Expert Review: Coronary Artery Disease

Typical angina without significant coronary stenosis: comparison of clinical profile, circadian presentation, and long-term follow-up between patients with and patients without vasospastic angina

The spectrum of patients with chest and no significant coronary stenosis is broad, with a wide range of lumen obstruction (from smooth completely normal coronary arteries to those with lesions <50%) and also including abnormal vasomotion (vasospastic angina-VA, microvascular spasm) or slow flow phenomenon1-4. One proposed underlying mechanism is endothelial dysfunction, which has been documented in either VA or non vasospastic angina5,6. Knowledge Gap Although the prognosis of patients with chest pain without significant coronary stenosis is good in terms of development of coronary events (fatal or nonfatal myocardial infarction, coronary death, new coronary heart disease) long-term studies are rare, and differences among different subgroups included in this wide syndrome remain unknown. Aim of the Study The study aimed to compare the baseline profile and follow events between patients with VA and tANCA. Methods Single-center, prospective, longitudinal study including all consecutive patients with typical angina without significant coronary stenosis (VA, n=273; tANCA, n=384). Several clinical, electrocardiographic and angiographic characteristics were recorded: circadian rhythm of angina, response to sublingual nitroglycerin, coronary angiography, stress test and provocation test response. Baseline treatments and modifications, clinical response and events (myocardial infarction, recurrent angina, repeated coronary angiography, revascularization and mortality) were assessed during follow up (mean follow up, 180months). Results The results could be summarized as follows: • tANCA patients had greater female predominance (61 vs. 18%), higher incidence of dyspnea to moderate exertion (49 vs. 12%), lower incidence of tobacco smoking (25 vs. 67%), but a similar low rate of diabetes (8.9 vs. 4.4%). • In both groups, however, dyspnea and smoking were associated with female and male sex, respectively. • tANCA patients showed lower but non-negligible frequency of early morning (25 vs. 67%) and evening angina (37 vs. 54%), similar rate of nocturnal angina (47 vs. 50%), and higher rate of emotional angina (49 vs. 31%). • Moreover, a high proportion of patients gained pain relief with nitroglycerin (97% in VA, 246/253, and 76% in tANCA, 231/306). • At 140 months, frequent angina (>10 episodes/year) was rare (VA: 7.1% vs. tANCA: 6.3%) as was the rate of cardiac death/myocardial infarction (7.3 vs. 6.0%, P=0.524).

Despite differences in the clinical profile between VA and tANCA patients, the present study unravels many similarities (there is notable sharing of nocturnal angina, response to nitroglycerin, and long-term presence and frequency of angina) that suggest more similarities in underlying mechanisms than heretofore suspected. Cumulative survival and survival free of myocardial infarction is high, with no differences between VA and tANCA patients.

Clinical Impact
Despite apparent differences in sex and risk factors, a number of patients from the two groups seemed to share similar triggering stimuli for typical angina at rest according to their coincidental circadian presentation of angina episodes and their positive response to nitroglycerin. Noteworthy, these observations would further support the existence of coronary vasoconstrictive mechanisms also in tANCA, and are in line with the concept of a continuous spectrum of coronary vasoconstriction of angina1. Therefore, this work represents a contribution toward this unclear field of ANCA patients, proposing, through clinical findings, links in the mechanisms of rest angina between VA and tANCA patients

Corresponding author from original paper
Jaume Figueras, MD, Coronary Care Unit, Cardiology Service, Hospital General Universitari Vall d’Hebron, Autonomous University of Barcelona, P. Vall d’Hebron 119–129, 08035 Barcelona, Spain
Tel: + 34 932 742 002; fax: +34 932 746 002


1.-Maseri A, Severi S, DeNes M, L’Abbate A, Chierchia S, Marzilli M, et al. ‘Variant’ angina: one aspect of a continuous spectrum of vasospastic myocardial ischemia. Pathogenetic mechanisms, estimated incidence and clinical and coronary arteriographic findings in 138 patients. Am J Cardiol 1978; 42:1019–1035.
2-Cannon RO III. Microvascular angina and the continuing dilemma of chest pain with normal coronary angiograms. J Am Coll Cardiol 2009; 54:877–885.
3-Crea F, Kaski JC, Maseri A. Key references on coronary artery spasm. Circulation. 1994;89(5):2442-6.
4.-Kaski JC. Pathophysiology and management of patients with chest pain and normal coronary arteriograms (cardiac syndrome X). Circulation. 2004 Feb 10;109(5):568-72.
5.-Cox ID, Kaski JC, Clague JR. Endothelial dysfunction in the absence of coronary atheroma causing Prinzmetal’s angina. Heart. 1997; 77(6): 584.
6.-Lanza GA, Sestito A, Sgueglia GA, Infusino F, Manolfi M, Crea F, et al. Current clinical features, diagnostic assessment and prognostic determinants of patients with variant angina. Int J Cardiol 2007; 118:41–47.

Citation: Coronary Artery Disease 2013, 24:374–380

Leave a Reply

Your email address will not be published. Required fields are marked *