Published online May 28, 2019. doi: 10.4329/wjr.v11.i5.62
Peer-review started: February 18, 2019
First decision: March 15, 2019
Revised: April 5, 2019
Accepted: May 21, 2019
Article in press: May 22, 2019
Published online: May 28, 2019
Processing time: 102 Days and 6.8 Hours
Cocaine is one of the most commonly illicit drugs involved in emergency department visits, amounting to a vast social and economic burden. Cocaine use disorder (CUD), a chronic relapsing condition, frequently leads to life-threatening vascular disease including stroke, coronary artery disease and myocardial infarction. Cocaine’s main vasoactive metabolite benzoylmethylecgonine, a tropane alkaloid, is associated with hematological effects on the vessel and the loss of the endothelium’s protective functions leading to elevated immune state including macrophage proliferation, atherosclerosis, and ischemic vascular disease. The life-style associated with chronic cocaine use (poor sleep and nutrition) further affects cardiovascular health.
Despite the known vascular toxicity associated with cocaine use, individuals with (iCUD) seeking addiction treatment receive mostly psychotherapy and psychiatric pharmacotherapy with no attention to vascular disease in the absence of clear symptoms. Little is known about the pre-clinical signs of cardiovascular risk in iCUD and early signs of vascular disease are undetected in this underserved population.
We aim to assess inflammation composition and plaque burden in individuals with cocaine use disorder aiming to quantify markers of atherosclerosis and vascular disease. The characterization of vascular disease in iCUD with no pre-clinical cardiovascular symptoms can inform development of future preventive and treatment protocols.
Advancements in multi-modal imaging technologies have been efficacious in early detection of atherosclerosis in asymptomatic populations who are at heightened risk for vascular disease. Simultaneous magnetic resonance imaging (MRI) and positron emission tomography (PET) allows for the precise quantification of inflammatory composition and plaque burden during a single non-operator dependent scan.
The bilateral carotid arteries were imaged with PET/MRI in iCUD asymptomatic for cardiovascular disease, healthy controls, and MRI in individuals with cardiovascular risk. PET with 18F-fluorodeoxyglucose evaluated vascular inflammation and 3-D dark-blood MRI assessed plaque burden including wall area and thickness. Addiction questionnaires assessed drug use and severity of addiction.
The MRI measure of wall structure was thicker in iCUD as compared to the controls and even as compared with the cardiovascular risk group, indicating greater carotid plaque burden. iCUD had also statistically significant larger wall area as compared to the healthy controls but not as compared to the cardiovascular risk group (the later results did not reach significance). These findings indicate structural wall similarities between the iCUD and cardiovascular risk study groups.
The majority of iCUD and controls had carotid FDG-PET signal greater than Target-to-Background ratios (TBR max) 1.6, indicating the presence of inflammation, yet, overall the observed inflammatory levels in both groups were mild (TBR max level under 3). In iCUD, wall area correlated with greater cocaine withdrawal and craving.
For the first time in cocaine addiction, this preliminary study used noninvasive simulations PET/MRI vascular imaging of the bilateral carotid arteries in cardiovascular disease-asymptomatic iCUD and two control groups, including healthy individuals and those with cardiovascular disease risk. Aligned with study hypothesis, we observed markers of elevated carotid artery plaque burden in iCUD, reaching similar (wall area) and even exceeding (wall thickness) levels of those in cardiovascular risk group. This plaque burden in iCUD was positively associated with extent of cocaine withdrawal and craving symptoms, indicative of a relationship between the severity of addiction and vascular disease state.
Several caveats limit generalizability of findings, including a small sample size, the limited number of women, and variance between groups in race and nicotine smoking. These factors were covaried in the current analyses, nonetheless, matching between groups in future studies would provide a better approximation of cardiovascular disease in iCUD.
This PET/MRI investigation showed that markers of cardiovascular disease abnormalities were detected in iCUD with no presenting clinical symptoms. Expanding this line of research to examination of iCUD with fewer years of lifetime cocaine use could provide further stratification of cardiovascular disease progression in this population. Broader trials are warranted to develop protocols for early detection of cardiovascular risk and preventive intervention in individuals with cocaine use disorder.