Systemic Action of Inflammatory Mediators in Patients with Essential Hypertension and Diastolic Chronic Heart Failure: A Clinical Pathophysiological Study

Abstract

The aim of this research was to correlate indicators of proinflammatory status and the structural/functional characteristics of the cardiovascular system comparatively in male and female patients with essential hypertension (EH) complicated by diastolic chronic heart failure (CHF) with preserved left ventricular ejection fraction (LVEF). The study included 104 middle-aged patients (55 males (M) and 49 females (F)) with first- or second-degree EH complicated by CHF with preserved LVEF. They all belonged to the low functional class of CHF, with LVEF ≥50%, first- or second-degree of LV diastolic dysfunction (LVDD), LV hypertrophy (LVH), and dilatation of the left atrium (LA) with a sinus rhythm and N-terminal brain natriuretic peptide >125 pg/mL. Serum levels of C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) were measured. To identify the relationship between the proinflammatory pattern and cardiovascular parameters, Spearman's rank correlation coefficients were determined. M had markedly higher levels of CRP, TNF-α, and IL-6 compared to F. However, all the mean values corresponded to the reference range. Significant direct associations of CRP level with the LV mass index (LVMI), relative wall thickness (RWT), LA volume index (LAVI), E/e' ratio, and systolic and diastolic blood pressure (SBP, DBP) existed in both M and F, as well as negative correlations of CRP with LVDD parameter e' and distance covered in a 6 min walk test. M and F had a positive association between IL-6 and LVMI, LAVI, E/e' ratio, SBP, RWT, and DBP, as well as strong negative associations between IL-6 and e' and distance passed in 6 min in each group. Significant direct correlations existed between serum TNF-α level and LVMI, RWT, LAVI, E/e', SBP, and DBP both in M and F. Furthermore, there were negative relationships of TNF-α level with e' and the distance covered for the 6 min walk. This study demonstrated a close relationship between the blood levels of proinflammatory autacoids and indicators of EH, exercise tolerance, LVH, LVDD, and LA enlargement, regardless of the patient's sex. Compared to female patients, male patients had stronger correlations of CRP, TNF-α, and IL-6 levels with indicators of LVDD degree.

Keywords: chronic heart failure; correlation analysis; diastolic dysfunction; essential hypertension; preserved ejection fraction; proinflammatory status; sex differences.

Figure 1

Scheme of the selection of study participants in the main group (combination of essential arterial hypertension and heart failure with preserved left ventricular ejection fraction). Abbreviations: CHF: chronic heart failure, LVEF: left ventricular ejection fraction, LVDD: left ventricular diastolic dysfunction.

Figure 2

An episode of echocardiography in Participant A. (male, 55 years old). In the Doppler mode (Fragment A), transmitral blood flow is shown with an assessment of Peaks E and A. In the tissue, the Doppler mode and the fibrous ring of the mitral valve movement are shown in the left ventricle early-filling phase.

Figure 3

Correlative association of the C-reactive protein serum level and the left atrium volume index in females with hypertension complicated by CHF with preserved left ventricle ejection fraction. Abbreviations: CRP: C-reactive protein, LAVI: left atrium volume index.

Figure 4

Correlative association of the C-reactive protein serum level and the left atrium volume index in males with hypertension complicated by CHF with preserved left ventricle ejection fraction. Abbreviations: CRP: C-reactive protein, LAVI: left atrium volume index.

Figure 5

Correlative association of tumor necrosis factor alpha serum levels and left ventricular myocardial mass index in females with hypertension complicated by CHF with preserved left ventricular ejection fraction. Abbreviations: TNF-α: tumor necrosis factor alpha, LVMI: left ventricular myocardial mass index.

Figure 6

Correlative association of tumor necrosis factor alpha serum levels and left ventricular myocardial mass index in males with hypertension complicated by CHF with preserved left ventricular ejection fraction. Abbreviations: TNF-α: tumor necrosis factor alpha, LVMI: left ventricular myocardial mass index.