Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium

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Brunner, Fabian J.Univ Heart & Vasc Ctr Hamburg, Dept Cardiol, D-20246 Hamburg, Germany (author)

Application of non-HDL cholesterol for population-based cardiovascular risk stratification : results from the Multinational Cardiovascular Risk Consortium

Article/chapterEnglish2019

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Elsevier,2019
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LIBRIS-ID:oai:DiVA.org:umu-167054
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-167054URI
https://doi.org/10.1016/S0140-6736(19)32519-XDOI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-401185URI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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Background: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment.Methods: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol.Findings: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7–59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0–20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0–1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6–2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0–1·3 to 2·3, 2·0–2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced.Interpretation: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician–patient communication about primary prevention strategies.

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Waldeyer, ChristophUniv Heart & Vasc Ctr Hamburg, Dept Cardiol, D-20246 Hamburg, Germany (author)
Ojeda, FranciscoUniv Heart & Vasc Ctr Hamburg, Dept Cardiol, D-20246 Hamburg, Germany (author)
Salomaa, VeikkoNatl Inst Hlth & Welf, Helsinki, Finland (author)
Kee, FrankQueens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland (author)
Sans, SusanaCatalan Dept Hlth, Barcelona, Spain,Boston Univ, Framingham, MA USA;NHLBI, Framingham Study, Framingham, MA USA,UCL, Dept Primary Care & Populat Hlth, London, England (author)
Thorand, BarbaraGerman Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany (author)
Giampaoli, SimonaNatl Inst Hlth ISS, Dept Cardiovasc Endocrine Metab Dis & Ageing, Rome, Italy (author)
Brambilla, PaoloUniv Milano Bicocca, Dept Med & Surg, Milan, Italy (author)
Tunstall-Pedoe, HughUniv Dundee, Cardiovasc Epidemiol Unit, Inst Cardiovasc Res, Dundee, Scotland (author)
Moitry, MarieUniv Hosp Strasbourg, Dept Epidemiol & Publ Hlth, Strasbourg, France,Charite Berlin Univ Med, Dept Cardiol, Campus Benjamin Franklin, Berlin, Germany;German Ctr Cardiovasc Res, Partner Site Berlin, Berlin, Germany (author)
Iacoviello, LiciaIRCCS Neuromed, Dept Epidemiol & Prevent, Pozzilli, Italy;Univ Insubria, Dept Med & Surg, Res Ctr Epidemiol & Prevent Med, Varese, Italy (author)
Veronesi, GiovanniUniv Insubria, Dept Med & Surg, Res Ctr Epidemiol & Prevent Med, Varese, Italy (author)
Grassi, GuidoUniv Milano Bicocca, Med Clin, Dept Med & Surg, Milan, Italy (author)
Mathiesen, Ellisiv B.Univ Tromso, Univ Tromso Arctic, Dept Clin Med, Tromso, Norway;Univ Hosp North Norway, Dept Neurol & Neurophysiol, Tromso, Norway (author)
Söderberg, StefanUmeå universitet,Kardiologi,Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden;Umea Univ, Ctr Heart, Umea, Sweden(Swepub:umu)stso0001 (author)
Linneberg, AllanBispebjerg & Frederiksberg Hosp, Ctr Clin Res & Prevent, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark (author)
Brenner, HermannGerman Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany (author)
Amouyel, PhilippeUniv Lille, Risk Factors & Mol Determinants Aging Dis, Lille, France;INSERM, Lille, France;CHU Lille, Lille, France;Inst Pasteur, Lille, France (author)
Ferrieres, JeanToulouse Univ, Sch Med, Toulouse, France (author)
Tamosiunas, AbdonasLithuanian Univ Hlth Sci, Inst Cardiol, Kaunas, Lithuania (author)
Nikitin, Yuriy P.Russian Acad Sci, Siberian Branch, Inst Cytol & Genet, Res Inst Internal & Prevent Med,Branch Fed Res Ct, Novosibirsk, Russia (author)
Drygas, WojciechNatl Inst Cardiol, Dept Epidemiol Cardiovasc Dis Prevent & Hlth Prom, Warsaw, Poland (author)
Melander, OlleLund Univ, Dept Clin Sci, Malmo, Sweden (author)
Jöckel, Karl-HeinzUniv Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany (author)
Leistner, David M. (author)
Shaw, Jonathan E.Baker Heart & Diabet Inst, Melbourne, Vic, Australia (author)
Panagiotakos, Demosthenes B.Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece (author)
Simons, Leon A.Univ New South Wales, Sydney, NSW, Australia;St Vincents Hosp, Sydney, NSW, Australia (author)
Kavousi, MaryamUniv Med Ctr Rotterdam, Erasmus Med Ctr, Dept Epidemiol, Rotterdam, Netherlands (author)
Vasan, Ramachandran S.Columbia Univ, Dept Med, New York, NY USA;Columbia Univ, Dept Epidemiol, New York, NY USA (author)
Dullaart, Robin P. F.Univ Groningen, Dept Endocrinol, Univ Med Ctr Groningen, Groningen, Netherlands (author)
Wannamethee, S. Goya (author)
Risérus, Ulf,1967-Uppsala universitet,Klinisk nutrition och metabolism(Swepub:uu)ulfriser (author)
Shea, Steven (author)
de Lemos, James A.Univ Texas Southwestern Med Ctr Dallas, Div Cardiol, Dallas, TX 75390 USA (author)
Omland, TorbjornAkershus Univ Hosp, Dept Cardiol, Div Med, Lorenskog, Norway;Univ Oslo, Inst Clin Med, Ctr Heart Failure Res, Oslo, Norway (author)
Kuulasmaa, KariNatl Inst Hlth & Welf, Helsinki, Finland (author)
Landmesser, UlfCharite Berlin Univ Med, Dept Cardiol, Campus Benjamin Franklin, Berlin, Germany;German Ctr Cardiovasc Res, Partner Site Berlin, Berlin, Germany;Berlin Inst Hlth, Berlin, Germany (author)
Blankenberg, StefanUniv Heart & Vasc Ctr Hamburg, Dept Cardiol, D-20246 Hamburg, Germany;German Ctr Cardiovasc Res, Partner Site Hamburg Kiel Lubeck, Hamburg, Germany (author)
Zeller, T. (author)
Lackner, K. (author)
Wild, P. (author)
Peters, A. (author)
Meisinger, C. (author)
Voelzke, H. (author)
Doerr, M. (author)
Nauck, M. (author)
Schoettker, B. (author)
Lorenz, T. (author)
Makarova, N. (author)
Schmidt, B. (author)
Klotsche, J. (author)
Koenig, W. (author)
Kontto, J. (author)
Mannisto, S. (author)
Jaaskelainen, T. (author)
Niiranen, T. (author)
Jousilahti, P. (author)
Metspalu, A. (author)
Alver, M. (author)
Donfrancesco, C. (author)
Signorini, S. G. (author)
Gianfagna, F. (author)
Costanzo, S. (author)
Woodward, M. (author)
Dobson, A. (author)
Giles, G. (author)
Hodge, A. (author)
Magliano, D. J. (author)
Wilsgaard, T. (author)
Lyngbakken, M. N. (author)
Hveem, K. (author)
Eliasson, M. (author)
Engstrom, G. (author)
Ingelsson, M. (author)
Jorgensen, T. (author)
Twerenbold, R. (author)
Dallongeville, J. (author)
Malyutina, S. (author)
Pajak, A. (author)
Bobak, M. (author)
Whincup, P. (author)
Pitsavos, C. (author)
Benjamin, E. J. (author)
Bakker, S. J. L. (author)
Ikram, M. K. (author)
Univ Heart & Vasc Ctr Hamburg, Dept Cardiol, D-20246 Hamburg, GermanyNatl Inst Hlth & Welf, Helsinki, Finland (creator_code:org_t)

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In:The Lancet: Elsevier394:10215, s. 2173-21830140-67361474-547X

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By the author/editor: Brunner, Fabian ...; Waldeyer, Christ ...; Ojeda, Francisco; Salomaa, Veikko; Kee, Frank; Sans, Susana; show more...; Thorand, Barbara; Giampaoli, Simon ...; Brambilla, Paolo; Tunstall-Pedoe, ...; Moitry, Marie; Iacoviello, Lici ...; Veronesi, Giovan ...; Grassi, Guido; Mathiesen, Ellis ...; Söderberg, Stefa ...; Linneberg, Allan; Brenner, Hermann; Amouyel, Philipp ...; Ferrieres, Jean; Tamosiunas, Abdo ...; Nikitin, Yuriy P ...; Drygas, Wojciech; Melander, Olle; Jöckel, Karl-Hei ...; Leistner, David ...; Shaw, Jonathan E ...; Panagiotakos, De ...; Simons, Leon A.; Kavousi, Maryam; Vasan, Ramachand ...; Dullaart, Robin ...; Wannamethee, S. ...; Risérus, Ulf, 19 ...; Shea, Steven; de Lemos, James ...; Omland, Torbjorn; Kuulasmaa, Kari; Landmesser, Ulf; Blankenberg, Ste ...; Zeller, T.; Lackner, K.; Wild, P.; Peters, A.; Meisinger, C.; Voelzke, H.; Doerr, M.; Nauck, M.; Schoettker, B.; Lorenz, T.; Makarova, N.; Schmidt, B.; Klotsche, J.; Koenig, W.; Kontto, J.; Mannisto, S.; Jaaskelainen, T.; Niiranen, T.; Jousilahti, P.; Metspalu, A.; Alver, M.; Donfrancesco, C.; Signorini, S. G.; Gianfagna, F.; Costanzo, S.; Woodward, M.; Dobson, A.; Giles, G.; Hodge, A.; Magliano, D. J.; Wilsgaard, T.; Lyngbakken, M. N ...; Hveem, K.; Eliasson, M.; Engstrom, G.; Ingelsson, M.; Jorgensen, T.; Twerenbold, R.; Dallongeville, J ...; Malyutina, S.; Pajak, A.; Bobak, M.; Whincup, P.; Pitsavos, C.; Benjamin, E. J.; Bakker, S. J. L.; Ikram, M. K.; show less...

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