Early and late response-to-injury in patients undergoing transradial coronary angiography: arterial remodeling in smokers

Abstract

Objectives: To investigate the effect of smoking on vascular response to transradial coronary angiography (TCA).

Background: Cigarette smoking is the most important modifiable cardiovascular risk factor associated with endothelial dysfunction.

Methods: Radial artery flow-mediated vasodilation (RA-FMD), local stiffness (fractional diameter change), intima-media thickness (IMT), luminal and external arterial diameter were measured in 40 current smokers (CS) and former smokers (FS) at 6-14 months at the site of previous TCA and contralateral control artery. Vascular regenerative capacity was studied as chemotactic cell migration in vitro and ex vivo (n=10) and the time course of endothelial functional recovery following RA-FMD up to 72 h after TCA (n=10).

Results: At 10 ± 3 months after TCA, subjects exhibited significant local stiffening and increased IMT as compared to the control arm. These late structural changes were significantly more pronounced in CS as compared to FS. IMT thickening correlated with packyears, number of daily cigarettes, and inversely with RA-FMD. Nitric oxide synthase (NOS)-dependent chemotaxis of CS' circulating angiogenic cells was impaired. Ex vivo incubation of endothelial cells with CS' plasma inhibited NOS-dependent endothelial wound closure and chemotaxis. In vivo, TCA acutely decreased RA-FMD. At 24 h, RA-FMD had recovered in FS but remained impaired at 24 h and only recovered at 48 h in CS.

Conclusion: In active smokers, transradial coronary angiography is associated with delayed early recovery from transient endothelial dysfunction, decreased NOS-dependent vascular regeneration, and late arterial remodeling pointing towards potential harmful effects of transradial coronary angiography on vascular function in distinct subsets of patients.

Keywords: Smoking; endothelial function; intima media thickness; prevention; transradial coronary angiography.

Figure 1

(A) Study flow and (B) schematic of experimental setup: after cannulation of the right radial artery (RA), a coronary angiography catheter is advanced through the RA and coronary angiography is performed. Measurements with high resolution ultrasound were taken at the level of sheath insertion and the contralateral arm served as an internal control. Longitudinal images of the radial artery over the heart cycle, before and after ischemia induced by a forearm cuff allowed determination of endothelial function (FMD), local stiffness (FDC), and structural remodeling (IMT, internal and external diameter).

Figure 2

Endothelial function and late local arterial stiffness following TCA. Radial artery (A) flow-mediated dilation (FMD) and (B) FDC were measured 10 months after a transradial catheterization (TCA) in the interventional arm and the contralateral control arm in current smokers (CS, red) and former smokers (FS, black). *p<0.05 vs control arm #p<0.05 vs. FS (n=40). “C” denominates control arm and “TCA” the arm which was used as access site for TCA.

Figure 3

Late arterial remodeling of radial artery following TCA. (A) IMT, (B) external diameter, and (C) lumen were measured 6-14 month after a transradial catheterization (TCA) at the interventional arm and at the contralateral control arm in current smokers (CS, red) and former smokers (FS, black). CS exhibited significantly greater external diameter due to greater intima media thickness (IMT) as compared to FS and control arm (C). *p<0.05 vs. control arm #p<0.05 vs. FS. “C” denominates control arm and “TCA” the arm which was used as access site for TCA.

Figure 4

Correlation of IMT and smoking: (A) Packyears and IMT in CS (r=0.57, p<0.002, n=17) and in FS (r=0.63, p<0.001, n=23) and (B) IMT and the number of cigarettes consumed daily in CS (r=0.7, p<0.001, n=17).

Figure 5

Impairment of in vitro and ex vivo regenerative capacity in current smokers (CS). (A) Wound closure time (scratch assay) and (B) chemotaxis (Boyden chamber) were evaluated in human umbilical vein endothelial cells (HUVEC) with incubation of assay medium containing control bovine serum albumin (BSA), plasma isolated from CS (n=5; red), and FS (n=5, black). CS plasma impaired endothelial wound healing and NOS dependent chemotaxis in HUVEC; L-NMMA (NOS-inhibitor). (C) Circulating angiogenic cells (CACs) isolated from CS exhibited impaired NOS-dependent chemotaxis. *p<0.05 vs. FS. *p<0.05 vs. random cell movement without additives in the same group. HPF indicates high-power field.

Figure 6

Early recovery of transient endothelial dysfunction after TCA (n=10). Endothelial function measured as FMD at baseline before (-1 h), after 6, 24, 48, and 72 h in current smokers (CS) and former smokers (FS) undergoing TCA. Data are presented for the radial artery FMD on the interventional arm. *p<0.05 vs. baseline (-1 h), #p<0.05 vs. FS.