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

Brunner, FJ; Waldeyer, C; Ojeda, F; Salomaa, V; Kee, F; Sans, S; Thorand, B; Giampaoli, S; Brambilla, P; Tunstall-Pedoe, H; et al. Brunner, FJ; Waldeyer, C; Ojeda, F; Salomaa, V; Kee, F; Sans, S; Thorand, B; Giampaoli, S; Brambilla, P; Tunstall-Pedoe, H; Moitry, M; Iacoviello, L; Veronesi, G; Grassi, G; Mathiesen, EB; Söderberg, S; Linneberg, A; Brenner, H; Amouyel, P; Ferrières, J; Tamosiunas, A; Nikitin, YP; Drygas, W; Melander, O; Jöckel, K-H; Leistner, DM; Shaw, JE; Panagiotakos, DB; Simons, LA; Kavousi, M; Vasan, RS; Dullaart, RPF; Wannamethee, SG; Risérus, U; Shea, S; de Lemos, JA; Omland, T; Kuulasmaa, K; Landmesser, U; Blankenberg, S; Multinational Cardiovascular Risk Consortium (2019) Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium. Lancet, 394 (10215). pp. 2173-2183. ISSN 1474-547X https://doi.org/10.1016/S0140-6736(19)32519-X
SGUL Authors: Whincup, Peter Hynes

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Abstract

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. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research.

Item Type: Article
Additional Information: © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
Keywords: Multinational Cardiovascular Risk Consortium, General & Internal Medicine, 11 Medical and Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Population Health Research Institute (INPH)
Journal or Publication Title: Lancet
ISSN: 1474-547X
Language: eng
Dates:
DateEvent
14 December 2019Published
3 December 2019Published Online
1 October 2019Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
HEALTH-F2–2011–278913Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
HEALTH-F3–2010–242244Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
G0601463Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
80983Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
81Z1710101German Centre for Cardiovascular ResearchUNSPECIFIED
PubMed ID: 31810609
Web of Science ID: WOS:000502546300027
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/111526
Publisher's version: https://doi.org/10.1016/S0140-6736(19)32519-X

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