Background
Left ventricular hypertrophy (LVH), as defined by electrocardiography (ECG) or echocardiographic criteria, is a potential independent predictor of cardiovascular morbidity and mortality [
1,
2]. The mechanism of LVH development is not fully understood, but hemodynamic factors, such as increased afterload and activation of the renin–angiotensin–aldosterone system in the context of hypertension [
3,
4], are important for the development of LVH. Blood pressure is the strongest independent risk factor for LVH, and LVH has been observed in all stages of hypertension [
5]. However, LVH can also be present in normotensive subjects, and the severity of hypertension is far from explaining the changes in left ventricular mass index (LVMI) [
6]. Thus, nonhemodynamic mechanisms, such as metabolic factors and genetic factors, are likely to contribute to the development of LVH.
Nonhaemodynamic factors are likely to be involved in the pathogenesis of LVH, as increased blood pressure values explain less than 30% of variations in LVMI, both in normotensive and hypertensive subjects [
7]. Some risk factors, such as age, sex [
8], body mass index (BMI) [
9], SUA [
10], insulin resistance and diabetes mellitus [
11,
12], may all play roles in the pathogenesis of LVH. However, in China and other countries, most studies on LVH have mainly select middle-aged and elderly patients with hypertension, with a large age range and a large number of complications [
2,
4,
5,
8‐
12]. At present, there are no reports on the prevalence and related risk factors of LVH among young subjects in large population-based samples, especially in the rural young population of China. According to China Hypertension Survey 2012–2015 [
13], among Chinese adults ≥ 18 years old, the overall crude prevalence of hypertension was 27.9%, and the weighted prevalence was 23.2%. The prevalence of hypertension among young people aged 18–24, 25–34 and 35–44 years old was 4.0%, 6.1% and 15.0%, respectively, which increased compared with the Chinese hypertension survey in 2002 [
14], and the prevalence of LVH will continue to increase in the future. Therefore, it is of great significance to identify the prevalence and related risk factors of LVH in young subjects.
Therefore, we conducted cross-sectional and longitudinal analyses based on our previously established cohort to investigate related risk factors for ECG-LVH and its prevalence in a cohort of young Chinese individuals from the general population.
Discussion
Electrocardiographic left ventricular hypertrophy is a common manifestation of preclinical cardiovascular disease. Nonhaemodynamic factors are likely to be involved in the pathogenesis of LVH, and the severity of hypertension is far from explaining the changes in left ventricular mass. With this prospective cohort study, we were the first to investigate risk factors for ECG-LVH and its prevalence in a cohort of young Chinese individuals. We found that the prevalence of LVH diagnosed by the Cornell voltage-duration product in the overall population and the hypertensive population was 4.6% and 8.8%, respectively. Our study suggested that female sex, hypertension, SBP, SUA and CIMT were significantly associated with the risk of LVH in young people. In addition, fasting glucose, SBP and female sex are independent predictors of the occurrence of LVH in a young Chinese general population.
LVH appears to be highly prevalent in individuals with hypertension but also in the general population. Currently, there are no large epidemiological studies on the LVH detection rate and its risk factors in young Chinese populations. Several previous studies have investigated the prevalence of LVH in the general population. For example, Joji Ishikawa et al. [
23] found that in 10,755 individuals from the general Japanese population, the detection rate of LVH diagnosed by the Cornell voltage-duration product was 6.4% in all subjects and 11.0% in the hypertension subgroup. Lehtonen AO et al. [
24] found that the LVH detection rates according to the Cornell voltage criteria in individuals with normal blood pressure, hypertension grade 1 and hypertension grade 2 among the 5800 Finnish population were 5.1%, 9.0% and 13.1%, respectively. In line with these two studies, we found that the prevalence of LVH diagnosed by the Cornell voltage-duration product in the total young population and hypertensive population were 4.6% and 8.8%, respectively.
Currently, the mechanism of LVH development is not completely clear, except for hemodynamics, and its pathogenesis is related to age, sex, body mass, race, genetic factors, metabolic status (such as insulin resistance and hyperuricemia) and other factors [
8‐
12]. To the best of our knowledge, this is the first study to investigate risk factors for ECG-LVH in a cohort of young Chinese individuals from the general population. We observed that fasting glucose, SBP and female sex are independent predictors of the occurrence of LVH in the fourth year of follow-up. Female, higher fasting glucose and SBP can increase the risk of LVH. Blood pressure is the strongest independent risk factor for LVH, and that approximately 30% of hypertensive patients may have LVH, and the detection rate of LVH is positively correlated with the severity of hypertension. [
24] Blood glucose is closely associated with insulin levels, and increased glucose levels may cause hyperinsulinemia. Our observation is similar to that of Lin et al., who observed that baseline fasting glucose is correlated with the 4-year change in LVMI and is an independent predictor for LVMI and the occurrence of LVH after a 4-year follow-up in normotensive healthy elderly subjects without diabetes mellitus [
25].Insulin itself could induce cardiovascular hypertrophy by acting on insulin growth factor receptors and simulating cell proliferation and lipid deposition [
26,
27]. In addition, our results showed that SUA and CIMT were significantly associated with the risk of LVH in young people.
Yoshio Iwashima et al. [
28] showed that SUA is independently associated with LVMI and suggest that hyperuricemia combined with LVH is an independent and powerful predictor for Cardiovascular disease in asymptomatic subjects with essential hypertension. In line with this study, we found that SUA was significantly associated with LVH in correlation and logistic regression analyses in this Chinese cohort. In addition, many studies have shown that SUA may impair NO generation, induce endothelial dysfunction, and promote oxidative metabolism and smooth muscle cell proliferation [
28,
29], which are known to induce cardiac hypertrophy. These results suggest that cardiac hypertrophy may be partially attributable to an increase in UA itself. Similar to what we found, Nam-ho Kim et al. [
30] conducted a cross-sectional study with 9266 middle-aged and elderly individuals from the general populations in Korea and found that compared with other quartile groups, the risk of LVH increased by 48% in the highest quartile of CIMT. Carotid IMT thickening was associated with the presence of endothelial dysfunction, oxidative stress, inflammatory mediators and metabolic factors, which can lead to myocardial collagen hyperplasia and fibrosis aggravation and may thereby promote LVH [
30,
31].
In our study, we also found that sex was significantly associated with LVH in the young population. Numerous studies have confirmed that there are sex differences in LVH, and the prevalence of LVH in females was higher than that in males, regardless of the use of ECG or echocardiography. A retrospective analysis of 30 studies showed that the prevalence of LVH diagnosed by ECG in hypertensive patients was 35.6%-40.9%, among which the detection rates were 36.0%-43.5% in males and 37.9%-46.2% in females [
32]. A study also showed that the prevalence of LVH in Chinese hypertension patients diagnosed by echocardiography was significantly higher in females than in males [
33]. Currently, the mechanism of the correlation between sex and LVH has not been fully elucidated but may be related to ECG diagnostic methods [
21,
22], sex differences in the size and mass of the left ventricle and its response to chronic pressure load [
34,
35], and sex hormones factors [
35].
Some limitations of our study merit consideration. First, our results were obtained from young northern Chinese individuals and consequently may not be generalizable to other age and ethnic groups with different demographics. Second, we used electrocardiograms to diagnose LVH at the follow-up in 2017 and failed to conduct echocardiography. Echocardiographic detection of LVH provides more accurate estimates of LVMI than ECGs. Although echocardiography is the preferred method to diagnose LVH in clinical practice, ECGs are commonly used as the first-line instrument for detecting LVH due to its convenience, cost-effectiveness, good reproducibility and availability in large cohort settings. Finally, some participants were lost during the follow-up period, and the number of subjects with LVH during the follow-up period was relatively small. However, as we know, the subjects of this study are young individuals from the general population who are currently in the period of subclinical target organ damage, and the prevalence of hypertension and cardiovascular disease is relatively low. Clarifying the risk factors for Cardiovascular disease in young populations is of great significance for the primary prevention of cardiovascular disease, and we will continue to follow up.
In conclusion, our study shows female sex, hypertension, SBP, SUA and CIMT were significantly associated with the risk of LVH in the young Chinese population. AND fasting glucose, SBP and female sex are independent predictors of the occurrence of LVH in the fourth year of follow-up. Our study suggests that, even in an apparently healthy, relatively young population, in addition to the active control of blood pressure, regular monitoring of SUA and fasting glucose and the lowering of UA and glucose if necessary, may be actively considered to reduce the risk of left ventricular hypertrophy.
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