2026-04-29T18:25:02Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/175112024-09-27T07:57:29Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Toribio-Fernández, Raquel author Tristão-Pereira, Catarina author Carlos Silla-Castro, Juan author Callejas, Sergio author Oliva, Belen author Fernandez-Nueda, Irene author Garcia-Lunar, Ines author Perez-Herreras, Cristina author María Ordovás, José author Martin, Pilar author Blanco-Kelly, Fiona author Ayuso, Carmen author Lara-Pezzi, Enrique author Fernandez-Ortiz, Antonio author Garcia-Alvarez, Ana author Dopazo, Ana author Sanchez-Cabo, Fatima author Ibáñez, Borja author Cortes-Canteli, Marta author Fuster, Valentin author 2024-01-23 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. Circ Res. 2024 Jan 23. 10.1161/CIRCRESAHA.123.323921 1524-4571 Circulation research 38258600 http://hdl.handle.net/20.500.12105/17511 Apolipoprotein E-ε2 and Resistance to Atherosclerosis in Midlife-The PESA Observational Study.