Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses

E. Sofianopoulou; S. K. Kaptoge; S. Afzal; T. Jiang; D. Gill; T. E. Gundersen; T. R. Bolton; E. Allara; M. G. Arnold; A. M. Mason; R. Chung; L. A. M. Pennells; F. Shi; L. Sun; P. Willeit; N. G. Forouhi; C. Langenberg; S. J. Sharp; S. Panico; G. Engstrom; O. Melander; T. Y. N. Tong; A. Perez-Cornago; M. Norberg; I. Johansson; V. Katzke; B. Srour; Sanchez M. Jose; D. Redondo-Sanchez; A. Olsen; C. C. Dahm; K. Overvad; M. Brustad; G. Skeie; C. Moreno-Iribas; N. C. Onland-Moret; Y. T. van der Schouw; K. K. Tsilidis; A. K. Heath; C. Agnoli; V. Krogh; I. H. de Boer; C. J. Kobylecki; Y. Colak; A. Zittermann; J. Sundstrom; P. Welsh; E. Weiderpass; E. K. Aglago; P. Ferrari; R. Clarke; Boutron M. -C.; G. Severi; C. MacDonald; R. Providencia; G. Masala; Ros R. Zamora; J. Boer; W. M. Verschuren; P. Cawthon; L. L. Schierbeck; C. Cooper; M. B. Schulze; M. M. Bergmann; A. Hannemann; S. Kiechl; H. Brenner; N. M. van Schoor; J. R. Albertorio; Carlotta SACERDOTE; A. Linneberg; L. L. Karhus; J. M. Huerta; L. Imaz; C. Joergensen; Y. Ben-Shlomo; A. Lundqvist; J. Gallacher; N. Sattar; A. M. Wood; N. J. Wareham; B. G. Nordestgaard; Angelantonio E. Di; J. Danesh; A. S. Butterworth; S. Burgess

doi:10.1016/S2213-8587(21)00263-1

Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses

E. Sofianopoulou, S. K. Kaptoge, S. Afzal, T. Jiang, D. Gill, T. E. Gundersen, T. R. Bolton, E. Allara, M. G. Arnold, A. M. Mason, R. Chung, L. A. M. Pennells, F. Shi, L. Sun, P. Willeit, N. G. Forouhi, C. Langenberg, S. J. Sharp, S. Panico, G. EngstromO. Melander, T. Y. N. Tong, A. Perez-Cornago, M. Norberg, I. Johansson, V. Katzke, B. Srour, Sanchez M. Jose, D. Redondo-Sanchez, A. Olsen, C. C. Dahm, K. Overvad, M. Brustad, G. Skeie, C. Moreno-Iribas, N. C. Onland-Moret, Y. T. van der Schouw, K. K. Tsilidis, A. K. Heath, C. Agnoli, V. Krogh, I. H. de Boer, C. J. Kobylecki, Y. Colak, A. Zittermann, J. Sundstrom, P. Welsh, E. Weiderpass, E. K. Aglago, P. Ferrari, R. Clarke, Boutron M. -C., G. Severi, C. MacDonald, R. Providencia, G. Masala, Ros R. Zamora, J. Boer, W. M. Verschuren, P. Cawthon, L. L. Schierbeck, C. Cooper, M. B. Schulze, M. M. Bergmann, A. Hannemann, S. Kiechl, H. Brenner, N. M. van Schoor, J. R. Albertorio, Carlotta SACERDOTE, A. Linneberg, L. L. Karhus, J. M. Huerta, L. Imaz, C. Joergensen, Y. Ben-Shlomo, A. Lundqvist, J. Gallacher, N. Sattar, A. M. Wood, N. J. Wareham, B. G. Nordestgaard, Angelantonio E. Di, J. Danesh, A. S. Butterworth, S. Burgess

Dipartimento di Scienze della Salute

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

Abstract

Background: Randomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. We aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks. Methods: Observational analyses were undertaken using data from 33 prospective studies comprising 500 962 individuals with no known history of coronary heart disease or stroke at baseline. Mendelian randomisation analyses were performed in four population-based cohort studies (UK Biobank, EPIC-CVD, and two Copenhagen population-based studies) comprising 386 406 middle-aged individuals of European ancestries, including 33 546 people who developed coronary heart disease, 18 166 people who had a stroke, and 27 885 people who died. Primary outcomes were coronary heart disease, defined as fatal ischaemic heart disease (International Classification of Diseases 10th revision code I20-I25) or non-fatal myocardial infarction (I21-I23); stroke, defined as any cerebrovascular disease (I60-I69); and all-cause mortality. Findings: Observational analyses suggested inverse associations between incident coronary heart disease, stroke, and all-cause mortality outcomes with 25(OH)D concentration at low 25(OH)D concentrations. In population-wide genetic analyses, there were no associations of genetically-predicted 25(OH)D with coronary heart disease, stroke, or all-cause mortality. However, for the participants with vitamin D deficiency (25[OH]D concentration <25 nmol/L), genetic analyses provided strong evidence for an inverse association with all-cause mortality (odds ratio [OR] per 10 nmol/L increase in genetically-predicted 25[OH]D concentration 0·69 [95% CI 0·59–0·80]; p<0·0001) and non-significant inverse associations for stroke (0·85 [0·70–1·02], p=0·09) and coronary heart disease (0·89 [0·76–1·04]; p=0·14). A finer stratification of participants found inverse associations between genetically-predicted 25(OH)D concentrations and all-cause mortality up to around 40 nmol/L. Interpretation: Stratified Mendelian randomisation analyses suggest a causal relationship between 25(OH)D concentrations and mortality for individuals with low vitamin D status. Our findings have implications for the design of vitamin D supplementation trials, and potential disease prevention strategies. Funding: British Heart Foundation, Medical Research Council, National Institute for Health Research, Health Data Research UK, Cancer Research UK, and International Agency for Research on Cancer.

Lingua originale	Inglese
pagine (da-a)	837-846
Numero di pagine	10
Rivista	The Lancet Diabetes and Endocrinology
Volume	9
Numero di pubblicazione	12
DOI	https://doi.org/10.1016/S2213-8587(21)00263-1
Stato di pubblicazione	Pubblicato - 2021

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10.1016/S2213-8587(21)00263-1

https://hdl.handle.net/11579/199632

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Sofianopoulou, E., Kaptoge, S. K., Afzal, S., Jiang, T., Gill, D., Gundersen, T. E., Bolton, T. R., Allara, E., Arnold, M. G., Mason, A. M., Chung, R., Pennells, L. A. M., Shi, F., Sun, L., Willeit, P., Forouhi, N. G., Langenberg, C., Sharp, S. J., Panico, S., ... Burgess, S. (2021). Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses. The Lancet Diabetes and Endocrinology, 9(12), 837-846. https://doi.org/10.1016/S2213-8587(21)00263-1

@article{98ef4b6b6d8749839efc66b6add773c8,

title = "Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses",

abstract = "Background: Randomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. We aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks. Methods: Observational analyses were undertaken using data from 33 prospective studies comprising 500 962 individuals with no known history of coronary heart disease or stroke at baseline. Mendelian randomisation analyses were performed in four population-based cohort studies (UK Biobank, EPIC-CVD, and two Copenhagen population-based studies) comprising 386 406 middle-aged individuals of European ancestries, including 33 546 people who developed coronary heart disease, 18 166 people who had a stroke, and 27 885 people who died. Primary outcomes were coronary heart disease, defined as fatal ischaemic heart disease (International Classification of Diseases 10th revision code I20-I25) or non-fatal myocardial infarction (I21-I23); stroke, defined as any cerebrovascular disease (I60-I69); and all-cause mortality. Findings: Observational analyses suggested inverse associations between incident coronary heart disease, stroke, and all-cause mortality outcomes with 25(OH)D concentration at low 25(OH)D concentrations. In population-wide genetic analyses, there were no associations of genetically-predicted 25(OH)D with coronary heart disease, stroke, or all-cause mortality. However, for the participants with vitamin D deficiency (25[OH]D concentration <25 nmol/L), genetic analyses provided strong evidence for an inverse association with all-cause mortality (odds ratio [OR] per 10 nmol/L increase in genetically-predicted 25[OH]D concentration 0·69 [95% CI 0·59–0·80]; p<0·0001) and non-significant inverse associations for stroke (0·85 [0·70–1·02], p=0·09) and coronary heart disease (0·89 [0·76–1·04]; p=0·14). A finer stratification of participants found inverse associations between genetically-predicted 25(OH)D concentrations and all-cause mortality up to around 40 nmol/L. Interpretation: Stratified Mendelian randomisation analyses suggest a causal relationship between 25(OH)D concentrations and mortality for individuals with low vitamin D status. Our findings have implications for the design of vitamin D supplementation trials, and potential disease prevention strategies. Funding: British Heart Foundation, Medical Research Council, National Institute for Health Research, Health Data Research UK, Cancer Research UK, and International Agency for Research on Cancer.",

author = "E. Sofianopoulou and Kaptoge, {S. K.} and S. Afzal and T. Jiang and D. Gill and Gundersen, {T. E.} and Bolton, {T. R.} and E. Allara and Arnold, {M. G.} and Mason, {A. M.} and R. Chung and Pennells, {L. A. M.} and F. Shi and L. Sun and P. Willeit and Forouhi, {N. G.} and C. Langenberg and Sharp, {S. J.} and S. Panico and G. Engstrom and O. Melander and Tong, {T. Y. N.} and A. Perez-Cornago and M. Norberg and I. Johansson and V. Katzke and B. Srour and Jose, {Sanchez M.} and D. Redondo-Sanchez and A. Olsen and Dahm, {C. C.} and K. Overvad and M. Brustad and G. Skeie and C. Moreno-Iribas and Onland-Moret, {N. C.} and {van der Schouw}, {Y. T.} and Tsilidis, {K. K.} and Heath, {A. K.} and C. Agnoli and V. Krogh and {de Boer}, {I. H.} and Kobylecki, {C. J.} and Y. Colak and A. Zittermann and J. Sundstrom and P. Welsh and E. Weiderpass and Aglago, {E. K.} and P. Ferrari and R. Clarke and -C., {Boutron M.} and G. Severi and C. MacDonald and R. Providencia and G. Masala and Zamora, {Ros R.} and J. Boer and Verschuren, {W. M.} and P. Cawthon and Schierbeck, {L. L.} and C. Cooper and Schulze, {M. B.} and Bergmann, {M. M.} and A. Hannemann and S. Kiechl and H. Brenner and {van Schoor}, {N. M.} and Albertorio, {J. R.} and Carlotta SACERDOTE and A. Linneberg and Karhus, {L. L.} and Huerta, {J. M.} and L. Imaz and C. Joergensen and Y. Ben-Shlomo and A. Lundqvist and J. Gallacher and N. Sattar and Wood, {A. M.} and Wareham, {N. J.} and Nordestgaard, {B. G.} and Di, {Angelantonio E.} and J. Danesh and Butterworth, {A. S.} and S. Burgess",

year = "2021",

doi = "10.1016/S2213-8587(21)00263-1",

language = "English",

volume = "9",

pages = "837--846",

journal = "The Lancet Diabetes and Endocrinology",

issn = "2213-8587",

publisher = "Elsevier BV",

number = "12",

}

Sofianopoulou, E, Kaptoge, SK, Afzal, S, Jiang, T, Gill, D, Gundersen, TE, Bolton, TR, Allara, E, Arnold, MG, Mason, AM, Chung, R, Pennells, LAM, Shi, F, Sun, L, Willeit, P, Forouhi, NG, Langenberg, C, Sharp, SJ, Panico, S, Engstrom, G, Melander, O, Tong, TYN, Perez-Cornago, A, Norberg, M, Johansson, I, Katzke, V, Srour, B, Jose, SM, Redondo-Sanchez, D, Olsen, A, Dahm, CC, Overvad, K, Brustad, M, Skeie, G, Moreno-Iribas, C, Onland-Moret, NC, van der Schouw, YT, Tsilidis, KK, Heath, AK, Agnoli, C, Krogh, V, de Boer, IH, Kobylecki, CJ, Colak, Y, Zittermann, A, Sundstrom, J, Welsh, P, Weiderpass, E, Aglago, EK, Ferrari, P, Clarke, R, -C., BM, Severi, G, MacDonald, C, Providencia, R, Masala, G, Zamora, RR, Boer, J, Verschuren, WM, Cawthon, P, Schierbeck, LL, Cooper, C, Schulze, MB, Bergmann, MM, Hannemann, A, Kiechl, S, Brenner, H, van Schoor, NM, Albertorio, JR, SACERDOTE, C, Linneberg, A, Karhus, LL, Huerta, JM, Imaz, L, Joergensen, C, Ben-Shlomo, Y, Lundqvist, A, Gallacher, J, Sattar, N, Wood, AM, Wareham, NJ, Nordestgaard, BG, Di, AE, Danesh, J, Butterworth, AS & Burgess, S 2021, 'Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses', The Lancet Diabetes and Endocrinology, vol. 9, n. 12, pagg. 837-846. https://doi.org/10.1016/S2213-8587(21)00263-1

Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses. / Sofianopoulou, E.; Kaptoge, S. K.; Afzal, S. et al.
In: The Lancet Diabetes and Endocrinology, Vol. 9, N. 12, 2021, pag. 837-846.

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

TY - JOUR

T1 - Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses

AU - Sofianopoulou, E.

AU - Kaptoge, S. K.

AU - Afzal, S.

AU - Jiang, T.

AU - Gill, D.

AU - Gundersen, T. E.

AU - Bolton, T. R.

AU - Allara, E.

AU - Arnold, M. G.

AU - Mason, A. M.

AU - Chung, R.

AU - Pennells, L. A. M.

AU - Shi, F.

AU - Sun, L.

AU - Willeit, P.

AU - Forouhi, N. G.

AU - Langenberg, C.

AU - Sharp, S. J.

AU - Panico, S.

AU - Engstrom, G.

AU - Melander, O.

AU - Tong, T. Y. N.

AU - Perez-Cornago, A.

AU - Norberg, M.

AU - Johansson, I.

AU - Katzke, V.

AU - Srour, B.

AU - Jose, Sanchez M.

AU - Redondo-Sanchez, D.

AU - Olsen, A.

AU - Dahm, C. C.

AU - Overvad, K.

AU - Brustad, M.

AU - Skeie, G.

AU - Moreno-Iribas, C.

AU - Onland-Moret, N. C.

AU - van der Schouw, Y. T.

AU - Tsilidis, K. K.

AU - Heath, A. K.

AU - Agnoli, C.

AU - Krogh, V.

AU - de Boer, I. H.

AU - Kobylecki, C. J.

AU - Colak, Y.

AU - Zittermann, A.

AU - Sundstrom, J.

AU - Welsh, P.

AU - Weiderpass, E.

AU - Aglago, E. K.

AU - Ferrari, P.

AU - Clarke, R.

AU - -C., Boutron M.

AU - Severi, G.

AU - MacDonald, C.

AU - Providencia, R.

AU - Masala, G.

AU - Zamora, Ros R.

AU - Boer, J.

AU - Verschuren, W. M.

AU - Cawthon, P.

AU - Schierbeck, L. L.

AU - Cooper, C.

AU - Schulze, M. B.

AU - Bergmann, M. M.

AU - Hannemann, A.

AU - Kiechl, S.

AU - Brenner, H.

AU - van Schoor, N. M.

AU - Albertorio, J. R.

AU - SACERDOTE, Carlotta

AU - Linneberg, A.

AU - Karhus, L. L.

AU - Huerta, J. M.

AU - Imaz, L.

AU - Joergensen, C.

AU - Ben-Shlomo, Y.

AU - Lundqvist, A.

AU - Gallacher, J.

AU - Sattar, N.

AU - Wood, A. M.

AU - Wareham, N. J.

AU - Nordestgaard, B. G.

AU - Di, Angelantonio E.

AU - Danesh, J.

AU - Butterworth, A. S.

AU - Burgess, S.

PY - 2021

Y1 - 2021

N2 - Background: Randomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. We aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks. Methods: Observational analyses were undertaken using data from 33 prospective studies comprising 500 962 individuals with no known history of coronary heart disease or stroke at baseline. Mendelian randomisation analyses were performed in four population-based cohort studies (UK Biobank, EPIC-CVD, and two Copenhagen population-based studies) comprising 386 406 middle-aged individuals of European ancestries, including 33 546 people who developed coronary heart disease, 18 166 people who had a stroke, and 27 885 people who died. Primary outcomes were coronary heart disease, defined as fatal ischaemic heart disease (International Classification of Diseases 10th revision code I20-I25) or non-fatal myocardial infarction (I21-I23); stroke, defined as any cerebrovascular disease (I60-I69); and all-cause mortality. Findings: Observational analyses suggested inverse associations between incident coronary heart disease, stroke, and all-cause mortality outcomes with 25(OH)D concentration at low 25(OH)D concentrations. In population-wide genetic analyses, there were no associations of genetically-predicted 25(OH)D with coronary heart disease, stroke, or all-cause mortality. However, for the participants with vitamin D deficiency (25[OH]D concentration <25 nmol/L), genetic analyses provided strong evidence for an inverse association with all-cause mortality (odds ratio [OR] per 10 nmol/L increase in genetically-predicted 25[OH]D concentration 0·69 [95% CI 0·59–0·80]; p<0·0001) and non-significant inverse associations for stroke (0·85 [0·70–1·02], p=0·09) and coronary heart disease (0·89 [0·76–1·04]; p=0·14). A finer stratification of participants found inverse associations between genetically-predicted 25(OH)D concentrations and all-cause mortality up to around 40 nmol/L. Interpretation: Stratified Mendelian randomisation analyses suggest a causal relationship between 25(OH)D concentrations and mortality for individuals with low vitamin D status. Our findings have implications for the design of vitamin D supplementation trials, and potential disease prevention strategies. Funding: British Heart Foundation, Medical Research Council, National Institute for Health Research, Health Data Research UK, Cancer Research UK, and International Agency for Research on Cancer.

AB - Background: Randomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. We aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks. Methods: Observational analyses were undertaken using data from 33 prospective studies comprising 500 962 individuals with no known history of coronary heart disease or stroke at baseline. Mendelian randomisation analyses were performed in four population-based cohort studies (UK Biobank, EPIC-CVD, and two Copenhagen population-based studies) comprising 386 406 middle-aged individuals of European ancestries, including 33 546 people who developed coronary heart disease, 18 166 people who had a stroke, and 27 885 people who died. Primary outcomes were coronary heart disease, defined as fatal ischaemic heart disease (International Classification of Diseases 10th revision code I20-I25) or non-fatal myocardial infarction (I21-I23); stroke, defined as any cerebrovascular disease (I60-I69); and all-cause mortality. Findings: Observational analyses suggested inverse associations between incident coronary heart disease, stroke, and all-cause mortality outcomes with 25(OH)D concentration at low 25(OH)D concentrations. In population-wide genetic analyses, there were no associations of genetically-predicted 25(OH)D with coronary heart disease, stroke, or all-cause mortality. However, for the participants with vitamin D deficiency (25[OH]D concentration <25 nmol/L), genetic analyses provided strong evidence for an inverse association with all-cause mortality (odds ratio [OR] per 10 nmol/L increase in genetically-predicted 25[OH]D concentration 0·69 [95% CI 0·59–0·80]; p<0·0001) and non-significant inverse associations for stroke (0·85 [0·70–1·02], p=0·09) and coronary heart disease (0·89 [0·76–1·04]; p=0·14). A finer stratification of participants found inverse associations between genetically-predicted 25(OH)D concentrations and all-cause mortality up to around 40 nmol/L. Interpretation: Stratified Mendelian randomisation analyses suggest a causal relationship between 25(OH)D concentrations and mortality for individuals with low vitamin D status. Our findings have implications for the design of vitamin D supplementation trials, and potential disease prevention strategies. Funding: British Heart Foundation, Medical Research Council, National Institute for Health Research, Health Data Research UK, Cancer Research UK, and International Agency for Research on Cancer.

UR - https://iris.uniupo.it/handle/11579/199632

U2 - 10.1016/S2213-8587(21)00263-1

DO - 10.1016/S2213-8587(21)00263-1

M3 - Article

SN - 2213-8587

VL - 9

SP - 837

EP - 846

JO - The Lancet Diabetes and Endocrinology

JF - The Lancet Diabetes and Endocrinology

IS - 12

ER -

Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses

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