In the present study, we used GAM to elucidate the non-linear relationship between MHT and GLS among participants. As the probability of MHT arises, GLS gradually decreases. In the fully adjusted model, the -14% of GLS was considered the critical value to represent absolute myocardial damage caused by MHT.
First, we evaluated the relationship between MHT and GLS through univariate regression analysis, and further confirmed the relation by multivariate regression after adjusting for the influence of the confounding factors. Since a previous study suggested that LVMI had a reduced GLS [12], we also adjusted LVMI for analysis. Next, in order to identify the mutual influence between the related factors, we conducted an interaction analysis. The results indicated that MHT and GLS had a strong relation in various situations. Finally, since GLS was a continuous variable, we plotted the fitting curve based on the dose–response relationship and found a nonlinear trend. With the help of the inflection point of the curve, we identified the risk threshold of GLS based on different MHT risk levels. To the best of our knowledge, this is the first description of the non-linear relation between MHT and GLS in a community-dwelling population.
Pickering et al. proposed the concept of MHT and emphasized the importance of identifying patients with MHT [13]. Since then, many studies have been done on the prognosis of MHT. A substudy of PAMELA cohort focusing on MHT patients showed that after follow-up for 10 years, the risk of new-onset left ventricular hypertrophy was high even after adjusting for confounding factors (OR: 2.22, P=0.025), emphasizing that this phenomenon represents the risk of heart damage with a poor prognosis [14]. The damage of MHT occurs at early stage as it elongates the longitudinal fibers, thickens myocardial fibers and ventricular wall, and remodels myocardium due to long-term increased afterload [15]. Compared with persistent hypertension, the attack of MHT is more insidious and poorly controllable; therefore, early recognition of MHT-related cardiomyocyte damage before heart failure is extremely important.
Two-dimensional (2D) speckle-tracking echocardiography technique, which can quantify myocardial strain by GLS measurement, has been validated by tagged CMR imaging and widely considered to be able to early detect myocardial damage even if the LVEF is preserved in various lesions[16-18]. Pathophysiologically, high levels of end-systolic wall stress, hypertrophic myocardium, and increased left ventricular stiffness play an important role in reducing the shortening of longitudinal subepicardial myocardial fibers, in accordance with the mechanism of cardiac impairment by MHT [19]. The latest guidelines also suggests that for patients with near-normal EF, global longitudinal strain has shown prognostic value, while prognostic information from EF is relatively less useful[20]. Santos et al. compared baseline GLS in 91 patients with pre-hypertension (systolic blood pressure 120–139 mm Hg or diastolic blood pressure 80–89 mm Hg, and not taking antihypertensive medication) and 105 patients with stage I hypertension (BP 140–159 or 90–99 mm Hg, and no current use of BP‐lowering medication); the result showed that stage I hypertension already has an impaired GLS accounting to about 1% [21]. Although the 1% difference in GLS appears insignificant, studies have shown that a small decrease in GLS is a powerful indicator of hospitalization for heart failure, cardiovascular death, or cardiac arrest [22]. In terms of GLS evaluation in MHT, Tadic, et al. previously retrospected 56 MHT patients and found that longitudinal strains was progressively deteriorated from normotensive group, particularly in the endocardial and midmyocardial layers [23]. Luo, et al. studied 40 young MHT patients and also concluded the similar results [24]. Both two studies compared the GLS difference between MHT and NHT, confirming the role of GLS in the assessment of cardiac function in MHT, but the correlation between MHT and GLS as well as potential cut-off value were not well defined. Our study included more MHT patients and strengthened the lower GLS in MHT than NHT by excluding disturbance or interaction from confounding factors. More importantly, we described the dose–response relationship and defined a critical value of -14% as MHT-related myocardial damage. One explanation for this trend is that the pathology of MHT analogous to the early damage of hypertension, the changes of extracellular matrix and myocardial fibrosis mainly affect the subendocardium. Longitudinal fibers are more prone to fibrosis and hemodynamic overload due to their prominent subendocardial position. The more fibers damage, the less GLS. Therefore, based on this special relation, turning to early identification of MHT-related reversible cardiac damage by means of GLS may be a better way to discern potential victims and make further treatment decision.
Besides, similar to previous studies, lower GLS is also associated with lower mitral valve annulus diastolic velocity (E/A and E/E'), lower LVEF, more LVPWd and LVM, which represents the relationships among shortened systolic, impaired diastole, and advanced LV remodeling [24-25].
Our research also has limitations. First, the single-center retrospective study design prevents us from detecting causal relationships. Second, with the fact that the participants were from one community with unique population characteristics, life style and dietary culture, the extrapolation of our conclusions is limited. Finally, further follow-up studies are needed to explore whether the decrease in GLS in MHT patient group is associated with adverse events.