Elsevier

Atherosclerosis

Volume 262, July 2017, Pages 154-162
Atherosclerosis

Review article
Vascular disease in cocaine addiction

https://doi.org/10.1016/j.atherosclerosis.2017.03.019Get rights and content

Highlights

  • Cocaine induces immune responses including cytokine elevations. Chronic cocaine use is associated with functional brain impairments potentially mediated by vascular pathology. Paradoxically, during the period when prevention efforts could make a difference, this population receives psychosocial treatment at best.

  • We review major findings of cocaine-induced vasoconstriction, endothelial dysfunction, and accelerated atherosclerosis, emphasizing acute, chronic, and secondary effects of cocaine.

  • Given the known vascular toxicity cocaine induces further compounded by smoking and alcohol comorbidity and interacting with the progressing age of the crack generation, there is a public health imperative to identify pre-symptomatic markers of vascular impairments in cocaine addiction.

Abstract

Cocaine, a powerful vasoconstrictor, induces immune responses including cytokine elevations. Chronic cocaine use is associated with functional brain impairments potentially mediated by vascular pathology. Although the Crack-Cocaine epidemic has declined, its vascular consequences are increasingly becoming evident among individuals with cocaine use disorder of that period, now aging. Paradoxically, during the period when prevention efforts could make a difference, this population receives psychosocial treatment at best.

We review major postmortem and in vitro studies documenting cocaine-induced vascular toxicity. PubMed and Academic Search Complete were used with relevant terms.

Findings consist of the major mechanisms of cocaine-induced vasoconstriction, endothelial dysfunction, and accelerated atherosclerosis, emphasizing acute, chronic, and secondary effects of cocaine. The etiology underlying cocaine's acute and chronic vascular effects is multifactorial, spanning hypertension, impaired homeostasis and platelet function, thrombosis, thromboembolism, and alterations in blood flow. Early detection of vascular disease in cocaine addiction by multimodality imaging is discussed. Treatment may be similar to indications in patients with traditional risk-factors, with few exceptions such as enhanced supportive care and use of benzodiazepines and phentolamine for sedation, and avoiding β-blockers.

Given the vascular toxicity cocaine induces, further compounded by smoking and alcohol comorbidity, and interacting with aging of the crack generation, there is a public health imperative to identify pre-symptomatic markers of vascular impairments in cocaine addiction and employ preventive treatment to reduce silent disease progression.

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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