Study on the evaluation of left atrial structure and function in patients with H-type hypertension using 4D automated left atrial quantitative

Abstract

Background

This study employed four-dimensional automated left atrial quantitative analysis (4D Auto LAQ) technology to assess left atrial structure and function in patients with H-type hypertension and to investigate the impact of serum homocysteine (Hcy) level on the left atrium in patients with primary hypertension.

Methods

A total of 173 patients with primary hypertension newly diagnosed between December 2023 and December 2024 were enrolled and divided into two groups: H-type hypertension (n = 85) and non-H-type hypertension (n = 88). Additionally, 60 healthy volunteers were recruited as the control group.

Results

The results showed that compared with the non-H-type hypertension group and the control group, the H-type hypertension group exhibited statistically significant differences in Hcy, total cholesterol, triglycerides, estimated glomerular filtration rate (eGFR), and uric acid (p < 0.05). Additionally, there was a decrease (p < 0.05) in left atrial reservoir systolic longitudinal strain (LASr), left atrial systolic longitudinal strain (LASct), left atrial reservoir systolic circumferential strain (LASr-c), and left atrial systolic circumferential strain (LASct-c). Multiple linear regression analysis identified plasma Hcy levels as an independent associated factor for decreased left atrial strain parameters, including LASr (β=-0.246, p < 0.001), LASct (β=-0.279, p < 0.001), LASr-c (β=-0.333, p < 0.001), and LASct-c (β=-0.303, p < 0.001).

Conclusions

In conclusion, patients with H-type hypertension have decreased left atrial strain parameters, and when serum Hcy levels rise, the degree of strain dysfunction gradually gets worse. This suggests that these parameters could be used as an early indicator of left atrial myocardial injury in patients with H-type hypertension.

Introduction

Hypertension serves as a crucial risk factor linked to cardiovascular and cerebrovascular diseases, possessing the potential to inflict varying degrees of damage on target organs, such as the brain, heart, kidneys, eyes, and arteries [1]. In recent years, hypertension has emerged as one of the primary challenges in the prevention and control of chronic diseases in China. A 2018 study conducted on a prospective cohort of 12,952 Chinese adults indicated that the age-standardized prevalence of hypertension in China demonstrated an overall upward trend from 1993 to 2015 [2]. Epidemiological data suggest that approximately three-quarters of Chinese patients diagnosed with essential hypertension also present with hyperhomocysteinemia (HHcy) [3].

HHcy, a pathological condition characterized by serum homocysteine (Hcy) ≥ 10 µmol/L, is a relatively independent influence on a wide range of cardiovascular and cerebrovascular diseases [4, 5]. Studies have shown that HHcy is significantly associated with the development of cardiovascular and cerebrovascular diseases and their adverse outcomes. Its pathophysiological mechanisms may be related to factors such as Hcy-induced vascular endothelial cell damage, induction of oxidative stress, and lipid metabolism disorders [6–8]. The dual and synergistic effects of hypertension and HHcy significantly increase the probability of cardiovascular events and affect the prognosis of cardiovascular and cerebrovascular diseases [5, 9, 10]. In a prospective case-control study involving 39,165 follow-up Chinese adults, it was discovered that hypertensive patients with HHcy exhibited an 11.7-fold and 10.7-fold elevation in the risk of stroke and stroke-related mortality, respectively [11]. Based on the clinical characteristics of this type of hypertensive patients in China, and to emphasize their potential risks and hazards, scholars in the medical field in China have proposed to define primary hypertension accompanied by HHcy as H-type hypertension [12].

The left atrium (LA) plays a crucial role in the maintenance of normal cardiac function, with its primary function being the regulation of left ventricular filling [13]. Due to its anatomical structure, which is marked by a thin myocardial wall, the LA exhibits a limited compensatory capacity for hemodynamic load, resulting in earlier structural and functional alterations compared to the left ventricle [14, 15]. Recent studies have further confirmed that the LA reservoir and contraction strain provide more accurate reflections of left ventricular filling pressures as well as left ventricular longitudinal strain [16].

It has been demonstrated that early changes in left atrial strain function in hypertensive patients are prioritized over changes in left atrial volume, followed by further progression to LA dilatation, subclinical left ventricular dysfunction, and ultimately heart failure [17]. Therefore, considering the high prevalence of H-type hypertension and the elevated risk of cardiovascular events, an early and systematic evaluation of LA structure and function in patients with H-type hypertension can facilitate the timely determination of the extent of myocardial damage. Particularly, the left atrial strain function holds significant research value and is highly valuable in assisting with the optimization of treatment regimens and prognostic risk assessment in clinical practice.

Echocardiography, as a non-invasive clinical procedure with dynamic real-time visualization and good cost-effectiveness, is often the preferred method for diagnosing and evaluating cardiac structure and function. With the continuous advancement of new ultrasound technologies, techniques such as 2D speckle tracking echocardiography (2D-STE), 3D speckle tracking echocardiography (3D-STE), and 4D automated left atrial quantitative (4D Auto LAQ) have been developed [18]. These techniques permit the measurement of volumetric parameters of the LA and functional parameters of the strain, thereby reflecting structural and functional changes.

The 4D Auto LAQ technology enables real-time, multi-angle simultaneous acquisition of structural information from the full cardiac cycle of LA through dynamic volumetric imaging with four-dimensional ultrasound. This technology analyzes the volumetric parameters and longitudinal and circumferential strain function parameters of LA through automated tracking algorithms, effectively circumventing the dependence of the traditional 2D-STE on the angle of image acquisition and the lack of temporal resolution of 3D-STE [19, 20]. It significantly improves the temporal and spatial resolution of the data and repeatability, rendering it more efficient, reliable, and accurate than the 2D and 3D speckle tracking techniques [21]. However, there is still a paucity of studies applying the 4D Auto LAQ technique to assess LA structure and function in patients with H-type hypertension.

In summary, this study aimed to apply the 4D Auto LAQ technique to assess the degree of LA structural alteration and functional impairment in patients with H-type hypertension. Furthermore, it sought to explore the impact of serum Hcy levels—as a diagnostic criterion—on the LA of patients with primary hypertension, and to evaluate the clinical utility of LA strain function parameters and volumetric parameters. The quantitative analysis of LA structure and function in patients with H-type hypertension has the potential to provide objective evidence for early diagnosis of LA myocardial damage and the development of early intervention strategies in clinical practice.

Materials and methods

Study population

This cross-sectional study involved 180 patients with the initial diagnosis of essential hypertension who attended the Second Affiliated Hospital of Nanchang University from December 2023 to December 2024 were included. Sixty healthy volunteers matched with the case group in terms of age, sex, body mass index (BMI), and heart rate, and normalized by echocardiography, as well as the exclusion of hypertensive disorders, HHcy, and other organic diseases, were also collected as a normal control group.

The study was reviewed and approved by the Biomedical Research Ethics Committee of the Second Affiliated Hospital of Nanchang University (Ethics Approval No. 202492). All data was extracted from electronic medical records and analyzed in accordance with the principles of the Declaration of Helsinki. This study did not utilize protected health information and ensured the de-identification of all data, thereby eliminating the requirement for patient-informed consent.

Inclusion criteria

1. All collected patients with primary hypertension met the diagnostic criteria outlined in the Chinese Guidelines for the Prevention and Treatment of Hypertension (2024 revision) [22]: three standardized measurements of office blood pressure on non-same days without the use of antihypertensive medication, which were consistent with a systolic blood pressure (SBP) ≥ 140 mmHg and/or a diastolic blood pressure (DBP) ≥ 90 mmHg. Patients should first sit down and rest for five minutes before having their blood pressure measured. The measurement should be taken 30–60 s later, and the average of two readings should be recorded. If the difference between two readings of SBP or DBP is more than 10 mmHg, the measurement should be repeated, and the average of three readings should be recorded. Secondary factors should be excluded by comprehensive clinical evaluation (e.g., plasma renin activity, blood and urine aldosterone, blood and urine cortisol, renal artery ultrasonography, etc.).

2. Left ventricular ejection fraction (LVEF) ≥ 50%;

3. Sinus rhythm;

4. Age ≥ 18 years;

5. Complete relevant blood biochemical tests and clinical examination results, with complete data.

Exclusion criteria

• 6.Previous history of coronary artery disease, or diagnosis of coronary artery disease by clinical assessment at this visit: coronary artery stenosis of more than 50% on coronary CT, coronary imaging, or coronary angiography;
• 7.Severe organic heart disease, such as severe valvular heart disease and dilated cardiomyopathy;
• 8.Severe liver or kidney disease;
• 9.Use of drugs that affect serum Hcy levels, such as folic acid and vitamins, within the last 1 month;
• 10.Study subjects with substandard image quality of transthoracic echocardiography.

Grouping of study subjects

In the present study, the screened subjects with essential hypertension (n = 173) were typed according to the relevant diagnostic criteria [12]: cases with serum Hcy concentration ≥ 10 µmol/L were included in the H-type hypertension group (n = 85); cases with serum Hcy < 10 µmol/L were categorized as the non-H-type hypertension group (n = 88). The flowchart of study participant enrollment is shown in Fig. 1.

Fig. 1.

Flowchart for the selection of research subjects

Technology and methodology

Two-dimensional echocardiography

In the study, all subjects were systematically evaluated by transthoracic two-dimensional echocardiography, and the acquisition and measurement of the relevant parameters strictly followed the standardized procedures established in the current edition of the guidelines for transthoracic echocardiography in adults [23].

The subject was placed in the left lateral position, connected to an electrocardiogram, and instructed to breathe calmly. The left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), interventricular septum thickness (IVST), and left ventricular posterior wall thickness (LVPWT) were measured in parasternal left ventricular long-axis view, using the M5s probe of a GE Vivid E95 ultrasound machine with a probe frequency of 2.0-4.5 MHz. LVEF was calculated by Simpson’s method.

In apical 4-chamber cardiac views, the peak early diastolic mitral flow velocity (E) was measured using pulsed Doppler, and the average of the peak early diastolic motion velocities of the septal and lateral wall sides of the mitral annulus (e’) was measured by switching to the tissue Doppler mode, and the ratio of E/e’ was calculated [24].

4D automated left atrial quantitative

The subject was placed in the left lateral position, connected to the electrocardiogram, instructed to breathe calmly, and used a GE Vivid E95 ultrasound 4 V probe with a probe frequency of 1.0–5.0 MHz placed at the apex of the heart, selecting the three-plane splicing mode, and then adjusting the instrument gain, depth, and focus functions to make the image focus on the LA in four-chamber, three-chamber, and two-chamber views, and then switching the instrument to the four dimensions. The ultrasound frame rate was adjusted to be not less than 40% of the subject’s heart rate and at least 25 frames per second to achieve the best image quality. The four-dimensional images of six consecutive cardiac cycles were acquired and stored.

Import the image data into the EchoPAC 204 workstation, select the 4D Auto LAQ analysis mode, adjust the angle and position of the image to place the marking point at the center of the mitral annulus in the 4-chamber, 3-chamber, and 2-chamber views, and then click on Review. The workstation will automatically identify and outline the endocardial boundary of the LA. When the system does not recognize the endocardial boundary well, it can manually adjust the endocardial boundary of the LA at different times to exclude the pulmonary veins and the left atrial appendage. Clicking on Result, the workstation will automatically display all the LA volumetric parameters and strain function parameters obtained from the 4D Auto LAQ analysis.

Volume parameters include: left atrial minimum volume (LAVmin), left atrial maximum volume (LAVmax), left atrial pre-systolic volume (LAVpreA), left atrial volume index (LAVI), left atrial ejection volume (LAEV), and left atrial ejection fraction (LAEF). The strain function parameters include: left atrial reservoir longitudinal strain (LASr), left atrial conduit longitudinal strain (LAScd), left atrial contraction longitudinal strain (LASct), left atrial reservoir circumferential strain (LASr-c), left atrial conduit circumferential strain (LAScd-c), left atrial contraction circumferential strain (LASct-c) [25]. The positive and negative values of the strain function parameter are indicative of the direction of myocardial motion. Due to the cyclic changes in left atrial motion, during the reservoir phase, the LA diastolizes the myocardium to store blood, and the strain function parameter displays a positive strain value; whereas in the pipeline and systolic phases, the LA contracts the myocardium to fill the left ventricle, and the strain function parameter displays a negative strain value at this time.

Statistical analysis

It was analyzed using SPSS 27.0 software. Normality of the measures was assessed by normality tests, with normally or approximately normally distributed data expressed as mean ± standard deviation and non-normally distributed data expressed as median (interquartile spacing). Categorical data were expressed as frequencies and percentages (n, %). Post hoc multiple comparisons were performed using one-way ANOVA with Bonferroni correction for measurement data among the three study groups; categorical data were compared using chi-square tests. Correlations between different parameters were quantified by Spearman correlation analysis.

To investigate the independent factors associated with 4D Auto LAQ parameters, this study employed multiple linear regression analysis. Based on literature review and clinical experience, potential predictive variables were preliminarily screened, primarily including: demographic characteristics (such as age, gender), blood pressure, renal function indicators (such as eGFR), metabolic indicators (such as Hcy, UA, blood lipids), and left ventricular diastolic function parameters [26–28]. Perform univariate analysis on the aforementioned variables, selecting those with P < 0.1. Core variables with established significant clinical importance (e.g., age, blood pressure) are also pre-selected for inclusion in the final model. Perform multicollinearity diagnostics using the variance inflation factor (VIF) for all candidate independent variables to ensure model stability. Incorporate the filtered variables into a multiple linear regression model and employ stepwise regression to identify independent influencing factors. This approach aims to statistically identify predictors that remain significantly associated with the outcome variable after controlling for known clinically important factors, while avoiding potential bias that may arise from relying solely on univariate p-values.

Intraclass correlation coefficients (ICC) were calculated to assess the intra- and inter-observer agreement of the 4D Auto LAQ parameters, respectively, and ICC > 0.75 was considered good agreement. P < 0.05 indicates statistically significant differences.

General clinical information and blood biochemical test indices

General clinical data: age, gender, heart rate, BMI, SBP, DBP, and hypertension classification.

Blood biochemical tests: Hcy, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), estimated glomerular filtration rate (eGFR), and uric acid (UA).

Result

Comparison of clinical data in control, non-H-type hypertension, and H-type hypertension groups

This was a cross-sectional study, and finally 233 study subjects were included after screening by exclusion criteria, including 60 in the control group (32 males and 28 females), 88 in the non-H-type hypertension group (52 males and 36 females), and 85 in the H-type hypertension group (54 males and 31 females). As shown in Table 1, the results of the comparison of the clinical data of the control, non-H-type hypertension, and H-type hypertension groups are summarized. One-way ANOVA and chi-square test showed that there were no statistically significant differences in age, gender, BMI, heart rate, and LDL-c among the control, non-H-type hypertension, and H-type hypertension groups (P > 0.05), whereas there were between-group differences in SBP, DBP, Hcy, TC, TG, HDL-c, eGFR, and UA among the three groups (P < 0.05). There was no statistically significant difference in SBP, DBP, and hypertension grading in the H-type hypertension group compared to the non-H-type hypertension group (P > 0.05). In blood biochemical tests, Hcy, TC, TG, and UA were increased (P < 0.05), and eGFR was decreased (P < 0.05) in the H-type hypertension group as compared to the non-H-type hypertension group and the control group. Significant variability in HDL-c was seen only between the H-type hypertension group and the control group (P < 0.05).

Table 1.

Comparison of clinical data between the control group, non-H-type hypertension group, and H-type hypertension group

Clinical information	Control (n = 60)		Non-HTH (n = 88)	HTH (n = 85)	F/χ²		P
Age (years)	44.98 ± 12.34		46.90 ± 10.74	47.65 ± 12.67	0.907		0.405
Sex (n, %)					1.515		0.469
Male	32(53.33)		52(59.09)	54(63.53)
Female	28(46.67)		36(40.91)	31(36.47)
BMI (kg/m2)	24.60 ± 2.01		24.96 ± 2.35	25.47 ± 2.43	2.633		0.074
HR (beats/min)	73.92 ± 9.47		76.35 ± 10.08	74.82 ± 10.57	1.113		0.330
SBP (mmHg)	116.90 ± 8.45		163.47 ± 15.55*	162.67 ± 17.34*	216.357		< 0.001
DBP (mmHg)	73.68 ± 6.58		102.08 ± 10.10*	103.29 ± 11.62*	189.361		< 0.001
Hypertension grading (n, %)					0.136		0.934
Grade 1	-		31(35.23)	28(32.94)
Grade 2	-		30(34.09)	31(36.47)
Grade 3	-		27(30.68)	26(30.59)
Hcy (µmol/L)	8.27 ± 0.71		8.81 ± 0.87	15.85 ± 5.14*#	141.848		< 0.001
TC (mmol/L)	4.62 ± 0.90		4.75 ± 0.99	5.22 ± 1.03*#	7.982		< 0.001
TG (mmol/L)	1.42 ± 0.55	1.68 ± 0.93		2.05 ± 1.08*#	8.874	< 0.001
HDL-c (mmol/L)	1.30 ± 0.33	1.24 ± 0.29		1.17 ± 0.26*	4.178	0.017
LDL-c (mmol/L)	2.70 ± 0.71	2.74 ± 0.93		2.91 ± 0.77	1.379	0.254
eGFR (mL/min/1.73 m²)	102.55 ± 14.61	98.00 ± 15.15		90.34 ± 15.76*#	12.073	< 0.001
UA (µmol/L)	343.48 ± 74.45	368.89 ± 97.91		412.48 ± 95.27*#	10.753	< 0.001

*P < 0.05 compared with the control group; ^#P < 0.05 compared with the non-H-type hypertension group. HTH H-type hypertension, BMI Body mass index, SBP Systolic blood pressure, DBP Diastolic blood pressure, Hcy Homocysteine, TC Total cholesterol, TG Triglyceride, HDL-c High-density lipoprotein cholesterol, LDL-c Low-density lipoprotein cholesterol, eGFR Estimated glomerular filtration rate, UA Uric acid

Comparison of 2D echocardiographic parameters in control, non-H-type hypertension, and H-type hypertension groups

As shown in Table 2, there were no significant intergroup differences in LVEDD, LVESD, LVEF, and E in the control, non-H-type hypertension, and H-type hypertension groups (P > 0.05), while the differences in LAD, IVST, LVPWT, e’, and E/e’ were statistically significant (P < 0.05). Among them, compared with the control group, LAD and E/e’ were increased (P < 0.05), IVST and LVPWT were thickened (P < 0.05), and e’ was reduced (P < 0.05) in both the non-H-type hypertension group and the H-type hypertension group; the differences in LAD, IVST, LVPWT, e’, and E/e’ between the non-H-type hypertension group and the H-type hypertension group were not statistically significant (P > 0.05).

Table 2.

Comparison of 2D echocardiographic parameters in control, non-H-hypertensive, and H-hypertensive groups

Variables	Control (n = 60)	Non-HTH (n = 88)	HTH (n = 85)	F	P
LAD (mm)	34.70 ± 2.88	36.51 ± 3.40*	36.75 ± 3.62*	7.468	< 0.001
LVEDD (mm)	45.80 ± 3.44	46.17 ± 3.57	46.89 ± 3.11	2.026	0.134
LVESD (mm)	29.57 ± 2.85	29.51 ± 2.67	30.16 ± 2.31	1.604	0.203
IVST (mm)	8.83 ± 1.20	10.34 ± 1.27*	10.61 ± 1.27*	39.288	< 0.001
LVPWT (mm)	8.28 ± 0.88	9.41 ± 1.08*	9.72 ± 1.20*	32.874	< 0.001
LVEF (%)	64.88 ± 4.21	65.19 ± 3.72	64.81 ± 3.26	0.255	0.775
E (cm/s)	71.15 ± 16.95	71.39 ± 16.72	67.68 ± 14.41	1.295	0.254
e’ (cm/s)	10.31 ± 2.28	8.99 ± 1.57*	8.46 ± 2.27*	14.794	< 0.001
E/e’	7.06 ± 1.60	8.03 ± 1.72*	8.35 ± 2.08*	9.066	< 0.001

*P < 0.05 compared with the control group; #P < 0.05 compared with the non-H-type hypertension group. HTH H-type hypertension, LAD Left atrial anteroposterior diameter, LVEDD Left ventricular end-diastolic internal diameter, LVESD Left ventricular end-systolic internal diameter, IVST Interventricular septal thickness, LVPW Left ventricular posterior wall thickness, LVEF Left ventricular ejection fraction, E mitral valve early diastolic peak blood flow velocity, e’ Mean early diastolic peak motion velocity of the septal and lateral wall sides of the mitral annulus

Comparison of 4D auto LAQ parameters in control, non-H-type hypertension, and H-type hypertension groups

Table 3 reflects the comparative results of the LA volume parameters and strain function parameters obtained from the 4D Auto LAQ in the control, non-H-type-hypertensive, and H-type-hypertensive groups. LA volume parameters showed that LAVmin, LAVmax, LAVpreA, and LAVI were higher in the non-H-type hypertension group and the H-type hypertension group than in the control group (P < 0.05), whereas LAEF was lower (P < 0.05). The differences in LAVmin, LAVmax, LAVpreA, and LAVI were not statistically significant in the H-type hypertension group compared to the non-H-type hypertension group (P > 0.05). LA strain function parameters showed that LASr, LAScd, LASct, LASr-c, and LASct-c were lower in the non-H-type hypertension group and the H-type hypertension group compared with the control group (P < 0.05). LASr, LASct, LASr-c, and LASct-c were more severely impaired in the H-type hypertension group compared with the non-H-type hypertension group (P < 0.05). The difference in LAEV and LAScd-c between the three groups was not statistically significant (P > 0.05). Figure 2 demonstrates the results manipulation interface when applying the 4D Auto LAQ technique to the analysis of the control, non-H-type hypertension, and H-type hypertension groups of study subjects.

Table 3.

Comparison of 4D auto LAQ parameters in control, non-H-type hypertension, and H-type hypertension groups

Variables	Control (n = 60)	Non-HTH (n = 88)	HTH (n = 85)	F	P
LAVmin(ml)	18.73 ± 3.97	22.48 ± 4.61*	23.76 ± 5.97*	18.445	< 0.001
LAVmax (ml)	42.15 ± 5.14	46.69 ± 7.03*	47.80 ± 9.64*	10.154	< 0.001
LAVpreA (ml)	27.05 ± 4.43	31.28 ± 5.89*	32.98 ± 7.53*	16.304	< 0.001
LAVI (ml/m2)	24.68 ± 3.70	26.93 ± 5.08*	27.08 ± 6.58*	4.152	0.017
LAEV(ml)	23.42 ± 3.65	24.22 ± 5.00	24.04 ± 5.72	0.481	0.619
LAEF(%)	55.72 ± 6.83	51.83 ± 7.06*	50.29 ± 7.37*	10.473	< 0.001
LASr(%)	27.62 ± 4.37	24.88 ± 4.26*	21.02 ± 4.17*#	44.136	< 0.001
LAScd(%)	-14.92 ± 3.84	-13.30 ± 4.05*	-12.67 ± 3.76*	6.025	0.003
LASct(%)	-13.07 ± 3.48	-11.62 ± 3.89*	-8.49 ± 3.21*#	30.596	< 0.001
LASr_c(%)	35.45 ± 5.55	31.92 ± 5.46*	26.74 ± 3.84*#	57.108	< 0.001
LAScd_c(%)	-14.30 ± 3.67	-13.43 ± 5.03	-12.81 ± 3.50	2.228	0.110
LASct_c(%)	-21.27 ± 4.95	-18.56 ± 5.19*	-14.05 ± 4.26*#	42.458	< 0.001

*P < 0.05 compared with the control group; ^#P < 0.05 compared with the non-H-type hypertension group. HTH H-type hypertension, LAVmin Left atrial minimum volume, LAVmax Left atrial maximum volume, LAVpreA Left atrial presystolic volume, LAVI Left atrial volumetric index, LAEV Left atrial ejection volume, LAEF Left atrial ejection fraction, LASr Longitudinal strain in left atrial storage phase, LAScd Left atrial canal phase longitudinal strain, LASct Left atrial systolic longitudinal strain, LASr-c Left atrial reservoir phase circumferential strain, LAScd-c Left atrial canal phase circumferential strain, LASct-c Left atrial systolic circumferential strain

Fig. 2.

4D Auto LAQ parameters in control group (A), non-H-type hypertension group (B), and H-type hypertension group (C)

Correlation analysis of 4D auto LAQ strain function parameters

The study employed Spearman’s correlation analysis to reveal an association between several indices and parameters of LA strain function. Table 4; Fig. 3 show the results of correlation analysis between LA strain function parameters and different variables in the non-H-type hypertension group and the H-type hypertension group. In the general clinical data, SBP was negatively correlated with LASr (r=-0.188, P = 0.013) and LASr-c (r=-0.282, P < 0.001); DBP was negatively correlated with LASr (r=-0.164, P = 0.031), LASr-c (r=-0.367, P < 0.001), and LASct-c (r=-0.210, P = 0.006). Among the blood biochemical tests, Hcy was negatively correlated with LASr (r=-0.385, P < 0.001), LASct (r=-0.398, P < 0.001), LASr-c (r=-0.431, P < 0.001), and LASct-c (r=-0.465, P < 0.001) (see Fig. 4). TC was negatively correlated with LASr (r=-0.309, P < 0.001), LASct (r=-0.248, P < 0.001) and LASr-c (r=-0.206, P = 0.006); TG was negatively correlated with LASr (r=-0.353, P < 0.001), LASct (r=-0.216, P = 0.004), LASr-c (r=-0.277, P < 0.001) and LASct-c (r=-0.207, P = 0.006); eGFR was positively correlated with LASr (r = 0.227, P = 0.003) and LASr-c (r = 0.174, P = 0.022); UA was negatively correlated with LASr (r=-0.383, P < 0.001), LASct (r=-0.292, P < 0.001), LASr-c (r=-0.266, P < 0.001) and LASct-c (r=-0.269, P < 0.001). E/e’, an index of left ventricular diastolic function, was negatively correlated with LASr (r=-0.239, P = 0.002), LASr-c (r=-0.284, P < 0.001), and LASct-c (r=-0.253, P < 0.001).

Table 4.

Correlation analysis of 4D auto LAQ strain function parameters in non-H-type-hypertension and H-type-hypertension groups

Variables	LASr		LASct		LASr-c		LASct-c
	r	P	r	P	r	P	r	P
Age	-0.123	0.107	0.122	0.110	-0.076	0.321	0.059	0.439
SBP	-0.188	0.013	-0.056	0.463	-0.282	< 0.001	-0.089	0.245
DBP	-0.164	0.031	-0.121	0.112	-0.367	< 0.001	-0.210	0.006
Hcy	-0.385	< 0.001	-0.398	< 0.001	-0.431	< 0.001	-0.465	< 0.001
TC	-0.309	< 0.001	-0.248	< 0.001	-0.206	0.006	-0.102	0.184
TG	-0.353	< 0.001	-0.216	0.004	-0.277	< 0.001	-0.207	0.006
HDL-c	0.119	0.118	0.136	0.074	0.135	0.077	0.124	0.104
eGFR	0.227	0.003	0.104	0.175	0.174	0.022	0.086	0.260
UA	-0.383	< 0.001	-0.292	< 0.001	-0.266	< 0.001	-0.269	< 0.001
E/e’	-0.239	0.002	-0.039	0.608	-0.284	< 0.001	-0.253	< 0.001

LASr Longitudinal strain in the left atrial reservoir phase, LASct Longitudinal strain in the left atrial systole phase, LASr-c Circumferential strain in the left atrial reservoir phase, LASct-c circumferential strain in the left atrial systole phase, SBP Systolic blood pressure, DBP Diastolic blood pressure, Hcy Homocysteine, TC Total cholesterol, TG Triglycerides, HDL-c High-density lipoprotein cholesterol, eGFR Estimated glomerular filtration rate, UA Uric acid, E mitral peak early diastolic blood flow velocity, e’ mean mitral annular septal and lateral wall side peak early diastolic motion velocity

Fig. 3.

Heatmap of spearman correlation of functional parameters of left atrial strain in the non-H-type hypertension group and the H-type hypertension group

Fig. 4.

Scatterplot of correlation of Hcy with LASr (A), LASct (B), LASr-c (C), and LASct-c (D), respectively

As shown in Table 5, after variable screening, the multivariate linear regression model was statistically significant. The analysis revealed the following independent negative correlations: Hcy was negatively correlated with LASr (β=-0.246, P < 0.001), LASct (β=-0.279, P < 0.001), LASr-c (β=-0.333, P < 0.001), and LASct-c (β=-0.303, P < 0.001). UA was negatively correlated with LASr (β=-0.268, P < 0.001), LASct (β=-0.162, P = 0.030), LASr-c (β=-0.136, P = 0.038) and LASct-c (β=-0.143, P = 0.047). E/e’ was negatively correlated with LASr (β=-0.209, P = 0.002), LASr-c (β=-0.207, P = 0.001) and LASct-c (β=-0.247, P < 0.001). DBP was negatively correlated with LASr-c (β=-0.307, P < 0.001) and LASct-c (β=-0.140, P = 0.042). TC was negatively correlated with LASr (β=-0.213, P = 0.001) and LASct (β=-0.197, P = 0.005). Age was negatively correlated with LASr (β=-0.159, P = 0.017) and LASr-c (β=-0.130, P = 0.045).

Table 5.

Multiple linear regression of 4D auto LAQ strain function parameters in non-H-type-hypertension and H-type-hypertension groups

Implicit variables	Variables	β	P
LASr	Age	-0.159	0.017
	DBP	-0.080	0.217
	Hcy	-0.246	< 0.001
	TC	-0.213	0.001
	UA	-0.268	< 0.001
	E/e’	-0.209	0.002
LASct	Age	0.061	0.399
	DBP	-0.036	0.614
	Hcy	-0.279	< 0.001
	TC	-0.197	0.005
	UA	-0.162	0.030
	E/e’	-0.100	0.163
LASr-c	Age	-0.130	0.045
	DBP	-0.307	< 0.001
	Hcy	-0.333	< 0.001
	TC	-0.087	0.160
	UA	-0.136	0.038
	E/e’	-0.207	0.001
LASct-c	Age	0.051	0.471
	DBP	-0.140	0.042
	Hcy	-0.303	< 0.001
	TC	-0.062	0.360
	UA	-0.143	0.047
	E/e’	-0.247	< 0.001

β-values are standardized regression coefficients. LASr Longitudinal strain during left atrial reservoir phase, LASct Longitudinal strain during left atrial systole, LASr-c Circumferential strain during left atrial reservoir phase, LASct-c Circumferential strain during left atrial systole, DBP Diastolic blood pressure, Hcy Homocysteine, TC Total cholesterol, UA Uric acid, E mitral valve early peak diastole blood flow velocity, e’ mean mitral annular septal and lateral wall side peak early diastolic motion velocity

4D auto LAQ consistency check of strain function parameters

In this study, 30 cases were selected for consistency testing from a sample of 233 cases using a random sampling method, where the 4D Auto LAQ strain function parameters of ultrasound images were measured and independently analyzed by the same measurer and by another senior practitioner, and subsequently assessed for intra-measurement and inter-measurement consistency by ICC. The results, as shown in Table 6, showed good agreement for all parameters, with intra-observer and inter-observer ICC values above 0.75.

Table 6.

4D auto LAQ strain function parameter consistency tests

Strain function parameters	Intra-observer			Inter-observer
	ICC	95% CI	P	ICC	95% CI	P
LASr	0.908	0.817–0.955	< 0.001	0.884	0.771–0.943	< 0.001
LAScd	0.804	0.629–0.901	< 0.001	0.888	0.778–0.945	< 0.001
LASct	0.873	0.752–0.938	< 0.001	0.896	0.793–0.949	< 0.001
LASr-c	0.935	0.789–0.975	< 0.001	0.905	0.804–0.891	< 0.001
LAScd-c	0.880	0.764–0.941	< 0.001	0.879	0.761–0.940	< 0.001
LASct-c	0.885	0.721–0.949	< 0.001	0.826	0.659–0.914	< 0.001

ICC Intracluster correlation coefficient

Discussion

According to epidemiological statistics, H-type hypertension patients account for about 80% of essential hypertension patients [3]. H-type hypertension is affected by the combination of hypertension and HHcy, and it has a higher incidence of cardiovascular events and poorer long-term outcomes [29]. The LA anatomically connects the four pulmonary veins to the left ventricle, playing a pivotal role in regulating cardiac filling [30]. Research indicates that abnormalities in LA strain parameters may represent earlier markers of remodeling-related cardiac remodelling compared to traditional two-dimensional echocardiographic measurements of LA structure and function [31]. Alterations in its structure and function are closely associated with the development and prognosis of cardiovascular diseases, and it has been demonstrated to be a significant biomarker for the progression of heart failure [32].

The core pathophysiological mechanism by which elevated Hcy levels cause LA dysfunction in hypertensive patients is a cascade reaction process in which Hcy serves as a key synergistic factor. Firstly, elevated Hcy directly damages vascular endothelial cells and cardiomyocytes by inducing oxidative stress and suppressing endogenous antioxidant pathways (such as Nrf2/HO-1), thereby exacerbating the vascular remodeling and increased afterload on the heart caused by hypertension itself [33–35]. Secondly, Hcy-mediated renal vascular injury and ischaemia impair renal function (decreased eGFR), leading to reduced clearance of Hcy and UA and consequently further elevating their serum levels [36]. UA interacts metabolically with Hcy through pathways such as inducing endothelial dysfunction, activating the renin-angiotensin system, and inhibiting nitric oxide synthase, thereby forming a vicious cycle [37]. The aforementioned processes are intricately linked with Hcy-mediated lipid metabolism disorders, inflammatory responses, and hypercoagulable states [8, 12, 38], collectively promoting the onset and progression of myocardial fibrosis (including the LA). This leads to reduced left ventricular diastolic compliance and elevated filling pressures, thereby subjecting the LA to prolonged abnormal pressure and volume overload. Consequently, myocardial injury and fibrosis occur, followed by functional decompensation manifegeneralizedeneralised reduction in strain parameters. Ultimately, this leads to marked structural enlargement of the LA and a reduction in LAEF.

In the present study, it was demonstrated that, apart from elevated Hcy, patients with H-type hypertension frequently exhibited increased TC, TG, and UA, along with decreased eGFR. Correlation analysis revealed that TC, TG, and UA were negatively correlated with several LA strain parameters, while eGFR was positively correlated. In multiple regression analysis, TC was independently correlated with LASr and LASct, although TG did not demonstrate a significant correlation with LA strain function parameters. However, previous studies have demonstrated that triglycerides and their related metabolites can serve as important independent risk factors in the assessment of cardiovascular disease risk [39]. UA levels were strongly associated with the risk of developing hypertension and were significantly positively associated with the risk of developing H-type hypertension [40]. Furthermore, research has reported that UA is independently associated with reduced strain function during the LA filling phase, consistent with the findings of this study [28]. This also indirectly confirms that eGFR, as an indicator of renal function, may possess a protective effect in conjunction with LA strain function.

Conventional 2D ultrasound showed that LAD, IVST, LVPWT, and E/e’ increased, and e’ decreased in the hypertension group versus the control group, whereas there was no significant difference in LVEDD, LVED, LVEF, and E between the three groups. 4D Auto LAQ volumetric parameters showed that the volume parameters LAVmin, LAVmax, LAVpreA, and LAVI increased in the hypertension group compared to the control group, while LAEF was decreased. This is similar to the findings of Sun et al. [41], suggesting that LA enlargement and impaired active emptying capacity in patients with essential hypertension precede the structural and systolic changes of the left ventricle, the mechanism of which may be the increase in cardiac afterload due to long-term hypertension, and the left ventricle needs to indirectly increase the load on the LA by compensating for the resultant diastolic decompensation. This ultimately results in the ejection function of the LA being diminished and structurally dilated. In addition, the LA strain function parameters LASr, LAScd, LASct, LASr-c, and LASct-c were reduced in the hypertension group, reflecting the reduced LA strain function due to chronic pressure loading [42, 43]. The multiple regression analysis conducted in this study indicated that age, DBP, and E/e’ are independently correlated with LA strain function parameters. In line with the extant research evidence, increasing age, heightened blood pressure, and left ventricular diastolic dysfunction are identified as significant determinants contributing to the impairment of LA strain function [26, 44].

In comparison with the non-H-type hypertension group, the values of LASr, LASct, LASr-c, and LASct-c were lower in the H-type hypertension group. This indicates that the LA myocardial function in the H-type hypertension group was more severely impaired, and the changes in strain function were especially prominent during the LA reservoir and systolic phases. Multiple regression analysis verified the significant correlation between serum Hcy levels and the aforementioned strain parameters, suggesting that the abnormal alterations in LA function among patients with H-type hypertension may be closely associated with the mechanism of Hcy-mediated myocardial injury [12, 45]. Zheng et al. [46] found that left ventricular diastolic function was significantly lower in patients with H-type hypertension compared to patients with non-H-type hypertension. Furthermore, it was discovered that serum Hcy levels were positively correlated with the degree of cardiac damage, suggesting that Hcy is a key synergistic factor in exacerbating cardiac damage in hypertensive patients. Notably, LA volume parameters did not differ between H and non-H hypertensive groups, suggesting that the functional impact of Hcy may precede structural remodeling. This study focuses on patients with H-type hypertension, selected for their distinct clinical high-risk profile and unique pathophysiological mechanisms. The controlled design demonstrates that under comparable blood pressure loads, elevated Hcy levels induce additional LA dysfunction. This underscores the necessity for routine screening and intervention of HHcy in hypertension management, providing imaging evidence to guide risk stratification and precision management.

The 4D Auto LAQ technology is based on full-volume three-dimensional ultrasound imaging. It does not rely on geometric model assumptions, overcomes angular limitations, and enables simultaneous, precise assessment of LA volume changes and strain function with higher spatio-temporal resolution and reproducibility [47]. The study findings indicated that, in comparison with conventional 2D ultrasound, the 4D Auto LAQ technique was capable of detecting reduced LA strain function parameters in patients with H-type hypertension when conventional parameters and LA volumes exhibited no disparities between the hypertensive groups. This finding implies that the 4D Auto LAQ technique may possess the ability to detect subclinical myocardial injury induced by Hcy at an earlier stage. The primary aim of this study is to investigate the feasibility and distinctive value of this emerging technology in patients with H-type hypertension. Consequently, this study offers preliminary evidence for the application of 4D Auto LAQ in the early functional assessment of individuals with H-type hypertension, establishing a methodological basis for future large-scale prognostic research.

The present study is a single-center cross-sectional study, which could not clarify the causal relationship between H-type hypertension and abnormal LA function. A large-scale multicenter prospective cohort study is needed to follow up and further investigate the causal association and prognostic significance of LA damage in H-type hypertension. Although the inclusion criteria for this study were a newly identified group of patients with essential hypertension, the usual lag in hypertensive patients’ knowledge of their condition may lead to an inaccurate course of the patient’s disease, which, in turn, ignores the impact of cardiac remodeling on LA due to disease progression. Furthermore, current clinical research on 4D Auto LAQ technology remains limited, and its clinical application value warrants further investigation.

This study has not yet considered the potential synergistic effects between primary hypertension and HHcy, which may exacerbate LA dysfunction. It is suggested that future studies may utilize 4D Auto LAQ technology to evaluate the synergistic interaction between hypertension and Hcy, with a view to further clarifying the extent of impact from different serum Hcy levels on the LA. This would establish a more comprehensive reference standard for assessing LA structure and function in patients with H-type hypertension and HHcy.

Conclusion

This study employed the 4D Auto LAQ technique to confirm that patients with H-type hypertension exhibit significant LA strain dysfunction before marked structural enlargement of the LA. This dysfunction manifests as reduced LASr, LASct, LASr-c, and LASct-c values, with the severity of impairment closely correlated with elevated serum Hcy levels. This suggests that homocysteine-aggravated LA functional impairment may precede overt structural remodeling. LA strain parameters may serve as early indicators of myocardial injury in the LA of H-type hypertensive patients, providing objective imaging evidence for formulating clinical early intervention strategies.

Abbreviations

DBP

Diastolic blood pressure

eGFR

Estimated glomerular filtration rate

Hcy

Homocysteine

HDL-c

High-density lipoprotein cholesterol

HHcy

Hyperhomocysteinemia

ICC

Intraclass correlation coefficients

IVST

Interventricular septum thickness

LA

Left atrial

LAD

Left atrial diameter

LAEF

Left atrial ejection fraction

LAEV

Left atrial ejection volume

LAScd

Left atrial conduit longitudinal strain

LAScd-c

Left atrial conduit circumferential strain

LASct

Left atrial contraction longitudinal strain

LASct-c

Left atrial contraction circumferential strain

LASr

Left atrial reservoir longitudinal strain

LASr-c

Left atrial reservoir circumferential strain

LAVI

Left atrial volume index

LAVmax

Left atrial maximum volume

LAVmin

Left atrial minimum volume

LAVpreA

Left atrial pre-systolic volume

LDL-c

Low-density lipoprotein cholesterol

LVEDD

Left ventricular end-diastolic diameter

LVEF

Left ventricular ejection fraction

LVESD

Left ventricular end-systolic diameter

LVPWT

Left ventricular posterior wall thickness

SBP

Systolic blood pressure

TC

Total cholesterol

TG

Triglycerides

UA

Uric acid

4D Auto LAQ

4D automated left atrial quantitative

Authors’ contributions

HX, conceptualization, writing original draft. WXL, methodology, resources. CSY, validation, writing original draft. MWH, software. WQQ, formal analysis. SZY, visualization. YCY, data curation. ZCQ, funding acquisition, writing-review & editing. All authors read and approved the final manuscript.

Funding

This research was funded by the National Natural Science Foundation of China, grant number 82260349.

Data availability

The data and materials are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

The study was reviewed and approved by the Biomedical Research Ethics Committee of the Second Affiliated Hospital of Nanchang University (Ethics Approval No. 202492). All data was extracted from electronic medical records and analyzed in accordance with the principles of the Declaration of Helsinki. This study did not utilize protected health information and ensured the de-identification of all data, thereby eliminating the requirement for patient-informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.