Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/17511
Título
Apolipoprotein E-ε2 and Resistance to Atherosclerosis in Midlife-The PESA Observational Study.
Autor(es)
Toribio-Fernández, Raquel | Tristão-Pereira, Catarina | Carlos Silla-Castro, Juan | Callejas, Sergio CNIC | Oliva, Belen CNIC | Fernandez-Nueda, Irene CNIC | Garcia-Lunar, Ines CNIC | Perez-Herreras, Cristina | María Ordovás, José | Martin, Pilar CNIC | Blanco-Kelly, Fiona | Ayuso, Carmen | Lara-Pezzi, Enrique CNIC | Fernandez-Ortiz, Antonio CNIC | Garcia-Alvarez, Ana CNIC | Dopazo, Ana CNIC | Sanchez-Cabo, Fatima CNIC | Ibáñez, Borja CNIC | Cortes-Canteli, Marta CNIC | Fuster, Valentin
Fecha de publicación
2024-01-23
Cita
Circ Res. 2024 Jan 23.
Idioma
Inglés
Tipo de documento
journal article
Resumen
BACKGROUND
APOE is a known genetic contributor to cardiovascular disease, but the differential role APOE alleles play in subclinical atherosclerosis remains unclear.
METHODS
The PESA (Progression of Early Subclinical Atherosclerosis) is an observational cohort study that recruited 4184 middle-aged asymptomatic individuals to be screened for cardiovascular risk and multiterritorial subclinical atherosclerosis. Participants were APOE-genotyped, and omics data were additionally evaluated.
RESULTS
In the PESA study, the frequencies for APOE -ε2, -ε3, and -ε4 alleles were 0.060, 0.844, and 0.096, respectively. This study included a subcohort of 3887 participants (45.8±4.3 years of age; 62% males). As expected, APOE-ε4 carriers were at the highest risk for cardiovascular disease and had significantly greater odds of having subclinical atherosclerosis compared with ε3/ε3 carriers, which was mainly explained by their higher levels of LDL (low-density lipoprotein)-cholesterol. In turn, APOE-ε2 carriers were at the lowest risk for cardiovascular disease and had significantly lower odds of having subclinical atherosclerosis in several vascular territories (carotids: 0.62 [95% CI, 0.47-0.81]; P=0.00043; femorals: 0.60 [0.47-0.78]; P=9.96×10-5; coronaries: 0.53 [0.39-0.74]; P=0.00013; and increased PESA score: 0.58 [0.48-0.71]; P=3.16×10-8). This APOE-ε2 atheroprotective effect was mostly independent of the associated lower LDL (low-density lipoprotein)-cholesterol levels and other cardiovascular risk factors. The protection conferred by the ε2 allele was greater with age (50-54 years: 0.49 [95% CI, 0.32-0.73]; P=0.00045), and normal (<150 mg/dL) levels of triglycerides (0.54 [0.44-0.66]; P=4.70×10-9 versus 0.90 [0.57-1.43]; P=0.67 if ≥150 mg/dL). Omics analysis revealed an enrichment of several canonical pathways associated with anti-inflammatory mechanisms together with the modulation of erythrocyte homeostasis, coagulation, and complement activation in ε2 carriers that might play a relevant role in the ε2's atheroprotective effect.
CONCLUSIONS
This work sheds light on the role of APOE in cardiovascular disease development with important therapeutic and prevention implications on cardiovascular health, especially in early midlife.
REGISTRATION
URL: https://www.clinicaltrials.gov: NCT01410318.
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DOI
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