Effect of Short-Term Abstinence on Cocaine-Induced Endothelial Dysfunction and Platelet Activation

Cocaine abuse is associated with an increased risk of cardiac and cerebrovascular events, such as myocardial infarction, sudden cardiac death, and ischemic stroke. The underlying mechanisms leading to these complications are not fully understood although intravascular thrombus formation and accelerated atherosclerosis are prominent findings. We have previously shown (Pereira et al. J Thromb Haemost 2009; 7[suppl 2]: 232a) that chronic cocaine use is associated with markers of endothelial dysfunction and platelet activation in subjects studied after recent consumption. It has been suggested that many of the adverse effects of cocaine on the vessel wall are due to its acute effects related to the sympathomimetic properties of the drug. However, from a pathogenic standpoint, we hypothesized that important pathologic consequences, such as early onset atherosclerosis and regional brain perfusion, defects, are not solely explained by the acute vasomotor actions of cocaine.

The main aim of this work was to investigate the effect of short-term abstinence on markers of endothelial injury and platelet activation in chronic cocaine consumers.

. We studied 23 cocaine dependent individuals (aged 19–52years mean age 30 years) who met DSM-IV criteria for cocaine dependence, seeking treatment for cocaine abuse and 25 healthy controls (aged 20–49 years, mean age 31 years). Samples were obtained at admission within 72 hours of drug exposure and after 4 weeks of strict, controlled abstinence in a rehabilitation clinic.

Endothelial cell damage was assessed by enumerating circulating endothelial cells (CECs) and plasma levels of soluble markers: soluble intercellular adhesion molecule (sICAM); monocyte chemoattractant protein (MCP-1), von Willebrand factor (VWF) and high-sensitivity C reactive protein (hs-CRP). Plasma levels of soluble CD40L (sCD40L), NAP-2 and RANTES were determined to demonstrate platelet activation in vivo.

Markers of endothelial cell damage/activation and platelet activation, were significantly higher in cocaine dependents individuals after recent consumption (baseline) as compared with the controls. The variations observed after 4 weeks drug withdrawal (post-abstinence) are shown in Table 1:

Our results demonstrate that cocaine use is associated to endothelial dysfunction and platelet activation which are prominent findings after recent consumption. Evidence of endothelial cell activation/damage is still present after 4 weeks of strict and controlled abstinence when markers of platelet activation returned to their baseline levels. Taken together, these observations suggest that cocaine induced-endothelial cell damage is maintained independent of the acute effect of the drug on the blood vessels. The persistence of this condition may play a role in long-term ischemic complications associated with cocaine abuse such as early onset atherosclerosis and regional brain perfusion defects. Further studies on the mechanisms underlying cocaine-induced endothelial dysfunction might provide novel strategies to improve endothelial function as part of the treatment in recently abstinent cocaine addicts.

No relevant conflicts of interest to declare.