Khat Chewing and Cardiovascular Disease.

Khat chewing is a deeply rooted habit in Yemen. It has social, economic, and medical problems. Chronic use of khat chewing increases the risk of many medical complications. Cathinone, the main khat leaf constituent, has an indirect sympathomimetic action. The effect of khat chewing and cathinone on the cardiovascular system have been identified, including increased risk of hypertension and acute cardiovascular events, as well as increased risk of cardiovascular complications among patients presenting with Acute Coronary Syndrome who are khat chewers. Copyright:

INTRODUCTION

Fresh leaves from the khat tree are chewed daily in Yemen for their euphoric properties. Leaves are soft with a good leaf taste for chewing [Figure 1]. The leaves contain the major pharmacological active constituent. Cathinone is a sympathomimetic amine with properties similar to those of amphetamine.[1] The market value of the khat and its potency depends on the concentration of cathinone in these leaves which differ from one type to another according to the geographical area of cultivation.[2]

Figure 1

Khat leaves and Khat bands.

Most people in Yemen chew khat leaves daily as a social habit. Women and children chew khat on a larger scale than before. A few years ago, khat chewing was mainly among men. Schoolchildren are chewing khat to increase their energy for studying their lessons. Khat is chewed during wedding parties and funeral gatherings [Figure 2].

Figure 2

Khat chewers at a wedding party

It is estimated that 90% of males and more than 50% of females chew khat daily.[3] Furthermore, the habit itself changed dramatically toward very heavy chewing. The quantity of khat chewed and the number of hours spent are considerable. The substance is even used in soft drinks, energy drinks, etc.

Khat chewing is a social and deeply rooted habit that controls the life of Yemeni people. Their diet, time of sleep, time off work, family duties and family budget, personal relationships, and all activities in society are linked to the khat issue. Mohammed Mahmood AL-Zubairy,[4] a famous Yemeni figure, had said “Khat is the First ruler in Yemen.”

Khat chewing has paralyzed the productive power of society and caused many social, financial, and medical problems. Most importantly, khat chewing has affected the cardiovascular system.

Khat chewing is the main factor against modernization in Yemen. This article will review the detrimental effects of khat chewing on the cardiovascular system.

Constituent of khat leaves

Khat leaves contain three main alkaloids: cathinone, or pseudoephedrine (cathine), and norephedrine.[5] The highest concentration of these amines was found in the young leaves,[6] and this is why khat chewers prefer to chew fresh leaves due to their potent effect.

Cathinone is an amphetamine-like substance that releases endogenous catecholamine from peripheral and central neurons.[7] Kalix in 1992 reported that cathinone is a natural amphetamine.[1]

Cathinone effect

Cathinone is the most potent constituent of khat leaves as a stimulant of the central nervous system,[8] cathinone, like amphetamine, acts as an indirect sympathomimetic agent which facilitates the release of catecholamines from the sympathetic nerve terminal.[910] In addition, cathinone has a local effect on blood vessels that is independent of noradrenaline release and stimulation of α-adrenoceptors. This is probably through the recently identified trace amine-associated receptors.[11] Therefore, cathinone has a direct and indirect effect on the blood vessels, and it causes a dose-related blood vessel vasoconstriction in aortic ring preparation and was more potent than noradrenaline in larger doses [Figure 3].[12]

Figure 3

Cathinone is more potent in larger doses

Effect of khat chewing on systemic blood pressure

Khat chewing has been linked to increases in blood pressure during the khat session time. Chronic use of khat has been associated with systemic hypertension[13] and an increase in heart rate.[1415] This was concordant with the level of cathinone in the blood.[1617]

When khat chewers volunteer to chew khat leaves for 1 hour only, the cathinone peak occurs in 1.5–3.5 h.[17] A longer period of chewing khat leaves needs continuous leaves supply to the mouth. Absorption of cathinone from the mouth of the chewer takes place slowly and lasts in the blood for a long time. We can assume that cathinone will last in the blood for almost 24 h in those chewing khat day and night and in those who chew khat for more than 8 h. Its presence in the blood will increase the blood pressure by direct and indirect vasoconstriction effect.[12] Chronic use of khat chewing definitely will cause permanent hypertension, worsen the already hypertensive level, and make the management and controlling of high blood pressure very difficult.

More studies to show the cathinone level in patients who chew khat for 8 h or more are warranted.

Khat effect on the coronary arteries

Khat chewing has a detrimental effect on the heart and blood vessels. Tension, insomnia, loss of appetite, and lack of physical activity are associated with khat chewing, which consequently affects the cardiovascular system negatively.

Khat also increases the desire to smoke more cigarettes during the session and is associated with an increased risk of passive smoking during “khat parties” and socialization. All these factors increase the risk of khat chewing to the development of coronary artery disease and in particular acute myocardial infarction (AMI). In a case‒control study, khat chewing was significantly higher among the AMI case group than in the control group (odds ratio = 5.0, 95% confidence interval: 1.9–13.1) with a dose‒response relationship. The heavy khat chewers have a 39-fold increased risk of AMI. The study concluded that khat chewing is an independent dose-related risk factor for the development of myocardial infarction (MI).[18]

Khat chewing increases heart rate and hypertension during the khat effective period time, and this contributes to the change in the circadian rhythm of AMI presentation. AMI may be precipitated by increased oxygen demands and peripheral and coronary vasoconstriction. AMI during the khat effective period (2 pm to midnight) was 59% among khat chewer patients compared with only 34% of nonkhat chewers who presented in this period time.[19]

Amphetamine misuse had been reported to cause AMI[2021] and cathinone has been reported to be a natural amphetamine by (Kalix 1992),[1] Therefore, Amphetamine and cathinone misuses will cause coronary vasoconstriction and produce AMI. We previously hypothesized that cathinone misuse will not only change the circadian rhythm of AMI presentation but also will cause AMI. Therefore, a laboratory study was carried out on the guinea pig isolated Langendorff heart preparation, and we demonstrated that cathinone caused coronary vasoconstriction and had negative inotropic effects.[12] Another laboratory study had been carried out on pig coronary arteries. Cathinone caused vasoconstriction of a pig's left anterior descending coronary artery, and the effect of cathinone was independent of an indirect sympathomimetic mechanism through α1-adrenoceptors and endothelium. Therefore, cathinone, the main ingredient of khat leaves, produces direct vasoconstriction on the coronary arteries.[11] Clinical and angiographic studies had supported the coronary vasospasm as the main mechanism of AMI and the reasons behind the increased incidence of a heart attack in khat chewers.[192223]

Gulf Registry of Acute Coronary Events-2 study showed worse outcomes among khat chewers with acute coronary syndrome (ACS) patients. Khat chewers had a higher risk of death, recurrent myocardial ischemia, cardiogenic shock, ventricular arrhythmia, and stroke compared to nonkhat users.[24] The effects of aspirin and thrombolytic therapy among AMI were less effective among khat chewers in two separate studies (unpublished data). This effect needs further studies to confirm the role of khat chewing on platelet aggregation and the thrombolytic effect.

Khat chewing and dilated cardiomyopathy

Acute cardiomyopathy secondary to intravenous amphetamine abuse had been reported.[2526]

Cathinone in khat leaves is similar to amphetamine and more likely to have the same mechanism of action in producing cardiomyopathy. A study involved 50 Yemeni patients with dilated cardiomyopathy who were regular khat chewers. Patients with secondary dilated cardiomyopathy were excluded. The histopathological study of the heart muscle showed myocyte hypertrophy and interstitial fibrosis. Khat chewing contributes to the occurrence of dilated cardiomyopathy in young patients (20–50 years) with inherited predisposition.[27]

One of the most important issues is to stop khat chewing during the management of heart failure of any cause due to khat effect on the cardiac muscle and stress of tachycardia and increase oxygen demand which contributes to the worsening of the heart condition.

Cardiac arrhythmias

Khat chewing is believed to increase the risk of cardiac arrhythmias; however, data on this association are very limited.

CONCLUSION

Khat chewing is a real medical problem in Yemen. It results in many medical complications, in particular in the cardiovascular system. It increases heart rate and high blood pressure and increases the risk of MI probably by causing coronary artery spasms. Khat chewers have an increased risk of stroke and cardiac death among patients with ACS. It is similar to amphetamine in being associated with cardiomyopathy and worsening and complicating the management of already heart failure patients. Further studies are needed to clarify the serious effect of khat on the cardiovascular system and in the management of AMI and heart failure patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.