Heart failure withpreserved ejection fraction (HFpEF) is a severe disease with an often unfavorable outcome. The prevalence of HFpEF continues to increase, while effective treatment options remain elusive. All the medical strategies used toimprove the outcome in a heart failure with reduced ejection fraction proved ineffective in HFpEF, which was probably due to the different mechanisms ofdevelopment of these two types of heart failure and the diversity of the HFpEF phenotypes. According to the current paradigm of HFpEF development, a chronic mild pro-inflammatory statecauses a coronary microvascular endothelial inflammation, with further myocardial fibrosis and diastolic dysfunction progression. This inflammatory paradigm of HFpEF has been confirmed with someevidence, and suppressing the inflammation may become a novel strategy for treating and managing HFpEF. This review summarizes current concepts about a microvascular inflammation in hypertrophied myocardium and provides a translational perspective of the anti-inflammatory and immunomodulatory approaches in HFpEF.
Background and aims: Chronic inflammation associated with the uncontrolled activation of innate and acquired immunity plays a fundamental role in all stages of atherogenesis. Monocytes are a heterogeneous population and each subset contributes differently to the inflammatory process. A high level of lipoprotein(a) (Lp(a)) is a proven cardiovascular risk factor. The aim of the study was to investigate the association between the increased concentration of Lp(a) and monocyte subpopulations in patients with a different severity of coronary atherosclerosis. Methods: 150 patients (124 males) with a median age of 60 years undergoing a coronary angiography were enrolled. Lipids, Lp(a), autoantibodies, blood cell counts and monocyte subpopulations (classical, intermediate, non-classical) were analyzed. Results: The patients were divided into two groups depending on the Lp(a) concentration: normal Lp(a) < 30 mg/dL (n = 82) and hyperLp(a) ≥ 30 mg/dL (n = 68). Patients of both groups were comparable by risk factors, autoantibody levels and blood cell counts. In patients with hyperlipoproteinemia(a) the content (absolute and relative) of non-classical monocytes was higher (71.0 (56.6; 105.7) vs. 62.2 (45.7; 82.4) 103/mL and 17.7 (13.0; 23.3) vs. 15.1 (11.4; 19.4) %, respectively, p < 0.05). The association of the relative content of non-classical monocytes with the Lp(a) concentration retained a statistical significance when adjusted for gender and age (r = 0.18, p = 0.03). The severity of coronary atherosclerosis was associated with the Lp(a) concentration as well as the relative and absolute (p < 0.05) content of classical monocytes. The high content of non-classical monocytes (OR = 3.5, 95% CI 1.2–10.8) as well as intermediate monocytes (OR = 8.7, 2.5–30.6) in patients with hyperlipoproteinemia(a) were associated with triple-vessel coronary disease compared with patients with a normal Lp(a) level and a low content of monocytes. Conclusion: Hyperlipoproteinemia(a) and a decreased quantity of classical monocytes were associated with the severity of coronary atherosclerosis. The expansion of CD16+ monocytes (intermediate and non-classical) in the presence of hyperlipoproteinemia(a) significantly increased the risk of triple-vessel coronary disease.
Heart failure withpreserved ejection fraction (HFpEF) is a severe disease with an often unfavorable outcome. The prevalence of HFpEF continues to increase, while effective treatment options remain elusive. All the medical strategies used toimprove the outcome in a heart failure with reduced ejection fraction proved ineffective in HFpEF, which was probably due to the different mechanisms ofdevelopment of these two types of heart failure and the diversity of the HFpEF phenotypes. According to the current paradigm of HFpEF development, a chronic mild pro-inflammatory statecauses a coronary microvascular endothelial inflammation, with further myocardial fibrosis and diastolic dysfunction progression. This inflammatory paradigm of HFpEF has been confirmed with someevidence, and suppressing the inflammation may become a novel strategy for treating and managing HFpEF. This review summarizes current concepts about a microvascular inflammation in hypertrophied myocardium and provides a translational perspective of the anti-inflammatory and immunomodulatory approaches in HFpEF.
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