Heightened systemic oxidative stress critically accelerates worsening carotid atherosclerosis in patients with ischemic stroke

Abstract

BACKGROUND: Both increased oxidative and inflammatory stresses are implicated in atherogenesis. However, little is known about their role in atherosclerotic progression in patients already at the advanced cardiovascular continuum. OBJECTIVE: To investigate the impact of oxidative and inflammatory stress on the progression of carotid atherosclerosis in patients with established ischemic stroke. METHODS: A total of 43 consecutive patients (mean age 65.7 +/- 8.8 years; male 70%) with primary or recurrent ischemic stroke (>6 months) were recruited from our medical outpatient clinics. High resolution ultrasound (Agilent Sonos 5500, Philips, USA) was used to assess burden of carotid atherosclerosis in terms of maximum intima-media thickness (mIMT). Serum malodialdehyde (MDA) and high-sensitivity C-reactive protein (hsCRP) were respectively measured as markers of systemic oxidative and inflammatory stress. RESULTS: These patients showed a mean mIMT of 2.25 +/- 0.98 mm. Serum MDA (Pearson r=0.32, P=0.035) and hsCRP (Pearson r=0.41, P=0.007) were both positively associated with mIMT. Adjusting for potential confounders by multivariate model (age, gender, hypertension, diabetes mellitus, hyperlipidemia, smoking history, use of aspirin/ statins/ antihypertensives and body-mass index), each 1 c，M increase in serum MDA independently predicted increase in mIMT by 0.79mm(95%CI [0.23 1.36], P=0.008). Furthermore, each 1 mg/L increase of hsCRP was independently predictive of increase in mIMT by 0.06 mm (95%CI [0.01 0.12], P=0.017). Hyperlipidemia and diabetes accounted for IMT increase by 0.56 mm (95%CI [0.04 - 1.08], P=0.037) and 0.53 mm (95%CI [0.01- 1.05], P=0.046) respectively. CONCLUSIONS: This study demonstrated that systemic oxidative stress strongly accelerates secondary progression of carotid atherosclerosis in patients with established ischemic stroke, independent of and above all conventional risk factors including systemic inflammation. This suggests that effective reduction of oxidative stress should be a major therapeutic target in patients at the advanced cardiovascular continuum.