Endothelial Dysfunction and Procoagulant Activity in Acute Ischemic Stroke

Abstract

Endothelium-dependent vasodilator function may be regarded as an index of inflammation. Endothelial
dysfunction has been observed in stroke patients and has been related to stroke physiopathology, stroke
subtypes, clinical severity, and outcome. Our aim was to measure systemic vascular function directly (using
forearm flow mediated dilatation) in patients with acute ischemic stroke and to clarify whether recent acute
ischemic stroke is associated with impaired vascular function. Patients who were not eligible for thrombolytic therapy because of delayed arrival were randomly recruited to the study after signing a consent form.
All 43 patients were conscious and had an acute ischemic stroke. Brain CT was performed on admission,
and clinical evaluation was carried out by a neurologist on admission and four days later. Vascular responsiveness was evaluated by ABI and by endothelial function measurements on admission. Levels of P-selectin were measured during the first 24 hrs and on day 4. Forty-three patients (28 men and 15 women) and 23
healthy men (control) were enrolled in the study. Patients were older (62.4±12.5 y vs 44.2±11.6 y,
p=0.001), had worse endothelial dysfunction (–4.4±7.4% vs 16.6±7.6%, p=0.001), and had a higher BMI
(28±6 vs 24±5, p=0.001). No gender effect was found in endothelial function (–5.1±7.8% vs –2.5±6.6%,
p=0.25) and ABI (1.0±0.26 vs 1.0±0.5, p=0.29). However, men had lower BMIs compared to women
(26.8±5.8 vs 31.4±5.5, p=0.01). The neurological scale decreased from 4.9±3.4 to 3.2±3.0 on day 4
(p=0.001). In men, it was 4.8±3.8 on admission, and decreased to 3.2±3.4 on day 4 (p=0.001). In women, it
was 5.0±2.7, and decreased to 3.3±2.3 on day 4 (p=0.001). P-selectin levels were high on admission
(68.0±55.5 pg/ml) and increased 4 days later (102.3±72.0 pg/ml) (p=0.01). Men had higher levels on
admission (79.1± 66.7 pg/ml vs 48.9± 15.4 pg/ml, p=0.02) and rose on day 4 to 113.6±82.6 pg/ml (p=0.05);
in women P-selectin increased from 48.9± 15.4 pg/ml to 83.5±46.4 pg/ml (p=0.01), without gender effect
on day 4 (113.6±82.6 pg/ml [men] vs 83.5±46.4 pg/ml [women] (p=0.08)). None of the univariate models
seemed statistically significant---gender (p=0.448), age (p=0.100), BMI (p=0.607), ABI (p=0.103), FMD%
(p=0.456), and P-selectin (p=0.195). Patients with acute stroke had severe endothelial dysfunction during
the first 24 hrs with high P-selectin levels that further increased over the first week. Vascular instability and
procoagulant activity are still in progress in the first days following acute stroke and patients are at risk to
develop more vascular events at that time.