Review articleVascular disease in cocaine addiction
Section snippets
Phenomenology contributing to vascular damage
Cocaine, compared to other illicit drugs, poses a particular risk for vascular disease and is most involved in emergency room visits (40.3%), with highest rates for men aged 35–44 years, amounting to a vast social and economic burden [1]. Cocaine-induced damage to the cardiovascular and cerebrovascular systems is widely reported, and is linked with hypertension, tachycardia, ventricular arrhythmias [2], myocardial infarction [3], [4], stroke [4], [5], resulting in severe functional impairments
Search strategy
We present the main mechanisms of acute and chronic cocaine-induced toxicity on vessels, brain and heart (Fig. 1) and the common vascular and systemic effects of cocaine use in humans (Fig. 2). Particular attention was given to the imaging studies that measured cocaine-induced changes to the human heart, brain, and arteries (Table 1), since these methods are gaining a central role as markers of inflammatory disease. Review methodology included search in two electronic databases (PubMed and
Pharmacodynamics of cocaine
Cocaine's main vasoactive metabolite benzoylmethylecgonine, a tropane alkaloid, is a sodium channel blocker, which produces enhanced sympathetic activity at low doses [13], [14] (Fig. 1, center box). At high doses, cocaine is markedly more dangerous than other central nervous system stimulants, including amphetamines [15], and can cause sudden cardiac death through its effect on sodium channels and local anesthetic actions [13], [14], [16]. Cocaine crosses the blood–brain-barrier perhaps better
Acute effects of cocaine
Cocaine's acute hematological effects on the vessel (Fig. 1, upper box) [10], [23], [24] center on the loss of the endothelium's protective functions, a common denominator in the pathogenesis of ischemic vascular disease [35], [36]. Cocaine releases endothelin-145, which is found to be elevated in CUD and declines with detoxification [36], [46], [47]. When vessels are stressed, endothelin-1 (a vasoconstrictor protein produced by vascular endothelial cells) is elevated and nitric oxide (a blood
Chronic effects of cocaine
Cocaine's chronic effects on the vessel (Fig. 1, upper box) [10], [23], [24] consist of repeated endothelial damage leading to premature and severe atherosclerosis in various organs [10], [19].
In the heart, the significant interaction of cocaine with norepinephrine transporters [26], [27] can lead to left ventricular dysfunction by effect of dilation, reduction of ejection phase and reduced contractility [70]. Despite some controversy [3], [53], [71], left ventricular hypertrophy (as shown in
Secondary effects of cocaine
In addition to cocaine-specific effects, there are secondary harms resulting from synergetic effects between multiple environmental, psychosocial and behavioral factors comprising the addiction phenomenology that could in turn enhance potential vascular damage. These factors include the life-course and complexity of CUD, comprised of years (often, decades) of concomitant alcohol and/or tobacco and/or other drug use, potentiating vascular toxicity. The issue is complicated further by the fact
Prevention and treatment
Cocaine use promotes vascular disease, while also influencing the course of disease management, and therapy. Here too, it is helpful to briefly review prevention and treatment recommendations separately for acute vascular events.
Preventing acute events in pre-symptomatic individuals must include special consideration. First, in terms of risk detection, studies with CUD document that Framingham risk scores label the majority of CUD as low risk, underestimating the indications for preventive
Future directions: urgent need for early detection of a complex disease process in a vulnerable and aging population
As evident from this review, there is ample data on cocaine-induced endothelial dysfunction, vasoconstriction, and accelerated atherosclerosis. Given the known vascular toxicity cocaine induces [13], [23], further compounded by cigarette smoking and alcohol comorbidity [32], [73], [96] and interacting with the progressing age of the crack generation [97], [98], there is a public health imperative to identify presymptomatic markers of vascular impairments in CUD.
Chest pain [8], [13], [76] and
Conclusion
With the proliferation of coronary artery and vascular disease among cocaine users, more procedures are required for early detection and prevention of cardiovascular and cerebrovascular associated morbidity and mortality in this population. Prevention of cocaine-induced systemic complications could be considered as part of a harm reduction strategy. Consequently, cocaine use should be included in protocols and guidelines as a risk factor for cardiovascular, cerebrovascular and other vascular
Conflict of interest
The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript.
Financial support
NIDA T32-DA007135-31, Department of Preventive Medicine support, Icahn School of Medicine at Mount Sinai (KB); NIDA R21DA034954 (RZG); NIH/NHLBI R01 HL071021 (ZAF).
Author contributions
Keren Bachi: literature search, literature analysis and interpretation, writing first and consecutive drafts, and flow chart and figure design.
Venkatesh Mani: vascular imaging commentary.
Devi Jeyachandran: medical terminology and content commentary.
Zahi A Fayad: vascular imaging, and treatment commentary.
Rita Z Goldstein: cocaine use disorder commentary.
Nelly Alia-Klein: study design, figure design, interpretation, and writing.
Acknowledgments
We thank Nora D. Volkow, Salvador Sierra, and Jill Gregory, for their input on this manuscript.
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2022, Canadian Journal of CardiologyCitation Excerpt :As reviewed previously,45 repeated bouts of accelerated hypertension directly damage the endothelium. In addition to acute vasoconstriction attributable to norepinephrine, cocaine use is associated with increased circulating levels of the potent vasoconstrictor endothelin-1 and decreased availability of the vasodilator NO.42 Cocaine also activates platelets and is proinflammatory, additional factors that contribute to accelerated vasculopathy.45,46 Cocaine-induced endothelial damage promotes activation of fibrinogen and von Willebrand factor and leads to platelet aggregation.