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Inflammation, non-endothelial dependent coronary microvascular function and diastolic function-Are they linked?

ABSTRACT: PURPOSE:Systemic 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. METHODS:In 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. RESULTS:CMD 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). CONCLUSION:This 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.

SUBMITTER: Suhrs HE

PROVIDER: S-EPMC7365405 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Inflammation, non-endothelial dependent coronary microvascular function and diastolic function-Are they linked?

Suhrs Hannah E HE Schroder Jakob J Bové Kira B KB Mygind Naja D ND Frestad Daria D Michelsen Marie M MM Lange Theis T Gustafsson Ida I Kastrup Jens J Prescott Eva E

PloS one 20200716 7

<h4>Purpose</h4>Systemic 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.<h4>Methods</h4>In 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 biomark ...[more]

PMID: 32673354

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Project description:Background Coronary microvascular dysfunction (CMD) has been considered as a possible cause of cardiac diastolic dysfunction. The current study evaluated the association between cardiac diastolic dysfunction and CMD, and their prognostic implications in patients without significant left ventricular systolic dysfunction and epicardial coronary stenosis. Methods and Results A total of 330 patients without left ventricular systolic dysfunction (ejection fraction ≥50%) and significant epicardial coronary stenosis (fractional flow reserve >0.80) were analyzed. Cardiac diastolic dysfunction was defined by echocardiographic parameters (early diastolic transmitral flow velocity/early diastolic mitral annular velocity, e' velocity, tricuspid regurgitation velocity, and left atrial volume index). Overt CMD was defined as coronary flow reserve <2.0 and index of microcirculatory resistance ≥25 U. The primary end point was cardiovascular death or admission for heart failure during 5 years of follow-up. In patients without left ventricular systolic dysfunction and significant epicardial coronary stenosis, prevalence of cardiac diastolic dysfunction and overt CMD was 25.5% and 11.2%, respectively. Overt CMD was independently associated with cardiac diastolic dysfunction (adjusted odds ratio, 3.440 [95% CI, 1.599-7.401]; P=0.002). Patients with cardiac diastolic dysfunction showed significantly higher risk of the primary outcome than those without (adjusted hazard ratio [HR], 2.996 [95% CI, 1.888-4.755]; P<0.001). Patients with overt CMD also showed significantly higher risk of the primary outcome than those without (adjusted HR, 2.939 [95% CI, 1.642-5.261]; P<0.001). Presence of overt CMD was associated with significantly increased risk of cardiovascular death among the patients with cardiac diastolic dysfunction (43.8% versus 14.5%; P=0.006) but not in patients without cardiac diastolic dysfunction (interaction P<0.001). Inclusion of overt CMD into the model with cardiac diastolic dysfunction significantly improved predictive ability for cardiovascular death or heart failure admission (conconrdance index, 0.719 versus 0.737; P for comparison=0.034). Conclusions There was significant association between the presence of cardiac diastolic dysfunction and overt CMD. Both cardiac diastolic dysfunction and overt CMD were associated with increased risk of cardiovascular death or admission for heart failure. Integration of overt CMD into cardiac diastolic dysfunction showed improvement of the risk stratification in patients without significant left ventricular systolic dysfunction and epicardial coronary stenosis. Registration DIAST-CMD (Prognostic Impact of Cardiac Diastolic Function and Coronary Microvascular Function) registry; Unique identifier: NCT05058833.

Project description:Objectives- Coronary endothelial dysfunction is a precursor of atherosclerosis and adverse outcomes. Whether endothelial dysfunction is a localized or generalized phenomenon in humans remains uncertain. We simultaneously measured femoral and coronary vascular function with the hypothesis that peripheral vascular endothelial function will be reflective of coronary endothelial function. Approach and Results- Eighty-five subjects underwent coronary angiography for evaluation of chest pain or abnormal stress tests. Endothelium-dependent and -independent vascular function were measured using intracoronary and intrafemoral infusions of acetylcholine and sodium nitroprusside, respectively. Coronary flow reserve was assessed using intracoronary adenosine infusion. Flow velocity was measured in each circulation using a Doppler wire (FloWire, EndoSonics). Coronary vascular resistance and femoral vascular resistance were calculated as mean arterial pressure (mm Hg)/coronary blood flow (mL/min) and mean arterial pressure (mm Hg)/femoral average peak velocity (cm/s), respectively. Mean age was 53±11 years, 37% were female, 44% had hypertension, 12% had diabetes mellitus, and 38% had obstructive coronary artery disease. There was a correlation between the change in femoral vascular resistance with acetylcholine and acetylcholine-mediated changes in both the coronary vascular resistance ( r=0.27; P=0.014) and in the epicardial coronary artery diameter ( r=-0.25; P=0.021), indicating that subjects with normal endothelial function in the femoral circulation had normal endothelial function in the coronary epicardial and microcirculation and vice versa. The coronary vasodilator response to adenosine also correlated with the femoral vasodilatation with acetylcholine ( r=0.4; P=0.0002). There was no correlation between the coronary and femoral responses to sodium nitroprusside. Conclusions- Endothelial functional changes in the peripheral and coronary circulations were modestly correlated. Thus, peripheral microvascular endothelial function reflects endothelium-dependent coronary epicardial and microvascular function and the coronary flow reserve. Visual Overview- An online visual overview is available for this article.

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Inflammation, non-endothelial dependent coronary microvascular function and diastolic function-Are they linked?

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Inflammation, non-endothelial dependent coronary microvascular function and diastolic function-Are they linked?

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