Association between cholesterol efflux capacity and peripheral artery disease in coronary heart disease patients with and without type 2 diabetes: from the CORDIOPREV study

Authors: YUBERO-SERANO, ELENA - University Of Cordova (UCO), Spain; ALCALA-DIAZ, JUAN - University Of Cordova (UCO), Spain; GUTIERREZ-MARISCAL, FRANCISCO - University Of Cordova (UCO), Spain; ARRINAS DE LARRIVA, ANTONIO - University Of Cordova (UCO), Spain; PENA-ORIHUELA, PATRICIA - University Of Cordova (UCO), Spain; BLANCO-ROJO, RUTH - Biosearch Life; MARTINEZ-BOTAS, JAVIER - Instituto De Salud Carlos Iii; TORRES-PENA, JOSE - University Of Cordova (UCO), Spain; PEREZ-MARTINEZ, PABLO - University Of Cordova (UCO), Spain; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DELGADO-LISTA, JAVIER - University Of Cordova (UCO), Spain; GOMEZ-CORONADO, DIEGO - Instituto De Salud Carlos Iii; LOPEZ-MIRANDA, JOSE - University Of Cordova (UCO), Spain

Submitted to: Cardiovascular Diabetology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/11/2021
Publication Date: 3/25/2021
Citation: Yubero-Serano, E.M., Alcala-Diaz, J.F., Gutierrez-Mariscal, F., Arrinas De Larriva, A.P., Pena-Orihuela, P.J., Blanco-Rojo, R., Martinez-Botas, J., Torres-Pena, J.D., Perez-Martinez, P., Ordovas, J.M., Delgado-Lista, J., Gomez-Coronado, D., Lopez-Miranda, J. 2021. Association between cholesterol efflux capacity and peripheral artery disease in coronary heart disease patients with and without type 2 diabetes: from the CORDIOPREV study. Cardiovascular Diabetology. 20:72. https://doi.org/10.1186/s12933-021-01260-3.
DOI: https://doi.org/10.1186/s12933-021-01260-3

Interpretive Summary: Peripheral arterial disease (PAD) in the legs or lower extremities is the narrowing or blockage of the vessels that carry blood from the heart to the legs. It is primarily caused by the buildup of fat and cholesterol in the arteries, which is called atherosclerosis. High-density lipoprotein (HDL), also known as "good cholesterol," promotes the exit of the cholesterol from the walls of the blood vessels and can prevent its build up and, thus, atherosclerosis. This work conducted by scientists at the HNRCA in Boston, in collaboration with Spanish investigators, aimed to elucidate the relation between HDL, the presence of PAD, and the influence of diabetes. This was conducted in patients (n=1002) enrolled in the CORDIOPREV study. The presence of PAD was related to the action of HDL in patients without diabetes or with recent diabetes. However, such relation was not observed in long-term diabetic patients. These results support the importance of early detection of diabetes to prevent or reduce the high risk of cardiovascular events of these patients.

Technical 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 greater or equal to 0.9 and ABI greater than 0.9 and less than 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.