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

PLoS One. 2020 Jul 16;15(7):e0236035. doi: 10.1371/journal.pone.0236035. eCollection 2020.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angina Pectoris / epidemiology*
  • Angina Pectoris / etiology
  • Angina Pectoris / metabolism
  • Angina Pectoris / pathology
  • Biomarkers / metabolism
  • Case-Control Studies
  • Coronary Circulation*
  • Coronary Vessels / physiopathology*
  • Cross-Sectional Studies
  • Diastole*
  • Female
  • Follow-Up Studies
  • Humans
  • Inflammation / metabolism
  • Inflammation / physiopathology*
  • Inflammation Mediators / metabolism
  • Male
  • Middle Aged
  • Prognosis
  • Stroke Volume*

Substances

  • Biomarkers
  • Inflammation Mediators

Grants and funding

This work was supported by the Danish Heart foundation, Bispebjerg and Frederiksberg University Hospital and The Danish Council for Independent Research. The grants described are for staffing and related expenses and not specifically for this study. No grant numbers allocated.