Association of plasma bone morphogenetic protein‐4 levels with arterial stiffness in hypertensive patients

Abstract

Background

Arterial stiffness interacts with hypertension, becoming an early marker of hypertension‐mediated target organ damage. This study aimed to assess the association between plasma concentrations of bone morphogenetic protein‐4 (BMP‐4) and arterial stiffness during hypertension.

Methods

Using cardio‐ankle vascular index (CAVI) to determine arterial stiffness status, 204 individuals with essential hypertension were classified into two groups, high CAVI (abnormal) group (n = 94) and low (normal) CAVI group (n = 110). Data were collected including clinical characteristics and laboratory measurements. Plasma levels of BMP‐4 were tested by using ELISA analysis.

Results

Plasma levels of BMP‐4 were substantially greater in high CAVI group than that in low CAVI group [38.51 (31.79–50.83) pg/mL vs. 31.15 (29.38–32.37) pg/mL; p < 0.001]. As shown by spearman correlation analysis, BMP‐4 concentrations were correlated with CAVI values in hypertensive individuals (r = 0.406, p < 0.001). After adjustment for potential confounders, elevated BMP‐4 levels were related with high CAVI (OR, 1.070; 95% CI, 1.003–1.108; p < 0.001). The best BMP‐4 cutoff value for identifying high CAVI, as determined by ROC curve analysis, was 33.34 pg/mL (AUC, 0.751; 95% CI, 0.683–0.818; p < 0.001).

Conclusion

Plasma levels of BMP‐4 are increased in hypertensive individuals with high CAVI. Elevated BMP‐4 levels are strongly correlated with higher CAVI values, implying a predictive value of BMP‐4 in arterial stiffness during hypertension.

Arterial stiffness can interact with hypertension, thereby becoming an early marker of hypertension‐mediated targeted organ damage. Plasma levels of BMP‐4 have the ability to identify increased arterial stiffness in patients with hypertension. CAVI, cardio‐ankle vascular index; BMP‐4, bone morphogenetic protein‐4.

1. INTRODUCTION

Hypertension is considered a risk factor for cardiovascular events. Despite great efforts to reduce hypertension‐related all‐cause mortality, the prevalence of hypertension continues to increase in developing countries, including China. ¹ Arterial stiffness is one of the common vascular complications that increase cardiovascular risks in hypertensive patients. ² , ³ Various processes contribute to the development of arterial stiffness, including renin‐angiotensin‐aldosterone system (RAAS) activation, inflammation, vascular calcification, adipokines, and insulin resistance. ²

The bone morphogenetic proteins (BMPs) are initially identified as important signaling molecules in bone formation and now are emerging as crucial players in the regulation of function in multiple tissues and organs. ⁴ , ⁵ , ⁶ The BMP family and related ligands are subdivided into at least four groups based on sequence similarity, and affinities for specific receptors ⁷ ; the BMP2/4 subgroup; the BMP5‐7 subgroup; the BMP9/10 subgroup and the growth and differentiation factor 5–7 subgroup. BMP‐4 is predominantly expressed in endothelial cells and can be induced by oscillatory shear stress in the early stage of atherosclerosis. ⁸ Mounting evidence suggested that BMP‐4 is an essential regulator in cardiovascular homeostasis and disorders ⁹ , ¹⁰ and functions as a proinflammatory, prooxidant, prohypertensive, and proatherogenic mediator in systemic arteries. ¹¹ , ¹² Specifically, BMP‐4 plays critical roles in the accurrence and development of hypertension. Chronic infusion of BMP‐4 generated considerable and increasing hypertension in mice through elevating the levels of vascular nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and the resulting overproduction of reactive oxygen species. This disrupted endothelial function in hypertensive mice. ¹² , ¹³

There are limited studies investigating whether the levels of circulating BMP‐4 in humans signify the commencement of early atherosclerosis. Recent studies found that plasma BMP‐4 levels were enhanced after resuscitation. ¹⁴ Interestingly, serum concentrations of BMP‐4 were strongly correlated with the likelihood of developing left ventricular hypertrophy in individuals with hypertension ¹⁵ while being negatively correlated with carotid atherosclerosis in individuals with diabetes mellitus. ¹⁶ However, the specific roles of BMP‐4 in arterial stiffness among patients who suffer from hypertension and atherosclerosis remain largely unclear. This work sought to evaluate the association between BMP‐4 and cardio‐ankle vascular index (CAVI) as a new measurement of arterial stiffness in hypertension.

2. MATERIALS AND METHODS

2.1. Patients

Participants of this study were hypertensive patients aged 18 years or above, recruited from the Department of Geriatrics ward in Beijing Tongren Hospital Affiliated to Capital Medical University between June 2021 and May 2022. Systolic blood pressure (SBP) or diastolic blood pressure (DBP) reading above 140/90 mmHg, any use of antihypertensive drugs, or a self‐reported history of hypertension, was considered hypertension. Based on the readings of the patient's blood pressure, hypertension was further divided into three grades: grade 1, grade 2, and grade 3. Grade 1 was defined as SBP between 140 and 159 mmHg or DBP between 90 and 99 mmHg. Grade 2 was described as having an SBP of between 160 and 179 mmHg or a DBP of between 100 and 109 mmHg, and Grade 3 was considered to have an SBP of more than 180 mmHg or a DBP of more than 110 mmHg. Following was a list of the exclusion criteria: secondary hypertension, chronic heart failure, acute coronary syndrome, peripheral arterial disease, atrial fibrillation, cerebrovascular illness (including stroke and transient ischemic attack), chronic kidney disease (estimated glomerular filtration rate [eGFR] < 45 ml/min/1.73m², calculated using the CKD‐EPI formula), ankle‐brachial index ≤0.9, acute infectious diseases, autoimmune diseases, and malignant neoplasms. This work was carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans after receiving approval from the Ethics Committee of Beijing Tongren Hospital Affiliated to Capital Medical University (No. TRECKY 2021–172).

2.2. Data collection

All patients' age, gender, cigarette use, alcohol consumption, duration of hypertension, blood pressure grading, history of diabetes mellitus, dyslipidemia, coronary heart disease, and hyperuricemia, as well as their medication history, were gathered from their comprehensive medical records. Smoking history was defined as participants who have smoked at least 20 packets of cigarettes in their lifetime and currently smoke cigarettes. ¹ Drinking history was defined as consuming at least one drink per month for a year. ¹⁷

All measurements were performed using standardized equipment. On admission, skilled nurses measured the patient's height, weight, blood pressure, heart rate, and body mass index (BMI; calculated as weight [kg]/height squared [m²]). Blood pressure and heart rate were measured with a newly calibrated device with a digital readout (Omron HEM‐7051, Tokyo, Japan). Patients should be seated for at least 5 min in a quiet room before blood pressure measurements and keep the upper arm at the heart level. The average of two blood pressure readings was recorded. ¹⁸ Biochemical tests included alanine aminotransferase (ALT), aspartate aminotransferase (AST), high‐sensitivity C‐reactive protein (hs‐CRP), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), creatinine, blood urea nitrogen (BUN), uric acid (UA), lipide profiles including total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), triglycerides (TG), high‐density lipoprotein cholesterol (HDL‐C) and lipoprotein (a) (LP (a)). Urine from the first void was analyzed to calculate the albumin to creatinine ratio. The level of HbA1c was determined using the fully automatic glycohemoglobin analyzer (HCL‐723G8, SYSMEX, Japan). Other blood samples were measured using the automatic biochemical analyzer (AU5821, BECKMAN, USA) in Beijing Tongren Hospital Clinical Laboratory. The Chronic Kidney Disease Epidemiology Collaboration derived the following equation to calculate eGFR ¹⁹ : eGFR = 141 × min (creatinine/κ, 1) α × max (creatinine/κ, 1) −1.209 × 0.993 age × 1.018 (if female). In this equation, α is equal to −0.411 for men and − 0.329 for women, κ is equal to 0.7 for men and 0.9 for women, and the terms min and max denote the minimum and maximum values, respectively.

2.3. Quantification of BMP‐4

Blood samples were collected in EDTA‐containing tubes. Plasma was separated from blood samples of patients by centrifugation at 3000 rpm for 10 min at 4°C. Before being examined, the plasma samples were kept at −80°C for storage. A human BMP‐4 Duoset ELISA kit (R & D Systems, Minneapolis, USA) was used to quantify plasma BMP‐4 levels as directed by the manufacturer. The samples were assayed in duplicate. Using the SpectraMax190 microplate reader, the optical density of each well was determined at 450 nm (Molecular Devices, CA, USA).

2.4. CAVI measurement

A VaSera VS‐1000 vascular screening device was used to calculate CAVI (Fukuda Denshi Co, Tokyo, Japa). Before the measurements, the patients rested in a supine posture on a bed for 10 min. The CAVI examination was conducted in accordance with the operating method, which required cuffing the ankles and brachium in a relaxing environment. Both wrists were positioned with electrodes for electrocardiography, and the sternum was positioned with a microphone for phonocardiography.

CAVI has been suggested as an indicator of arterial stiffness based on the stiffness parameter β. ²⁰ The following formula was used to compute the CAVI value: CAVI = a{(2ρ/ΔP) × ln (Ps/Pd) × PWV²} + b, ρ is blood density, Ps refers to SBP, Pd refers to DBP, ΔP = Ps‐Pd, PWV is pulse wave velocity between the aortic and ankle values, a and b are constants. The CAVI value was derived by averaging the left and right CAVI values. The abnormal value of CAVI (high CAVI) was ≥9, and CAVI <9 was defined as the normal value (low CAVI). ²¹ According to the CAVI values, hypertensive patients were divided into high (abnormal) CAVI group and low (normal) CAVI group.

2.5. Statistical analysis

SPSS version 27.0 for Windows was used to perform all statistical analysis (SPSS Inc). Shapiro‐Wilks tests were used to examine the distribution of quantitative variables. Continuous values with normal distribution were represented as the mean ± standard deviation, whereas discrete values were reported as the median with interquartile ranges (25th and 75th percentiles). The independent t‐test was used to compare continuous variables with normal distributions. The Mann–Whitney test was utilized to compare groups with non‐normal distributions. Categorical variables were expressed as the number and percentage of cases, and the chi‐square test was used to assess differences between groups. The relationship between the CAVI values and the levels of BMP‐4 was determined using the Spearman correlation analysis. To account for differences between the high CAVI and low CAVI groups, crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) of BMP‐4 were estimated using bivariate logistic regression. Four models were constructed step‐by‐step. Age, gender, and BMI were adjusted in Model 1; Duration of hypertension and smoking were further adjusted in Model 2; History of diabetes mellitus, dyslipidemia, and coronary heart disease was further adjusted in Model 3; and finally, we added the use of antiplatelet agents into Model 4. Using a receiver operating characteristic (ROC) curve, the predictive significance of BMP‐4 levels on arterial stiffness in hypertension individuals was identified. A p‐value below 0.05 was statistically significant.

3. RESULTS

3.1. Overall characteristics between high CAVI group and low CAVI group

The overall features of the two groups of hypertensive patients were listed in Table 1. A total of 204 subjects, including 94 patients with high CAVI and 110 patients with low CAVI were included. The mean age of the high CAVI group was 66.4 years and the percentage of males was 61.74%, while the mean age of the low CAVI group was 65.7 years and the proportion of males was 63.64%. There were no significant differences regarding gender, age, hypertension duration, blood pressure grading, history of drinking, history of diabetes mellitus, dyslipidemia, hyperuricemia, heart rate, blood pressure, the use of antihypertensive, antilipemic and antidiabetic agents between high CAVI and low CAVI groups. The levels of FBG, BUN, creatinine, UA, ALT, AST, hs‐CRP, LP (a), TG, HDL‐C, TC, and LDL‐C were comparable between the two groups. Compared with hypertensive individuals with low CAVI, patients with high CAVI had relatively lower levels of BMI and eGFR, more significant percentages of smoking, coronary heart disease and the use of antiplatelet agents.

TABLE 1.

Baseline characteristics between hypertensive individuals with high CAVI and those with low CAVI

Variables	High (abnormal) CAVI (n = 94)	Low (normal) CAVI (n = 110)	p value
Age (year)	66.40 ± 13.40	65.70 ± 12.06	0.693
Male, n (%)	58 (61.70)	70 (63.64)	0.776
Body mass index (kg/m2)	24.22 (23.12–26.81)	25.46 (23.77–27.55)	0.036
Smoking, n (%)	87 (92.55)	87 (79.09)	0.007*
Drinking, n (%)	78 (82.98)	80 (72.73)	0.081
Duration of hypertension (year)	13.50 (9.00–21.00)	10.00 (5.50–20.00)	0.097
Blood pressure grading			0.340
Grade 1, n (%)	7 (7.45)	8 (7.27)
Grade 2, n (%)	25 (26.60)	20 (18.18)
Grade 3, n (%)	62 (65.96)	82 (74.55)
Clinical comorbidity
Diabetes mellitus, n (%)	49 (52.13)	53 (48.18)	0.574
CHD, n (%)	27 (28.72)	14 (12.73)	0.004*
Dyslipidemia, n (%)	60 (63.83)	69 (62.73)	0.871
Hyperuricemia, n (%)	13 (13.82)	17 (15.45)	0.744
Laboratory data
FBG (mmol/L)	5.82 (5.21–7.20)	5.74 (5.00–6.80)	0.376
HbA1c (%)	6.15 (5.70–7.25)	5.90 (5.60–6.95)	0.272
BUN (mmol/L)	5.40 (4.80–6.30)	5.30 (4.30–6.20)	0.232
Creatinine (μmol/L)	72.00 (60.20–82.00)	70.30 (61.50–80.20)	0.541
eGFR (ml/min/1.73 m2)	77.04 ± 16.09	86.83 ± 17.71	< 0.001**
Uric acid (μmol/L)	341.00 (298.00–410.00)	346.00 (288.20–393.90)	0.911
ALT (U/L)	17.00 (13.00–25.00)	19.50 (13.00–28.00)	0.361
AST (U/L)	19.00 (17.00–23.00)	20.00 (17.00–24.00)	0.612
Hs‐CRP (mg/L)	0.75 (0.40–3.00)	0.90 (0.50–2.20)	0.651
Lipoprotein (a) (mg/dL)	11.00 (4.30–26.30)	9.80 (3.90–31.20)	0.888
TG (mmol/L)	1.41 (0.96–2.02)	1.27 (0.92–1.70)	0.296
TC (mmol/L)	4.12 (3.51–5.15)	4.58 (3.84–5.38)	0.120
LDL‐C (mmol/L)	2.33 (1.83–3.33)	2.75 (2.01–3.40)	0.184
HDL‐C (mmol/L)	1.17 (0.94–1.43)	1.19 (0.99–1.48)	0.417
ACR (mg/g)	6.71 (3.71–21.97)	4.40 (2.98–14.21)	0.205
BMP‐4 (pg/mL)	38.51 (31.79–50.83)	31.15 (29.38–32.37)	< 0.001**
CAVI	9.93 (9.30–10.95)	8.05 (7.50–8.40)	< 0.001**
SBP (mmHg)	132.73 ± 17.21	133.81 ± 15.01	0.636
DBP (mmHg)	75.40 ± 9.34	77.83 ± 9.55	0.068
Heart rate (bpm)	71.02 ± 11.04	72.22 ± 9.47	0.416
Medications, n (%)
Antihypertensive agents	33 (35.11)	40 (36.36)	0.852
Antiplatelet agents	31 (32.98)	22 (22.00)	0.035*
Antilipemic agents	53 (56.38)	56 (50.91)	0.435
Antidiabetic agents	42 (44.68)	42 (38.18)	0.347

Note: Data are given as mean ± standard deviation, median (25th and 75th percentiles) or valid percentages (n%). * p < 0.05. ** p < 0.001.

Abbreviations: ACR, albumin/creatinine ratio; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMP‐4, bone morphogenetic protein‐4; BUN, blood urea nitrogen; CAVI, cardio‐ankle vascular index; CHD, coronary heart disease; DBP, diabolic blood pressure; eGFR, estimated glomerular filtration rate; FBG, fasting blood glucose; HbA1c, glycated hemoglobin; HDL‐C, high‐density lipoprotein cholesterol; hs‐CRP, high‐sensitivity C‐reactive protein; LDL‐C, low‐density lipoprotein cholesterol; SBP, systolic blood pressure; TC, total cholesterol; TG, triglycerides.

3.2. Correlation between plasma BMP‐4 levels and CAVI values in hypertensive patients

Plasma levels of BMP‐4 were markedly elevated in hypertensive patients with high CAVI compared with those of low CAVI [38.51 (31.79–50.83) pg/mL vs. 31.15 (29.38–32.37) pg/mL; p < 0.001; Figure 1]. Correlation analysis indicated that plasma BMP‐4 concentrations were substantially linked with CAVI levels in hypertensive patients (r = 0.406, p < 0.001, Figure 2).

FIGURE 1.

Plasma levels of BMP‐4 in hypertensive individuals with high CAVI or those with low CAVI. CAVI, cardio‐ankle vascular index; BMP‐4, bone morphogenetic protein‐4

FIGURE 2.

Correlation between CAVI values and BMP‐4 levels in hypertensive patients. CAVI, cardio‐ankle vascular index; BMP‐4, bone morphogenetic protein‐4

3.3. The association between plasma BMP‐4 levels and high CAVI in hypertensive individuals

As seen in Figure 3, Univariate logistic regression analysis revealed that higher levels of BMP‐4 were notably linked with high CAVI in hypertensive individuals (OR, 1.073; 95% CI, 1.038–1.110; p < 0.001). After adjusting for gender, age, BMI, duration of hypertension, smoking, diabetes mellitus, dyslipidemia, coronary heart disease, and the use of antiplatelet medications, the concentration of BMP‐4 remained substantially linked with high CAVI in hypertensive individuals (OR, 1.070; 95% CI, 1.033–1.108; p < 0.001). Figure 4 illustrates the ROC curve for the BMP‐4 to distinguish high CAVI and low CAVI in hypertension. BMP‐4’s area under the curve was calculated to be 0.751 (95% CI, 0.683–0.818; p < 0.001). The best BMP‐4 cutoff value for detecting high CAVI in hypertensive individuals was 33.34 pg/mL, in which the sensitivity was 66.0%, and the specificity was 78.2%.

FIGURE 3.

Odds ratios of plasma BMP‐4 levels for hypertensive individuals with high (abnormal) CAVI or low (normal) CAVI. Model 1: adjusted for age, gender, and body mass index. Model 2: adjusted for all variables in model 1 in addition to hypertension duration and smoking status. Model 3: model 2 plus diabetes, dyslipidemia, and coronary heart disease, adjusted for all variables. Model 4: adjusted for all factors in model 3 in addition to the use of antiplatelet agents. BMP‐4, bone morphogenetic protein‐4; CAVI, cardio‐ankle vascular index

FIGURE 4.

ROC curve for BMP‐4 in predicting arterial stiffness measured by CAVI. BMP‐4, bone morphogenetic protein‐4; CAVI, cardio‐ankle vascular index; AUC, the area under the curve; ROC, receiver operating characteristic

4. DISCUSSION

In current work, we demonstrated, for the first time, that plasma BMP‐4 levels are positively associated with high CAVI in hypertensive patients, after adjusting for potential confounders. Furthermore, the ROC curve analysis revealed that BMP‐4 could predict increased arterial stiffness in hypertensive individuals, indicating a substantial role for BMP‐4 in the atherosclerosis process in the hypertensive population.

Arterial stiffness increases with age, as well as in various pathological status, such as obesity, smoking, diabetes mellitus, dyslipidemia, and hypertension. ²² It is becoming increasingly important in clinical applications as an early indicator of hypertension‐mediated targeted organ damage ²³ and is being thought as a potential therapeutic marker in hypertensive patients. There have been a number of mechanisms including vascular inflammation, vascular calcification, activation of RAAS, increased oxidative stress, insulin resistance, and adipokines, which ultimately result in artery stiffening. ² , ²⁴ In our present study, we had considered the effects of age, diabetes mellitus, dyslipidemia, smoking, and obesity assessed by BMI on arterial stiffness. After adjusting for the above potential confounders, the levels of BMP‐4 remained significantly associated with high (abnormal) CAVI in hypertensive individuals.

The BMP family, initially identified as important signaling molecules in bone formation, now are emerging as crucial players in the regulation of function in multiple tissues and organs. ⁴ , ²⁵ BMP‐4, induced by oscillatory shear stress and predominantly expressed in endothelial cells, is one of the common triggers for endothelial dysfunction in hypertension. ²⁶ A rising body of evidence indicates that BMP‐4 has proinflammatory and prooxidant properties in systemic arteries, ²⁷ implying that BMP‐4 signaling is crucial in the cardiovascular homeostasis and disorders, including hypertension, ¹² atherosclerosis, ²⁸ and cardiac dysfunction. ²⁹ However, studies investigating the relationship between BMP‐4 levels and arterial stiffness in the hypertension population are sparse.

Patients who had survived a cardiac arrest outside of a hospital exhibited greater plasma levels of BMP‐4 in comparison to those who had coronary artery disease or healthy volunteers. ¹⁴ Circulating BMP‐4 levels were similarly raised following surgery and were closely correlated with inflammation cytokines. This rise in circulating BMP‐4 may be alleviated by flurbiprofen, implying that BMP‐4 exerts proinflammatory features through the cyclooxygenase‐II signaling pathway. ³⁰ Recent studies indicate that BMP‐4 may be able to cause left ventricular hypertrophy in hypertensive patients. ¹⁵ Our present results showed that plasma concentrations of BMP‐4 were elevated in hypertensive individuals with high CAVI than those with low CAVI and were positively correlated with the CAVI values, implying that BMP‐4 might become a novel biomarker for arterial stiffness and early atherosclerosis. These findings are partially consistent with the findings of previous studies.

Nevertheless, there are still controversial for impacts of BMP4 on cardiorenal system. BMP‐4 levels were inversely related to carotid atherosclerosis, and individuals with diabetes mellitus had lower serum concentrations of both BMP‐4 and the antagonist noggin. ¹⁶ It was postulated that once the levels of BMP‐4 begin to increase, the concentrations of its antagonists may also start to rise to counterbalance the action of BMP‐4. ³¹ Individuals who suffered from chronic kidney disease (CKD) and coronary artery disease had increased serum levels of BMP‐4, whereas patients without CKD did not vary from one another in this regard. ³² This situation may be explained by an accumulation of BMP‐4 in the atherosclerotic vascular tissue, as suggested by the minimal study that has been done on the subjects. ⁸ , ²⁷

It is unknown how exactly increased BMP‐4 causes arterial stiffness in the hypertensive population since the particular mechanism responsible for this effect remains unknown. This study indicated that the risk of abnormal CAVI increased with plasma levels of BMP‐4, even after accounting for other variables that may be associated. Arterial stiffness may be caused by a number of conditions, including age, smoking, obesity, and many more. Given this, an increase in arterial stiffness cannot directly reflect the control of blood pressure management and the improvement of medication therapy in hypertensive individuals, of which clinical application is limited. When further ROC analysis was performed on the data from this study, it was shown that when the concentration of BMP‐4 reached the cut‐off value of 33.34 pg/mL, the test had high sensitivity and specificity for identifying and diagnosing increased arterial stiffness. Not only might BMP‐4 be used as an indicator for increased arterial stiffness in the hypertensive population and as a monitoring index for the improvement of hypertension‐related subclinical events, which has a specific clinical application value.

This current study has several limitations that must be considered. First, the subjects were selected among hospitalized patients, which may have caused a selection bias. Second, since this was a cross‐sectional study, it is impossible to determine the causal like with certainty. Finally, the sample size of the study was also somewhat limited. Therefore, more extensive prospective studies are needed to provide more confirmation.

5. CONCLUSIONS

In conclusion, plasma levels of BMP‐4 are elevated in hypertensive individuals with high CAVI. The increase of BMP‐4 is independently associated with higher CAVI values in patients with hypertension, implying that plasma BMP‐4 levels may serve as a predictive indicator of arterial stiffness in hypertensive individuals. Defining BMP‐4 as a new biomarker might help stratify the cardiovascular risk and offer potential therapeutic strategies for arterial stiffness. Clarifying the precise functions and underlying processes of BMP‐4 in arterial stiffness during hypertension calls for more studies.

FUNDING INFORMATION

This study was supported by the National Major Research Plan Training Program and General Program of the National Natural Science Foundation of China (No. 92168117; 81770253; 91849111), the Beijing Natural Science Foundation (No. 7222068), Clinical Research Incubation Program of Beijing Chaoyang Hospital Affiliated to Capital Medical University (CYFH202209) and the Reform and Development Program of Beijing Institute of Respiratory Medicine (ysrh2022002).

CONFLICT OF INTEREST

The authors declare that they have no conflict of interest.

Wang N, Guo Y, Dong Y, et al. Association of plasma bone morphogenetic protein‐4 levels with arterial stiffness in hypertensive patients. J Clin Lab Anal. 2022;36:e24746. doi: 10.1002/jcla.24746

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.