Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Application of non-HDL cholesterol for population-based cardiovascular risk stratification : results from the Multinational Cardiovascular Risk Consortium. / Brunner, Fabian J.; Waldeyer, Christoph; Ojeda, Francisco; Salomaa, Veikko; Kee, Frank; Sans, Susana; Thorand, Barbara; Giampaoli, Simona; Brambilla, Paolo; Tunstall-Pedoe, Hugh; Moitry, Marie; Iacoviello, Licia; Veronesi, Giovanni; Grassi, Guido; Mathiesen, Ellisiv B.; Söderberg, Stefan; Linneberg, Allan; Brenner, Hermann; Amouyel, Philippe; Ferrières, Jean; Tamosiunas, Abdonas; Nikitin, Yuriy P.; Drygas, Wojciech; Melander, Olle; Jöckel, Karl Heinz; Leistner, David M.; Shaw, Jonathan E.; Panagiotakos, Demosthenes B.; Simons, Leon A.; Kavousi, Maryam; Vasan, Ramachandran S.; Dullaart, Robin P.F.; Wannamethee, S. Goya; Risérus, Ulf; Shea, Steven; de Lemos, James A.; Omland, Torbjørn; Kuulasmaa, Kari; Landmesser, Ulf; Blankenberg, Stefan; Zeller, Tanja; Kontto, Jukka; Männistö, Satu; Metspalu, Andres; Lackner, Karl; Wild, Philipp; Peters, Annette; Meisinger, Christa; Donfrancesco, Chiara; Signorini, Stefano G.; Alver, Maris; Woodward, Mark; Gianfagna, Francesco; Costanzo, Simona; Wilsgaard, Tom; Eliasson, Mats; Jørgensen, Torben; Völzke, Henry; Dörr, Marcus; Nauck, Matthias; Schöttker, Ben; Lorenz, Thiess; Makarova, Nataliya; Twerenbold, Raphael; Dallongeville, Jean; Dobson, Annette; Malyutina, Sofia; Pajak, Andrzej; Engström, Gunnar; Bobak, Martin; Schmidt, Börge; Jääskeläinen, Tuija; Niiranen, Teemu; Jousilahti, Pekka; Giles, Graham; Hodge, Allison; Klotsche, Jens; Magliano, Dianna J.; Lyngbakken, Magnus N.; Hveem, Kristian; Pitsavos, Christos; Benjamin, Emelia J.; Bakker, Stephan J.L.; Whincup, Peter; Ikram, M. Kamran; Ingelsson, Martin; Koenig, Wolfgang.
I: The Lancet, Bind 394, Nr. 10215, 2019, s. 2173-2183.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Application of non-HDL cholesterol for population-based cardiovascular risk stratification
T2 - results from the Multinational Cardiovascular Risk Consortium
AU - Brunner, Fabian J.
AU - Waldeyer, Christoph
AU - Ojeda, Francisco
AU - Salomaa, Veikko
AU - Kee, Frank
AU - Sans, Susana
AU - Thorand, Barbara
AU - Giampaoli, Simona
AU - Brambilla, Paolo
AU - Tunstall-Pedoe, Hugh
AU - Moitry, Marie
AU - Iacoviello, Licia
AU - Veronesi, Giovanni
AU - Grassi, Guido
AU - Mathiesen, Ellisiv B.
AU - Söderberg, Stefan
AU - Linneberg, Allan
AU - Brenner, Hermann
AU - Amouyel, Philippe
AU - Ferrières, Jean
AU - Tamosiunas, Abdonas
AU - Nikitin, Yuriy P.
AU - Drygas, Wojciech
AU - Melander, Olle
AU - Jöckel, Karl Heinz
AU - Leistner, David M.
AU - Shaw, Jonathan E.
AU - Panagiotakos, Demosthenes B.
AU - Simons, Leon A.
AU - Kavousi, Maryam
AU - Vasan, Ramachandran S.
AU - Dullaart, Robin P.F.
AU - Wannamethee, S. Goya
AU - Risérus, Ulf
AU - Shea, Steven
AU - de Lemos, James A.
AU - Omland, Torbjørn
AU - Kuulasmaa, Kari
AU - Landmesser, Ulf
AU - Blankenberg, Stefan
AU - Zeller, Tanja
AU - Kontto, Jukka
AU - Männistö, Satu
AU - Metspalu, Andres
AU - Lackner, Karl
AU - Wild, Philipp
AU - Peters, Annette
AU - Meisinger, Christa
AU - Donfrancesco, Chiara
AU - Signorini, Stefano G.
AU - Alver, Maris
AU - Woodward, Mark
AU - Gianfagna, Francesco
AU - Costanzo, Simona
AU - Wilsgaard, Tom
AU - Eliasson, Mats
AU - Jørgensen, Torben
AU - Völzke, Henry
AU - Dörr, Marcus
AU - Nauck, Matthias
AU - Schöttker, Ben
AU - Lorenz, Thiess
AU - Makarova, Nataliya
AU - Twerenbold, Raphael
AU - Dallongeville, Jean
AU - Dobson, Annette
AU - Malyutina, Sofia
AU - Pajak, Andrzej
AU - Engström, Gunnar
AU - Bobak, Martin
AU - Schmidt, Börge
AU - Jääskeläinen, Tuija
AU - Niiranen, Teemu
AU - Jousilahti, Pekka
AU - Giles, Graham
AU - Hodge, Allison
AU - Klotsche, Jens
AU - Magliano, Dianna J.
AU - Lyngbakken, Magnus N.
AU - Hveem, Kristian
AU - Pitsavos, Christos
AU - Benjamin, Emelia J.
AU - Bakker, Stephan J.L.
AU - Whincup, Peter
AU - Ikram, M. Kamran
AU - Ingelsson, Martin
AU - Koenig, Wolfgang
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
U2 - 10.1016/S0140-6736(19)32519-X
DO - 10.1016/S0140-6736(19)32519-X
M3 - Journal article
C2 - 31810609
AN - SCOPUS:85076158283
VL - 394
SP - 2173
EP - 2183
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 10215
ER -
ID: 233721116