Elena M Yubero-Serrano1,2, Juan F Alcalá-Diaz3,4, Diego Gómez-Coronado4,5, Jose Lopez-Miranda6,7, Francisco M Gutierrez-Mariscal3,4, Antonio P Arenas-de Larriva3,4, Patricia J Peña-Orihuela3,4, Ruth Blanco-Rojo8, Javier Martinez-Botas4,5, Jose D Torres-Peña3,4, Pablo Perez-Martinez3,4, Jose M Ordovas9,10, Javier Delgado-Lista3,4. 1. Lipids and Atherosclerosis Unit. Servicio de Medicina Interna, Reina Sofia University Hospital, Maimonides Institute for Biomedical Research in Córdoba, University of Córdoba, Córdoba, Spain. helese35@hotmail.com. 2. CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, Spain. helese35@hotmail.com. 3. Lipids and Atherosclerosis Unit. Servicio de Medicina Interna, Reina Sofia University Hospital, Maimonides Institute for Biomedical Research in Córdoba, University of Córdoba, Córdoba, Spain. 4. CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, Spain. 5. Department of Biochemistry-Research, Hospital Universitario Ramón Y Cajal, Instituto Ramón Y Cajal de Investigacion Sanitaria (IRyCIS), Madrid, Spain. 6. Lipids and Atherosclerosis Unit. Servicio de Medicina Interna, Reina Sofia University Hospital, Maimonides Institute for Biomedical Research in Córdoba, University of Córdoba, Córdoba, Spain. jlopezmir@uco.es. 7. CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Madrid, Spain. jlopezmir@uco.es. 8. Research and Development Department, Biosearch Life, Granada, Spain. 9. Jean Mayer US Department of Agriculture Human Nutrition Research Center On Aging, Tufts University School of Medicine, Boston, MA, USA. 10. IMDEA-Food Institute, CEI UAM + CSIC, Madrid, Spain.
Abstract
BACKGROUND: Peripheral artery disease (PAD) is recognized as a significant predictor of mortality and adverse cardiovascular outcomes in patients with coronary heart disease (CHD). In fact, coexisting PAD and CHD is strongly associated with a greater coronary event recurrence compared with either one of them alone. High-density lipoprotein (HDL)-mediated cholesterol efflux capacity (CEC) is found to be inversely associated with an increased risk of incident CHD. However, this association is not established in patients with PAD in the context of secondary prevention. In this sense, our main aim was to evaluate the association between CEC and PAD in patients with CHD and whether the concurrent presence of PAD and T2DM influences this association. METHODS: CHD patients (n = 1002) from the CORDIOPREV study were classified according to the presence or absence of PAD (ankle-brachial index, ABI ≤ 0.9 and ABI > 0.9 and < 1.4, respectively) and T2DM status. CEC was quantified by incubation of cholesterol-loaded THP-1 cells with the participants' apoB-depleted plasma was performed. RESULTS: The presence of PAD determined low CEC in non-T2DM and newly-diagnosed T2DM patients. Coexisting PAD and newly-diagnosed T2DM provided and additive effect providing an impaired CEC compared to non-T2DM patients with PAD. In established T2DM patients, the presence of PAD did not determine differences in CEC, compared to those without PAD, which may be restored by glucose-lowering treatment. CONCLUSIONS: Our findings suggest an inverse relationship between CEC and PAD in CHD patients. These results support the importance of identifying underlying mechanisms of PAD, in the context of secondary prevention, that provide potential therapeutic targets, that is the case of CEC, and establishing strategies to prevent or reduce the high risk of cardiovascular events of these patients. Trial registration https://clinicaltrials.gov/ct2/show/NCT00924937 . Unique Identifier: NCT00924937.
BACKGROUND:Peripheral artery disease (PAD) is recognized as a significant predictor of mortality and adverse cardiovascular outcomes in patients with coronary heart disease (CHD). In fact, coexisting PAD and CHD is strongly associated with a greater coronary event recurrence compared with either one of them alone. High-density lipoprotein (HDL)-mediated cholesterol efflux capacity (CEC) is found to be inversely associated with an increased risk of incident CHD. However, this association is not established in patients with PAD in the context of secondary prevention. In this sense, our main aim was to evaluate the association between CEC and PAD in patients with CHD and whether the concurrent presence of PAD and T2DM influences this association. METHODS: CHD patients (n = 1002) from the CORDIOPREV study were classified according to the presence or absence of PAD (ankle-brachial index, ABI ≤ 0.9 and ABI > 0.9 and < 1.4, respectively) and T2DM status. CEC was quantified by incubation of cholesterol-loaded THP-1 cells with the participants' apoB-depleted plasma was performed. RESULTS: The presence of PAD determined low CEC in non-T2DM and newly-diagnosed T2DM patients. Coexisting PAD and newly-diagnosed T2DM provided and additive effect providing an impaired CEC compared to non-T2DM patients with PAD. In established T2DM patients, the presence of PAD did not determine differences in CEC, compared to those without PAD, which may be restored by glucose-lowering treatment. CONCLUSIONS: Our findings suggest an inverse relationship between CEC and PAD in CHD patients. These results support the importance of identifying underlying mechanisms of PAD, in the context of secondary prevention, that provide potential therapeutic targets, that is the case of CEC, and establishing strategies to prevent or reduce the high risk of cardiovascular events of these patients. Trial registration https://clinicaltrials.gov/ct2/show/NCT00924937 . Unique Identifier: NCT00924937.
Authors: Robert S Rosenson; H Bryan Brewer; M John Chapman; Sergio Fazio; M Mahmood Hussain; Anatol Kontush; Ronald M Krauss; James D Otvos; Alan T Remaley; Ernst J Schaefer Journal: Clin Chem Date: 2011-01-25 Impact factor: 8.327
Authors: Halim Abboud; Linsay Monteiro Tavares; Julien Labreuche; Antonio Arauz; Alan Bryer; Pablo M Lavados; Ayrton Massaro; Mario Munoz Collazos; Philippe Gabriel Steg; Bassem I Yamout; Eric Vicaut; Pierre Amarenco Journal: Stroke Date: 2019-04 Impact factor: 7.914
Authors: Ayman A Hussein; Kiyoko Uno; Kathy Wolski; Samir Kapadia; Paul Schoenhagen; E Murat Tuzcu; Steven E Nissen; Stephen J Nicholls Journal: J Am Coll Cardiol Date: 2011-03-08 Impact factor: 24.094
Authors: Leonardo De Luca; Giuseppe Di Pasquale; Lucio Gonzini; Francesco Chiarella; Antonio Di Chiara; Alessandro Boccanelli; Gianni Casella; Zoran Olivari; Stefano De Servi; Michele Massimo Gulizia; Andrea Di Lenarda; Stefano Savonitto; Leonardo Bolognese Journal: Eur J Intern Med Date: 2018-08-25 Impact factor: 4.487
Authors: Axel Haine; Sarah Kavanagh; Jeffrey S Berger; Connie N Hess; Lars Norgren; F Gerry R Fowkes; Brian G Katona; Kenneth W Mahaffey; Juuso I Blomster; Manesh R Patel; W Schuyler Jones; Frank W Rockhold; William R Hiatt; Iris Baumgartner Journal: J Am Coll Cardiol Date: 2020-02-18 Impact factor: 24.094
Authors: Alan T Hirsch; Ziv J Haskal; Norman R Hertzer; Curtis W Bakal; Mark A Creager; Jonathan L Halperin; Loren F Hiratzka; William R C Murphy; Jeffrey W Olin; Jules B Puschett; Kenneth A Rosenfield; David Sacks; James C Stanley; Lloyd M Taylor; Christopher J White; John White; Rodney A White; Elliott M Antman; Sidney C Smith; Cynthia D Adams; Jeffrey L Anderson; David P Faxon; Valentin Fuster; Raymond J Gibbons; Sharon A Hunt; Alice K Jacobs; Rick Nishimura; Joseph P Ornato; Richard L Page; Barbara Riegel Journal: Circulation Date: 2006-03-21 Impact factor: 29.690
Authors: Gregory G Schwartz; Anders G Olsson; Markus Abt; Christie M Ballantyne; Philip J Barter; Jochen Brumm; Bernard R Chaitman; Ingar M Holme; David Kallend; Lawrence A Leiter; Eran Leitersdorf; John J V McMurray; Hardi Mundl; Stephen J Nicholls; Prediman K Shah; Jean-Claude Tardif; R Scott Wright Journal: N Engl J Med Date: 2012-11-05 Impact factor: 91.245
Authors: Elena M Yubero-Serrano; Juan F Alcalá-Diaz; Diego Gómez-Coronado; Jose Lopez-Miranda; Francisco M Gutierrez-Mariscal; Antonio P Arenas-de Larriva; Patricia J Peña-Orihuela; Ruth Blanco-Rojo; Javier Martinez-Botas; Jose D Torres-Peña; Pablo Perez-Martinez; Jose M Ordovas; Javier Delgado-Lista Journal: Cardiovasc Diabetol Date: 2021-04-17 Impact factor: 9.951