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8. 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

9. 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

10. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis

Author

Chronic Kidney Disease Prognosis Consortium, Matsushita, K, van der Velde, M, Astor, Bc, Woodward, M, Levey, As, de Jong PE, Coresh, J, Investigators/Collaborators: Levey AS, Gansevoort R. T., El Nahas, M, Eckardt, Ku, Kasiske, Bl, Tonelli, M, Hemmelgarn, B, Wang, Y, Atkins, Rc, Polkinghorne, Kr, Chadban, Sj, Shankar, A, Klein, R, Klein, Be, Wang, H, Wang, F, Zhang, L, Liu, L, Shlipak, M, Sarnak, Mj, Katz, R, Fried, Lp, Jafar, T, Islam, M, Hatcher, J, Poulter, N, Chaturvedi, N, Rothenbacher, D, Brenner, H, Raum, E, Koenig, W, Fox, Cs, Hwang, Sj, Meigs, Jb, Cirillo, Massimo, Hallan, S, Lydersen, S, Holmen, J, Roderick, P, Nitsch, D, Fletcher, A, Bulpitt, C, Ohkubo, T, Metoki, H, Nakayama, M, Kikuya, M, Imai, Y, Gansevoort, Rt, Jassal, Sk, Barrett Connor, E, Bergstrom, J, Warnock, Dg, Muntner, P, Judd, S, Mcclellan, Wm, Cushman, M, Howard, G, Mcclure, La, Jee, Sh, Kimm, H, Yun, Je, Wen, Cp, Wen, Sf, Tsao, Ck, Tsai, Mk, Arnlöv, J, Auguste, P, Veldhuis, K, Camarata, L, Thomas, B, Manley, T., Chronic Kidney Disease Prognosis, Consortium, Matsushita, K, van der Velde, M, Astor, Bc, Woodward, M, Levey, A, de Jong, Pe, Coresh, J, Investigators/Collaborators: Levey AS, Gansevoort R. T., El Nahas, M, Eckardt, Ku, Kasiske, Bl, Tonelli, M, Hemmelgarn, B, Wang, Y, Atkins, Rc, Polkinghorne, Kr, Chadban, Sj, Shankar, A, Klein, R, Klein, Be, Wang, H, Wang, F, Zhang, L, Liu, L, Shlipak, M, Sarnak, Mj, Katz, R, Fried, Lp, Jafar, T, Islam, M, Hatcher, J, Poulter, N, Chaturvedi, N, Rothenbacher, D, Brenner, H, Raum, E, Koenig, W, Fox, C, Hwang, Sj, Meigs, Jb, Cirillo, Massimo, Hallan, S, Lydersen, S, Holmen, J, Roderick, P, Nitsch, D, Fletcher, A, Bulpitt, C, Ohkubo, T, Metoki, H, Nakayama, M, Kikuya, M, Imai, Y, Gansevoort, Rt, Jassal, Sk, Barrett Connor, E, Bergstrom, J, Warnock, Dg, Muntner, P, Judd, S, Mcclellan, Wm, Cushman, M, Howard, G, Mcclure, La, Jee, Sh, Kimm, H, Yun, Je, Wen, Cp, Wen, Sf, Tsao, Ck, Tsai, Mk, Arnlöv, J, Auguste, P, Veldhuis, K, Camarata, L, Thomas, B, Manley, T., Cardiovascular Centre (CVC), and Groningen Kidney Center (GKC)

Subjects
Male, CHRONIC KIDNEY-DISEASE, medicine.medical_specialty, Pathology, Population, Urology, Renal function, POOLED ANALYSIS, chemistry.chemical_compound, RISK-FACTOR, CYSTATIN-C, medicine, Risk of mortality, EQUATION, Albuminuria, Humans, Risk factor, Mortality, education, OLDER-ADULTS, Aged, Proportional Hazards Models, Creatinine, education.field_of_study, OUTCOMES, SERUM CREATININE, business.industry, Hazard ratio, General Medicine, Middle Aged, medicine.disease, PREVALENCE, RENAL-DISEASE, chemistry, Cardiovascular Diseases, Chronic Disease, Female, Kidney Diseases, medicine.symptom, business, Kidney disease, Glomerular Filtration Rate
Abstract

BACKGROUND: Substantial controversy surrounds the use of estimated glomerular filtration rate (eGFR) and albuminuria to define chronic kidney disease and assign its stages. We undertook a meta-analysis to assess the independent and combined associations of eGFR and albuminuria with mortality. METHODS: In this collaborative meta-analysis of general population cohorts, we pooled standardised data for all-cause and cardiovascular mortality from studies containing at least 1000 participants and baseline information about eGFR and urine albumin concentrations. Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality associated with eGFR and albuminuria, adjusted for potential confounders. FINDINGS: The analysis included 105,872 participants (730,577 person-years) from 14 studies with urine albumin-to-creatinine ratio (ACR) measurements and 1,128,310 participants (4,732,110 person-years) from seven studies with urine protein dipstick measurements. In studies with ACR measurements, risk of mortality was unrelated to eGFR between 75 mL/min/1.73 m(2) and 105 mL/min/1.73 m(2) and increased at lower eGFRs. Compared with eGFR 95 mL/min/1.73 m(2), adjusted HRs for all-cause mortality were 1.18 (95% CI 1.05-1.32) for eGFR 60 mL/min/1.73 m(2), 1.57 (1.39-1.78) for 45 mL/min/1.73 m(2), and 3.14 (2.39-4.13) for 15 mL/min/1.73 m(2). ACR was associated with risk of mortality linearly on the log-log scale without threshold effects. Compared with ACR 0.6 mg/mmol, adjusted HRs for all-cause mortality were 1.20 (1.15-1.26) for ACR 1.1 mg/mmol, 1.63 (1.50-1.77) for 3.4 mg/mmol, and 2.22 (1.97-2.51) for 33.9 mg/mmol. eGFR and ACR were multiplicatively associated with risk of mortality without evidence of interaction. Similar findings were recorded for cardiovascular mortality and in studies with dipstick measurements. INTERPRETATION: eGFR less than 60 mL/min/1.73 m(2) and ACR 1.1 mg/mmol (10 mg/g) or more are independent predictors of mortality risk in the general population. This study provides quantitative data for use of both kidney measures for risk assessment and definition and staging of chronic kidney disease. FUNDING: Kidney Disease: Improving Global Outcomes (KDIGO), US National Kidney Foundation, and Dutch Kidney Foundation.

Published
2010

11. 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

12. 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

13. Kidney function, albuminuria and risk of cardiovascular disease events in a population of older adults by creatinine- and cystatin C-based estimating equations

Author

Rothenbacher, D, Schöttker, B, Raum, E, Müller, H, Koenig, W, and Brenner, H

Subjects
ddc: 610, estimating equations, cystatin C, creatinine, cohort study, 610 Medical sciences, Medicine, kidney function, GFR
Abstract

Introduction: Kidney function is an established risk factor for cardiovascular disease (CVD) events [ref:1]. In a high risk CVD population it had been suggested that cystatin C based equations to estimate glomerular filtration rate (eGFR) show better prognostic value than creatinine (Cr) based[for full text, please go to the a.m. URL], Mainz//2011; 56. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 6. Jahrestagung der Deutschen Gesellschaft für Epidemiologie (DGEpi)

Published
2011
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14. Prognostic value of haemoglobin A1c and fasting plasma glucose for incident diabetes in a cohort of elderly and implications for screening

Author

Schöttker, B, Raum, E, Rothenbacher, D, Müller, H, and Brenner, H

Subjects
Fasting Plasma Glucose, Pre-Diabetes, Diabetes mellitus type 2, Elderly, ddc: 610, endocrine system diseases, Hemoglobin A1c, Screening Strategies, nutritional and metabolic diseases, 610 Medical sciences, Medicine, Prediction, Cohort Study
Abstract

Objective: The aim of this analysis is to compare screening strategies with haemoglobin A1c (A1C), fasting plasma glucose (FPG) or combined measures in the identification of individuals at high risk for diabetes. Methods: Applying American Diabetes Association (ADA) thresholds for FPG and A1C screening,[for full text, please go to the a.m. URL], Mainz//2011; 56. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 6. Jahrestagung der Deutschen Gesellschaft für Epidemiologie (DGEpi)

Published
2011
Full Text
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15. Statistical methods for the time-to-event analysis of individual participant data from multiple epidemiological studies

Author

Thompson, S. Kaptoge, S. White, I. Wood, A. Perry, P. Danesh, J. The Emerging Risk Factors Collaboration Thompson, S.G. Kaptoge, S. White, I.R. Wood, A.M. Perry, P.L. Tipping, R.W. Ford, C.E. Simpson, L.M. Walldius, G. Jungner, I. Chambless, L.E. Panagiotakos, D.B. Pitsavos, C. Chrysohoou, C. Stefanadis, C. Knuiman, M. Goldbourt, U. Benderly, M. Tanne, D. Whincup, P.H. Wannamethee, S.G. Morris, R.W. Willeit, J. Kiechl, S. Santer, P. Mayr, A. Lawlor, D.A. Yarnell, J.W.G. Gallacher, J. Casiglia, E. Tikhonoff, V. Nietert, P.J. Sutherland, S.E. Bachman, D.L. Keil, J.E. Cushman, M. Tracy, R.P. Tybjærg-Hansen, A. Nordestgaard, B.G. Benn, M. Frikke- Schmidt, R. Giampaoli, S. Palmieri, L. Panico, S. Vanuzzo, D. Gómez de la Cámara, A. Gómez- Gerique, J.A. Simons, L. McCallum, J. Friedlander, Y. Fowkes, F.G.R. Lee, A.J. Taylor, J. Guralnik, J.M. Wallace, R. Guralnik, J. Blazer, D.G. Guralnik, J.M. Guralnik, J.M. Khaw, K.-T. Brenner, H. Raum, E. Müller, H. Rothenbacher, D. Jansson, J.H. Wennberg, P. Nissinen, A. Donfrancesco, C. Salomaa, V. Harald, K. Jousilahti, P. Vartiainen, E. Woodward, M. D'Agostino, R.B. Vasan, R.S. Pencina, M.J. Bladbjerg, E.M. Jørgensen, T. Jespersen, J. Møller, L. Dankner, R. Chetrit, A. Lubin, F. Rosengren, A. Lappas, G. Björkelund, C. Lissner, L. Bengtsson, C. Cremer, P. Nagel, D. Tilvis, R.S. Strandberg, T.E. Kiyohara, Y. Arima, H. Doi, Y. Ninomiya, T. Rodriguez, B. Dekker, J.M. Nijpels, G. Stehouwer, C.D.A. Rimm, E. Pai, J.K. Sato, S. Kitamura, A. Iso, H. Goldbourt, U. Noda, H. Harald, K. Jousilahti, P. Vartiainen, E. Salonen, J.T. Tuomainen, T.-P. Deeg, D.J.H. Poppelaars, J.L. Meade, T.W. Cooper, J.A. Hedblad, B. Berglund, G. Engstrom, G. Verschuren, W.M.M. Blokstra, A. Cushman, M. Shea, S. Döring, A. Koenig, W. Meisinger, C. Mraz, W. Bas Bueno-de-Mesquita, H. Kuller, L.H. Grandits, G. Selmer, R. Tverdal, A. Nystad, W. Gillum, R. Mussolino, M. Rimm, E. Manson, J.E. Pai, J.K. Meade, T.W. Cooper, J.A. Cooper, J.A. Knottenbelt, C. Bauer, K.A. Naito, Y. Holme, I. Hankinson, S. Tverdal, A. Nystad, W. Nakagawa, H. Miura, K. Ducimetiere, P. Jouven, X. Crespo, C.J. Garcia Palmieri, M.R. Amouyel, P. Arveiler, D. Evans, A. Ferrieres, J. Schulte, H. Assmann, G. Shepherd, J. Packard, C.J. Sattar, N. Ford, I. Cantin, B. Després, J.-P. Dagenais, G.R. Barrett-Connor, E. Wingard, D.L. 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, G.D.O. Ben-Shlomo, Y. Howard, B.V. Zhang, Y. Umans, J. Onat, A. Davey-Smith, G. Wilsgaard, T. Ingelsson, E. Lind, L. Giedraitis, V. Lannfelt, L. Gaziano, J.M. Ridker, P. Gaziano, J.M. Ridker, P. Ulmer, H. Diem, G. Concin, H. Tosetto, A. Rodeghiero, F. Wassertheil-Smoller, S. Manson, J.E. Marmot, M. Clarke, R. Collins, R. Brunner, E. Shipley, M. Ridker, P. Buring, J. Shepherd, J. Cobbe, S.M. Robertson, M. He, Y. Marín Ibañez, A. Feskens, E.J.M. Kromhout, D. Collins, R. Di Angelantonio, E. Erqou, S. Kaptoge, S. Lewington, S. Orfei, L. Pennells, L. Perry, P.L. Ray, K.K. Sarwar, N. Alexander, M. Thompson, A. Thompson, S.G. Walker, M. Watson, S. Wensley, F. White, I.R. Wood, A.M.

Abstract

Background Meta-analysis of individual participant time-to-event data from multiple prospective epidemiological studies enables detailed investigation of exposure-risk relationships, but involves a number of analytical challenges. Methods This article describes statistical approaches adopted in the Emerging Risk Factors Collaboration, in which primary data from more than 1 million participants in more than 100 prospective studies have been collated to enable detailed analyses of various risk markers in relation to incident cardiovascular disease outcomes. Results Analyses have been principally based on Cox proportional hazards regression models stratified by sex, undertaken in each study separately. Estimates of exposure-risk relationships, initially unadjusted and then adjusted for several confounders, have been combined over studies using meta-analysis. Methods for assessing the shape of exposure-risk associations and the proportional hazards assumption have been developed. Estimates of interactions have also been combined using meta-analysis, keeping separate within-and between-study information. Regression dilution bias caused by measurement error and within-person variation in exposures and confounders has been addressed through the analysis of repeat measurements to estimate corrected regression coefficients. These methods are exemplified by analysis of plasma fibrinogen and risk of coronary heart disease, and Stata code is made available. Conclusion Increasing numbers of meta-analyses of individual participant data from observational data are being conducted to enhance the statistical power and detail of epidemiological studies. The statistical methods developed here can be used to address the needs of such analyses. © The Author 2010; all rights reserved.

Published
2010

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

Author

Tipping, R.W. Ford, C.E. Simpson, L.M. Walldius, G. Jungner, I. Folsom, A.R. Chambless, L. Panagiotakos, D. Pitsavos, C. Chrysohoou, C. Stefanadis, C. Goldbourt, U. Benderly, M. Tanne, D. Whincup, P. Wannamethee, S.G. Morris, R.W. Kiechl, S. Willeit, J. Santer, P. Mayr, A. Wald, N. Ebrahim, S. Lawlor, D. Yarnell, J. Gallacher, J. Casiglia, E. Tikhonoff, V. Nietert, P.J. Sutherland, S.E. Bachman, D.L. Cushman, M. Psaty, B.M. Tracy, R. Tybjærg-Hansen, A. Nordestgaard, B.G. Frikke-Schmidt, R. Kamstrup, P.R. Giampaoli, S. Palmieri, L. Panico, S. Vanuzzo, D. Pilotto, L. De La Cámara, A.G. Gómez Gerique, J.A. Simons, L. McCallum, J. Friedlander, Y. Fowkes, F.G.R. Lee, A. Smith, F.B. Taylor, J. Guralnik, J.M. Phillips, C.L. Wallace, R.B. Blazer, D.G. Brenner, H. Raum, E. Müller, H. Rothenbacher, D. Jansson, J.-H. Wennberg, P. Nissinen, A. Donfrancesco, C. Salomaa, V. Harald, K. Jousilahti, P. Vartiainen, E. Woodward, M. D’Agostino, R.B. Wolf, P.A. Vasan, R.S. Pencina, M.J. Bladbjerg, E.-M. 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.S. Strandberg, T.E. Rodriguez, B. Dekker, J. Nijpels, G. Stehouwer, C.D.A. Rimm, E. Pai, J.K. Sato, S. Iso, H. Kitamura, A. Noda, H. Salonen, J.T. Nyyssönen, K. Tuomainen, T.-P. Deeg, D.J.H. Poppelaars, J.L. Hedblad, B. Berglund, G. Engström, G. Verschuren, W.M.M. Blokstra, A. Döring, A. Koenig, W. Meisinger, C. Mraz, W. Bueno-De-Mesquita, H.B. Kuller, L.H. Grandits, G. Selmer, R. Tverdal, A. Nystad, W. Gillum, R.F. Mussolino, M. Hankinson, S. Manson, J.E. Cooper, J.A. Bauer, K.A. Naito, Y. Holme, I. Nakagawa, H. Miura, K. Ducimetiere, P. Jouven, X. Luc, G. Crespo, C.J. Garcia Palmieri, M.R. Amouyel, P. Arveiler, D. Evans, A. Ferrieres, J. Schulte, H. Assmann, G. Shepherd, J. Packard, C.J. Sattar, N. Ford, I. Cantin, B. Lamarche, B. Després, J.-P. Dagenais, G.R. Barrett-Connor, E. Daniels, L.B. Laughlin, G.A. Gudnason, V. Aspelund, T. Sigurdsson, G. Thorsson, B. Trevisan, M. Witteman, J. Kardys, I. Breteler, M.M.B. Hofman, A. Tunstall-Pedoe, H. Tavendale, R. Lowe, G. Ben-Shlomo, Y. Davey-Smith, G. Howard, B.V. Zhang, Y. Best, L. Umans, J. Onat, A. Njølstad, I. Mathiesen, E.B. Løchen, M.-L. Wilsgaard, T. Ingelsson, E. Sundström, J. Lind, L. Lannfelt, L. Gaziano, J.M. Stampfer, M. Ridker, P.M. Ulmer, H. Diem, G. Concin, H. Tosetto, A. Rodeghiero, F. Marmot, M. Clarke, R. Collins, R. Fletcher, A. Brunner, E. Shipley, M. Buring, J. Cobbe, S. Robertson, M. He, Y. Ibañez, A.M. Feskens, E. Kromhout, D. Walker, M. Watson, S. Di Angelantonio, E. Erqou, S. Kaptoge, S. Lewington, S. Orfei, L. Pennells, L. Perry, P.L. Ray, K.K. Sarwar, N. Alexander, M. Thompson, A. Thompson, S.G. Wensley, F. White, I.R. Wood, A.M. Danesh, J.

Abstract

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 firstever 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 personyears 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. ©2009 American Medical Association. All rights reserved.

Published
2009

23. The importance of social support for people with type 2 diabetes - a qualitative study with general practitioners, practice nurses and patients

Author

Goetz, K, Szecsenyi, J, Campbell, S, Rosemann, T, Rueter, G, Raum, E, Brenner, H, Miksch, A, Goetz, K, Szecsenyi, J, Campbell, S, Rosemann, T, Rueter, G, Raum, E, Brenner, H, and Miksch, A

Abstract

Objective: Social support is an important element of family medicine within a primary care setting, delivered by general practitioners and practice nurses in addition to usual clinical care. The aim of the study was to explore general practitioner's, practice nurse's and people with type 2 diabetes' views, experiences and perspectives of the importance of social support in caring for people with type 2 diabetes and their role in providing social support. Methods: Interviews with general practitioners (n=10) and focus groups with practice nurses (n=10) and people with diabetes (n=9). All data were audio-recorded, fully transcribed and thematically analysed using qualitative content analysis by Mayring.Results: All participants emphasized the importance of the concept of social support and its impacts on well-being of people with type 2 diabetes. Social support is perceived helpful for people with diabetes in order to improve diabetes control and give support for changes in lifestyle habits (physical activity and dietary changes). General practitioners identified a lack of information about facilities in the community like sports or self-help groups. Practice nurses emphasized that they need more training, such as in dietary counselling. Conclusions: Social support given by general practitioners and practice nurses plays a crucial role for people with type 2 diabetes and is an additional component of social care. However there is a need for an increased awareness by general practitioners and practice nurses about the influence social support could have on the individual's diabetes management., Zielsetzung: Soziale Unterstützung stellt ein wichtiges und ergänzendes Element in der hausärztlichen Versorgung dar. In der vorliegende Studie wurden die Einstellungen zu und Erfahrungen mit sozialer Unterstützung sowie deren Bedeutung im hausärztlichen Setting von Allgemeinärzten, Medizinischen Fachangestellten (MFA) und Patienten mit Diabetes mellitus Typ 2 erfasst.Methodik: Es wurden Interviews mit Allgemeinärzten (n=10) sowie Fokusgruppen mit MFAs (n=10) und Patienten mit Diabetes mellitus Typ 2 (n=9) durchgeführt. Die Daten wurden aufgezeichnet, transkribiert und thematisch unter Verwendung der qualitativen Inhaltsanalyse nach Mayring analysiert.Ergebnisse: Alle Teilnehmer betonen die Relevanz des Konzepts der sozialen Unterstützung und vor allem den daraus resultierenden Einfluss auf das Wohlbefinden von Patienten mit Diabetes mellitus Typ 2. Soziale Unterstützung wird von den befragten Patienten als hilfreiches Konzept empfunden, um die eigenen Werte zu verbessern und um Lebensstilveränderungen umzusetzen (körperliche Aktivität oder Ernährungsumstellung). Allgemeinärzte nehmen ihrerseits einen Mangel an Informationen über kommunale Angebote wie zum Beispiel Sportkurse oder auch Selbsthilfegruppen wahr. MFAs wünschen sich mehr Fortbildungsmöglichkeiten, um in der Praxis zum Beispiel Ernährungsberatung durchführen zu können. Fazit: Soziale Unterstützung durch Praxisteams in der hausärztlichen Versorgung spielt eine wichtige Rolle für Patienten mit Diabetes mellitus Typ 2. Allerdings sollten sich sowohl Allgemeinärzte als auch MFAs noch mehr darüber bewusst werden, welchen Einfluss und Nutzen soziale Unterstützung auf das individuelle Diabetesmanagement haben kann.

Published
2012

33. Association of a variant in the muscarinic acetylcholine receptor 2 gene (CHRM2) with nicotine addiction

Author

Mobascher, A., primary, Rujescu, D., additional, Mittelstraß, K., additional, Giegling, I., additional, Lamina, C., additional, Nitz, B., additional, Brenner, H., additional, Fehr, C., additional, Breitling, L.P., additional, Gallinat, J., additional, Rothenbacher, D., additional, Raum, E., additional, Müller, H., additional, Ruppert, A., additional, Hartmann, A.M., additional, Möller, H.J., additional, Gal, A., additional, Gieger, Ch., additional, Wichmann, H.E., additional, Illig, T., additional, Dahmen, N., additional, and Winterer, G., additional

Published
2010
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39. Genetic variations in the vitamin D binding protein and season-specific levels of vitamin D among older adults.

Author

Perna L, Felix JF, Breitling LP, Haug U, Raum E, Burwinkel B, Schöttker B, Brenner H, Perna, Laura, Felix, Janine F, Breitling, Lutz P, Haug, Ulrike, Raum, Elke, Burwinkel, Barbara, Schöttker, Ben, and Brenner, Hermann

Abstract

Background: Vitamin D insufficiency is common among older adults. Genome-wide association studies have found an association between variants in the vitamin D binding protein and serum levels of vitamin D. The quantification of this association among older women and men and its potential variation by season remain unexplored.Methods: Serum levels of 25-hydroxyvitamin D [25(OH)D] and genetic variants in the vitamin D binding protein were analyzed in 2160 women and 1581 men age 50 to 74 years participating in a large population-based cohort study (ESTHER study-epidemiologic study assessing chances of prevention and early detection of various chronic diseases, including cancer among older adults) in Germany. Serum levels of 25(OH)D were assessed in relation to four single nucleotide polymorphisms (SNPs; rs4588, rs2282679, rs1155563, and rs12512631) by descriptive and multivariate analysis.Results: Both heterozygous and homozygous women and men carrying the rare allele with SNPs rs4588, rs2282679, or rs1155563 had lower levels of 25(OH)D in summer months than those homozygous for the wild-type alleles. Adjusted differences ranged from 5.1 to 5.4 nmol/l among heterozygous carriers of the rare alleles and from 8.8 to 9.6 nmol/l among homozygous carriers of the rare alleles. During winter months, 25(OH)D differences by genotype were smaller among women and not apparent among men.Conclusions: Older women and men living in a high-latitude region and carrying the rare alleles of SNPs rs4588, rs2282679, or rs1155563 seem to benefit less from higher levels of ultraviolet radiation during the summer season. [ABSTRACT FROM AUTHOR]

Published
2013
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41. Serum oestrogen receptor alpha and beta bioactivity are independently associated with breast cancer: a proof of principle study.

Author

Widschwendter, M., Lichtenberg-Frate, H., Hasenbrink, G., Schwarzer, S., Dawnay, A., Lam, A., Menon, U., Apostolidou, S., Raum, E., Stegmaier, C., Jacobs, I. J., and Brenner, H.

Subjects
DRUG receptors, BREAST cancer research, SELECTIVE estrogen receptor modulators, SERUM, GREEN fluorescent protein, BREAST tumor diagnosis, BREAST tumors, COMPARATIVE studies, DNA, ESTRADIOL, GENES, RESEARCH methodology, MEDICAL cooperation, PROTEINS, QUESTIONNAIRES, RESEARCH, RESEARCH funding, EVALUATION research, PREDICTIVE tests, CASE-control method, POSTMENOPAUSE
Abstract

Background: Oestrogens play a crucial role in breast carcinogenesis. Earlier studies have analysed the serum levels of endogenous hormones measured by conventional assays. In this study, we analysed the capacity of serum from breast cancer cases and controls to transactivate the oestrogen receptor alpha (ER-alpha) and beta (ER-beta).Methods: We used a receptor oestrogen-responsive element (ERE) -- the green fluorescent protein (GFP)-reporter test system in Saccharomyces cerevisiae. Oestrogen receptor-alpha or ER-beta bioactivity was determined in serum from 182 randomly chosen postmenopausal women with breast cancer and from 188 age-matched controls.Results: High serum ER-alpha and ER-beta bioactivity were independently associated with the presence of breast cancer. Women whose levels of serum ER-alpha and ER-beta bioactivity were in the highest quintile among controls had a 7.57-(95% confidence interval (CI): 2.46-23.32; P=0.0004) and a 10.14 (95% CI: 3.19-32.23; P<0.0001)-fold risk for general and oestrogen receptor-positive breast cancer, respectively.Conclusion: The use of serum ER-alpha and ER-beta bioactivity assays as clinical tools in the management of breast cancer warrants further research. Future studies will dictate whether surrogate markers of ER-alpha and ER-beta bioactivity will provide a means to monitor the efficacy of anti-endocrine, adjuvant and chemopreventive strategies. [ABSTRACT FROM AUTHOR]

Published
2009
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42. Older smokers' motivation and attempts to quit smoking: epidemiological insight into the question of lifestyle versus addiction.

Author

Breitling LP, Rothenbacher D, Stegmaier C, Raum E, and Brenner H

Abstract

Background: Much media attention currently focuses on demands from the organized medical profession in Germany for an altered legal framework regarding remuneration for smoking-cessation interventions. With this development, the question whether smoking is an autonomously chosen lifestyle or, alternatively, an addiction constituting adisease in its own right has once again come to the fore of public debate. Methods: In apopulation-based study in the German state of Saarland, 10 000 persons aged 50 to 74 were questioned about their health-related behavior and medical history. The frequency of attempts to quit smoking, and of the motivation to do so, was analyzed in relation to the total number of smokers in the survey and was stratified with respect to existing illnesses whose cardiovascular risk potential is exacerbated by smoking. Results: Among 1528 persons who were smokers at the beginning of the study, 76% (95% confidence interval [GI]: 73.7%-78.0%) reported having tried to quit at least once. Among smokers with existing high-risk conditions, this figure was higher, reaching 89% (Gl: 83.1%-93.0%) in smokers with known cardiovascular disease. Only 11% of the smokers were content with their smoking behavior; 30% said they wanted to cut down, and 59% said they wanted to quit smoking entirely. Conclusions: Most older smokers in Germany would like to quit smoking and have tried to do so repeatedly without success. In particular, high-risk patients with comorbidities, whose number will further increase as the population ages, are highly motivated to quit smoking and would derive major benefit from effective assistance with smoking cessation. The description of smoking as an autonomously chosen lifestyle appears cynical and deserves to be vigorously rejected. [ABSTRACT FROM AUTHOR]

Published
2009
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43. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies

Author

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

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

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

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44. Two types of health care systems and their influence on the introduction of perinatal care: an epidemiological twin model in Berlin from 1950 to 1990.

Author

Arabin B, Raum E, Mohnhaupt A, and Schwartz FW

Abstract

Objectiues: When perinatal medicine emerged as a new medical discipline in the 1960s, Berlin was as one of the world's leading centers. During that time, the city was separated into two parts, each fostering its own health care system. After the destruction of the Berlin Wall, it was possible to speak with the citizens of East Berlin and to access their database systems. This created the singular opportunity to objectively compare the development of perinatal care in both parts of Berlin. Methods: Rates of maternal, perinatal, and infant mortality as well as the rate of preterm deliveries were evaluated over time and between East and West Berlin. The timing of introduction of 20 specific perinatal interventions was evaluated across 18 hospitals with more than 500 deliveries (11 in West Berlin and 7 in East Berlin). Interviews were conducted with 100 gynecologists, 100 midwives, and 100 women who had recently delivered their first child from each side of the city regarding their opinions of the importance of these interventions for the quality of perinatal medicine and how they would distribute a budget to improve maternity care. Results: Maternal, perinatal, and infant mortality decreased in both parts of Berlin until 1990 (p < 0.0001), without significant differences between East and West Berlin, though the preterm delivery rate was slightly lower in East Berlin compared with West Berlin (p < 0.06). Some new clinical techniques and treatments-such as cardiotocography, ultrasound, tocolytic therapy, and peridural anesthesia-were introduced earlier in West Berlin. In contrast, certain public health measures-such as maternal transport, screening programs for diabetes, and support of breastfeeding-were introduced much earlier in East Berlin. There were significant differences between the beliefs of gynecologists, midwives, and mothers in East and West Berlin. In general, citizens of East Berlin were more enthusiastic about technological medical advances, whereas citizens of West Berlin were more supportive of public health and alternative methods. In addition, there were significant differences between female and male physicians in their beliefs about how to improve health care, regardless of whether they resided in East or West Berlin. Conclusions: The results of this study may serve as a basis for reflection on how different social circumstances and health care policies can influence the improvement of maternal and child health care. [ABSTRACT FROM AUTHOR]

Published
1999
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46. Infection of human monocyte-derived macrophages with Chlamydia trachomatis induces apoptosis of T cells: a potential mechanism for persistent infection.

Author

Jendro, M C, Deutsch, T, Körber, B, Köhler, L, Kuipers, J G, Krausse-Opatz, B, Westermann, J, Raum, E, and Zeidler, H

Abstract

Viruses can escape T-cell surveillance by infecting macrophages and thereby induce apoptosis of noninfected T cells. This ability had not been demonstrated for bacteria. We investigated whether infection of macrophages with the important human pathogen Chlamydia trachomatis can induce T-cell apoptosis. Because Chlamydia-Mycoplasma coinfection is a frequent event, the ability of Mycoplasma fermentans-infected macrophages to induce T-cell apoptosis was also studied. Infected macrophages were cocultivated with autologous T cells in different activation states. Propidium iodide-based fluorescence-activated cell sorter analysis demonstrated that macrophages infected with viable chlamydiae induced T-cell death. Apoptosis was identified as the mode of death induction by using a terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling assay. Induction of T-cell death was macrophage dependent. Incubation of T cells with infectious chlamydiae in the absence of macrophages did not lead to T-cell apoptosis. UV irradiation of chlamydiae diminished the ability to induce death. T-cell death was induced by a cell-free supernatant of infected macrophages. Not only phytohemagglutinin-preactivated T cells but also non-mitogen-preactivated T cells were susceptible to C. trachomatis-induced apoptosis. In contrast, M. fermentans infection of macrophages did not induce T-cell death. Coinfection had no additional effect. In summary, intracellular chlamydial infection of macrophages can induce T-cell apoptosis. Apoptosis induction by chlamydiae possibly explains how persistently infected macrophages escape T-cell surveillance and why the Chlamydia-specific T-cell response is diminished during persistent chlamydial infection.

Published
2000

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

Author

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

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

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

48. In reply.

Author

Rothenbacher D, Stegmaier C, Raum E, Brenner H, and Breitling LP

Published
2010
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