1. IntroductionEssential hypertension (EH) is one of the most common cardiovascular diseases. EH can be defined as an elevation in blood pressure for an unexplained reason that increases the risk of brain, heart, and kidney events [1]. Hypertension is a long-course disease with many complications. It has a high rate of disability and mortality. It not only seriously affects patients’ quality of life, but also causes a huge burden on society. Therefore, we should take effective control of blood pressure levels. For example, early intervention therapy to prevent early-target organ damage caused by hypertension, and to reduce the incidence of coronary heart disease (CHD) and myocardial infarction (MI), as well as other cardiovascular events, should be implemented.Left ventricle hypertrophy (LVH) is a pathological process caused by the chronic cardiac stress load of EH [2]. However, structural changes in LVH in some hypertensive patients are manifested in the interventricular septum, which is called isolated ventricular septum hypertrophy (IVSH) [3]. IVSH is a common cardiac structural change in the early stage of hypertension because the ventricular septum is more sensitive to catecholamine stimulation than the left posterior wall and right ventricle [4]. The degree of IVSH caused by hypertension is positively correlated with blood pressure level. The higher the blood pressure level, the more obvious the degree of IVSH in patients. Since the interventricular septum thickness (IVSd) is easier to measure and to obtain than left ventricular mass by Doppler ultrasound, IVSd is often used as an early sensitivity index to evaluate LVH in patients with EH.

In this study, we aimed to explore the role of IVS, regarded as the categorical variable, on the prediction of the incidence and prognostic value of CHD and MI in the total and sex-stratified analyses in the Northeast China Rural Cardiovascular Health Study (NCRCHS).

4. Discussion

In this large Chinese population cohort, we showed that, in patients with hypertension, a significantly higher incidence of CHD and MI occurred in the IVS hypertrophy group compared to in the normal IVS group in the overall and female groups. This study demonstrated that abnormal IVS may be an independent prognostic factor for these adverse outcomes. Our study may help with the early intervention of hypertension-associated cardiovascular events in clinical practice.

Some studies have reported that IVS was associated with an increased risk of adverse outcomes. For example, in a hypertensive population study, researchers found that diastolic left ventricular filling dysfunction and cardiac dysrhythmias were increased among patients with isolated IVS hypertrophy and normal LV mass [3]. In a study of 51 apparently healthy pilots, Harpaz et al. demonstrated that isolated IVS hypertrophy was associated with hypertension, even with normal LV mass condition. This study revealed that IVS hypertrophy patients identified by echocardiography should be closely monitored for hypertension [18]. Grossman et al. also revealed that IVS predicts future systolic hypertension in young healthy pilots [19]. In a prospective elderly cohort study of 5888 participants, Gardin et al. found that the incidence of congestive heart failure (CHF) in women had significantly greater IVSd, whereas in men, the incidence of CHD, CHF, stroke, and all-cause mortality had significantly greater IVSd [20]. Apostolakis et al. demonstrated that moderately or severely abnormal IVSd was an independent predictor of stroke and all-cause mortality in atrial fibrillation patients. This may indicate that we should pay close attention to IVS hypertrophy regression in this population [21]. In patients undergoing aortic valve replacement, Straten et al. found that increased IVSd was a predictor of late mortality [22]. Given that IVSd was reported to be associated with adverse outcomes in a large number of studies, there were some explanations that may help us to understand our findings. First, IVS thickening may influence hemodynamics and activate the neurohumoral mechanism during the pathophysiology process, showing the possible links between IVS hypertrophy and adverse clinical outcomes. Second, hypertension is a risk factor of cardiovascular diseases [23,24,25]. It plays an important role in the progression of cardiovascular diseases. Third, IVS thickening causes LV hypertrophy, which has been shown to be a significant predictive factor of adverse cardiovascular outcomes [26,27]. In summary, IVSd evaluated by the echocardiography method as a key risk factor has significant implications for improving risk stratification and prediction. There are other causes of IVS hypertrophy: hypertrophic obstructive cardiomyopathy (HOCM), in which IVS is not proportional to the posterior wall of the left ventricle; the ratio of IVS, where the posterior wall of the left ventricle was ≥1.3, and there was a pressure difference in the left ventricular outflow tract [28]; chronic renal failure: these patients always have moderate-to-severe hypertension, and four of ten patients showed asymmetric septal hypertrophy (ASH) typical of hypertrophic cardiomyopathy (HCM) on echo [29]; and diabetes: Aman et al. reported that in spite of efforts to achieve good glycemic control during pregnancy, both fat mass and cardiac septal thickness were increased in newborn infants of women with T1DM and GDM. This condition seems to be related to glycemic control and fetal hyperinsulinemia [30].We found that IVS is more significant in females rather than males as a predictor of CHD and MI. There are some explanations for this: first, estrogen may protect premenopausal woman from CHD risk to some extent. Endothelium-dependent vasodilation was greater in premenopausal than in postmenopausal women [31]. The beneficial vasodilatory effect of estrogen has also been found in the coronary arteries [32]. However, in postmenopausal women, estrogen levels are decreased, and this protective effect is weakened. Second, Wenger pointed out that although chest pain was the most common symptom of MI for both sexes, more women were inclined to describe polypnea and extreme fatigue, which may lead to their delayed diagnosis and therapy [33]. Third, the long-term use of oral contraceptives was also a risk factor for cardiovascular diseases such as hypertension [34] and abnormal coagulation mechanisms [35]. Fourth, compared to men, middle-aged and elderly women were more likely to have decreased physical fitness, obesity, and overweight [36], which are also risk factors for CHD and MI. Last, cardiac rehabilitation was underused for women [37]. Therefore, educational messages from public health departments are needed to target racial and ethnic minority women regarding their presentation of acute MI and the vulnerability of women.Our study had some clinical significance. Now that IVSd has provided the prediction value of CHD and MI in adults with hypertension, we should pay attention to IVSd and avoid remodeling in the early stage. Angiotensin-converting enzyme inhibitors (ACEIs), a kind of drug used in the treatment of hypertension, have been reported to successfully reverse LV hypertrophy and myocardial fibrosis in spontaneously hypertensive rats [38,39]. ACEIs play pharmacological roles by reducing LV mass, regressing LV hypertrophy, decreasing vascular atherosclerosis, and improving vascular compliance [40]. Therefore, ACEI should be used in the early stage of IVS thickening to avoid LV remodeling and a series of cardiovascular events in further clinical practice.

However, there were some limitations in our study. First, this cohort was from a single-center study and was mainly located in the Northeast of China, and some patients were excluded in the follow-up due to the absence of ultrasonic data, which may have caused selection bias. Second, our study focused on the prognostic value of IVSd in hypertensive patients, so caution should be exercised when applying the results to the general population. Third, the follow-up time may have been too short to determine the presence of cardiovascular events. Therefore, a multi-center study and a longer follow-up time are necessary to further validate our conclusions.