Abstract
PurposeSystemic inflammation and coronary microvascular dysfunction (CMD) may be causal drivers of heart failure with preserved ejection fraction (HFpEF). We tested the hypothesis that subclinical inflammation is associated with non-endothelial dependent CMD and diastolic dysfunction.MethodsIn a cross-sectional study of 336 women with angina but no flow limiting coronary artery stenosis (180 with diabetes) and 95 asymptomatic controls, blood samples were analysed for 90 biomarkers of which 34 were part of inflammatory pathways. CMD was assessed as coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography and defined as CFVR<2.5. We used E/e’ as an indicator of diastolic function in age-adjusted linear regressions to assess correlations between biomarkers, CFVR and diastolic function.ResultsCMD was found in 59% of participants whereas only 4% fulfilled strict criteria for diastolic dysfunction. Thirty-five biomarkers, 17 of them inflammatory, were negatively correlated with CFVR and 25, 15 inflammatory, were positively correlated with E/e’. A total of 13 biomarkers, 9 inflammatory, were associated with both CFVR and E/e’. CFVR and E/e’ were only correlated in the subgroup of patients with CMD and signs of increased filling pressure (E/e’>10) (p = 0.012).ConclusionThis is the first study to link a large number of mainly inflammatory biomarkers to both CMD and E/e’, thus confirming a role of inflammation in both conditions. However, despite a high prevalence of CMD, few patients had diastolic dysfunction and the data do not support a major pathophysiologic role of non-endothelial dependent CMD in diastolic dysfunction.
Highlights
Coronary microvascular dysfunction (CMD) is associated with increased mortality, even in the absence of macrovascular coronary artery disease (CAD) [1, 2]
We explored this hypothesis in a population of diabetic (Group A) and non-diabetic (Group B) women with angina and no flow limiting CAD from the iPOWER (ImProve diagnOsis and treatment of Women with angina pEctoris and micRovessel disease) study as well as in controls (Group C)
In line with our findings, several of the biomarkers we found to be associated with both coronary flow velocity reserve (CFVR) and E/e’ were significantly correlated with E/e’ in a prognostic study of 86 patients with heart failure with preserved ejection fraction (HFpEF) by Hage et al.: Growth differentiation factor 15 (GDF-15), Tumor necrosis factor receptor 1 (TNFR1), Chitinase-3-like protein 1 (CHI3L1), Fatty acid-binding protein 4 (FABP4) and Soluble urokinase-type plasminogen activator receptor [20]
Summary
Coronary microvascular dysfunction (CMD) is associated with increased mortality, even in the absence of macrovascular coronary artery disease (CAD) [1, 2]. Hypertension and dyslipidemia contribute to a pro-inflammatory state that induces oxidative stress in the microvascular endothelium, leading to both endothelial dependent or non-endothelial dependent CMD [4, 5]. Because of cross-talk between endothelial cells and cardiomyocytes, endothelial inflammation may lead to myocardial functional alterations [6,7,8], contributing to adverse cardiac prognosis [9, 10]. The same comorbidities mentioned above that have been associated with microvascular dysfunction have been associated with cardiac diastolic dysfunction [11, 12]. It has been suggested that angina with no obstructive CAD is pathophysiologically linked to HFpEF [13], but evidence supporting a direct pathophysiological link between CMD and cardiac diastolic dysfunction remains limited [14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
