Early sign of atherosclerosis in slow coronary flow and relationship with angiotensin-converting enzyme I/D polymorphism

Abstract

Increase in carotid artery intima-media thickness (IMT) is an early sign of atherosclerosis. Slow coronary flow (SCF) is characterized by delay of opacification of coronary arteries in coronary angiography in the absence of any evident obstructive lesion, but its etiopathogenesis remains unclear. Genes that regulate the renin angiotensin system also play a role in developing cardiovascular system disorders. The presence of deletion (D) allele in angiotensin converting enzyme (ACE) gene polymorphism is associated with coronary artery disease. The aim of this study was to investigate the carotid artery IMT measurement, as an early sign of atherosclerosis, in patients with SCF and without SCF and also to assess the effect of the renin-angiotensin gene system on carotid IMT. Forty-four patients with angiographically proven SCF and 44 cases with normal coronary flow (NCF) pattern with similar risk profile were enrolled in the study. Coronary flow patterns of the cases were determined by thrombolysis in myocardial infarction (TIMI) frame count method. Intima-media thickness was measured by recording ultrasonographic images of both the left and right common carotid artery with a 12-MHz linear array transducer. ACE I/D polymorphism and Angiotensin II tip 1 receptor (AT1R) A/C gene polymorphism were determined by polymerase chain reaction (PCR) amplification. Demographic characteristics and coronary artery disease risk factors of SCF and NCF groups were similar. Mean TIMI frame count and carotid IMT (mm) were significantly higher in the SCF group than controls (45.9 +/- 12 vs 23.3 +/- 3.7, P = 0.0001; 0.75 +/- 0.08 vs 0.69 +/- 0.06, P = 0.0001, respectively). Mean TIMI frame count was positively correlated with IMT of carotid artery in correlation analysis (r = 0.45, P = 0.0001). When analyzed in regard to ACE genotype in all subjects, IMT values were statistically different (0.78 +/- 0.06 for DD genotype, 0.72 +/- 0.05 for ID genotype, and 0.64 +/- 0.06 for II genotype, P = 0.0001). This difference remained significant in subgroup analyses for each genotype. No association could be observed between the AT1R A/C(1166) polymorphism and IMT of carotid artery measurement (P > 0.05). Lack of association was still observed with analysis carried out when genotype effect was assumed to be inherited as additive (CC versus AA versus AC) or dominant (AA versus AC+CC). Increased IMT in patients with SCF shows that subclinical atherosclerosis may play role in this phenomenon. This increase was most marked in the presence of D allele of ACE genotype, which is associated with vascular hypertrophy.

Endothelial function and germ-line ACE I/D, eNOS and PAI-1 gene profiles in patients with coronary slow flow in the Canakkale population : multiple thrombophilic gene profiles in coronary slow flow : cardiovascular topic

“…Tanriverdi et al reported that the ACE I/D polymorphism correlated with carotid intima–media thickness, which is a sign of subclinical atherosclerosis 11. These findings suggest that endothelial dysfunction and diffuse atherosclerosis may play a role in the pathogenesis of CSF.…”

“…Serum ACE activity is higher in subjects with deletion/deletion (D/D) alleles than in subjects with I and D alleles and is related to hypertension and cardiovascular disease 8,9. The frequency of the DD genotype and D allele was reported to be higher in SCF patients 10,11…”

Endothelial Dysfunction and Increased Carotid Intima-Media Thickness in the Patients with Slow Coronary Flow

“…The endothelium plays a crucial role for initiation of atherosclerosis in early stage. Endothelial dysfunction was considered as early marker of atherosclerosis (21, 22). In this study, the FMD was significantly lower in slow flow group than in control and low FMD were independently related with slow coronary flow in regression analysis.…”

Estudo da associação dos polimorfismos da ECA e do AGT e fenótipos de risco cardiovascular em amostra feminina de Ouro Preto

“…Muitos estudos clínicos relataram a eficácia de agentes que inibem a atividade da ECA e de receptores da angiotensina II, no tratamento da aterosclerose. 80,40 A ativação do sistema renina-angiotensina-aldosterona (SRAA)…”

“…constitui-se num fator de risco para processos de desenvolvimento da aterosclerose. 80,40 A angiotensina II age nos receptores AT1 e AT2. A estimulação dos receptores AT1 está associada à disfunção endotelial, principalmente como conseqüência de um aumento na produção de espécies reativas de oxigênio, vasoconstrição, ativação plaquetária, maior liberação do fator inibidor da ativação do plasminogênio tipo 1 (PAI-1).…”