Ischemia and No Obstructive Coronary Artery Disease: Prevalence and Correlates of Coronary Vasomotion Disorders

Abstract

Background: Determine the prevalence and correlates of microvascular and vasospastic angina in patients with symptoms and signs of ischemia but no obstructive coronary artery disease (INOCA).

Methods: Three hundred ninety-one patients with angina were enrolled at 2 regional centers over 12 months from November 2016 (NCT03193294). INOCA subjects (n=185; 47%) had more limiting dyspnea (New York Heart Association classification III/IV 54% versus 37%; odds ratio [OR], 2.0 [1.3-3.0]; P=0.001) and were more likely to be female (68% INOCA versus 38% in coronary artery disease; OR, 1.9 [1.5 to 2.5]; P<0.001) but with lower cardiovascular risk scores (ASSIGN score median 20% versus 24%; P=0.003). INOCA subjects had similar burden of angina (Seattle Angina Questionnaire) but reduced quality of life compared with coronary artery disease; subjects (EQ5D-5 L index 0.60 versus 0.65 units; P=0.041).

Results: An interventional diagnostic procedure with reference invasive tests including coronary flow reserve, microvascular resistance, and vasomotor responses to intracoronary acetylcholine (vasospasm provocation) was performed in 151 INOCA subjects. Overall, 78 (52%) had isolated microvascular angina, 25 (17%) had isolated vasospastic angina, 31 (20%) had both, and 17 (11%) had noncardiac chest pain. Regression analysis showed inducible ischemia on treadmill testing (OR, 7.5 [95% CI, 1.7-33.0]; P=0.008) and typical angina (OR, 2.7 [1.1-6.6]; P=0.032) were independently associated with microvascular angina. Female sex tended to associate with a diagnosis of microvascular angina although this was not significant (OR, 2.7 [0.9-7.9]; P=0.063). Vasospastic angina was associated with smoking (OR, 9.5 [2.8-32.7]; P<0.001) and age (OR, 1.1 per year, [1.0-1.2]; P=0.032].

Conclusions: Over three quarters of patients with INOCA have identifiable disorders of coronary vasomotion including microvascular and vasospastic angina. These patients have comparable angina burden but reduced quality of life compared to patients with obstructive coronary artery disease. Microvascular angina and vasospastic angina are distinct disorders that may coexist but differ in associated clinical characteristics, symptoms, and angina severity.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03193294.

Keywords: angina pectoris; dyspnea; microvascular angina; prevalence; quality of life.

Figure 1.

Study overview—prevalence of coronary vasomotion disorders in ischemia and no obstructive coronary artery disease (INOCA). Figure showing screening and enrollment process with a total of 185 INOCA patients and 206 oCAD patients. IDP indicates interventional diagnostic procedure; MVA, microvascular angina; oCAD, obstructive epicardial disease; and VSA, vasospastic angina.

Figure 2.

Invasive assessment for coronary vasomotion disorders in angina. A, Shows different diagnoses within ischemia and no obstructive coronary artery disease (INOCA) population while (B) shows the heterogenous nature of microvascular angina. ACh indicates acetylcholine; CFR, coronary flow reserve; IDP, interventional diagnostic procedure; IMR, index of microcirculatory resistance (abnormal ≥25); MVA, microvascular angina; and VSA, vasospastic angina.

Figure 3.

Differences in angina and quality of life between microvascular angina (MVA) and vasospastic angina (VSA). Figure showing the differences in angina and quality of life (QoL) score with VSA group having almost 20% lower overall angina summary score compared with MVA. SAQ indicates Seattle Angina Questionnaire.