Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure (HF) with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties of statins, such as anti-inflammatory, antihypertrophic, antifibrotic, and antioxidant effects, are generally accepted and may be beneficial in HF, especially in HFpEF. Numerous observational clinical trials have consistently shown a beneficial prognostic effect of statins in patients with HFpEF, while the results of two larger trials in patients with HFrEF have been controversial. Such differences may be related to a more pronounced impact of the pleiotropic properties of statins on the pathophysiology of HFpEF and pro-inflammatory comorbidities (arterial hypertension, diabetes mellitus, obesity, chronic kidney disease) that are more common in HFpEF. This review discusses the potential mechanisms of statin action that may be beneficial for patients with HFpEF, as well as clinical trials that have evaluated the statin effects on left ventricular diastolic function and clinical outcomes in patients with HFpEF.
Heart Failure , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Stroke Volume , Humans , Heart Failure/drug therapy , Heart Failure/physiopathology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Stroke Volume/drug effects , Ventricular Function, Left/drug effects , Clinical Trials as Topic
In this study we analyzed the concentration of lipoprotein(a) (Lp(a)), PCSK9-Lp(a) complexes and the circulating monocyte subsets in coronary atherosclerosis. For this study, 257 patients with coronary atherosclerosis and 68 patients without stenotic atherosclerosis in the coronary, carotid and lower extremity arteries (control group) were enrolled. The monocyte subpopulations (classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++) were analyzed by direct immunofluorescence and flow cytometry. The Lp(a) and PCSK9-Lp(a) complexes in the serum were detected by ELISA. The concentration of Lp(a) was higher in the coronary atherosclerosis group compared with the controls (23.0 (9.1; 73.3) mg/dL versus 10.7 (4.7; 25.0) mg/dL, p < 0.05). No correlations between the level of Lp(a) and the concentration of the PCSK9-Lp(a) complexes, nor between the level of Lp(a) or PCSK9 and the total number of monocytes, were observed in either group. A slight positive correlation between the concentration of PCSK9-Lp(a) complexes and the absolute level of monocytes was obtained (r = 0.20, p = 0.002) in the patients with atherosclerosis due to the intermediate monocyte subsets (r = 0.33, p = 0.04). According to regression analysis, both the PCSK9-Lp(a) complexes concentration and BMI were related to the absolute number of blood monocytes in patients with atherosclerosis. Further studies are required to determine the pathogenetic contribution of PCSK9-Lp(a) complexes to the development of atherosclerosis.
Aims: The authors examined the phenotype of circulating monocytes in patients with coronary atherosclerosis depending on age. Methods: A total of 121 patients were categorized into three groups according to the severity of coronary atherosclerosis assessed by angiography and into two groups depending on age above/below the median 60.0 (range: 56.0-66.0). Classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16+ monocytes were analyzed via direct immunofluorescence and flow cytometry. Results and conclusions: In patients >60 years of age, the severity of atherosclerosis was associated with the decreased number of classical monocytes in the blood. In patients under 60 years of age, this relationship was not observed. The authors hypothesize that the contribution of different subtypes of blood monocytes to the development of atherosclerosis may vary with age.
