Gabriella Oliva

Vitamin C prevents endothelial dysfunction induced by acute exercise in patients with intermittent claudication

In patients with intermittent claudication, exercise is associated with a marked increase in oxidative stress, likely responsible for systemic endothelial perturbation. In 31 claudicant patients, we assessed the effect of vitamin C administration on the acute changes induced by maximal and submaximal exercise in endothelium-dependent, flow-mediated dilation (FMD), and in plasma levels of thiobarbituric acid-reactive substances (TBARS) and soluble intercellular adhesion molecule-1 (sICAM-1). In 16 claudicants, maximal exercise reduced FMD (from 8.5+/-0.9 to 3.7+/-0.8%, P<0.01), and increased plasma levels of TBARS (from 1.93+/-0.06 to 2.22+/-0.1 nmol/ml, P<0.02) and of sICAM-1 (from 282+/-17 to 323+/-19 ng/ml, P<0.01). In eight of these patients, randomized to vitamin C, exercise-induced changes in FMD and biochemistry were abolished. This beneficial effect was not observed in the eight patients randomized to saline. In 15 patients, who walked until the onset of claudication pain (submaximal exercise), and in ten control subjects, who performed maximal exercise, no changes were observed with exercise. Thus, in claudicants, vitamin C prevents the acute, systemic impairment in endothelial function induced by maximal exercise. This finding provides a rationale for trials investigating antioxidant therapy and cardiovascular risk in patients with intermittent claudication.

Inflammatory status and endothelial function in asymptomatic and symptomatic peripheral arterial disease.

Peripheral arterial disease (PAD) is a predictor of cardiovascular risk. However, it is unknown whether PAD severity influences inflammatory status and endothelial function, which play a major role in atherosclerosis. Accordingly, we measured brachial artery flow-mediated dilation (FMD), and plasma levels of several inflammatory markers in 15 control subjects, and 19 asymptomatic and 19 symptomatic PAD patients. Each symptomatic patient was matched to an asymptomatic patient for age, sex, risk factors, presence of cardiovascular disease, and pharmacological treatments. Asymptomatic patients had similar inflammatory profiles as controls, but lower median FMD (11.7% vs 8.5%, p < 0.01). Compared with asymptomatic patients, symptomatic patients had higher median C-reactive protein (1.5mg=l vs 6.0 mg=l, p < 0.05) and interleukine-6 (1.5 pg=ml vs 3.5 pg=ml, p < 0.05), and lower FMD (8.5% vs 5.1%, p < 0.01). In the 38 PAD patients, the ankle=brachial pressure index correlated positively with FMD (p < 0.01), and negatively with C-reactive protein (p < 0.05), soluble intercellular adhesion molecule-1 (p < 0.05) and soluble vascular cell adhesion molecule-1 (p < 0.05). Thus, in PAD, endothelial function and inflammatory status are related to the severity of the circulatory impairment. This finding may contribute to the explanation of the increasingly poor prognosis with increased PAD severity.

Intermittent claudication and endothelial dysfunction

The endothelium regulates homeostasis in healthy blood vessels. When affected by injurious stimuli it becomes dysfunctional, thus eliciting changes that predispose to atherosclerosis. Patients with intermittent claudication show a systemic endothelial dysfunction that may result from a variety of factors. In particular, inflammation could play a key role because, in claudicants, endothelial dysfunction negatively correlates with plasma levels of high-sensitivity C-reactive protein, an acute-phase reactant. Future studies will clarify whether interventions that improve endothelial function will improve the clinical outcome of patients with peripheral arterial disease by reducing their cardiovascular risk.