STRUCTURAL DIFFERENCES IN CARDIAC ULTRASOUND BETWEEN H-TYPE AND NON-H-TYPE HYPERTENSION

1. Introduction

Essential hypertension (EH) poses a significant public health challenge globally and represents a major threat to human health. Studies indicate that approximately 80% of patients with hypertension fail to achieve blood pressure levels within the target range recommended by international guidelines.^1,2 Additionally, the Framingham Heart Study demonstrated a strong positive correlation between the prevalence of hypertension and advancing age.³ The harmful combined impact of hypertension and hyperhomocysteinemia (hHcy) on the cardiovascular system, referred to as H-type hypertension (HHT), has been identified in recent years.⁴ This condition is characterized by increased plasma homocysteine (Hcy) levels, with hHcy typically defined as an Hcy concentration exceeding 10 $\mu$mol/L.^5,6 An increase of 5 $\mu$mol/L in the plasma Hcy level is linked to a 59% greater risk of cerebrovascular disease and a 32% higher risk of coronary artery disease. In contrast, reducing Hcy levels by 3 $\mu$mol/L decreases the incidence of ischemic heart disease by 11% and stroke by 19%.⁷

Hypertension and hHcy are among the leading contributors to cardiovascular diseases.^8,9 Community-based studies in China have revealed a high prevalence of hypertension coexisting with hHcy.^10,11 For instance, a survey of 20,702 adults showed that 80.3% of patients had hHcy.¹² Elevated Hcy levels are not only linked to hypertension but also closely associated with target-organ damage, particularly cardiac structural and functional alterations.^13,14 Patients with HHT often have cardiac abnormalities, including left atrial enlargement, myocardial hypertrophy, myocardial ischemia, and cardiac dysfunction, with more pronounced left ventricular remodeling.⁸ Furthermore, patients with both hypertension and hHcy experience five times higher cardiovascular events compared with those with hypertension alone and 25–30 times higher compared with the general population.¹⁵

Previous studies have provided insights into the role of Hcy in cardiovascular diseases. However, the mechanisms underlying the relationship between HHT and cardiac structural remodeling remain inadequately elucidated. This is particularly true in elderly patients with hypertension. The differences in cardiac structure between HHT and non-H-type hypertension (NHHT), as well as the specific impact of Hcy levels on left ventricular remodeling, warrant further investigation in these patients. Therefore, this study was conducted to evaluate the echocardiographic structural differences between elderly patients with HHT and NHHT and to elucidate the relationship between Hcy levels and left ventricular remodeling, thus providing a theoretical basis for clinical diagnosis and treatment.

2. Materials and Methods

2.1. Patient information

This study enrolled 300 patients with EH treated at the Department of Cardiology at Xining First People’s Hospital from January 2017 to December 2020. The cohort comprised 160 men aged 60–85 years and 140 women aged 60–80 years, with an average age of $68.5\pm 11.5$ years. The inclusion criteria were as follows: patients with a diagnosis of hypertension based on the 2020 updated global hypertension management guidelines by the International Society for Hypertension¹⁶; patients with a documented history of hypertension; those who resided locally for more than 10 years; and those with systolic blood pressure (SBP) of 140mm Hg or higher and/or diastolic blood pressure (DBP) exceeding 90mm Hg (1mm Hg $=$ 0.133kPa).

The exclusion criteria were as follows: patients with secondary hypertension, hereditary diseases, metabolic disorders, obesity, rheumatic heart disease, coronary artery disease, bundle branch block, fever or infections, acute or chronic infectious conditions, chronic obstructive pulmonary disease, pulmonary hypertension, chronic cor pulmonale, liver or kidney impairment, or immune system abnormalities. The participants were categorized into two groups according to the serum Hcy levels: HHT group ($n=150$) (defined as EH with Hcy levels $\ge 10\mu$mol/L, comprising 83 men and 67 women aged 60–85 years, with an average age of $68.2\pm 11.3$ years); and NHHT group ($n=150$) (defined as EH with Hcy levels $<10\mu$mol/L, including 77 men and 73 women aged 60–85 years, with an average age of $67.3\pm 11.7$ years).

No statistically significant differences were found between the two groups in terms of age, sex, medical history, long-term living environment, dietary habits, or use of regular antihypertensive medication. The study was approved by the medical ethics committee of our institution, and all patients and their families provided informed consent.

2.2. Research methods

2.2.1. Measurement of biochemical parameters

Fasting venous blood samples (6mL) were collected in the morning from patients with hypertension. The plasma was separated by centrifugation within 2h of collection. Biochemical analyzers were employed to measure Hcy, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC) levels, and liver and renal function parameters. All tests were conducted in strict accordance with the manufacturer’s instructions for the respective reagent kits.

2.2.2. Blood pressure monitoring

All participants underwent a 24h continuous blood pressure monitoring. The average SBP and DBP during the monitoring period were recorded.

2.2.3. Echocardiographic assessment

The cardiac structure and function were evaluated using a Philips fully digital intelligent color Doppler ultrasound device equipped with a 1–5MHz probe (SGCART model, Xining First People’s Hospital). The parameters measured included left atrial dimension (LA), interventricular septal thickness (IVST), left ventricular end-diastolic dimension (LVEDD), left ventricular posterior wall thickness (LVPWT), and left ventricular ejection fraction (LVEF). Each parameter was measured over three successive cardiac cycles, and the average value was calculated. The left ventricular mass (LVM) and left ventricular mass index (LVMI) were computed using the Devereux correction formula.¹⁷

The LVM was calculated using the following equation:

The criterion for diagnosing left ventricular hypertrophy (LVH) was as follows:

2.3. Statistical analysis

The statistical analysis of data was performed using GraphPad Prism 8.0. The Shapiro–Wilk test was used to assess the distribution of the continuous variables; all data conformed to a normal distribution. Continuous variables were expressed as mean ± standard deviation ($\bar{x}\pm S$). The categorical data were analyzed using the chi-square test, and the comparisons between groups were conducted using the t-test. Pearson’s correlation was employed for correlation analysis. A P-$\mathrm{\text{value}}<0.05$ indicated a statistically significant difference.

3. Results

3.1. The clinical information

A comparison of the clinical information between the HHT and NHHT groups revealed no statistically significant differences in general clinical parameters such as hypertension duration, age, sex ratio, smoking status, DBP, TC, TG, HDL-C, LDL-C, and liver and renal function levels ($p>0.05$). However, the HHT group exhibited significantly higher SBP and Hcy levels compared with the NHHT group ($p<0.05$). The results are presented in Table 1.

3.2. Comparison of antihypertensive medication use

The results revealed no notable differences in antihypertensive medication use between the HHT and NHHT groups ($p>0.05$). The results are presented in Table 2.

3.3. Comparison of echocardiographic parameters

The results also revealed no significant differences in LA, LVEDD, or LVEF between the two groups. However, the HHT group demonstrated significantly higher LVPWT, IVST, and LVMI compared with the NHHT group ($p<0.05$, Table 3). Furthermore, the prevalence of LVH was markedly higher in the HHT group, with 118 cases (78.7%) versus 75 cases (50.0%) in the NHHT group (${\chi }^2=5.183$, $p<0.0001$). These findings underscored the association of HHT with more pronounced left ventricular structural changes.

3.4. Correlation analysis of LVMI with Hcy and SBP

Pearson’s correlation analysis revealed a positive correlation between LVMI and both Hcy ($r=0.386$, $p<0.001$) and SBP levels ($r=0.536$, $p<0.001$). The results are presented in Table 4.

4. Discussion

Hypertension is one of the leading health threats globally. Also, HHT has garnered increasing attention due to its close association with cardiovascular and cerebrovascular complications as well as peripheral vascular sclerosis. However, global awareness, control rate, and medication adherence for HHT remain suboptimal. This study enrolled elderly patients with EH to compare the cardiac structural features between HHT and NHHT groups.

Elevated blood pressure increases the cardiac load in patients with HHT. The hemodynamic burden of hypertension further escalates, particularly in the presence of myocardial infarction, cardiomyopathy, or myocarditis, potentially leading to significant structural and functional cardiac changes in the heart and ultimately resulting in heart failure.¹⁸ Our study revealed that SBP was notably higher in the HHT group than in the NHHT group, aligning with previous findings.^19,20 For instance, Kharlamova and Il’icheva²¹ identified a positive correlation between Hcy levels, LVMI, and left ventricular thickness.

The echocardiographic results in our study revealed that the LVPWT, IVST, and LVMI were significantly higher in the HHT group than in the NHHT group. LVMI, as a sensitive and precise marker, provided a reliable reflection of the structural changes in the ventricles. These findings aligned with those of Yuan,²² who compared left ventricular structural parameters using echocardiography among HHT, NHHT, and healthy control groups. They observed that IVST, LVPW, LVEDD, and LVMI were significantly elevated in both HHT and NHHT groups compared with the control group. Therefore, it was inferred that structural remodeling and hypertrophy of the left ventricle and interventricular septum were more severe in HHT, which was likely due to the combined effects of hypertension and elevated Hcy levels. The limited capacity of cardiomyocytes to metabolize Hcy further exacerbated myocardial damage, leading to hypertrophy, interstitial fibrosis, and impaired left ventricular diastolic function.

No significant differences were observed in LA diameter, LVEDD, or LVEF between the two groups. This might be due to factors such as fluid retention and valvular regurgitation, which reduced the sensitivity and specificity of these parameters. Several reasons could explain these findings. First, the limited sample size might have constrained the statistical power to detect minor differences in these parameters. Second, the study was based solely on Hcy levels and hence might not fully account for other potential contributors to cardiac remodeling, such as the duration and severity of hypertension or additional metabolic disorders. Third, the influence of medication use, particularly antihypertensive and lipid-lowering drugs, might have masked the differences in these parameters between the two groups. Additionally, fluid retention and valvular regurgitation reduced the sensitivity and specificity of these parameters. Future studies should consider stratifying patients based on these factors to minimize potential biases. Further, our study identified a positive correlation between LVMI, the most sensitive index of cardiac ultrasound, and both Hcy and SBP. This highlighted the critical role of Hcy in left ventricular remodeling. Therefore, monitoring and controlling Hcy levels and managing blood pressure are essential in preventing ventricular remodeling and mitigating the adverse outcomes of HHT. These findings offer new perspectives on the clinical management of hypertension and a foundation for future investigations.

This study had several limitations. First, Hcy metabolism was influenced by various factors, such as renal dysfunction, which affected Hcy levels. The blood creatinine level alone may not accurately reflect renal function in patients with normal serum creatinine but decreased glomerular filtration rate. Second, the study focused on only elderly patients, and, therefore, the results might not be applicable to other age groups. Additionally, the limited sample size could introduce bias and restrict the applicability of the findings. Future studies should include larger sample sizes and involve multi-center investigation to further validate these results. Finally, the cross-sectional design of this study prevented the evaluation of the long-term impact of HHT on cardiovascular complications and cardiac structural changes.

5. Conclusion

This study showed that HHT caused more pronounced cardiac target-organ damage compared with NHHT, as evidenced by higher SBP, LVPWD, IVSD, and LVMI. The coexistence of hypertension and elevated Hcy level exerted a synergistic impact on left ventricular remodeling. These findings underscored the importance of early identification and intervention for HHT. Proactive management of Hcy, alongside effective blood pressure control, is crucial for preventing ventricular remodeling and reducing the occurrence of cardiovascular complications.

Our study highlighted the clinical relevance of Hcy and LVMI in HHT; however, its cross-sectional design restricted the evaluation of long-term outcomes. Future studies with larger cohorts and extended follow-up should be conducted to better understand the relationship between HHT, cardiac remodeling, and cardiovascular events. These efforts may help refine hypertension management strategies and improve clinical outcomes for patients with HHT.

Acknowledgments

This study was supported by the Basic Scientific Research Project of Hebei Provincial Department of Education (Grant No. JJC2024059) and the Xining Municipal Science and Technology Bureau (Grant No. 2017-k-07).

ORCID

Jiyu Yang  https://orcid.org/0009-0007-3914-5871

Zongjin Li  https://orcid.org/0000-0003-2134-2651

Wu Wang  https://orcid.org/0009-0007-0776-0247

Qijuan Li  https://orcid.org/0009-0007-0483-5055

Chengying Yan  https://orcid.org/0009-0002-3021-5056

Ye Lin  https://orcid.org/0009-0007-0633-9151

Dongmei Liu  https://orcid.org/0000-0002-6960-7412