Drugs of Misuse: Focus on Vascular Dysfunction

Abstract

Common drugs of misuse, including cannabis, opioids, stimulants, alcohol, and anabolic steroids, have strikingly disparate acute and chronic vascular effects, leading to a wide range of clinical cardiovascular presentations. Acute cannabis smoking has been associated with increased risk for myocardial infarction and ischemic stroke in otherwise healthy young people. However, it remains uncertain if people who exclusively smoke cannabis have increased risk for accelerated atherosclerosis similar to that found in people who exclusively smoke tobacco cigarettes. Cocaine and methamphetamines, both stimulants, increase risk for stroke, myocardial infarction, aortic dissection, and accelerated atherosclerosis, but only methamphetamine use is strongly linked to pulmonary hypertension. Chronic alcohol use is strongly associated with chronic hypertension and hemorrhagic stroke, but perhaps confers a lower risk for myocardial infarction. Finally, anabolic steroid use, presumably through adverse effects on circulating lipids and the hematopoietic system, is associated with increased risk for accelerated atherosclerosis and myocardial infarction. Physicians, especially cardiologists, emergency medicine, and internal medicine physicians, should be familiar with the short- and long-term vascular consequences of use of these substances, thereby ensuring appropriate, specific, and informed counselling and treatment.

Figure 1.

Cannabis Smoking: Vascular Sequelae and Potential Mechanisms. See text for full discussion. Depending of the frequency and mode of use, acute cannabis has sympathomimetic effects, increasing heart rate and blood pressure. This increase in myocardial oxygen demand is accompanied by decreased oxygen supply due to vasospasm and elevated carbon monoxide levels (combusted cannabis). Cannabinoid 1 (CB1) receptors on platelets and vascular endothelial cells may lead to platelet activation and thrombosis, inflammation and endothelial dysfunction. These factors likely underlie the increased risk for acute myocardial infarction and stroke that occur soon after cannabis use, often in young people without cardiac risk factors. Whether cannabis, especially the cannabis available today with its marked high concentrations of delta-9-tetrahydrocannabinol, increases risk of accelerated atherosclerosis and the entity of cannabis arteritis, remain uncertain, and deserves further study.

Figure 2.

Cocaine Use: Vascular Sequelae and Potential Mechanisms. See text for full discussion. Cocaine blocks norepinephrine re-uptake, leading to marked increases in heart rate and blood pressure. Increased norepinephrine may be accompanied by increased endothlin-1 release and decreased nitric oxide availability, and may promote increased platelet aggregation. These acute effects may precipitate acute myocardial infarction, stroke, and less commonly aortic dissection. Oxidative stress and inflammatory pathways are activated which may lead to endothelial damage, and over time, accelerated vasculopathy. This in turn, may lead to accelerated atherosclerosis and long-term increased risk for myocardial infarction or stroke, and possibly pulmonary hypertension.

Figure 3.

Methamphetamine Use: Vascular Sequelae and Potential Mechanisms. See text for full discussion. The underlying pathophysiology and vascular sequelae are very similar to those of cocaine use, with some important differences. The half-life of methamphetamine is longer than cocaine, perhaps contributing to the more severe vasculopathy and increased risk for hemorrhagic stroke compared to cocaine. Additionally, methamphetamine use is associated with an increased risk for pulmonary hypertension, which is both irreversible and associated with a worse prognosis (even on therapy) compared to pulmonary hypertension from other causes.

Figure 4.

Alcohol-induced Hypertension: Potential mechanisms. See text for full discussion. Alcohol acutely increases sympathetic nerve activity and increases renin and angiotensin II levels. Through metabolism of alcohol, reactive oxidative species are generated, leading to further increases in angiotensin II, production of 20-hydroxyeicosatetraenoic acid (20-HETE), endothelin 1 and 2, and a reduction in NO availability, creating a vasoconstrictor-vasodilator imbalance. Additionally, alcohol may cause dysregulation of calcium cycling in vascular smooth muscle further increasing vasoconstriction. Alcohol-induced hypertension increases risk of hemorrhagic stroke. Conversely, through antithrombotic, and potentially anti-inflammatory effects, and favorable effects on lipids, alcohol may be associated with a lower risk of myocardial infarction, although this association has been challenged.