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The Journal of Clinical Hypertension logoLink to The Journal of Clinical Hypertension
. 2020 Sep 23;22(11):2069–2076. doi: 10.1111/jch.14025

Circulating choline is associated with coronary artery stenosis in patients with hypertension: A cross‐sectional study of Chinese adults

Fei Guo 1,2,3,4,5, Xueting Qiu 6, Yuanting Zhu 6, Zhirong Tan 1,2,3,4, Zhenyu Li 6,✉, Dongsheng Ouyang 1,2,3,4,5,✉
PMCID: PMC8030004  PMID: 32966687

Abstract

Choline is an important nutrient involved in multiple biosynthesis pathways. However, whether circulating choline levels are associated with the risk of hypertension (HTN) and artery stenosis in HTN remains unknown. We investigated the correlations of plasma choline with HTN and coronary artery injury and explored the utility of plasma choline as a diagnostic biomarker for HTN and artery stenosis. 193 HTN patients and 154 age‐ and sex‐matched healthy controls (CON) were recruited in this study. Fasting plasma choline was detected using liquid chromatography tandem mass spectrometry. Choline levels were significantly higher in HTN without artery stenosis (HTN‐AS) than CON (8.07 [7.19‐9.24] μM vs 7.03 [6.21‐8.13] μM, P < .01) group and were further upregulated in HTN with artery stenosis (HTN + AS) (8.63 [7.09‐10.59] μM, P < .01) group. Patients with multivessel disease (MVD) also exhibited higher choline levels than those with single vessel disease (SVD) (8.64 [7.16‐10.55] μM vs 8.04(6.74‐9.38) μM, P < .01). Increased choline levels were independently associated with the risk of HTN (OR = 1.2, 95% CI: 1‐1.45, P = .05), HTN + AS (OR = 1.27, 95% CI: 1.09‐1.48, P < .01), and MVD (OR = 1.16, 95% CI: 1.02‐1.31, P = .02) after adjustment for multiple risk factors. Receiver operating characteristic (ROC) analysis showed that choline had an area under curve (AUC) score of 0.69, 0.67, and 0.63 in determining HTN, HTN + AS, and MVD. In conclusion, higher choline levels were associated with increased risk of HTN and artery stenosis in hypertensive patients.

Keywords: artery stenosis, Choline, diagnostic biomarker, hypertension, multivessel disease

1. INTRODUCTION

Approximately 3.5 billion adults now have non‐optimal systolic blood pressure levels around the world, which means one in four adults has hypertension (HTN). 1 A survey conducted from October 2012 to December 2015 to assess the prevalence of HTN in China has revealed that over 240 million of the Chinese adult population aged ≥18 years had HTN, and another 430 million had pre‐HTN, which consequently resulted in an increase of blood pressure‐related morbidity and mortality. 2 , 3

Elevated blood pressure was demonstrated to be linked with cardiovascular disease. The underlying mechanism might be atherosclerosis induced by inflammatory immune cells infiltrating in vasculature which were activated by hypertensive stimuli such as angiotensin II (Ang II). 4 Approximately two‐thirds of adults who have hypertension at the age of 30 years have a 40% higher risk of experiencing a CVD event than sex‐ and age‐matched healthy controls. 5

Hypertension is also the leading single contributor to all‐cause death and disability according to data from multiple clinical studies. 6 Tremendous efforts have been put into studies of onset of HTN and HTN‐related vascular injury. However, there are still considerable number of hypertensive patients in China who were not aware of their vascular injury conditions until onset of first stroke, 7 , 8 indicating an urgent demand for rapid and sensitive biomarkers for better risk stratification of HTN and HTN‐induced CVD.

Choline is an essential nutrient and acts as a precursor of lipoproteins, membrane phospholipids, and the neurotransmitter acetylcholine. 9 Growing data have suggested that choline is the main precursor of gut microbiota metabolite trimethylamine N‐oxide (TMAO), which positively correlated with atherosclerosis and metabolic syndrome. 10 , 11 Konstantinova and his colleagues have shown that high choline plasma concentrations were associated with unfavorable cardiovascular disease risk profile. 12 To our knowledge, whether circulating choline levels are associated with HTN and coronary artery stenosis in HTN has not been evaluated. In this study, we evaluated the associations of plasma choline with HTN and the extent of coronary artery stenosis in HTN, as quantified by the burden of coronary atherosclerotic lesion, and number of diseased coronary vessels, by utilizing a hospital‐based cross‐sectional study in HTN patients and their healthy controls, aimed to test whether the plasma choline could be used as a potential biomarker for evaluation and risk stratification of HTN and coronary artery stenosis in HTN.

2. MATERIALS AND METHODS

2.1. Study population and design

1395 blood samples from patients who were either hospitalized for coronary angiography or visited for health screen in Xiangya Hospital at Central South University from June 2014 to September 2019 were randomly collected. 193 hypertensive patients (HTN) with available data of coronary angiography, aged 25‐70, were included in this study. HTN was defined as seated resting systolic blood pressure (SBP) ≥140 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg. Age‐ and sex‐matched control group (CON, n = 154) was an independently recruited set without known HTN and CVD. All participants were informed and provided written consent. HTN patients were stratified into two groups according to their artery stenosis conditions: the group with coronary artery stenosis (HTN + AS, n = 148) and the group without coronary artery stenosis (HTN‐AS, n = 45). Coronary artery stenosis was defined as ≥ 50% stenosis in at least one main coronary artery (determined by quantitative coronary angiogram analysis). We further divided the HTN + AS group into single vessel disease (SVD, n = 59) and multivessel disease (MVD, n = 89). SVD and MVD were defined as one or more major coronary vessels exhibiting ≥ 50% stenosis. Subjects with an active infection, malignancy, severe liver or renal diseases, intestinal dysfunction, gastrointestinal surgery history, and choline supplementation in recent 6 months were excluded.

Clinical information including age, sex, height, weight, and body mass index (BMI) was retrospectively collected from each subject's medical records. Fasting blood samples were collected using vacutainer tubes containing EDTA and immediately centrifuged and frozen at −80°C until analysis.

2.2. Laboratory test

Choline and TMAO in plasma were determined by high‐performance liquid chromatography–tandem mass spectrometry (HPLC‐MS) as previously reported. 13 To be brief, A volume of 50 μl of either the plasma sample or standards was combined with 100 μL of acetonitrile containing 10 μM of internal standards (d9‐choline or d9‐TMAO) and then centrifuged at 14 000 g for 15 minutes. The supernatant was analyzed after injection into a normal‐phase silica column (2.1 × 50 mm, 2.7 μm) and equilibrated with 19% solution A (10 mmol/l ammonium formate and 0.1% formate acid in water) and 81% solution B (acetonitrile) under isocratic elution with the flow rate of 0.3 mL/min. Routine biochemical measurements were performed on an automatic biochemical analyzer (HITACHI7170S).

2.3. Statistical analysis

Baseline characteristics are presented as means ± standard deviations (SD) for normal distribution parameters of continuous variables, or medians (interquartile ranges, IQR) for non‐normal distribution parameters of continuous variables, or numbers and percentages for categorical variables. Student's t test or the Mann‐Whitney U test was used for differences evaluation between two groups. One‐way ANOVA was conducted to examine group differences for the putative risk factors. Bonferroni post hoc tests were employed to find any statistical differences of those risk factors within each two groups. Spearman correlation analysis was performed for the correlation between choline and TMAO concentrations. Odds ratios (ORs) of HTN, coronary artery stenosis in HTN, and multivessel disease in relation to plasma concentrations of choline were calculated using conditional logistic regression models, with or without adjustment for age, sex, body mass index, systolic blood pressure, and fasting blood glucose (Glu). The area under the receiver operating characteristics (ROC) curve was calculated to test the accuracy of plasma choline at discriminating HTN patients from healthy controls, HTN with coronary artery stenosis from those without, and MVD from SVD in HTN. A 2‐tailed P < .05 was considered to be statistically significant.

3. RESULTS

3.1. Baseline characteristics

Baseline characteristics of all participants stratified by CON, HTN‐AS, and HTN + AS are summarized in Table 1. Remarkably, patients without artery stenosis had higher plasma choline concentrations than the control group (8.07(7.19‐9.24) μM vs 7.03(6.21‐8.13) μM, P < .01). HTN patients with artery stenosis exhibited even higher choline concentrations than CON and HTN‐AS groups (8.63(7.09‐10.59) μM, P < .01) (Figure 1A). Unlike choline, although remarkably upregulated TMAO concentrations were observed in HTN + AS compared to CON (1.88 [0.87‐2.88] μM vs 1.16 [0.3‐1.82] μM, P < .01), there is no significant difference of TMAO between HTN‐AS and CON groups (1.23 [0.34‐2.35] μM vs 1.16(0.3‐1.82) μM, P > .05, Figure 1B). Spearman analysis further showed a modest correlation of choline and TMAO concentrations (R = 0.14, P = .01, Figure 1C). Besides, we observed elevated choline concentrations in MVD hypertensive patients compared to SVD patients (8.64 [7.16‐10.55] μM in MVD vs 8.04 [5.74‐9.38] μM in SVD, P < .01) (Figure 2).

Table 1.

Baseline characteristics of subjects stratified by CON, HTN‐AS, and HTN + AS

CON HTN‐AS HTN + AS P
Male (n, %) 90 (58%) 25 (56%) 83 (57%) .83
Age (years) 57 ± 1 58 ± 1 58 ± 1 .08
Height (cm) 161 ± 1 163 ± 1 163 ± 1 .22
Weight (kg) 63 ± 1 66 ± 1 66 ± 1 .01
BMI (kg/m2) 24 ± 1 25 ± 1 25 ± 1 .01
SBP (mm Hg) 124 (115‐130) 130 (125‐146) 136 (128‐151) <.01
DBP (mm Hg) 76 (70‐78) 80 (75‐85) 80 (75‐90) <.01
HR (bmp) 70 (64‐79) 72 (67‐80) 71 (65‐78) .3
WBC (109/L) 6.1 (5.2‐7.7) 6.5 (5.3‐8) 7 (5.9‐8.5) <.01
Glu (mmol/L) 4.94 (4.6‐5.52) 5 (4.75‐5.89) 5.43 (5‐6.91) <.01
HbAlc (%) 5.7 (5.63‐5.7) 5.7 (5.43‐5.8) 6.1 (6‐6.9) .01
Cr (μmol/L) 78.6 (72.63‐93.48) 77.75 (67.5‐87.43) 77.9 (73.7‐92) .78
TG (mmol/L) 1.25 (1‐1.91) 1.24 (0.95‐1.95) 1.26 (1.22‐2) .73
TC (mmol/L) 4.29 (3.9‐5.22) 4.13 (3.62‐4.83) 4.24 (3.59‐5.37) .71
HDL (mmol/L) 1.12 (0.94‐1.34) 1.2 (0.98‐1.48) 1.1 (0.82‐1.21) .63
LDL (mmol/L) 2.72 (2.24‐3.14) 2.64 (2.04‐2.98) 2.67 (2.14‐3.41) .93
ALT (U/L) 20.05 (15.8‐28.93) 19.88 (15.75‐29.55) 21.3 (16.3‐31.7) .08
AST (U/L) 21.95 (18.5‐26.48) 21.16 (18.65‐25.78) 22.05 (18.2‐29.4) .1
CK‐MB (U/L) 15.85 (11.55‐19.18) 15.93 (12.18‐21.05) 15.7 (11.5‐18.2) .27
Choline (μM) 7.03 (6.21‐8.13) 8.07 (7.19‐9.24) 8.63 (7.09‐10.59) <.01
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Continuous data are presented as means ± SD or medians (interquartile ranges), and categorical variables are presented as counts (%).

Figure 1.

Figure 1

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Comparison of plasma choline and TMAO levels in CON, HTN patients without artery stenosis, and HTN patients with artery stenosis. CON, control group. HTN‐AS, HTN patients without artery stenosis. HTN + AS, HTN patients with artery stenosis. A, choline levels in different groups. B, TMAO levels in different groups. C, scatter plot figure of TMAO and choline. R, correlation coefficient

Figure 2.

Figure 2

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Relationships between plasma choline levels and the number of diseased vessels. SVD, single vessel disease. MVD, multivessel disease

HTN patients had higher weight, BMI, SBP, DBP, fasting blood glucose, percentage of glycosylated hemoglobin (HbAlc) levels, and white blood cells (WBC) than their healthy counterparts. However, age, sex, height, heart rate (HR), creatinine (Cr), triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), glutamic‐pyruvic transaminase (AST), low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), and creatine kinase isoenzyme‐MB (CK‐MB) levels were similar between groups.

3.2. Association of plasma choline levels with the risk of HTN, AS in HTN, and MVD

Logistic regression analysis showed that choline was an independent predictor of HTN without any adjustment (OR = 1.43, 95% CI: 1.22‐1.67, P < .01) (Table 2). The significant predictive value of choline was preserved after adjustment for traditional risk factors associated with HTN including age, sex, BMI, SBP, and Glu (OR = 1.2, 95% CI: 1‐1.45, P = .05). Furthermore, elevated choline levels were also associated with higher risk of coronary artery stenosis (unadjusted: OR = 1.18, 95% CI: 1‐1.4, P = .05; adjusted: OR = 1.27, 95% CI: 1.09‐1.48, P < .01) and MVD (unadjusted: OR = 1.13, 95% CI: 1.02‐1.27, P = .03; adjusted: OR = 1.16, 95% CI: 1.02‐1.31, P = .02) in HTN patients with or without adjustment for other risk factors (Table 2).

Table 2.

Association of choline levels with HTN, artery stenosis and multivessel disease

HTN AS in HTN Multivessel disease
OR 95% CI P OR 95% CI P OR 95% CI P
Unadjusted 1.43 1.22‐1.67 <.01 1.18 1‐1.4 .05 1.13 1.02‐1.27 .03
Adjusted a 1.2 1‐1.45 .05 1.27 1.09‐1.48 <.01 1.16 1.02‐1.31 .02
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Abbreviation: AS, artery stenosis.

a

Adjusted for age, sex, BMI, SBP, and Glu.

3.3. ROC analysis for choline in distinguishing HTN from control group and HTN with artery stenosis from those without

ROC analysis was performed to evaluate the discriminatory power of choline in predicting events of HTN, artery stenosis in HTN, and multivessel disease. As shown in Figure 3, the area under curve (AUC) of choline for determining HTN was 0.69 (95% CI: 0.63‐0.76, P < .01), and the cutoff value of plasma choline to determine HTN was 8.59 μM with 58.7% sensitivity and 94.1% specificity (Figure 3A). More than that, we also observed good performances of choline levels in predicting artery stenosis and multivessel disease with AUCs of 0.67 (95% CI: 0.58‐0.76, P < .01 for artery stenosis) (Figure 3B) and 0.63 (95% CI: 0.54‐0.72, P < .01 for MVD) (Figure 3C). The cutoff values were 7.68 μM for artery stenosis and 8.31 μM for MVD. The corresponding sensitivity and specificity were 58.7% and 70.9% for artery stenosis and 59.3% and 60% for MVD in HTN, respectively.

Figure 3.

Figure 3

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ROC curves of choline for discriminating HTN from CON, HTN patients with artery stenosis from those without, and multivessel disease from single vessel disease. AUC indicates area under the receiver operating characteristic curve. A, ROC curves of choline for diagnosing HTN, the best cutoff value is 8.59 μM, the likelihood of correctly predicting an event was up to 69% (AUC, P < .01); B, ROC curves of choline for diagnosing artery stenosis in HTN, the best cutoff value is 7.68 μM, the likelihood of correctly predicting an event was up to 67% (AUC, P < .01); C, ROC curves of choline for diagnosing multivessel disease, the best cutoff value is 8.31 μM, the likelihood of correctly predicting an event was up to 63% (AUC, P < .01)

4. DISCUSSION

In this study, we examined the association between plasma choline concentrations and the risk of HTN and coronary artery stenosis in a southern Chinese population. We observed higher choline concentrations in HTN patients than healthy control group, and the concentrations of choline were further elevated in hypertensive patients with artery stenosis compared to those without. We further revealed the strong associations of choline with extent of vessel injury in hypertensive patients. This is the first study demonstrating that circulating choline levels were not only independent risk factors for HTN but also potential markers for the evaluation of artery injury in HTN.

Hypertension is a complex condition, and 90% of the cases are classified as essential hypertension where the exact cause is unknown. Current therapies for hypertension mainly include calcium channel blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and thiazides. 14 Studies also suggested that reduction in blood pressure was associated with management of insulin resistance. 15 However, even the traditional therapies successfully lower blood pressure in most individuals, and there are still a group of patients who are resistant to those treatments. Not only that, even blood pressure was controlled with traditional medicine, many hypertensive patients remain at risk for CVD, indicating involvement other underlying mechanisms such as inflammation.

In chronic inflammatory responses, immune cells including monocytes and T cells could be stimulated to release pro‐inflammatory cytokines such as interleukin‐6 (IL‐6), interleukin‐1 beta (IL‐1β), and tumor necrosis factor‐alpha (TNF‐α). These pro‐inflammatory cytokines are considered to be inflammatory markers with the strongest association with hypertension, since accumulating studies have demonstrated higher plasma IL‐6, IL‐1β, and TNF‐α levels in hypertensive patients compared to normotensive patients. 16 , 17 , 18 In experimental hypertension mouse model, inhibition of IL‐6 and interleukin‐17 (IL‐17) resulted in lower blood pressure in response to Ang II stimulation, 19 , 20 and knockdown of IL‐6 was also shown to inhibit hypertension. 21 These data all suggested the direct link of inflammation with hypertension due to the activation of immune cells. Interestingly, our recent study has confirmed that elevated choline levels were associated with slow coronary flow (SCF) phenomenon, which was closely linked to vascular endothelial activation by macrophage‐induced inflammation. 22 Choline is predominantly used for the synthesis of phosphatidylcholine (PC) in immune cells. Previous experiments have indicated the associations between choline levels and activation of immune cells including macrophages and acutely increased PC synthesis. 23 , 24 Shayne and his colleagues have found that LPS stimulation of macrophages could increase choline uptake and metabolism, 25 and limiting the availability of choline could reduce the capacity of pro‐inflammatory cytokines secretion. 26 Furthermore, Jia's study demonstrated that choline would upregulate the expression of pro‐inflammatory factors such as TNF‐α and C‐reactive protein (CRP), and promote inflammatory response. 27 These results indicated that high choline concentrations might lead to elevated synthesis of related metabolites and activation of immune cells, which could induce endothelial inflammation. Coincidentally, we found that the number of white blood cells was significantly higher in HTN‐AS and HTN + AS group than in CON group (Table 1). Meanwhile, the choline concentrations also upregulated in hypertensive patients compared to healthy control group in our study (Figure 1A). These results may suggest the correlations of potential inflammatory mechanisms with abnormal choline levels in HTN. However, more data and larger sample size will be needed to further verify the potential mechanisms of choline in immune cells activation.

Hypertensive stimuli such as Ang II may lead to progressive stiffening of the arterial vasculature, damage of vascular collagen, and slowly developed atherosclerosis, all of which result in an increased risk of CVD complications. Hypertension can be diagnosed based on repeated BP measurements, while artery injuries in HTN are normally ignored in the early stages due to lack of effective biomarkers, which lead to the low control rate of CVD in China for decades, and there are no signs of abatement of CVD. Thus, exploring possible factors associated with artery stenosis in HTN is of vital importance for assessment and preventing cardiovascular disease and target organ damage in the population.

Choline is used not only as an essential nutrient but also in therapeutics for infants’ neural tube defects. 28 Lacking of dietary choline can lead to nonalcoholic fatty liver disease and muscle damage. 29 However, the supplementation of high‐choline diet closely linked with CVD pathogenesis in both humans and animals. 11 Ren and his colleagues demonstrated that high choline‐treated mice exhibited significant dyslipidemia and hyperglycemia with impaired liver and vascular endothelium. 30 Interestingly, we also observed that fasting blood glucose levels increased along with choline concentrations in hypertensive patients compared to CON group (Table 1). We did not find any differences in lipid levels, such as LDL, HDL, TC, and TG, between the HTN and CON groups. However, the hypertensive patients were heavier than control group in our study population. Guo subjected mice with 3% dietary choline water for 8 weeks and revealed the associations between elevated endothelin 1 (ET‐1) and declined endothelin nitric oxide synthase (eNOS) and nitric oxide (NO) levels with high‐choline diet. 31 Growing evidence indicates that nitric oxide (NO) reduction under pathophysiological conditions is related to the development of endothelial dysfunction, while endothelial dysfunction is a driving force in CVD development. Zuo and his colleagues evaluated the associations between plasma choline and atrial fibrillation (AF) and revealed that choline was an independent risk factor for AF with odds ratio of 1.12 after adjustment for sex and age. 32 Accordingly, in our study, we found remarkably elevated choline levels in HTN patients with artery stenosis compared to those without. Notably, in our study, we failed to find any differences of CK‐MB levels, a novel marker of myocardial injury, between HTN patients with and without artery injury (Table 1). However, the logistic regression still indicated upregulated choline concentrations as an independent risk factor for artery injury after adjustment of multiple traditional risk factors (Table 2), which suggested choline as a more sensitive indicator for CVD risk in HTN. A previous study has indicated the instant leaking of choline from ischemic tissues into plasma in patients with severe repetitive arrythmias and hemodynamic compromise. 33 This study may help to explain the remarkably elevated choline in HTN patients with artery stenosis compared with those without. However, other confounding factors such as dietary intake and genetic variation in choline metabolism should be taken into account and investigated in future work.

Recent data have suggested that dietary choline could be metabolized by gut microbes to trimethylamine (TMA), and TMA could be oxidized by flavin monooxygenase‐3 (FMO3) in liver and turned to TMAO, which was linked to the risk of cardiovascular diseases such as atherosclerosis, stroke, and hypertension. 11 Li demonstrated that elevated circulating TMAO levels could contribute to the induction of vascular inflammation and oxidative stress, which leads to endothelial dysfunction. 34 Ueland's study reported both elevated TMAO and choline levels in patients with chronic heart failure and indicated the independent role of TMAO in inducing heart failure. 35 Interestingly, although we did not observe any statistical differences of TMAO concentrations between HTN patients without artery stenosis and healthy controls, we still found remarkably upregulated TMAO in HTN patient with artery stenosis compared with those without and healthy controls (Figure 1B). We also observed a weak but significant correlation between plasma concentrations of choline and TMAO (Figure 1C). These data may also help in partially explaining the important role of circulating choline as a risk factor for vessel injury in HTN. Previous data suggested that plasma choline could be utilized as a sensitive diagnostic indicator for the progression of acute ischemic stroke. 36 Our study expanded those findings by demonstrating the risk‐predicting power of choline in not only HTN but also artery stenosis in HTN as well as multivessel disease by ROC analysis. Taken together, our study proposed that plasma choline could be served as a reliable, convenient and noninvasive biomarker for risk stratification of HTN as well as for the as evaluation of the extent of vessel injury in HTN. It is noteworthy that the present study was an observational study, and the causal relationships between choline and HTN or artery stenosis remained elusive. Further investigations are warranted for evaluating the cardiovascular benefits led by therapeutic interventions on choline management and the precise mechanisms.

This study had several limitations. It was a cross‐sectional study, and we were unable to evaluate the future risk of choline in HTN. The number of subjects, particularly the number of HTN‐AS patients, was small in our study. The study was based in single‐center which made the selection bias inevitable. Although we elucidated the strong associations of choline with HTN and artery injury after adjustment for multiple traditional HTN and CVD risk factors, large concentration overlap was observed between HTN patients with or without artery injuries. Therefore, the diagnostic performance of choline in determining vascular lesions is indistinct yet. Other potential factors which might also influence the results, such as nutritional status and microbiota background, were not assessed in our study. Future work will be needed for the underlying mechanisms by which elevated choline contributed to HTN and artery stenosis.

5. CONCLUSIONS

In conclusion, the current study explored the correlation of plasma choline concentrations with HTN and artery injury in HTN. Our data suggested that the levels of plasma choline were positively correlated with HTN and coronary vessel injury, and plasma choline could be a useful biomarker for risk stratification of HTN and artery stenosis.

CONFLICT OF INTEREST

All authors have no conflict of interest.

AUTHOR CONTRIBUTIONS

DO, ZL, and FG: research idea, study design, and writing manuscript. YZ and XQ: sample and data acquisition. FG and ZT: sample analysis. FG: statistical analysis. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.

ETHICAL APPROVAL AND CONSENT TO PARTICIPATE

The study plan was approved by the Ethical Committee of Xiangya Hospital of Central South University.

STATEMENT OF HUMAN AND ANIMAL RIGHTS

All human studies have been reviewed by the committee and have been performed in accordance with the ethical standards laid down in an appropriate version of the 1964 Declaration of Helsinki.

INFORMED CONSENT

All participants gave their informed consent prior to their inclusion in the study.

CONSENT FOR PUBLICATION

The consent to publish was obtained from all participants in this study.

ACKNOWLEDGMENTS

The authors thank the support of Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples.

Guo F, Qiu X, Zhu Y, Tan Z, Li Z, Ouyang D. Circulating choline is associated with coronary artery stenosis in patients with hypertension: A cross‐sectional study of Chinese adults. J Clin Hypertens. 2020;22:2069–2076. 10.1111/jch.14025

Funding information

This work was funded by grant National Development of Key Novel Drugs for Special Projects of China (2017ZX09304014), the Natural Science Foundation of Hunan Province (2019JJ50966), and also supported by the Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples (2017TP1037).

Contributor Information

Zhenyu Li, Email: 801940@csu.edu.cn, Email: liyu1552@csu.edu.cn.

Dongsheng Ouyang, Email: 801940@csu.edu.cn, Email: liyu1552@csu.edu.cn.

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