Clinical Features of Coronary Artery Spasm Pathogenesis and Treatment

Coronary artery spasm (CAS) plays an important role in the pathogenesis of ischemic heart disease, including angina pectoris, myocardial infarction, and sudden death, occurring most often from midnight to early morning. CAS is prevalent among East Asians and is associated with an aldehyde dehydrogenase 2 (ALDH2)-deficient genotype (ALDH2*2) and alcohol flushing, which is prevalent among East Asians but is virtually non-existent in other populations. ALDH2 eliminates not only acetaldehyde but also other toxic aldehydes from lipid peroxidation and tobacco smoking, thereby protecting tissues and cells from oxidative damage.

Coronary artery spasm (CAS), which is a reversible vasoconstriction driven by a spontaneous vascular smooth muscle hypercontractility and vascular wall hypertonicity narrowing the lumen of normal or atherosclerotic coronary arteries compromising the myocardial blood flow, is recognized recently under the chapter of myocardial infarction with nonobstructive coronary arteries (MINOCA). Several features were attributed to this complex ischemic entity over time passing by “A variant form of angina pectoris or variant angina”, “variant of the variant”, “coronary vasospastic angina”, “a false-positive STEMI”, and “forgotten coronary disorder”.

CAS prevalence varies widely among races and between countries, but it remains the main cause of ischemic heart disease with nonobstructive coronary lesions . It was estimated at 50% in patients presenting with angina and 57% in whom presenting with ACS. In fact, CAS is more common in males than females, individuals aged between 40 and 70 years, and more in Japanese (24.3%) followed by Taiwanese (19.3%) and Caucasian (7.5%) populations. The widespread use of calcium channel blockers, statins, angiotensin II receptor blockers, and converting enzyme inhibitors, smoking awareness campaigns, and declining tendency of physicians to carry out coronary vasoreactivity tests contribute to a reduction in CAS prevalence, particularly in Japan.

The main risk factors for CAS are age, smoking, hypertension, LDL-cholesterol, diabetes mellitus, and Hs-CRP.Moreover, smoking has a great impact on CAS in male gender, younger subjects, and Japanese population as opposed to female gender, older individuals, and Caucasian population. 

Precipitating Factors

A long-term mental stress, a light exercise especially in the early morning, cold exposure, hyperventilation, magnesium deficiency, valsalva maneuver, alcohol consumption, cocaine use pharmacological sympathomimetic or parasympathomimetic or beta blocking or anticholinesterase agents , phentermine consumption , and platelets activation via vasoconstriction agents (thromboxane and serotonin) can precipitate CAS. As well, an alcohol ingestion following a stressful event can induce CAS within several hours.

Endothelial Dysfunction

The nitric oxide (NO) produced by a normal functional endothelium enhances vasodilatation via suppressing the release of vasoconstrictors agents such as angiotensin II and endothelium I. Therefore, the deficiency in NO due to dysfunctional endothelial nitric oxide synthase explains the fact that different endothelium-dependent vasodilators such as ergonovine, histamine, acetylcholine, and serotonin, which are supposed to induce coronary vasodilatation, provoke vasoconstriction in patients with CAS.

Genetics

Genetic polymorphisms or mutations coding for angiotensin converting enzyme, paraoxonase I , adrenergic receptors , inflammatory mediators, endothelial nitric oxide synthase , and serotoninergic receptors play a role in the pathogenesis of CAS. Studies identified some susceptible genes such as those coding for NADH/NADPH oxidase in male gender, interleukin-6 and stromelysin-1 in female gender , e-NOS in Caucasian and mostly in Asian populations , and ALDH (aldehyde dehydrogenase) activity . ALDH2 deficiency, most common in the East Asian population, is strongly associated with CAS , with an increased effect due to the coexistence of smoking and/or alcohol. 

Current modalities of coronary imaging detect CAS-specific findings. For example, intravascular ultrasound study (IVUS) provides clues to differentiate vasospastic angina from nonvasospastic angina. It identifies a small lesion site plaque volume and burden and a diffuse coronary intimal thickening reflecting intimal hyperplasia in vasospastic angina as well as different plaque components appearing as a hypoechoic, less-calcified, and fibrous-dominant plaque. Therefore, IVUS studies contribute to understand the pathophysiology of CAS. IVUS detects the presence of occult atherosclerotic lesions at the site of focal coronary artery spasm even in the lack of angiographic disease.

CAS is a complex multifactorial disease that can lead to serious complications. A wide clinical spectrum is attributed, and sudden cardiac death may well be the uncovering event. As a result, an early recognition and appropriate medical approach is primordial. The prevalence of CAS tends do decrease with wide spread use of ACE inhibitors and statins and diminished performance of spasm provocation tests which are considered time consuming in highly active cardiac centers.