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

Abstract

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

Increased Capillary Permeability in Heart Induces Diastolic Dysfunction Independently of Inflammation, Fibrosis, or Cardiomyocyte Dysfunction

“…A unifying, but untested, theory of the pathophysiology of HFpEF suggests that comorbidities, especially metabolic conditions, lead to systemic inflammation, which triggers endothelial and microvascular dysfunction. 2–5 This inflammation is presumed to increase diastolic left ventricular stiffness by increasing the deposition of collagen in the myocardial interstitium, reducing the elasticity of titin 6,7 and by an inadequate cellular degradation of destabilized proteins and their interstitial accumulation. 8…”

Effect of empagliflozin on coronary microvascular function in patients with type 2 diabetes mellitus–A randomized, placebo-controlled cross-over study

“…Blood samples were analyzed by Olink Proteomics, Uppsala, Sweden using the predefined cardiovascular disease panel II and III, measuring 184 protein biomarkers related to the cardiovascular system by real-time polymerase chain reaction. Further description of these biomarker panels is found in previous studies [5,6] and https://www.olink.com/ products/. Studies from our study group on microvascular function have looked for associations with cardiovascular biomarkers using the olink biomarker panels in different populations [5,6] and therefore we found it interesting to explore possible changes in biomarker levels in this population upon intervention.…”

“…Further description of these biomarker panels is found in previous studies [5,6] and https://www.olink.com/ products/. Studies from our study group on microvascular function have looked for associations with cardiovascular biomarkers using the olink biomarker panels in different populations [5,6] and therefore we found it interesting to explore possible changes in biomarker levels in this population upon intervention.…”

Understanding the Role of SERCA2a Microdomain Remodeling in Heart Failure Induced by Obesity and Type 2 Diabetes

“…While a growing body of science has nicely focused on the clinical characteristics and diagnosis of HFpEF, including investigations into potential biomarkers [ 13 , 28 , 29 ], it is the investigation of HFpEF at the cell signaling level that is required for us to truly dissect the pathophysiology of HFpEF. In past work, the lack of suitable HFpEF animal models that are comparable to the clinical manifestation of obesity and T2D HFpEF has been a major impediment.…”