RESULTS
The characteristics of the participants are presented in Table 1. Participants were divided into two groups based on their NT-proBNP levels being above or below 250 pg/ml with high NT-proBNP levels being observed in 4.6% of patients in the selected cohort. High NT-proBNP levels were more prevalent in men and in a high proportion of the Russian population. Participants with high NT-proBNP levels were significantly older and had larger weights, body mass indexes, higher glycosylated hemoglobin levels, creatinine levels, and high-sensitive C-reactive protein levels. Furthermore, participants with higher NTproBNP levels displayed a higher percentage of cardiac pathology (by Hx, echocardiogram, or ECG), whereas the majority (85.3%) of participants in this group had no cardiac diagnosis; however, 71% were taking antihypertensive drugs, indicating a high prevalence of hypertension. Low-density lipoprotein (LDL) and total cholesterol levels were lower, probably because of the higher prescription rate of lipid-lowering drugs in this group.
Table 2 presents age- and sex-related normal ranges for atrial strain and SR values in a selection of 1069 healthy individuals (619 females and 450 males). ACS, ATS, atrial SR E were significantly dependent on age and sex, being higher with age and reduced in males. LASI increased with age and male sex, while PACS SR S and SR A showed no significant age- and sex-related changes.
Systolic and diastolic conventional and strain derived atrial and ventricular parameters are listed in Table 3 grouped by EF≥50%, EF<50% and AF. In each group, we aimed to identify the indicators of high and low NT-proBNP levels.
In all groups, NT-proBNP was highly correlated with lower atrial S/SR, higher LASI, some indicators of impaired relaxation such as lower basal E velocity and LV PL, SR, and E, and indicators of higher filling pressures such as higher E/e´. The E/A ratio was higher only in the AF group, and systolic parameters were significantly lower only in the EF<50% group. In the EF≥50% group, EDV and ESV were slightly, but insignificantly, reduced, and the LV mass was higher, indicating the presence of LV hypertrophy in subclinical heart failure with normal EF.
The mean values and differences between the three groups are shown in Table S1. Compared with the EF≥50% group, the EF<50% and AF groups displayed lower atrial and ventricular diastolic S/SR and velocities. LASI increased with reduced EF and AF, whereas the Doppler-derived diastolic functional parameters in AF were not significantly different. However, parameters with one-sided changes during diastolic dysfunction, like tricuspid regurgitation peak gradient, E/e´, and LA volume, indicated significant diastolic dysfunction of the low EF ventricles with AF.
Tables 4, 5, and 6 display univariate and multiple binary logistic regression analyses for systolic and diastolic echocardiographic parameters in relation to normal and high NT-proBNP levels for the EF≥50% (Table 4), EF<50% (Table 5), and AF (Table 6) groups. In participants with EFs more than or equal to 50% (Table 4), univariate regression showed a large number of diastolic and systolic parameters as indicators for the presence of high NT-proBNP levels. Multiple regression analysis revealed that ATS and MV-DT were the strongest independent indicators of a normal EF. In the EF<50% group (Table 5), the results of the univariate analysis were similar, whereas PACS, LV, and LVESV were independent indicators of the presence of high NT-proBNP by multiple binary regression. In the smallest group with AF (Table 6), only univariate regression was performed because the number of positive cases was too low for a reliable result in the multiple regression analysis. Similar to hearts without AF, all atrial S/R parameters and many systolic and diastolic parameters indicated the presence of high NT-proBNP levels. Figure 3 shows the ROC curves for both groups with low and normal EF for the combination of parameters of the multiple regression analyses discriminating the presence of high NT-proBNP levels. For normal EF, the combination of parameters did not significantly increase the area under the curve (AUC), whereas adding PACS to MV DT and ESV significantly increased the AUC from 0.719 to 0.805. The intra- and interobserver variability by intra-class correlation shown in Table S2 shows acceptable to good reproducibility for all atrial S/SR parameters.