As a result of this study, we found that, in hypertensive patients with preserved left ventricular function, LAV min, LAEİ, using Beta blocker, mean diastolic blood pressure, and LV-S’ were associated with heart rate independent of other factors.
Cardiac remodeling in hypertension involves an imbalance in the production of collagen types 1 and 3, which carries the main stress in the extracellular matrix[8]. Increased stress especially in the subendocardial region causes heterogeneous myocardial fibrosis to form and enlarge. This irregular collagen production and myocardial fibrosis are associated with decreased GLS and cause early deterioration in systolic function in hypertensive patients[9]. Hypertension is also associated with morphological and functional abnormalities in LA. LA size increase and tissue doppler LA strain fluctuations are common findings in strain imaging in hypertensive patients[10].
In literature, heart rate is associated with survival in both healthy individuals and individuals with different underlying CV diseases. High heart rate can cause poor outcomes by affecting the CV system in many ways (ventricular workload, myocardial oxygen consumption, endothelial stress, increase in aortic/arterial stiffness, decrease in myocardial oxygen delivery). Therefore, treatment approaches aim to decrease heart rate and increase survival[11].
When the baseline characteristics of the groups are examined in our study, it is noteworthy that diabetes mellitus and age parameters, which are the most important risk factors in determining the CV risk score, are higher in the group with low heart rate. Diabetes mellitus and age are used as the most important risk factors in many CV risk scoring systems. In a meta-analysis by Saikhan et al., GLS has been defined as a prognostic marker for CV mortality and morbidity and its worsening has been defined as a conventional risk factor[12]. Risk factors affecting GLS, such as aging, hypertension, and potentially leading to cardiovascular diseases, are common features of longitudinal population-based elderly samples. Even if LVEF is normal in the elderly patient population, it is known that GLS changes with the effect of these risk factors[13,14]. In the study of Enomoto et al., there was no difference between the groups in terms of age and heart rate characteristics. Strain values were found to be better in the control group without diabetes mellitus and hypertension than in the group with hypertension only. Although the strain value of the group with only diabetes mellitus tended to be better than the group with diabetes mellitus and hypertension, it did not show statistical significance[15]. In the study of Elizabeth Kraigher-Krainer et al., high heart rate was found to negatively affect GLS[16]. In our study, parallel to the aforementioned result, despite diabetes mellitus and advanced age which adversely affect GLS, it was found that the GLS value in the group with low heart rate tended to be better than the group with high heart rate (-19.3±3 vs. -18.2±2.7 p:0.07). The reason for this may be that the beta-blocker group was chosen as an additional drug in the possible long-term follow-up of hypertension (37.5% vs. 22.7% p:0.036). When evaluated together with the results of our study, heart rate should also be considered when reaching the target blood pressure in the treatment of hypertension, with or without diabetes mellitus. For this purpose, beta-blocker and non-dihydropyridine calcium channel blocker groups should also be in the back of our minds, especially in drug selection with advancing age.
LA has an important role in the regulation of LV filling and contributes to one-third of the cardiac output[17]. LA has also been identified as an important biomarker of CV disease and adverse outcomes[6, 18]. While LA size was previously used as a biomarker, LA function is increasingly being evaluated along with it[19]. Strain parameters are relatively independent of coupling effects and are less load-dependent than conventional parameters of LA function[7]. Poor LA strain is associated with, advanced age, high frequency of atrial fibrillation, left ventricle hypertrophy, poor left, and right ventricular systolic function and poor LV diastolic function[20]. However, the relationship between heart rate and LA strain parameters could not be directly demonstrated. In our study, the reason for the poor left atrial size and strain values in the group with low heart rate may be explained the direct effect of advanced age and diabetes mellitus, as well as the direct effect of its negative effects on diastolic dysfunction. There are many studies supporting this situation. Studies showing the relationship between age and LA strain and strain rate are small. In the study of Boyd et al., which had results consistent with our study, it has been shown that LA systolic strain and strain rates decrease significantly with aging[21]. Diabetes mellitus affects LA enlargement and dysfunction independently of other risk factors. In many studies, it has been shown that LA reservoir and conduit functions are impaired in diabetic patients[22]. In the study of Kadappu et al., 73 Type 2 diabetes mellitus patients were compared with the control group according to their age and gender. In the diabetes group, hypertension and LA volume index was shown to be increased independent of the effect of diastolic dysfunction. LA global strain value was found to be decreased in the diabetes group compared to the control group, and this effect was did not change with increased diastolic dysfunction group[23]. These findings were also confirmed by Muranaka et al.'s study in which strain evaluation of LV and LA functions in diabetic patients was performed[24]. In our study, results consistent with the literature were obtained and the pLASRcd value in the first group was found to be lower than in the second group (-1.3±0.38 vs. - 1.5±0.61 P:0.031), while the pLASRr value tended to be lower in the first group (-1.3±0.34 vs. - 1.54±0.42 P:0.056). In our study, it is seen that low heart rate can not prevent the negative changes in LA structure and functions that develop with the effect of diabetes mellitus and age.
LV diastolic dysfunction occurs as a result of hypertension, changes occur in the size and functions of the LA along with the severity of the LV diastolic dysfunction[25]. Apart from hypertension, obesity, female gender, diabetes mellitus, age factors also affect LV diastolic dysfunction. In our study, LA size-functions and LV diastolic status are consistent with the literature. Diastolic parameters in the first group tends to be worse than the second group (E/Em, 5.62±4.29 vs. 4.38±3.92, p:0.073), LA dimensions increased (LAV max, 60.8±15.5 vs. 52.9±16.3, p:0.007, LAV min, 28.8±9.5 vs. 22.6±7.9, p:<0.001) and worsening of functions were detected (LAEF, 52.8 ±8.5 vs. 56.1 ±8.5, p:0.035, LAEİ, 1.19±0.44 vs. 1.36±0.47, p:0.044). In the study of Salako et al., it was shown that there was no improvement in cardiac structural changes despite antihypertensive treatment[26]. Similarly, in the study of Chan et al., it was shown that LA dimensions did not regress to normal levels by keeping blood pressure within normal limits with anti-hypertensive treatment[25]. In our study, it is seen that the positive effect of heart rate on left ventricular GLS is not apparent in LA strain parameters (pLASRr, 1.3±0.34 vs. 1.54±0.42, p:0.056, pLASRcd, -1.3±0.38 vs. -1.5±0.61, p:0.031, GLSLV, -19.3±3 vs. -18.2±2.7, p:0.071). Therefore, with opportunistic blood pressure measurements and detection of hypertension at an early stage, adverse events can be prevented or delayed with different targets such as GLS.
In multivariate analysis, although there was no difference between the groups in LA strain values; LAEİ and LAV min values, which showed structural and functional changes, were different in favor of the group with high heart rate. This situation, as we mentioned before, due to poor LV diastolic functions caused by diabetes mellitus and aging, as well as their independent negative effects. Especially in the early period, aiming to control the heart rate along with the blood pressure target may have a positive effect on the functional and structural changes in LA. Preventing or reversing the structural and functional deteriorations in LA can also prevent atrial arrhythmia that may occur in the future and possible cerebrovascular stroke situations.
4.1. Limitations
Being a single-centered study and limited number of patients are our primary limitations. Other limitations are the lack of randomization and long-term follow-up. More reliable results can be obtained with multicenter studies and a larger patient population.