Impaired coronary flow velocity reserve is associated with cardiovascular risk factors but not with angina symptoms.

OBJECTIVES: Coronary microvascular dysfunction (CMD) is considered to cause angina pectoris in a large proportion of women with no obstructive coronary artery disease (CAD). However, data supporting a relation between angina pectoris and CMD are limited. We compared CMD in women with angina with asymptomatic women and evaluated the relation between presence of CMD, angina characteristics, cardiovascular risk factors and results of stress testing. METHODS: In a cross-sectional study, we included 1684 women with angina and <50% coronary artery stenosis on invasive angiography. Asymptomatic women from the community-based Copenhagen City Heart Study served as reference group (n=102). Coronary microvascular function was determined by coronary flow velocity reserve (CFVR) assessed by transthoracic Doppler stress echocardiography. CFVR < 2 was defined as CMD. Symptoms were obtained from standardised angina questionnaires and results of stress testing from health records. RESULTS: Median CFVR was 2.33 (IQR 2.00-2.75) in symptomatic women versus 2.60 (2.19-2.95) in asymptomatic (p=0.007). CFVR <2 was found in 25% of symptomatic and in 19% of asymptomatic women. Symptomatic women had a greater risk factor burden. After adjusting for age, hypertension, diabetes, smoking and heart rate the difference in CFVR between groups disappeared (p=0.213). We found no associations between CFVR and angina characteristics, symptom burden or results from stress testing. CONCLUSIONS: Impaired CFVR is more prevalent in symptomatic than in asymptomatic women and related to the cardiovascular risk factors hypertension, diabetes, smoking and increased heart rate. Neither a positive bicycle test, single photon emission CT stress test nor chest pain characteristics identify women with impaired CFVR among women with angina and no obstructive CAD. Results may question the concept of microvascular angina as currently defined.

Myocardial CT perfusion compared with transthoracic Doppler echocardiography in evaluation of the coronary microvascular function: An iPOWER substudy.

BACKGROUND: A significant number of women with angina and no obstructive coronary artery disease (CAD; <50% stenosis) have coronary microvascular dysfunction (CMD) which carries an adverse cardiovascular prognosis. Coronary microvascular function can be evaluated by transthoracic Doppler echocardiography (TTDE) as a coronary flow velocity reserve (CFVR) and by static CT myocardial perfusion (CTP) as a myocardial perfusion reserve (MPR). Whether these methods are correlated is not known. We assessed the correlation between CFVR and MPR and investigated whether women with angina, CMD and no obstructive CAD have reduced MPR compared with asymptomatic women. METHODS: Static CTP with adenosine-induced vasodilation and TTDE of the left anterior descending artery with dipyridamole-induced vasodilation were successfully performed and analysed in 99 women with stable angina and no obstructive CAD and 33 asymptomatic women with no obstructive CAD. CMD was defined as CFVR < 2. RESULTS: Correlation between rate-pressure product corrected MPR and CFVR was weak but significant (r = .23; p = .007). MPR was highest among asymptomatic women with normal CFVR (median [interquartile range; IQR] 158 [145-181] %). Symptomatic women with normal CFVR had reduced MPR (148 [134-162] %; age-adjusted p < .001); however, the lowest MPR was found in symptomatic women with CMD (140 [129-164] %; age-adjusted p < .001), independent of cardiovascular risk factors and haemodynamic parameters (p = .017). CONCLUSION: Women with angina, CMD and no obstructive CAD had markedly diminished MPR compared with asymptomatic women. Correlation between CFVR and MPR was weak, suggesting that CTP and TTDE are not interchangeable for detection of CMD.

Accelerated collagen turnover in women with angina pectoris without obstructive coronary artery disease: An iPOWER substudy.

Aim Collagens are major cardiac extracellular matrix components, known to be actively remodelled and accumulated during diffuse myocardial fibrosis. We evaluated whether accelerated collagen turnover described by neo-epitope biomarkers reflecting collagen formation and degradation separates patients with diffuse myocardial fibrosis from asymptomatic controls. Methods and results Seventy-one women with angina pectoris without significant coronary artery disease assessed by invasive coronary angiogram were included. Competitive enzyme-linked immunosorbent assays (ELISAs) measuring circulating protein fragments in serum assessed the formation and degradation of collagen type III (Pro-C3, C3M and C3C), IV (P4NP7S and C4M), V (Pro-C5 and C5M) and VI (Pro-C6 and C6M), and degradation of collagen type I (C1M). Serum samples from 32 age-matched asymptomatic women were included as controls. Symptomatic women presented significantly elevated levels of Pro-C6, C3C, C3M, C4M and C8-C ( p < 0.0001-0.0058) and significantly decreased levels of Pro-C3, C5M and C6M ( p < 0.0001-0.041), reflecting accelerated collagen turnover and an imbalanced collagen formation and degradation compared to controls. Cardiac magnetic resonance T1 mapping was performed to determine extracellular volume fraction and thus diffuse myocardial fibrosis. A significant association was identified between C5M and extracellular volume fraction by cardiac magnetic resonance ( p = 0.01). Conclusion Women with angina pectoris, but without significant obstructive coronary artery disease, showed an imbalanced collagen turnover compared to asymptomatic controls. The examined biomarkers are tools to monitor active collagen remodelling in patients with angina pectoris, in risk of developing myocardial fibrosis.