoge, S, Lewington, S, Orfei, L, Pennells, L, Perry, P, Ray, K, Sarwar, N, Scherman, M, Thompson, A, Watson, S, Wensley, F, White, Ir, and Wood, A. M.
Subjects: Databases, Factual, Nutrition and Disease, Epidemiology, Inflammatory markers, middle-aged men, Disease, Leukocyte Count, c-reactive protein, Risk Factors, Voeding en Ziekte, adult-treatment-panel, Prospective Studies, Myocardial infarction, Prospective cohort study, education.field_of_study, biology, plasma-fibrinogen, Asia, Eastern, Confounding, density-lipoprotein cholesterol, Cardiovascular disease, Lipids, myocardial-infarction, Coronary heart disease, Cardiovascular Diseases, Meta-analysis, Lipoproteins, HDL, high blood cholesterol, medicine.medical_specialty, low-dose aspirin, Population, 10-year follow-up, SDG 3 - Good Health and Well-being, Albumins, medicine, Humans, education, Triglycerides, VLAG, Inflammation, Estimation, business.industry, C-reactive protein, medicine.disease, Surgery, Emergency medicine, biology.protein, business, coronary-heart-disease, Biomarkers
Abstract: Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age-and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily,with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.
Published: 2007

91. Socioeconomic Deprivation Is Associated with Worse Survival After Heart Transplantation in England

Author: Evans, J.D., primary, Kaptoge, S., additional, Di Angelantonio, E., additional, Lewis, C., additional, Parameshwar, J., additional, and Pettit, S.J., additional
Published: 2016
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92. Interventions to reduce vasovagal reactions in blood donors: a systematic review and meta-analysis

Author: Fisher, S. A., primary, Allen, D., additional, Dorée, C., additional, Naylor, J., additional, Di Angelantonio, E., additional, and Roberts, D. J., additional
Published: 2016
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93. Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis

Author: Freitag, DF, Butterworth, AS, Willeit, P, Howson, JMM, Burgess, S, Kaptoge, S, Young, R, Ho, WK, Wood, AM, Sweeting, M, Spackman, S, Staley, JR, Ramond, A, Harshfield, E, Nielsen, SF, Grande, P, Lange, LA, Bown, MJ, Jones, GT, Scott, RA, Bevan, S, Porcu, E, Thorleifsson, G, Zeng, LY, Kessler, T, Nikpay, M, Do, R, Zhang, WH, Hopewell, JC, Kleber, M, Delgado, GE, Nelson, CP, Goel, A, Bis, JC, Dehghan, Abbas, Ligthart, Symen, Smith, AV, Qu, LM, van 't Hof, FNG, de Bakker, PIW, Baas, AF, van Rij, A, Tromp, G, Kuivaniemi, H, Ritchie, MD, Verma, SS, Crawford, DC, Malinowski, J, de Andrade, M, Kullo, IJ, Peissig, PL, McCarty, CA, Bottinger, EP, Gottesman, O, Crosslin, DR, Carrell, DS, Rasmussen-Torvik, LJ, Pacheco, JA, Huang, J, Timpson, NJ, Kettunen, J, Ala-Korpela, M, Mitchell, GF, Parsa, A, Wilkinson, IB, Gorski, M, Li, Yunlei, Franceschini, N, Keller, MF, Ganesh, SK, Langefeld, CD, Bruijn, L, Brown, MA, Evans, DM, Baltic, S, Ferreira, MA, Baurecht, H, Weidinger, S, Franke, A, Lubitz, SA, Muller-Nurasyid, M, Felix, Janine, Smith, NL, Sudman, M, Thompson, SD, Zeggini, E, Panoutsopoulou, K, Nalls, MA, Singleton, A, Polychronakos, C, Bradfield, JP, Hakonarson, H, Easton, DF, Thompson, D, Tomlinson, IP, Dunlop, M, Hemminki, K, Morgan, G, Eisen, T, Goldschmidt, H, Allan, JM, Henrion, M, Whiffin, N, Wang, YF, Chubb, D, Houlston, RS, Iles, MM, Bishop, DT, Law, MH, Hayward, NK, Luo, Y, Nejentsev, S, Barbalic, M, Crossman, D, Sanna, S, Soranzo, N, Markus, HS, Wareham, NJ, Rader, DJ, O Reilly, M, Assimes, T, Harris, TB, Hofman, Bert, Franco Duran, OH, Gudnason, V, Tracy, R, Psaty, BM, Farrall, M, Watkins, H, Hall, AS, Samani, NJ, Marz, W, Clarke, R, Collins, R, Kooner, JS, Chambers, JC, Kathiresan, S, McPherson, R, Erdmann, J, Kastrati, A, Schunkert, H, Stefansson, K, Thorsteinsdottir, U, Walston, JD, Tybjaerg-Hansen, A, Alam, DS, Majumder, AA, Di Angelantonio, E, Chowdhury, R, Nordestgaard, BG, Saleheen, D, Thompson, SG, Danesh, J, Freitag, DF, Butterworth, AS, Willeit, P, Howson, JMM, Burgess, S, Kaptoge, S, Young, R, Ho, WK, Wood, AM, Sweeting, M, Spackman, S, Staley, JR, Ramond, A, Harshfield, E, Nielsen, SF, Grande, P, Lange, LA, Bown, MJ, Jones, GT, Scott, RA, Bevan, S, Porcu, E, Thorleifsson, G, Zeng, LY, Kessler, T, Nikpay, M, Do, R, Zhang, WH, Hopewell, JC, Kleber, M, Delgado, GE, Nelson, CP, Goel, A, Bis, JC, Dehghan, Abbas, Ligthart, Symen, Smith, AV, Qu, LM, van 't Hof, FNG, de Bakker, PIW, Baas, AF, van Rij, A, Tromp, G, Kuivaniemi, H, Ritchie, MD, Verma, SS, Crawford, DC, Malinowski, J, de Andrade, M, Kullo, IJ, Peissig, PL, McCarty, CA, Bottinger, EP, Gottesman, O, Crosslin, DR, Carrell, DS, Rasmussen-Torvik, LJ, Pacheco, JA, Huang, J, Timpson, NJ, Kettunen, J, Ala-Korpela, M, Mitchell, GF, Parsa, A, Wilkinson, IB, Gorski, M, Li, Yunlei, Franceschini, N, Keller, MF, Ganesh, SK, Langefeld, CD, Bruijn, L, Brown, MA, Evans, DM, Baltic, S, Ferreira, MA, Baurecht, H, Weidinger, S, Franke, A, Lubitz, SA, Muller-Nurasyid, M, Felix, Janine, Smith, NL, Sudman, M, Thompson, SD, Zeggini, E, Panoutsopoulou, K, Nalls, MA, Singleton, A, Polychronakos, C, Bradfield, JP, Hakonarson, H, Easton, DF, Thompson, D, Tomlinson, IP, Dunlop, M, Hemminki, K, Morgan, G, Eisen, T, Goldschmidt, H, Allan, JM, Henrion, M, Whiffin, N, Wang, YF, Chubb, D, Houlston, RS, Iles, MM, Bishop, DT, Law, MH, Hayward, NK, Luo, Y, Nejentsev, S, Barbalic, M, Crossman, D, Sanna, S, Soranzo, N, Markus, HS, Wareham, NJ, Rader, DJ, O Reilly, M, Assimes, T, Harris, TB, Hofman, Bert, Franco Duran, OH, Gudnason, V, Tracy, R, Psaty, BM, Farrall, M, Watkins, H, Hall, AS, Samani, NJ, Marz, W, Clarke, R, Collins, R, Kooner, JS, Chambers, JC, Kathiresan, S, McPherson, R, Erdmann, J, Kastrati, A, Schunkert, H, Stefansson, K, Thorsteinsdottir, U, Walston, JD, Tybjaerg-Hansen, A, Alam, DS, Majumder, AA, Di Angelantonio, E, Chowdhury, R, Nordestgaard, BG, Saleheen, D, Thompson, SG, and Danesh, J
Abstract: Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who ca
Published: 2015

94. Evaluation of Effectiveness and Cost-Effectiveness of a Clinical Decision Support System in Managing Hypertension in Resource Constrained Primary Health Care Settings: Results From a Cluster Randomized Trial

Author: Anchala, R, Kaptoge, S, Pant, H, Di Angelantonio, E, Franco Duran, OH, Prabhakaran, D, Anchala, R, Kaptoge, S, Pant, H, Di Angelantonio, E, Franco Duran, OH, and Prabhakaran, D
Abstract: Background-Randomized control trials from the developed world report that clinical decision support systems (DSS) could provide an effective means to improve the management of hypertension (HTN). However, evidence from developing countries in this regard is rather limited, and there is a need to assess the impact of a clinical DSS on managing HTN in primary health care center (PHC) settings. Methods and Results-We performed a cluster randomized trial to test the effectiveness and cost-effectiveness of a clinical DSS among Indian adult hypertensive patients (between 35 and 64 years of age), wherein 16 PHC clusters from a district of Telangana state, India, were randomized to receive either a DSS or a chart-based support (CBS) system. Each intervention arm had 8 PHC clusters, with a mean of 102 hypertensive patients per cluster (n= 845 in DSS and 783 in CBS groups). Mean change in systolic blood pressure (SBP) from baseline to 12 months was the primary endpoint. The mean difference in SBP change from baseline between the DSS and CBS at the 12th month of follow-up, adjusted for age, sex, height, waist, body mass index, alcohol consumption, vegetable intake, pickle intake, and baseline differences in blood pressure, was -6.59 mm Hg (95% confidence interval: -12.18 to -1.42; P=0.021). The cost-effective ratio for CBS and DSS groups was $ 96.01 and $ 36.57 per mm of SBP reduction, respectively. Conclusion-Clinical DSS are effective and cost-effective in the management of HTN in resource-constrained PHC settings.
Published: 2015

95. Body-mass index, abdominal adiposity, and cardiovascular risk Reply

Author: Wormser, D, Di Angelantonio, E, Sattar, N, Collins, R, Thompson, S, Danesh, J, and Collaboratio, E
Published: 2011

96. Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data

Author: Wensley, F, Gao, P, Burgess, S, Kaptoge, S, Di Angelantonio, E, Shah, T, Engert, JC, Clarke, R, Davey-Smith, G, Nordestgaard, BG, Saleheen, D, Samani, NJ, Sandhu, M, Anand, S, Pepys, MB, Smeeth, L, Whittaker, J, Casas, JP, Thompson, SG, Hingorani, AD, Danesh, J, Eiriksdottir, G, Harris, TB, Launer, LJ, Gudnason, V, Folsom, AR, Andrews, G, Ballantyne, CM, Hall, AS, Braund, PS, Balmforth, AJ, Whincup, PH, Morris, R, Lawlor, DA, Lowe, GDO, Timpson, N, Ebrahim, S, Ben-Shlomo, Y, Tybjaerg-Hansen, A, Zacho, J, Brown, M, Ricketts, SL, Ashford, S, Lange, L, Reiner, A, Cushman, M, Tracy, R, Wu, C, Ge, J, Zou, Y, Sun, A, Hung, J, McQuillan, B, Thompson, P, Beilby, J, Warrington, N, Palmer, LJ, Wanner, C, Drechsler, C, Hoffmann, MM, Fowkes, FGR, Tzoulaki, I, Kumari, M, Miller, M, Marmot, M, Onland-Moret, C, van der Schouw, YT, Boer, JM, Wijmenga, C, Khaw, K-T, Vasan, RS, Schnabel, RB, Yamamoto, JF, Benjamin, EJ, Schunkert, H, Erdmann, J, Koenig, IR, Hengstenberg, C, Chiodini, B, Franzosi, MG, Pietri, S, Gori, F, Rudock, M, Liu, Y, Lohman, K, Humphries, SE, Hamsten, A, Norman, PE, Hankey, GJ, Jamrozik, K, Rimm, EB, Pai, JK, Psaty, BM, Heckbert, SR, Bis, JC, Yusuf, S, Xie, C, Collins, R, Bennett, D, Kooner, J, Chambers, J, Elliott, P, Maerz, W, Kleber, ME, Boehm, BO, Winkelmann, BR, Melander, O, Berglund, G, Koenig, W, Thorand, B, Baumert, J, Peters, A, Manson, J, Cooper, JA, Talmud, PJ, Ladenvall, P, Johansson, L, Jansson, J-H, Hallmans, G, Reilly, MP, Qu, L, Li, M, Rader, DJ, Watkins, H, Hopewell, J, Frossard, P, Sattar, N, Robertson, M, Shepherd, J, Schaefer, E, Hofman, A, Witteman, JCM, Kardys, I, Dehghan, A, de Faire, U, Bennet, A, Gigante, B, Leander, K, Peters, B, Maitland-van der Zee, AH, de Boer, A, Klungel, O, Greenland, P, Dai, J, Liu, S, Brunner, E, Kivimaki, M, O'Reilly, D, Ford, I, Packard, CJ, Dis, CRPCH, CIHDS, CC, CUPID, C, Medical Research Council (MRC), University of Groningen, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Pulmonology, and Coronel Institute of Occupational Health
Subjects: Male, Coronary Disease, Bioinformatics, Gene Frequency, MARKERS, Polymorphism (computer science), Risk Factors, Myocardial infarction, Prospective Studies, Prospective cohort study, General Environmental Science, Genetics, RISK, biology, General Engineering, Mendelian Randomization Analysis, General Medicine, Middle Aged, C-Reactive Protein, 1117 Public Health And Health Services, CARDIOVASCULAR-DISEASE, Meta-analysis, symbols, Female, Life Sciences & Biomedicine, Ischaemic Heart Disease, Polymorphism, Single Nucleotide, Molecular Genetics, symbols.namesake, Medicine, General & Internal, INFLAMMATION, Drugs: Cardiovascular System, General & Internal Medicine, medicine, INSTRUMENTAL VARIABLES, Humans, C Reactive Protein Coronary Heart Disease Genetics Collaboration (CCGC), Allele frequency, METAANALYSIS, POLYMORPHISMS, Science & Technology, business.industry, Research, C-reactive protein, medicine.disease, GENE, MYOCARDIAL-INFARCTION, ATHEROSCLEROSIS, Mendelian inheritance, biology.protein, General Earth and Planetary Sciences, business
Abstract: Objective To use genetic variants as unconfounded proxies of C reactive protein concentration to study its causal role in coronary heart disease. Design Mendelian randomisation meta-analysis of individual participant data from 47 epidemiological studies in 15 countries. Participants 194 418 participants, including 46 557 patients with prevalent or incident coronary heart disease. Information was available on four CRP gene tagging single nucleotide polymorphisms (rs3093077, rs1205, rs1130864, rs1800947), concentration of C reactive protein, and levels of other risk factors. Main outcome measures Risk ratios for coronary heart disease associated with genetically raised C reactive protein versus risk ratios with equivalent differences in C reactive protein concentration itself, adjusted for conventional risk factors and variability in risk factor levels within individuals. Results CRP variants were each associated with up to 30% per allele difference in concentration of C reactive protein (P
Published: 2011

97. Lipoprotein-associated phospholipase A(2) activity and mass in relation to vascular disease and nonvascular mortality

Author: Parish, S, Offer, A, Thompson, A, Link, E, Di Angelantonio, E, Bowman, L, Armitage, J, Danesh, J, Collins, R, and Collaborati, H
Published: 2010

98. CLINICAL OUTCOMES ASSOCIATED WITH ENDOSCOPIC RADIAL ARTERY HARVEST: A SYSTEMATIC REVIEW AND SELECTIVE META-ANALYSIS

Author: Burns, D.J., primary and Di Angelantonio, E., additional
Published: 2015
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99. Bayesian methods for meta-analysis of causal relationships estimated using genetic instrumental variables

Author: Burgess, Stephen, Thompson, Simon G, CRP CHD Genetics Collaboration, Burgess, S, Thompson, SG, Andrews, G, Samani, NJ, Hall, A, Whincup, P, Morris, R, Lawlor, DA, Davey Smith, G, Timpson, N, Ebrahim, S, Ben-Shlomo, Y, Brown, M, Ricketts, S, Sandhu, M, Reiner, A, Psaty, B, Lange, L, Cushman, M, Hung, J, Thompson, P, Beilby, J, Warrington, N, Palmer, LJ, Nordestgaard, BG, Tybjaerg-Hansen, A, Zacho, J, Wu, C, Lowe, G, Tzoulaki, I, Kumari, M, Yamamoto, JF, Chiodini, B, Franzosi, M, Hankey, GJ, Jamrozik, K, Palmer, L, Rimm, E, Pai, J, Heckbert, S, Bis, J, Anand, S, Engert, J, Collins, R, Clarke, R, Melander, O, Berglund, G, Ladenvall, P, Johansson, L, Jansson, J-H, Hallmans, G, Hingorani, A, Humphries, S, Manson, J, Watkins, H, Hopewell, J, Saleheen, D, Frossard, R, Danesh, J, Sattar, N, Robertson, M, Shepherd, J, Schaefer, E, Hofman, A, Witteman, JCM, Kardys, I, de Faire, U, Bennet, A, Ford, I, Packard, C, Lawlor, Debbie A, Davey Smith, George, Casas, JP, Smeeth, L, Wensley, F, Bowden, J, Di Angelantonio, E, Gao, P, Shah, T, Verzilli, C, Walker, M, Whittaker, J, Danesh, John [0000-0003-1158-6791], Sandhu, Manjinder [0000-0002-2725-142X], Burgess, Stephen [0000-0001-5365-8760], Di Angelantonio, Emanuele [0000-0001-8776-6719], Thompson, Simon [0000-0002-5274-7814], and Apollo - University of Cambridge Repository
Subjects: Genetic Markers, C-Reactive Protein, Models, Statistical, Phenotype, Meta-Analysis as Topic, Fibrinogen, Humans, Bayes Theorem, Biostatistics, Polymorphism, Single Nucleotide
Abstract: Genetic markers can be used as instrumental variables, in an analogous way to randomization in a clinical trial, to estimate the causal relationship between a phenotype and an outcome variable. Our purpose is to extend the existing methods for such Mendelian randomization studies to the context of multiple genetic markers measured in multiple studies, based on the analysis of individual participant data. First, for a single genetic marker in one study, we show that the usual ratio of coefficients approach can be reformulated as a regression with heterogeneous error in the explanatory variable. This can be implemented using a Bayesian approach, which is next extended to include multiple genetic markers. We then propose a hierarchical model for undertaking a meta-analysis of multiple studies, in which it is not necessary that the same genetic markers are measured in each study. This provides an overall estimate of the causal relationship between the phenotype and the outcome, and an assessment of its heterogeneity across studies. As an example, we estimate the causal relationship of blood concentrations of C-reactive protein on fibrinogen levels using data from 11 studies. These methods provide a flexible framework for efficient estimation of causal relationships derived from multiple studies. Issues discussed include weak instrument bias, analysis of binary outcome data such as disease risk, missing genetic data, and the use of haplotypes.
Published: 2010

100. Bayesian methods for meta-analysis of causal relationships estimated using genetic instrumental variables

Author: Burgess, S, Thompson, SG, Andrews, G, Samani, NJ, Hall, A, Whincup, P, Morris, R, Lawlor, DA, Davey Smith, G, Timpson, N, Ebrahim, S, Ben-Shlomo, Y, Brown, M, Ricketts, S, Sandhu, M, Reiner, A, Psaty, B, Lange, L, Cushman, M, Hung, J, Thompson, P, Beilby, J, Warrington, N, Palmer, LJ, Nordestgaard, BG, Tybjaerg-Hansen, A, Zacho, J, Wu, C, Lowe, G, Tzoulaki, I, Kumari, M, Yamamoto, JF, Chiodini, B, Franzosi, M, Hankey, GJ, Jamrozik, K, Palmer, L, Rimm, E, Pai, J, Heckbert, S, Bis, J, Anand, S, Engert, J, Collins, R, Clarke, R, Melander, O, Berglund, G, Ladenvall, P, Johansson, L, Jansson, JH, Hallmans, G, Hingorani, A, Humphries, S, Manson, J, Watkins, H, Hopewell, J, Saleheen, D, Frossard, R, Danesh, J, Sattar, N, Robertson, M, Shepherd, J, Schaefer, E, Hofman, A, Witteman, JC, Kardys, I, de Faire, U, Bennet, A, Ford, I, Packard, C, Casas, JP, Smeeth, L, Wensley, F, Bowden, J, Di Angelantonio, E, Gao, P, Shah, T, Verzilli, C, Walker, M, and Whittaker, J
Subjects: Genetic Markers, Statistics and Probability, Epidemiology, Bayesian probability, Context (language use), Bayes Theorem, Biostatistics, Polymorphism, Single Nucleotide, Article, Hierarchical database model, Bayes' theorem, Meta-Analysis as Topic, Statistics, Mendelian randomization, Econometrics, Humans, Models, Statistical, Instrumental variable, C-Reactive Protein/genetics/metabolism, Fibrinogen, Regression, Fibrinogen/metabolism, C-Reactive Protein, Phenotype, Meta-analysis
Abstract: Genetic markers can be used as instrumental variables, in an analogous way to randomization in a clinical trial, to estimate the causal relationship between a phenotype and an outcome variable. Our purpose is to extend the existing methods for such Mendelian randomization studies to the context of multiple genetic markers measured in multiple studies, based on the analysis of individual participant data. First, for a single genetic marker in one study, we show that the usual ratio of coefficients approach can be reformulated as a regression with heterogeneous error in the explanatory variable. This can be implemented using a Bayesian approach, which is next extended to include multiple genetic markers. We then propose a hierarchical model for undertaking a meta-analysis of multiple studies, in which it is not necessary that the same genetic markers are measured in each study. This provides an overall estimate of the causal relationship between the phenotype and the outcome, and an assessment of its heterogeneity across studies. As an example, we estimate the causal relationship of blood concentrations of C-reactive protein on fibrinogen levels using data from 11 studies. These methods provide a flexible framework for efficient estimation of causal relationships derived from multiple studies. Issues discussed include weak instrument bias, analysis of binary outcome data such as disease risk, missing genetic data, and the use of haplotypes. Stat Med
Published: 2010

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