title: Clinical impact of angiotensin I converting enzyme polymorphisms in subjects with resistant hypertension.
abstract: Angiotensin I converting enzyme (ACE) insertion/deletion (I/D) polymorphism is thought to affect renin-angiotensin system (RAS) activity and development of cardiovascular disease; significant associations between I/D polymorphism and atherosclerosis, stroke, nephropathy, and early mortality were already found. We investigated whether Southern Italy resistant hypertensives presented an association between the presence of I and/or D alleles and early vascular damage, inflammation, and insulin resistance. One-hundred-fifty resistant hypertensives were enrolled, studied, and genotyped; carotid intima-media thickness (cIMT), arterial stiffness (AS), and HOMA indices were also evaluated. D allele was more prevalent, and 74 patients presented DD homozygosis. Sixty-eight patients had metabolic syndrome (MetS), without significant differences between DD and I allele carriers. DD genotype appeared strongly associated with higher HOMA values (p < 0.001), and also with both Augmentation Index (AIx, p = 0.003) and Pulse Wave Velocity (PWV, p = 0.023). A significant association was found between DD genotype and cIMT (p < 0.005), while no association between ACE genotype and the presence of carotid plaques. HOMA was correlated with AS (PWV: p < 0.001; AIx: p < 0.01). DD genotype appeared to be associated with AS and HOMA index, but not with inflammation, independently from blood pressure values and the presence of other MetS factors, confirming D allele as an independent risk marker. Vascular damage may develop and progress independently from other risk factors in resistant hypertensives, likely through the interplay between ACE gene, RAS activity, and insulin resistance.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, v. Consolare Valeria - Gazzi, Messina, Italy.
authors.forename: Egidio
authors.initials: E
authors.lastname: Imbalzano
authors.affiliation: UTIC and Cardiology, Hospital "Pugliese-Ciaccio" of Catanzaro, Catanzaro, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Vatrano
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, v. Consolare Valeria - Gazzi, Messina, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Quartuccio
authors.affiliation: Department of Surgical, Medical and Molecular Pathology and Critic Area, University of Pisa, Pisa, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Di Stefano
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, v. Consolare Valeria - Gazzi, Messina, Italy. oriana.aragona@hotmail.it.
authors.forename: Caterina Oriana
authors.identifier: http://orcid.org/0000-0002-1314-6602
authors.initials: CO
authors.lastname: Aragona
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, v. Consolare Valeria - Gazzi, Messina, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Mamone
authors.affiliation: Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Messina, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: D'Ascola
authors.affiliation: Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Messina, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Scuruchi
authors.affiliation: Department of Surgical, Medical and Molecular Pathology and Critic Area, University of Pisa, Pisa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Felice
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, v. Consolare Valeria - Gazzi, Messina, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Trapani
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, v. Consolare Valeria - Gazzi, Messina, Italy.|UTIC and Cardiology, Hospital "Pugliese-Ciaccio" of Catanzaro, Catanzaro, Italy.|Department of Surgical, Medical and Molecular Pathology and Critic Area, University of Pisa, Pisa, Italy.|Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Messina, Italy.|Department of Statistics, University of Messina, Messina, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Alibrandi
authors.affiliation: UTIC and Cardiology, Hospital "Pugliese-Ciaccio" of Catanzaro, Catanzaro, Italy.
authors.forename: Vincenzo Antonio
authors.initials: VA
authors.lastname: Ciconte
authors.affiliation: UTIC and Cardiology, Hospital "Pugliese-Ciaccio" of Catanzaro, Catanzaro, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ceravolo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, v. Consolare Valeria - Gazzi, Messina, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Saitta
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, v. Consolare Valeria - Gazzi, Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mandraffino
mesh_terms: D000328:Adult; D000368:Aged; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D005260:Female; D006801:Humans; D006973:Hypertension / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: ACE genotype; Arterial stiffness; Insulin resistance; Renin angiotensin system; Resistant hypertension