Statin effects on the lipidome: Predicting statin usage and implications for cardiovascular risk prediction

Statin effects on the lipidome: Predicting statin usage and implications for cardiovascular risk prediction

Statin therapy is a highly successful and cost-effective strategy for the prevention and treatment of cardiovascular diseases (CVD). Adjusting for statin usage is crucial when exploring the association of the lipidome with CVD to avoid erroneous conclusions. However, practical challenges arise in re...

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Main Authors: Changyu Yi, Kevin Huynh, Yvette Schooneveldt, Gavriel Olshansky, Amy Liang, Tingting Wang, Habtamu B. Beyene, Aleksandar Dakic, Jingqin Wu, Michelle Cinel, Natalie A. Mellett, Gerald F. Watts, Joseph Hung, Jennie Hui, John Beilby, Joanne E. Curran, John Blangero, Eric K. Moses, John Simes, Andrew M. Tonkin, Leonard Kritharides, David Sullivan, Jonathan E. Shaw, Dianna J. Magliano, Agus Salim, Corey Giles, Peter J. Meikle, A. Tonkin, P. Aylward, D. Colquhoun, P. Glasziou, P. Harris, D. Hunt, A. Keech, S. MacMahon, P. Magnus, D. Newel, P. Nestel, N. Sharpe, J. Shaw, R.J. Simes, P. Thompson, A. Thomson, M. West, H. White, S. Simes, W. Hague, S. Caleo, J. Hall, A. Martin, S. Mulray, P. Barter, L. Beilin, R. Collins, J. McNeil, P. Meier, H. Willimott, D. Smithers, P. Wallace, J. Baker, M. Hobbs, D. Sullivan, N. Anderson, G. Hankey, J. Watson, M. Arulchelvam, S. Chup, J. Daly, J. Hanna, A. Leach, M. Lee, J. Loughhead, H. Lundie-Jenkin, J. Morrison, S. Netting, A. Nguyen, H. Pater, R. Philip, G. Pinna, D. Rattos, S. Ryerson, V. Sazhin, R. Walsh, A. Clague, M. Mackie, J. Yallop, K. Boss, M. Whiting, M. Shepard, J. Leach, M. Gandy, J. Joughin, J. Seabrook, R. Abraham, J. Allen, F. Bates, I. Beinart, E. Breed, D. Brown, N. Bunyan, D. Calvert, T. Campbell, D. Condon-Paoloni, B. Conway, L. Coupland, J. Crowe, N. Cunio, B. Cuthbert, N. Cuthbert, S. D’Arcy, P. Davidson, B. Dwyer, J. England, C. Friend, G. Fulcher, S. Grant, K. Hellestrand, M. Kava, L. Kritharides, D. McGill, H. McKee, A. McLean, M. Neaverson, G. Nelson, M. O’Neill, C. Onuma, F. O’Reilly, A. Owensby, D. Owensby, J. Padley, G. Parnell, S. Paterson, C. Pawsey, R. Portley, K. Quinn, D. Ramsay, M. Russell, J. Ryan, B. Sambrook, L. Shields, J. Silberberg, S. Sinclair, P. Taverner, D. Taylor, M. Taylor, M. Threlfall, J. Turner, A. Viles, J. Waites, R. Walker, W. Walsh, K. Wee, P. West, R. Wikramanayake, D. Wilcken, J. Woods, R.K. Barnett, Z. Bogetic, H. Briggs, A. Broughton, L. Brown, A. Buncle, P. Calafiore, L. Carrick, Y. Cavenett, L. Champness, R. Clark, H. Connor, J. Counsell, J. Deague, G. Derwent-Smith, A. Driscoll, B. Feldtmann, L. Fisher, B. Forge, A. Hamer, H. Harrap, S. Hodgens, M. Hooten, J. Hurley, B. Jackson, J. Johns, J. Krafchek, H. Larwill, I. Lyall, S. Marks, M. Martin, B. Mason, J. McCabe, C. Medley, L. Morgan, L. Mullan, D. Ogilvy, G. Phelps, P. Phillips, H. Prendergast, D. Rose, G. Rudge, W. Ryan, M. Sallaberger, G. Savige, B. Sia, A. Soward, C. Steinfort, K. Tankard, J. Tippett, B. Tyack, J. Voukelatis, M. Wahlqvist, N. Walker, S. Whitten, R. Yee, M. Zanoni, R. Ziffer, K. Anderson, G. Aroney, C. Atkinson, K. Boyd, R. Bradfield, G. Cameron, D. Careless, A. Carle, P. Carroll, T. Carruthers, D. Chaseling, B. Cooke, S. Coverdale, B. Currie, M. d’Emden, F. Ekin, R. Elder, T. Elsley, L. Ferry, C. Gnanaharan, K. Graham, K. Gunawardane, C. Hadfield, C. Halliday, R. Halliday, A. Heyworth, B. Hicks, P. Hicks, T. Htut, L. Hughes, J. Humphries, H. LeGood, J. Nye, D. O’Brien, G. Real, K. Roberts, L. RossLee, J. Sampson, I. Scott, H. Smith, V. Smith-Orr, Y. Tan, B. Wicks, J. Wicks, S. Woodhouse, J. Bradley, L. Callaway, A. Calvert, J. Crettenden, A. Dufek, B. Dunn, C. Dunphy, D. Gow, I. Hamilton-Craig, K. Herewane, S. Keynes, L. McLeay, R. McLeay, L. Ng, C. Thomas, P. Tideman, L. Wilson, R. Yeend, C. Zhang, Y. Zhang, P. Bradshaw, M. Brooks, R. Burton, J. Garrett, K. Gotch-Martin, J. Hargan, B. Hockings, G. Lane, S. Ross, R. Cutforth, D. D’Silva, W. Hitchener, V. Kimber, G. Kirkland, P. Neid, R. Parkes, B. Singh, C. Singh, M. Smith, S. Smith, M. Templer, N. Whitehouse, R. Allen-Narker, R. Anandaraja, S. Anandaraja, P. Barclay, S. Baskaranathan, P. Bridgman, J. Brown, J. Bruning, J. Calton, M. Clark, D. Clarke, T. Cook, R. Coxon, M. Denton, A. Doone, R. Easthope, J. Elliott, C. Ellis, P. FosterPratt, C. Frenneux, M. Frenneux, D. Friedlander, D. Fry, L. Gibson, M. Gluyas, A. Hall, K. Hall, H. Hart, P. Healy, J. Hedley, P. Heuser, H. Ikram, D. Jardine, J. Kenyon, H. King, T. Kirk, T. Lawson, P. Leslie, G. Lewis, E. Low, R. Luke, S. Mann, D. McClean, D. McHaffie, L. Nairn, H. Patel, L. Pearce, K. Ramanathan, R. Rankin, J. Reddy, S. Reuben, R. Ronaldson, D. Roy, H. Roy, P. Scobie, D. Scott, J. Scott, K. Skjellerup, R. Stewart, D. Walters, T. Wilkins, A. Vitanachy, P. Wright, A. Zambanini
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Journal of Lipid Research
Subjects:
lipidomics
cardiovascular disease
statins
regularized linear models
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227525000604
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Summary:Statin therapy is a highly successful and cost-effective strategy for the prevention and treatment of cardiovascular diseases (CVD). Adjusting for statin usage is crucial when exploring the association of the lipidome with CVD to avoid erroneous conclusions. However, practical challenges arise in real-world scenarios due to the frequent absence of statin usage information. To address this limitation, we demonstrate that statin usage can be accurately predicted using lipidomic data. Using three large population datasets and a longitudinal clinical study, we show that lipidomic-based statin prediction models exhibit high prediction accuracy in external validation. Furthermore, we introduce a re-weighted model, designed to overcome a ubiquitous limitation of prediction models, namely the need for predictor alignment between training and target data. We demonstrated that the re-weighted models achieved comparable prediction accuracy to ad hoc models which use the aligned predictor between training and target data. This innovation holds promise for significantly enhancing the transferability of statin prediction and other ‘omics prediction models, especially in situations where predictor alignment is incomplete. Our statin prediction model now allows for the inclusion of statin usage in lipidomic analyses of cohorts even where statin use is not available, improving the interpretability of the resulting analyses.
ISSN:0022-2275

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