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dc.contributor.authorBrunner, Fabian J.
dc.contributor.authorWaldeyer, Christoph
dc.contributor.authorOjeda, Francisco
dc.contributor.authorSalomaa, Veikko
dc.contributor.authorKee, Frank
dc.contributor.authorSans, Susana
dc.contributor.authorThorand, Barbara
dc.contributor.authorGiampaoli, Simona
dc.contributor.authorBrambilla, Paolo
dc.contributor.authorTunstall-Pedoe, Hugh
dc.contributor.authorMoitry, Marie
dc.contributor.authorIacoviello, Licia
dc.contributor.authorVeronesi, Giovanni
dc.contributor.authorGrassi, Guido
dc.contributor.authorMathiesen, Ellisiv B.
dc.contributor.authorSöderberg, Stefan
dc.contributor.authorLinneberg, Allan
dc.contributor.authorBrenner, Hermann
dc.contributor.authorAmouyel, Philippe
dc.contributor.authorFerrières, Jean
dc.contributor.authorTamosiunas, Abdonas
dc.contributor.authorNikitin, Yuriy P.
dc.contributor.authorDrygas, Wojciech
dc.contributor.authorMelander, Olle
dc.contributor.authorJöckel, Karl-Heinz
dc.contributor.authorLeistner, David M.
dc.contributor.authorShaw, Jonathan E.
dc.contributor.authorPanagiotakos, Demosthenes B.
dc.contributor.authorSimons, Leon A.
dc.contributor.authorKavousi, Maryam
dc.contributor.authorVasan, Ramachandran S.
dc.contributor.authorDullaart, Robin P.F.
dc.contributor.authorWannamethee, S. Goya
dc.contributor.authorRisérus, Ulf
dc.contributor.authorShea, Steven
dc.contributor.authorde Lemos, James A.
dc.contributor.authorOmland, Torbjørn
dc.contributor.authorKuulasmaa, Kari
dc.contributor.authorLandmesser, Ulf
dc.contributor.authorBlankenberg, Stefan
dc.date.accessioned2020-02-26T10:03:19Z
dc.date.available2020-02-26T10:03:19Z
dc.date.issued2019-12-03
dc.description.abstract<i>Background</i> - 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.<p> <p><i>Methods</i> - 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.<p> <p><i>Findings</i> - 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.<p> <p><i>Interpretation</i> - 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.en_US
dc.identifier.citationBrunner, F.J., Waldeyer, C., Ojeda, F., Salomaa, V., Kee, F., Sans, S. ... Blankenberg, S. (2019). Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium. <i>The Lancet, 394</i>(10215), 2173-2183.en_US
dc.identifier.cristinIDFRIDAID 1778333
dc.identifier.doi10.1016/S0140-6736(19)32519-X
dc.identifier.issn0140-6736
dc.identifier.issn1474-547X
dc.identifier.urihttps://hdl.handle.net/10037/17510
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalThe Lancet
dc.relation.projectIDinfo:eu-repo/grantAgreement/EU/FP7-HEALTH/278913/?/Biomarker for Cardiovascular Risk Assessment in Europe/BiomarCaRE/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EU/FP7-HEALTH/242244/?/Consortium on Health and Ageing: Network of Cohorts in Europe and the United States/CHANCES/en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2019 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700en_US
dc.subjectVDP::Medisinske Fag: 700en_US
dc.titleApplication of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortiumen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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