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J Clin Hypertens (Greenwich). 2011;13:744–749. ©2011 Wiley Periodicals, Inc.
Despite the increased risk of myocardial infarction, aortic dissection, and arrhythmias in patients with hypertension who use cocaine, the hemodynamic and arrhythmogenic effects of cocaine use have not been well characterized in this population. The authors hypothesized that patients with hypertension demonstrate extreme, transient changes in arterial pressures as well as new arrhythmic activity during cocaine use. Ambulatory blood pressures, heart rates, and electrocardiograms (AECGs) were recorded for 48 hours in 10 patients with a history of hypertension who smoke cocaine. Active cocaine use was identified through patient diaries and manual activation of the blood pressure cuff. Of the 10 patients studied (6 men, 7 African Americans, age 49±8 years), 8 were taking antihypertensive medications. The mean blood pressure prior to cocaine use was 126/77 mm Hg and average increase in systolic, diastolic, and mean arterial pressure after use was 74 mm Hg, 30 mm Hg, and 45 mm Hg, respectively (P<.0001 for all). There was no significant change in heart rate. AECGs demonstrated arrhythmic activity during cocaine use, including 6 patients with increased atrial and ventricular ectopy, 2 patients with episodes of nonsustained atrial tachycardia, and 1 patient with 3 episodes of nonsustained monomorphic ventricular tachycardia. Cocaine use resulted in extreme elevations in arterial pressures in patients with hypertension taking medication. Cocaine use was also associated with an increase in arrhythmic activity. These findings may underlie the heightened risk of myocardial infarction, aortic dissection, and potentially lethal arrhythmias in patients with hypertension who use cocaine.
Cocaine is the second most abused illicit drug and the most frequent cause of drug-related deaths in the United States.1 It is estimated that more than 14 million people worldwide and 0.3% of the global population aged 15 to 64 years abuse cocaine regularly.2 According to data from the Drug Abuse Warning Network from 2005, cocaine is also the most frequently cited illicit drug in emergency department visits in the United States, responsible for more than 448,000 visits annually.3
Cocaine-related morbidity is due to its deleterious effects on the cardiovascular (CV) system. Cocaine exerts its sympathomimetic and arrhythmogenic effects primarily by two mechanisms: via blockade of presynaptic reuptake of monoamine neurotransmitters and through impedance of the fast inward sodium channels responsible for phase 0 depolarization, similar to class I antiarrhythmic agents.4,5 Cocaine is also responsible for epicardial coronary vasoconstriction, enhanced platelet aggregation, and premature coronary atherosclerosis.6 The physiologic effects of cocaine use are associated with life-threatening CV events including acute coronary syndromes, sudden cardiac death, and hypertensive crises leading to stroke and aortic dissection.6
Hypertension is the most important CV risk factor worldwide, contributing to one half of all coronary heart disease and approximately two thirds of the cerebrovascular disease burden.7 It is estimated that nearly 30% of the US population 18 years and older carries the diagnosis of hypertension, and among those affected, up to 50% have not reached goal blood pressure (BP) measurements according to national guidelines.8,9 Although long-term cocaine use has not been associated with the development of chronic hypertension, the prevalence of hypertension in the cocaine-using population remains as high as 18% in some studies.10,11 Additionally, cocaine use in hypertensive patients has been associated with increased incidence of acute myocardial infarction, aortic dissection, renal failure, and intracerebral hemorrhage.12–17
Despite these associations, the hemodynamic and arrhythmogenic effects of cocaine use have not been well described in the hypertensive population. The purpose of this study was to characterize variations in BP, heart rate, and ambulatory electrocardiograms (AECGs) in patients with hypertension during cocaine use.
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The results of this study demonstrate that smoking cocaine has a pronounced effect on arterial pressures among individuals with hypertension, despite the use of antihypertensive medication. Cocaine use was also associated with increased arrhythmic activity, but did not cause a significant change in heart rate, even though none of the individuals studied were taking atrioventricular nodal-blocking agents.
Cocaine is a powerful sympathomimetic agent that causes acute elevations in arterial pressures. The major mechanism of action is through blockade of peripheral norepinepherine reuptake and direct stimulation of central sympathetic activity.18–20 In addition, cocaine induces arterial vasoconstriction through preferential stimulation of α-adrenergic receptors and alteration in endothelial production of endothelin and nitric oxide.6,18 The net effect on systolic and diastolic pressures in the general population that has been described is an increase of 20 mm Hg and 10 mm Hg, respectively.4,21 These are modest increases in BP that are equivalent to mild exercise and are not alone believed to be sufficient to result in the CV complications observed in healthy users.22 Likely, coexisting changes to the coronary vasculature, primarily that of premature atherosclerosis, in addition to the prothrombotic effects of cocaine use underlie the development of the CV complications observed in long-term users.
Cocaine use in patients with hypertension is associated with end-organ damage not commonly observed in the general population of users, but more typically observed during acute hypertensive crises. In a retrospective study of 38 cases of aortic dissection performed by our group, 14 cases were associated with cocaine use and, of those, 11 had a previous diagnosis of hypertension.13 In addition, one half of patients with known coronary artery disease who presented to 29 community acute care hospitals with cocaine-associated myocardial infarctions carried the diagnosis of hypertension.12 Acute cocaine use has also been associated with the development of renal failure and intracerebral hemorrhage in patients with long-standing hypertension.14–16
The extreme increases in arterial pressures after cocaine use that we observed in this cohort is likely accountable for the higher incidence of CV emergencies among individuals with hypertension. Cocaine use resulted in an average increase in systolic and diastolic BPs of 74 mm Hg and 30 mm Hg, respectively, with 8 of 10 patients reaching diastolic pressures ≥110 mm Hg. These dramatic elevations in BP were observed despite the majority of our patient population being treated with antihypertensive medications and having well-controlled BPs at baseline.
One possible explanation for the high BPs observed is that all individuals in our study smoked crack cocaine. In contrast to other modes of administration of cocaine, the onset of action of crack cocaine is within seconds after ingestion with a peak effect occurring in 1 to 3 minutes.6 Many of the initial studies of cocaine use were performed in the setting of the cardiac catheterization laboratory in which cocaine was administered intravenously.23,24 The short half-life of crack cocaine may also predispose abusers to use crack cocaine repeatedly and at higher doses, which, in turn, may exacerbate the hemodynamic effects. Additionally, a phenomenon called sensitization exists that may serve as a model for humans and repeated drug use.25 Sensitization was demonstrated in rodents who, when repeatedly given a stimulant, exhibited greater responses compared with stimulant-naive rodents. In a subsequent rodent study, repeated administration of cocaine following drug-free intervals resulted in increases in BP but not in heart rate, similar to our findings in humans.26,27 A human study of repeated smoked cocaine in experienced cocaine users also resulted in increases in baseline and peak systolic pressures in addition to heart rates.28
In addition to using crack cocaine, all of the study patients had chronic hypertension. Autonomic dysregulation has long been suggested in the pathophysiology of essential hypertension. Andersen and colleagues demonstrated increased rates of sympathetic fiber activity in peroneal nerves of borderline hypertensive patients,29 and hypertensive patients have been found to have elevated levels of total plasma norepinepherine levels as well as excessive renal release of catecholamines.30,31 It has also been suggested that altered adrenergic receptivity underlies the development of hypertension.32,33 Thus, it is possible that cocaine use creates increases in plasma catecholamines, which, when superimposed on a hyperexcitable autonomic nervous system, result in the marked elevations in arterial pressures that were observed in the current study.
Our patient cohort demonstrated increased arrhythmic activity during the hour surrounding cocaine use that was not observed in the hour prior to use. All but 1 patient demonstrated increased frequency of atrial and/or ventricular premature depolarizations during cocaine use. In addition, 1 patient with no known coronary artery disease or cardiac risk factors besides hypertension experienced 3 episodes of nonsustained monomorphic ventricular tachycardia with cocaine use.
Cocaine is a known cardiac toxin that has been associated with nearly every cardiac tachyarrhythmia.34 These rhythm disturbances are likely responsible for the heightened prevalence of sudden cardiac death among cocaine users previously observed in a study by our group.35 Experimental models by O’Leary and colleagues36 demonstrated cocaine’s ability to block fast inward sodium channels responsible for phase 0 depolarization, similar to the pharmacokinetics of class I antiarrhythmic agents, while also disrupting cardiac potassium and calcium channels. ECG findings recorded during cocaine use include prolongation in PR, QRS, and QTc intervals, changes in ST-segment morphology, and development of a Brugada-like pattern.34,37 Cocaine is also responsible for accelerated atherosclerosis, dilated cardiomyopathy, left ventricular hypertrophy, and coronary spasm, all of which result in the formation of a vulnerable substrate for arrhythmogenesis.6,38–40 Hypertension is an independent risk factor for cardiac arrhythmias and sudden cardiac death through the promotion of ventricular hypertrophy and cardiac remodeling. Combined with cocaine’s ability to induce tachycardia and ischemia, it is not surprising that patients with hypertension who abuse cocaine are largely susceptible to both benign and malignant arrhythmias.
All of the patients in our study developed an increase in heart rate during cocaine use, although the degree of change was not significant. Previous studies have demonstrated an average rise in heart rate during cocaine use of 20 to 30 beats per minute in patients with a resting heart rate of approximately 60 beats per minute.4,21,22 The average baseline heart rate in our study cohort was notably higher than in these previous studies, and heart rates achieved during cocaine use were similar in absolute magnitude. The increase in baseline heart rate may have been a result of chronic cocaine use as previously described in a similar population of experienced users.28 Of note, despite the majority of our patients taking antihypertensive medications, none reported use of direct atrioventricular nodal-blocking agents.