Relationship between ambulatory arterial stiffness index and the severity of angiographic atherosclerosis in patients with H-type hypertension and coronary artery disease

ABSTRACT

Objective

To investigate coronary artery disease (CAD) and its correlation with the ambulatory arterial stiffness index (AASI) in patients with H-type hypertension (essential hypertension combined with hyper-homocysteinemia) and coronary heart disease (CHD).

Methods

Patients with essential hypertension and CHD who were undergoing coronary angiography were enrolled. The general clinical data, biochemical indicators, ambulatory blood pressure monitoring results and coronary angiography results of the selected patients were collected, and the AASI and Gensini scores were calculated. According to homocysteine (Hcy) levels, the patients were divided into two groups: a study group and a control group. The differences in general clinical data, biochemical indexes, AASI scores and degree of coronary artery lesions between the two groups were compared. The correlation between the AASI and the Gensini score and the relationship between the AASI and the Gensini score of CAD and various factors were analyzed.

Results

Compared with the control group, the Hcy level in the study group was significantly increased (8.16 ± 2.33 vs 19.20 ± 2.36, P = .001). The 24-h diastolic blood pressure (DBP) in the study group was significantly lower than that in the control group (76.38 ± 9.33 vs 79.91 ± 9.25, P = .002), and the AASI was significantly higher than in the control group (0.62 ± 0.81 vs 0.420 ± 0.70, P = .001). The number of patients having coronary stenoses with a Gensini score of ≤ 38 was significantly lower in the study group than in the control group (21.3% vs 49.4%, P < .001). The number of patients with a Gensini score of ≥ 51 in the study group was significantly higher than in the control group (22.0% vs 18.8%, P < .001). There was a significant positive correlation between the AASI and the Gensini score in the study group (R = 0.732, P < .001). Hypertension duration (β = 0.168), diabetes history (β = 0.236), 24-h SBP (β = 0.122), 24-h DBP (β = -0.131), low-density lipoprotein cholesterol (β = 0.134) and Hcy (β = 0.233) were the influencing factors for AASI (P < .05). Both Hcy * AASI (β = 0.356) and Hcy × 24-h HR (β = 0.331) had a synergistic effect on the Gensini score (P = .017), with Hcy * AASI having a more significant effect on the Gensini score (P < .001).

Conclusion

The AASI was significantly increased in patients with H-type hypertension and CHD, which was associated with the severity of CAD. Therefore, Hcy levels and the AASI have a synergistic effect when evaluating the severity of CAD in patients with hypertensive CHD.

KEYWORDS:

• H-type hypertension
• ambulatory arterial stiffness index
• Gensini score
• coronary artery disease
• homocysteine

Introduction

Patients with essential hypertension and hyperhomocysteinemia (HHcy) are also defined as having H-type hypertension; it affects up to 75% of people and encompasses a large group of diseases that can lead to hypertensive target organ damage (1). Coronary atherosclerotic heart disease (CHD), as one of the most common types of target organ damage in patients with hypertension, has more severe coronary artery disease (CAD), a worse prognosis and higher mortality (2). Studies have shown that HHcy can increase the risk of cardiovascular disease. For every 5umol/L increase in Hcy level, the risk of coronary heart disease events increases by about 9% (3). Therefore, the early classification of CAD severity in patients with H-type hypertension and CHD and prompt intervention are particularly important in improving patient prognosis.

Currently, coronary angiography is the gold standard for assessing the severity of CAD (4), but because it is invasive and requires high equipment and operator skills, some primary hospitals do not perform it, and its clinical application is relatively limited. The ambulatory arterial stiffness index (AASI) is a quantitative index calculated from 24-h ambulatory blood pressure monitoring results and is an important additional method of assessing the severity of arteriosclerosis and CAD because of its noninvasive, economical and reproducible nature (5). Studies have shown that the AASI has an independent predictive value for an increased risk of cardiovascular events, cardiovascular mortality, and all-cause mortality in patients with atherosclerotic cardiovascular disease (6,7), and HHcy is also considered an independent risk factor for arterial stiffness and thromboembolic disease (8). However, few previous studies have investigated the relationship between the two and their potential interaction in the development of CAD in patients with hypertension and coronary heart disease (CHD). Therefore, this study aimed to investigate CAD in patients with H-type hypertension and CHD, analyze the correlation between the AASI and CAD and further investigate the role of the AASI in evaluating CAD in patients with hypertensive CHD. This will have important significance for the early prevention of the occurrence and development of CHD in clinical practice.

Materials and methods

Research subjects

This study was a retrospective study. Patients who were hospitalized in the Department of Cardiology of the Third People’s Hospital of Anyang from January 2018 to July 2020 who were diagnosed with essential hypertension and CHD and who underwent coronary angiography were selected as the study subjects. The inclusion criteria were as follows: (1) patients who met the diagnostic criteria of CHD (9), (2) patients who met the diagnostic criteria for dipper hypertension per the “Chinese Guidelines for the Prevention and Treatment of Hypertension” (2018 revised edition) (10), (3) patients who met the diagnostic criteria for essential hypertension per the “Chinese Guidelines for the Diagnosis and Treatment of Hypertension 2010” (11) (systolic arterial pressure ≥140 mmHg [1 mmHg = 0.133 kPa] or/and diastolic arterial pressure ≥90 mmHg on three or more different days), excluding secondary hypertension and (4) patients aged 18–80 years. The exclusion criteria were patients with (1) congenital heart disease, severe arrhythmia, heart failure, endocarditis, primary cardiomyopathy, valvular heart disease, etc., (2) coronary artery stenosis caused by non-coronary atherosclerosis, (3) cerebrovascular disease and mental illness, (4) severe infection (lungs and other systemic parts), (5) severe liver and kidney dysfunction, (6) severe malignant tumors and other rheumatic immune and connective tissue diseases and (7) nearly 2 weeks to take folic acid, vitamin B6 and other drugs affecting homocysteine (Hcy) metabolism.

A total of 320 patients were enrolled, including 145 males and 175 females. They were divided into two groups according to Hcy levels detected by blood biochemistry: The study group included patients with H-type hypertension and CHD (Hcy >15 µmol/L, n = 150), while the control group included patients with non-H-type hypertension and CHD (Hcy <15 µmol/L, n = 170) according to the diagnostic criteria of the “Chinese Guidelines for the Prevention and Treatment of Hypertension (Revised Edition 2018)” (10): plasma Hcy >15 µmol/L was diagnosed as HHcy. All selected patients provided signed informed consent, and this study was approved by the ethics committee of our hospital.

Methods

Biochemical assays

Serum creatinine, blood urea nitrogen, uric acid, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (ALT) and alanine aminotransferase (AST) were detected in all patients on the second day after admission. An Olympus AU270 automatic biochemical analyzer was operated by experienced laboratory physicians in our hospital, and detection was performed in strict accordance with the detection process specified in the manufacturer’s instruction manual. A Wuhan AK0016JULI5066 enzyme-linked immunosorbent assay kit was used to determine the concentration of Hcy in the samples.

Assessment of coronary artery lesions

All the participants underwent coronary angiography, and the number of diseased coronary arteries was counted. According to the angiography results, the Gensini score (12), which is commonly used internationally, was used to quantify the degree of coronary lesions as follows: 1 point: degree of vascular stenosis < 25%, 2 points: vascular stenosis 25%–49%, 4 points: vascular stenosis 50%–74%, 8 points: vascular stenosis 75%–89%, 16 points: vascular stenosis 90%–99%, 32 points: complete occlusion of blood vessels. For the coronary stenosis score, the Gensini score was multiplied by the corresponding coefficient (13).

AASI calculation

In all patients, the 24-h ambulatory blood pressure was measured using an automatic noninvasive ambulatory blood pressure measuring instrument once every 30 minutes; the daytime period was 06:00–22:00, and the nighttime period was 22:00–06:00. The effective blood pressure reading reached more than 85% of the number of times to be measured. Using systolic blood pressure (SBP) as an independent variable and diastolic blood pressure (DBP) as a dependent variable, a linear regression analysis was conducted to calculate the value of β: AASI = 1 - β.

Ambulatory blood pressure measurements

For 24 h ambulate blood pressure measurement, MGY-ABP1 (Beijing Meigaoyi Medical Equipment Co., Ltd., Beijing, China) ambulate blood pressure monitor was used uniformly. The day time was set at 6:00 to 22:00, and the measurement was made every 15 to 20 minutes. From 22:00 at night to 6:00 the next day, the measurement was made every 30 minutes. 24 h systolic blood pressure, 24 h diastolic blood pressure, and 24 h heart rate were observed to ensure effective blood pressure monitoring during the whole 24 h period, with at least one blood pressure reading every hour. Effective blood pressure readings should be at least 70% of the total number of times monitored, and blood pressure readings should be at least 20 during the day and at least 7 at night. The patient’s blood pressure was measured after a quiet rest for at least 5 minutes upon admission. The upper arm blood pressure was measured while the upper arm was placed at the heart level while sitting. The verified cuff electronic sphygmomanometer (Omron) was used to measure the blood pressure of the patient’s two upper arms, and the side with the higher blood pressure reading was taken as the upper arm. Repeat the blood pressure measurement at intervals of 1–2 minutes and record the average of the two readings. If the difference between the two readings is more than 5 mmHg, the blood pressure measurement should be repeated and the average of the three readings should be recorded (14).

Statistical analysis

All data were analyzed using the SPSS 21.0 software package. A Kolmogorov – Smirnov test was used to determine whether numerical variables conformed to a normal distribution, and it was confirmed that the numerical variables in this study all conformed to a normal distribution. The numerical variables were described in terms of mean ± standard, and comparisons between the two groups were performed using an independent-samples t test. Enumeration data were expressed as an example (%), and comparisons between groups were performed using an χ² test. Pearson’s correlation analysis and a multiple stepwise linear regression analysis were used to perform a correlation analysis (Spearman’s correlation analysis was used for data not conforming to a normal distribution). Multivariate linear regression test was used to analyze the influencing factors of AASI and Gensini-related in the study population, with gender and gender as adjustment variables. A value of P < .05 was considered statistically significant.

Result

Basic characteristics of research subjects

There was no significant difference in gender, age, body mass index (BMI), history of diabetes, course of hypertension, creatinine, urea nitrogen, serum uric acid, ALT, AST, TC, TG, LDL-C, HDL-C, admission SBP and DBP between the study group and the control group (P > .05). Compared with the control group, the Hcy level in the study group was significantly increased (8.16 ± 2.33 vs 19.20 ± 2.36), and the difference was statistically significant (P = .001) (see Table 1).

Table 1. Basic characteristics of included patients.

Variables	Control group (n = 170)	Study group (n = 150)	t/Z/${\chi }^2$ value	P value
Gender (male/female), %	80 (47.1)	65 (43.3)	0.231	.514
Age, year	69.97 ± 1.25	7.35 ± 9.33	-0.263	.912
BMI, kg/m^2	24.20 ± 3.10	23.79 ± 2.51	1.008	.242
Smoking	68 (4.0)	70 (46.7)	0.748	.387
Diabetes	48 (28.2)	46 (3.7)	1.071	.301
Course of coronary heart disease, year	3.0 (1, 7)	4.5 (3, 7)	9.44	.06
Hypertension course, year	7.84 ± 2.98	8.60 ± 3.60	1.805	.069
Serum creatinine, μmol/L	76.30 ± 2.74	68.78 ± 17.28	2.704	.794
Blood urea nitrogen, mmol/L	5.1 ± 1.71	4.10 ± 1.81	-0.873	.393
Blood uric acid, mmol/L	318.57 ± 86.42	328.29 ± 78.44	3.095	.342
Admission SBP, mmHg	139.45 ± 18.13	136.35 ± 16.76	-2.553	.102
Admission DBP, mmHg	75.60 ± 9.20	79.69 ± 9.52	-2.748	.007
AST, mmol/L	28.17 ± 1.30	3.72 ± 2.19	-1.167	.902
ALT, mmol/L	26.72 ± 2.18	26.13 ± 2.41	-0.172	.088
TG, mmol/L	1.39 ± .54	1.72 ± .71	-2.187	.103
TC, mmol/L	4.18 ± .95	4.29 ± .84	-0.838	.403
LDL-C, mmol/L	2.82 ± .85	3.49 ± .74	1.426	.084
HDL-C, mmol/L	2.16 ± .37	2.20 ± .34	1.179	.431
β-blockers	125 (73.5)	116 (77.3)	1.509	.201
ACEI/ARB	140 (82.4)	124 (82.7)	0.324	.569
CCB	81 (47.6)	70 (46.7)	0.311	.609
Diuretics	29 (17.1)	30 (2.0)	0.551	.458
Statins	170 (1.0)	150 (1.0)	-	-
Bayaspirin	170 (1.0)	150 (1.0)	-	-
Clopidogrel/Ticagrelor	170 (1.0)	150 (1.0)	-	-
Hcy, μmol/L	8.16 ± 2.33	19.20 ± 2.36	22.822	.001
24 h SBP, mmHg	134.19 ± 2.17	137.2 ± 3.23	1.231	.214
24 h DBP, mmHg	79.91 ± 9.25	76.38 ± 9.33	-3.263	.002
24 h PP, mmHg	52.95 ± 9.32	61.75 ± 11.02	-8.065	<.001
24 h HR, times/minute	64.20 ± 6.10	68.79 ± 7.51	1.908	.042
AASI	.420 ± .70	.62 ± .81	6.271	.001

Data are expressed as mean ± standard deviation or median (interquartile range) or n (%).

BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; PP: pulse pressure; AST: aspartate aminotransferase; ALT: Alanine aminotransferase; β-block: βreceptor blocker; TG: triglyceride; TC: Total cholesterol; LDL-C: low density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; ACEI: angiotensin converting enzyme inhibitor; ARB: Angiotensin receptor antagonist; CCB: calcium channel blocker; Hey: Homocysteine; AASI: ambulatory arterial stiffness index.

Ambulatory blood pressure parameters

There was no significant difference in 24-h SBP, 24-h PP and 24-h heart rate (HR) between the study group and the control group (P > .05). The 24-h DBP of the study group was significantly lower than that of the control group(76.38 ± 9.33 vs 79.91 ± 9.25), the AASI was significantly higher than in the control group (0.62 ± 0.81 vs 0.420 ± 0.70), and the differences had statistical significance (P = .002, P = .001). (see Table 1).

Coronary artery lesions

According to the results of coronary angiography, the Gensini score of each patient was calculated, and the degree of CAD was graded according to the tertile method: <38 points, 38–51 points, and > 51 points. The number of patients with a Gensini score of < 38 in the study group was significantly lower than that in the control group, and the difference had statistical significance (P < .05); the number of patients with a Gensini score of > 51 in the study group was significantly higher than that in the control group, and the difference had statistical significance (P < .05). However, there was no significant difference in the number of patients with a Gensini score of 38–51 between the two groups (P > .05) (see Table 2).

Table 2. Comparison of coronary artery lesions between two groups.

Observation indexes	Control group (n = 170)	Study group (n = 150)	${\chi }^2$ value	P value
Gensini scores			33.200	<.001
<38 points	84 (49.4)	32 (21.3)
38–51 points	53 (31.2)	52 (34.7)
>51 points	33 (19.4)	66 (44.0)

Data are expressed as n (%).

The AASI and the Gensini score

A bivariate correlation analysis was performed in the two groups, respectively, and there was a significant positive correlation between the AASI and the Gensini score in the study group (R = 0.732, P < .05), while there was no significant correlation between the AASI and the Gensini score in the control group (R = 0.136, P > .05) (see Table 3 and Figure 1).

Figure 1. Scatter plot of AASI and Gensini score in study group.

Table 3. Multiple linear regression analysis of variables and AASI.

Independent variable	β value	SE	βs value	t	P
Gender	0.012	0.016	0.036	0.737	.462
Age	0.001	0.001	0.06	1.213	.226
BMI	0.003	0.003	0.05	1.007	.315
Smoking history	-0.016	0.017	-0.047	-0.934	.351
Course of Hypertension	0.007	0.002	0.168	3.189	.002
History of diabetes	0.088	0.019	0.236	4.752	<.001
Blood creatinine	0.000	0.001	0.025	0.524	.601
Urea nitrogen	-0.007	0.005	-0.069	-1.394	.164
Blood uric acid	0.000	0	0.073	1.483	.139
TC	0.003	0.019	0.008	0.157	.875
TG	0.003	0.024	0.006	0.121	.904
LDL-C	0.035	0.013	0.134	2.684	.008
HDL-C	0.02	0.018	0.054	1.095	.274
Hcy	0.007	0.001	0.233	4.624	<.001
Admission SBP	-0.001	0.001	-0.038	-0.771	.442
Admission DBP	0.000	0.001	0.025	0.504	.615
24hSBP	0.002	0.001	0.122	2.428	.016
24hDBP	-0.003	0.001	-0.131	-2.65	.008
24hHR	-0.001	0.001	-0.055	-1.118	.264
24 h PP	0.009	0.021	0.036	1.361	.253

AASI: ambulatory arterial stiffness index; BMI: body mass index; TG: triglyceride; TC: Total cholesterol; LDL-C: low density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; Hcy: homocysteine; SBP: systolic blood pressure; DBP: diastolic blood pressure; HR: heart rate; PP: pulse pressure.

Multiple linear regression analysis of AASI influencing factors

The multivariate linear regression analysis of the AASI influencing factors was performed using the AASI as the dependent variable; gender, age, BMI, smoking history, diabetes history, hypertension course, serum creatinine, blood urea nitrogen, blood uric acid, TC, TG, LDL-C, HDL-C, Hcy, admission SDP/DBP, 24-h SBP, 24-h DBP, 24-h HR as independent variables and gender, smoking history and diabetes history as binary variables. For gender, males were assigned 1, and females were assigned 2, with nonsmoking history = 0, smoking history = 1 and no diabetes history = 0. For the diabetes history assignment, 1 was set as a dummy variable, and a multiple linear regression model was established. The results showed that the course of hypertension (β = 0.168), diabetes (β = 0.236), 24-h SBP (β = 0.122), 24-h DBP (β = -0.131), LDL-C (β = 0.134) and Hcy (β = 0.233) were the influencing factors for the AASI (P < .05) (see Table 4).

Table 4. Multiple linear regression analysis of variables and Gemini integral.

Independent variable	β value	SE	βs value	t	P
Gender	0.035	1.481	0.001	0.023	.981
Age	0.012	0.09	0.006	0.13	.897
BMI	0.147	0.245	0.027	0.598	.55
Smoking history	-2.522	1.527	-0.076	-1.651	.1
Course of Hypertension	0.145	0.211	0.034	0.688	.492
History of diabetes	4.741	1.732	0.129	2.737	.007
Blood creatinine	-0.063	0.046	-0.062	-1.372	.171
Urea nitrogen	-0.136	0.428	-0.015	-0.317	.751
Blood uric acid	-0.003	0.012	-0.013	-0.277	.782
TC	-1.114	1.692	-0.03	-0.659	.511
TG	2.772	2.18	0.057	1.272	.204
LDL-C	1.818	1.175	0.072	1.547	.123
HDL-C	1.882	1.656	0.051	1.136	.257
Hcy	1.363	0.128	0.515	10.64	<.001
Admission SBP	-0.003	0.071	-0.002	-0.037	.97
Admission DBP	0.045	0.078	0.026	0.571	.568
24hSBP	0.005	0.062	0.004	0.081	.935
24hDBP	0.039	0.09	0.02	0.436	.663
24hHR	-0.013	0.114	-0.005	-0.111	.912
AASI	17.089	5.184	0.174	3.297	.001
Hcy *24hSBP	0.053	0.117	0.079	0.453	.651
Hcy *24hDBP	0.169	0.154	0.717	1.1	.272
Hcy *24hHR	0.508	0.212	0.356	2.396	.017
Hcy*AASI	22.414	4.771	0.331	4.698	<.001

Sex and gender adjusted variables in the multiple linear regression variables.

AASI: ambulatory arterial stiffness index; BMI: body mass index; TG: triglyceride; TC: Total cholesterol; LDL-C: low density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; Hcy: homocysteine; SBP: systolic blood pressure; DBP: diastolic blood pressure; HR: heart rate.

Multiple linear regression analysis of Gensini-related influencing factors

The Gensini score was used as the dependent variable, and gender, age, BMI, smoking history, history of diabetes, duration of hypertension, serum creatinine, blood urea nitrogen, serum uric acid, ALT, AST, TC, TG, LDL-C, HDL-C, Hcy, admission SDP/DBP, 24-h SBP, 24-h DBP, 24-h HR and AASI were used as independent variables for a multiple linear regression analysis. The results showed that diabetes history (β = 0.129), Hcy (β = 0.515) and AASI (β = 0.174) were the influencing factors of the Gensini score (P < .05), as shown in Table 4. The interaction between Hcy and the ambulatory blood pressure parameters (Hcy *24-h DBP, Hcy × 24-h SBP, Hcy × 24-h HR, Hcy * AASI) was used as an interactive independent variable to establish a multiple linear regression model. The results showed that Hcy * AASI (β = 0.356) and Hcy × 24-h HR (β = 0.331) had a synergistic effect on the Gensini score (P < .05), while Hcy * AASI had a more significant effect on the Gensini score (P < .001) (see Table 5).

Table 5. Multiple linear regression analysis of interaction between Hey and ambulatory blood pressure parameters on Gensini score.

Independent variable	β value	SE	βs value	t	P
Hcy *24hSBP	0.053	0.117	0.079	0.453	.651
Hcy *24hDBP	0.169	0.154	0.717	1.1	.272
Hcy *24hHR	0.508	0.212	0.356	2.396	.017
Hcy*AASI	22.414	4.771	0.331	4.698	<.001

Sex and gender adjusted variables in the multiple linear regression variables.

SBP: systolic blood pressure; DBP: diastolic blood pressure; HR: heart rate; AASI: ambulatory arterial stiffness index.

Discussion

According to epidemiological data statistics from China, patients with H-type hypertension account for about 80.3% of the total number of patients with hypertension (15); accordingly, the prevention and treatment of hypertension in China should be focused on. Patients with H-type hypertension have a higher risk of target organ damage, including to the heart, brain and kidney, than patients without H-type hypertension (16). In particular, the disease is closely related to the occurrence of CAD and is considered to be an independent risk factor for cardiovascular disease. Arteriosclerosis is a very important predictor of cardiovascular and cerebrovascular events, such as myocardial infarction, stroke and heart failure, and is an abnormal embodiment of arterial structure and function and an important marker of arterial stiffness (17).

The assessment of arterial stiffness is being used increasingly in the clinical assessment of patients. Currently, the detection methods of arterial stiffness are divided into invasive and noninvasive tests (18). Invasive detection methods mainly include coronary angiography, intravascular ultrasound, computed tomography angiography and magnetic resonance angiography. Noninvasive detection methods mainly include pulse wave velocity, ankle – brachial index, cardio – ankle vascular index, pulse pressure, AASI and direct ultrasound detection. However, it is difficult for clinicians and researchers to select the methodology that best suits their specific use. Twenty-four-hour ambulatory blood pressure monitoring is widely used in clinical practice because of its low price, good repeatability and easy acceptance by patients, and clinicians and researchers are paying increasing attention to the value of the AASI in arteriosclerosis screening (5).

In this study, the AASI was used to indirectly reflect arterial vascular sclerosis by observing the magnitude of its value. The AASI of patients with H-type hypertension was much higher than that of patients without H-type hypertension, which is consistent with the findings of Yang et al (19). H-type hypertension may accelerate the occurrence and development of arteriosclerosis and is an important factor in target organ injury in hypertension. Therefore, in addition to blood pressure, pulse pressure and HR, which can affect the magnitude of their values by hemodynamic principles, the risk factors for arteriosclerosis may also affect the AASI (20). Patients with hypertension with long-term high-pressure blood flow experience arterial wall damage and poor vascular elasticity, thereby accelerating the occurrence and development of arteriosclerosis. Therefore, the AASI may have a close relationship with the course of hypertension.

The patients in our study were divided into two groups according to Hcy levels: patients with H-type hypertension and CHD and those with non-H-type hypertension and CHD. Comparing the degree of coronary artery stenosis between the two groups, it was found that the proportion of patients with a Gensini score of ≥ 51 was much higher in the patients with H-type hypertension and CHD than in those with non-H-type hypertension and CHD. However, patients with a Gensini score of < 38 accounted for a higher proportion of patients with non-H-type hypertensive CHD than those with H-type hypertensive CHD. These results suggest that the higher the Hcy level in patients with hypertension and CHD, the more severe the degree of coronary artery stenosis, indicating that high Hcy may accelerate coronary artery injury in patients with hypertension. Wang et al (21). also confirmed that plasma Hcy levels were associated with CAD stability, complexity and severity. Furthermore, it has been shown that Hcy levels have a significant positive correlation with the risk of developing heart disease (22).

In this study, we found a positive correlation between the AASI and the Gensini scores in patients with hypertensive CHD, especially for those with H-type hypertensive CHD. These results suggest that H-type hypertension may be an independent risk factor for coronary artery aggravation in patients with CHD, and the AASI may better reflect the severity of CAD in patients with H-type hypertension and CHD. The results of Zhu et al.’s study are consistent with the conclusions of our research (23). Homocysteine acts on the arterial vascular endothelium to affect endothelial function via a series of inflammatory responses, thereby promoting the formation of arterial stiffness (24). Hoshide et al (25). also found that daytime maximum systolic blood pressure increased the risk of stroke especially for those with a higher level of arterial stiffness presented by AASI. These data suggested that arterial stiffness manifested by AASI might be an effective indicator of cardiovascular risk factors (e.g., diabetes mellitus, hypertension), all of which had been shown to contribute to the development of coronary artery disease. However, the casual relationship between high AASI and severity of coronary stenosis is still underdetermined, requiring further studies revealing its pathogenesis.

This study has some limitations. Firstly, the sample size was small. This study was a retrospective and cross-sectional study, and the causal relationship between independent variables and dependent variables is not strong. At the same time, the prevalence of h-type hypertension is relatively lower than other previous studies. This is because the research object of this study is mainly the elderly in our single institution. In subsequent studies, we will include hypertensive patients from multiple centers to expand our sample size and strengthen the universality of the results. Secondly, because the ambulatory blood pressure measurement of hypertensive patients may be affected by factors such as snoring and sleep disorders, this may have affected the reliability of our conclusions. In addition, there was a lack of discussion on daytime AASI, nighttime AASI, AASI variability, blood pressure variability and other indicators. Finally, because AASI cannot monitor the effect of medical intervention on hypertension, the slope of the curve between SBP and DBP may be similar at the same pulse pressure. Although it can be easily obtained from ambulatory blood pressure monitoring (ABPM) readings, it is also controversial as a true measure of arterial stiffness. Therefore, in subsequent studies, we will conduct a larger prospective clinical study to explore the consistency between pulse wave velocity and AASI.

Conclusion

In conclusion, there is a certain relationship between HHcy and atherosclerosis, which may accelerate coronary artery injury in patients with hypertension. H-type hypertension may accelerate the occurrence and development of atherosclerosis and is an independent risk factor for coronary artery aggravation in patients with CHD. Homocysteine levels and the AASI have a synergistic effect on the evaluation of the severity of CAD in patients with hypertensive CHD. Finally, the AASI has some clinical significance for assessing the severity of CAD in patients with hypertensive CHD.

Authors’ contributions

L Dong, J Liu and Y Qin conceived of the study, WJ Yang, L Nie and HN Liu participated in its design and coordination and QH Hu, Y Sun and WY Cao helped to draft the manuscript. All authors read and approved the final manuscript.

Data availability of statement

All data generated or analyzed during this study are included in this published article.

Ethics approval and consent to participate

This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Anyang Third People’s Hospital. All participants signed an informed consent form for inclusion in the study.

Acknowledgments

We would like to express our gratitude to all those who helped us during the writing of this manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.