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Research Article | Open Access

Volume 2021 |Article ID 6689056 | https://doi.org/10.1155/2021/6689056

Lizhe Sun, Manyun Guo, Chenbo Xu, Xiangrui Qiao, Yiming Hua, Gulinigaer Tuerhongjiang, Bowen Lou, Ruifeng Li, Xiaofang Bai, Juan Zhou, Yue Wu, Jianqing She, Zuyi Yuan, "HDL-C/apoA-I Ratio Is Associated with the Severity of Coronary Artery Stenosis in Diabetic Patients with Acute Coronary Syndrome", Disease Markers, vol. 2021, Article ID 6689056, 10 pages, 2021. https://doi.org/10.1155/2021/6689056

HDL-C/apoA-I Ratio Is Associated with the Severity of Coronary Artery Stenosis in Diabetic Patients with Acute Coronary Syndrome

Academic Editor: Alexander Berezin
Received13 Nov 2020
Revised30 Mar 2021
Accepted15 Apr 2021
Published18 May 2021

Abstract

Background. Emerging evidence demonstrates that the lipid metabolism in acute coronary syndrome (ACS) patients with type 2 diabetes mellitus (T2DM) differs from nondiabetic patients. However, the distinct lipid profiles and their relationships with the severity of coronary artery stenosis and prognosis in patients with T2DM remain elusive. Method and Result. This single-center, prospective cohort study enrolled 468 patients diagnosed with ACS undergoing coronary angiography, consisting of 314 non-DM and 154 DM patients. The HDL-C/apoA-I ratio was significantly higher in DM patients with a multivessel (≥3 affected vessels) lesion than a single-vessel (1-2 affected vessels) lesion. Regression analyses showed that the HDL-C/apoA-I ratio was positively correlated to the number of stenotic coronary arteries in DM patients but not non-DM patients. However, Kaplan-Meier survival analysis revealed no significant difference in the major adverse cardiovascular event rate regarding different HDL-C/apoA-I levels in DM or non-DM ACS patients at the end of the 2-year follow-up. Conclusion. A higher HDL-C/apoA-I ratio is associated with increased severity of coronary artery stenosis in DM patients with ACS but not with the rate of major adverse cardiovascular events at the end of the 2-year follow-up.

1. Introduction

Acute coronary syndrome (ACS) is one of the major public health problems worldwide, which describes the range of acute myocardial ischemic states, including unstable angina (UA), non-ST elevated myocardial infarction (NSTEMI), and ST elevated myocardial infarction (STEMI) [1]. Hyperglycemia and dyslipidemia are risk factors for ACS [2]. Numerous studies have revealed that type 2 diabetes mellitus (T2DM) patients with ACS suffer from worse outcomes compared to their nondiabetic peers [36]. Our previous study demonstrated that hemoglobin A1c (HbA1c) was positively correlated with the severity of coronary artery stenosis in both diabetic and nondiabetic patients with ACS [7]; however, the underlying pathophysiological mechanism and clinical manifestations remain to be elucidated.

High-density lipoprotein cholesteryl (HDL-C) was ascribed as “good” cholesteryl and negatively correlated to the risk of cardiovascular diseases, as proven by several clinical and animal studies [8, 9]. The mechanisms of the antiatherogenic effects of HDL-C have been proved to be related to its involvement in the pathways of reverse cholesteryl transport, as well as antioxidation, anti-inflammation, and endothelial protection [8, 10]. However, HDL from T2DM patients showed impaired endothelial-protective capacities due to reduced endothelial progenitor cell-mediated endothelial repair [11]. A systemic review of 14 studies has also revealed that the anti-inflammatory effect of HDL was diminished in individuals with T2DM, although the underlying mechanisms remain to be elucidated [12]. These indicate that HDL may undergo functional remodeling during the progression of chronic inflammatory and metabolic diseases.

Apolipoprotein A-I (apoA-I) is the primary functional apolipoprotein component of HDL participating in cholesteryl traffic via multiple mechanisms [13]. For instance, apoA-I plays pivotal roles in the reverse cholesteryl transport pathway by modulating HDL-C formation and stabilization, binding to hepatic scavenger receptors, and activating lecithin-cholesteryl acyltransferase [14]. Overexpression of the human apoA-I gene on apoE-/- and LDLr-/- mice provided long-term protection on diet-induced atherosclerosis [15, 16]. A previous study indicated that the HDL-C/apoA-I ratio is a more effective marker for coronary artery disease than HDL-C alone [17]. However, it is unknown whether the HDL-C/apoA-I ratio correlates to the severity of coronary artery stenosis and prognosis of diabetic ACS patients.

In this present single-center, prospective study, by analyzing the circulating lipid profile and the major adverse cardiovascular events (MACEs) among ACS patients with or without DM, we aimed to evaluate the relationship between the HDL-C/apoA-I ratio and the severity of coronary artery stenosis and also to explore the short-term prognostic value of the HDL-C/apoA-I ratio in ACS patients.

2. Research Design and Methods

2.1. Study Design and Participants

This is a single-center, prospective cohort study in which 468 ACS patients were recruited, consisting of 229 UA, 71 NSTEMI, and 168 STEMI patients consecutively admitted to the First Affiliated Hospital of Xi’an Jiaotong University from January to December 2016. This study excluded patients who had severe noncardiac disease with an expected survival of less than 1 year, severe renal disease (plasma μmol/L), and chronic liver disease (alanine aminotransferase times the upper limit of normal) or over the age of 80 years. Written informed consent was obtained from all study participants with ethical committee approval from the First Affiliated Hospital of Xi’an Jiaotong University.

2.2. Data Collection and Laboratory Measurement

Baseline characteristics and clinical data were recorded from patients’ standard medical records. Blood HbA1c levels of all patients were measured within 3 h of admission using a Siemens DCA analyzer for quantitative assay. Both the concentrations of specific HbA1c and total hemoglobin were measured. The ratio was reported as percent HbA1c.

Venous blood samples were collected in the morning following an overnight fast for other baseline laboratory measurements. TC was detected using a detection kit from FUJIFILM™ via the HMMPS method; HDL-C, LDL-C, and VLDL-C were detected using a detection kit via the direct measurement method from FUJIFILM™; apoA, apoB, and apoE were measured using a detection kit from SEKISUI™ by turbidimetric inhibition immunoassay. All laboratory assays were performed in duplicate, and the results were averaged.

2.3. Assessment of Coronary Artery Stenosis

Selective coronary angiography was performed in multiple views by experienced clinicians. The severity of ACS was characterized by the number of coronary vessels with stenosis (>50% of the lumen diameter). A single-vessel lesion was defined as 1-2 affected vessels, and a multivessel lesion was defined as at least 3 affected vessels.

2.4. Outcome and Follow-Up

Follow-up information was obtained via telephone questionnaires or interviews in the hospital by the general practitioner. All-cause death, heart failure, nonfatal MI, and symptom-driven revascularization were defined as MACEs.

2.5. Statistical Analysis

All statistical analyses were performed using SPSS 18.0. Data were presented as frequencies and percentages for categorical variables and for continuous variables unless otherwise indicated. Differences between two independent groups were compared using the chi-squared test for categorical data, -test for normally distributed data, and nonparametric test for nonnormally distributed data. One-way ANOVA was used to compare continuous variables among multiple groups. Univariate linear regression analysis was used for calculating the correlation between the HbA1c, the HDL-C/apoA-I ratio, and the severity of coronary artery stenosis. Multivariate regression analysis was conducted to assess the independent contribution of different factors to coronary artery stenosis. DM and non-DM patients were divided into three groups based on tertiles of the HDL-C/apoA-I level. Kaplan-Meier survival curve analysis was conducted to represent the proportional risk of MACE for the HDL-C/apoA-I ratio in patients with or without DM. All probability values were two-tailed. was considered statistically significant.

3. Results

3.1. Study Population and Baseline Characteristics

A total of 1500 patients with a diagnosis of ACS were screened, of which 173 patients did not meet the inclusion criteria, 504 refused to participate, and 355 were not included in this study due to other reasons. 468 ACS patients were enrolled in the observational study, consisting of 314 non-DM (67.09%) and 154 DM (32.91%) patients. At the end of this study, 245 of 314 non-DM patients (78.03%) and 125 of 154 DM patients (81.71%) completed the 2-year follow-up survival analysis or reached endpoints (Figure 1).

Baseline characteristics of all patients and patients in the non-DM/DM subgroups are shown in Table 1. The 468 ACS patients had a mean age of years with a mean HbA1c of and a mean HDL-C/apoA-I ratio of  mmol/g. The mean number of affected vessels indicated by coronary angiography was in DM patients, significantly higher than that in non-DM patients (, ). Additionally, the HbA1c level was also higher in DM patients compared to non-DM ACS patients ( vs. , ). Although no differences were found in low-density lipoprotein cholesteryl (LDL-C), HDL-C, and apoA-I, the HDL-C/apoA-I ratio was lower in diabetic ACS patients than in non-DM patients ( vs. , ). No differences in other risk factors were found between the non-DM and DM ACS patients, such as age, gender, family history of coronary artery disease, history of hypertension, heart rate (HR), creatine, blood urea nitrogen (BUN), and medication at discharge.


CharacteristicsWhole ()Non-DM ()DM () value

Agens
Male, (%)365 (78.00)249 (79.30)116 (75.32)ns
BMI (kg/m2)ns
Current smoker, (%)135 (28.8)93 (29.62)42 (27.27)ns
Family history of CAD, (%)183 (39.10)129 (41.08)54 (35.06)ns
Hypertension, (%)255 (54.5)166 (52.87)89 (57.79)ns
Heart rate (bpm)ns
Systolic BP (mmHg)ns
Diastolic BP (mmHg)ns
LVEF (%)ns
Affected vessels<0.05
BUNns
Creatine (μmol/L)ns
hsCRP (mg/dL)ns
HDL-C (mmol/L)ns
LDL-C (mmol/L)ns
Triglyceride (mmol/L)ns
Lipoprotein A (mg/L)ns
apoA-I (g/L)ns
HbA1c (%)<0.001
HDL-C/apoA-I (mmol/g)<0.01
Medication at discharge
 Aspirin, (%)462 (98.7)309 (98.4)153 (99.4)ns
 Clopidogrel, (%)448 (95.7)300 (95.5)148 (96.1)ns
 Statin, (%)459 (98.1)309 (98.4)150 (97.4)ns
 ACEI/ARB, (%)417 (89.1)278 (88.5)139 (90.3)ns
 Beta-blockers, (%)410 (87.6)276 (87.9)134 (87.0)ns
 CCB, (%)102 (21.8)68 (21.7)34 (22.1)ns
Main diagnosis
 UA229 (48.9)150 (47.77)79 (51.30)ns
 NSTEMI71 (15.2)50 (15.92)21 (13.64)ns
 STEMI168 (35.9)114 (36.31)54 (35.06)ns

Data are and number (%). ACS: acute coronary syndrome; ACEI: angiotensin-converting enzyme inhibitor; apoA-I: apolipoprotein A-I; ARB: angiotensin receptor blocker; BMI: body mass index; BP: blood pressure; BUN: blood urea nitrogen; CAD: coronary artery disease; CCB: calcium channel blocker; CKMB: creatine kinase MB; DM: diabetes mellitus; HbA1c: hemoglobin A1c; HDL-C: high-density lipoprotein cholesterol; hsCRP: high-sensitivity C-reactive protein; LDL-C: low-density lipoprotein cholesterol; LVEF: left ventricular ejection fraction; NSTEMI: non-ST elevated myocardial infarction; STEMI: ST elevated myocardial infarction; UA: unstable angina.
3.2. Baseline Characteristics of Patients with Single- and Multivessel Lesions

Baseline characteristics of ACS patients with single-vessel (1-2 affected vessels) and multivessel (≥3 affected vessels) lesions are shown in Table 2. No differences were found in risk factors, including age, gender, BMI, heart rate, systolic/diastolic blood pressure (BP), creatine, left ventricular ejection fraction (LVEF), HDL-C, and LDL-C, between the single- and multivessel lesion groups in either all, non-DM, or DM ACS patients.


CharacteristicsAffected vessels value
1–2≥3

All
 Patient number, (%)213 (45.5)255 (54.5)
 Agens
 Male, (%)154 (75.9)196 (80.7)ns
 BMI (kg/m2)ns
 Heart rate (bpm)ns
 Systolic BP (mmHg)ns
 Diastolic BP (mmHg)ns
 LVEF (%)ns
 Creatine (μmol/L)ns
 HDL-C (mmol/L)ns
 LDL-C (mmol/L)ns
 Triglyceride (mmol/L)ns
 Lipoprotein A (mg/L)ns
 apoA-I (g/L)<0.05
 HbA1c (%)<0.05
 HDL-C/apoA-I (mmol/g)ns
Non-DM
 Patient number, (%)149 (47.5)165 (52.5)
 Agens
 Male, (%)107 (77.0)130 (83.3)ns
 BMI (kg/m2)ns
 HR (bpm)ns
 Systolic BP (mmHg)ns
 Diastolic BP (mmHg)ns
 LVEF (%)ns
 Creatine (μmol/L)ns
 HDL-C (mmol/L)ns
 LDL-C (mmol/L)ns
 Triglyceride (mmol/L)ns
 Lipoprotein A (mg/L)ns
 apoA-I (g/L)<0.05
 HbA1c (%)ns
 HDL-C/apoA-I (mmol/g)ns
DM
 Patient number, (%)64 (41.6)90 (58.4)
 Agens
 Male, (%)47 (73.4)66 (75.9)ns
 BMI (kg/m2)ns
 HR (bpm)ns
 Systolic BP (mmHg)ns
 Diastolic BP (mmHg)ns
 LVEF (%)ns
 Creatine (μmol/L)ns
 HDL-C (mmol/L)ns
 LDL-C (mmol/L)ns
 Triglyceride (mmol/L)ns
 Lipoprotein A (mg/L)ns
 apoA-I (g/L)ns
 HbA1c (%)<0.05
 HDL-C/apoA-I (mmol/g)<0.05

Data are and number (%). ACS: acute coronary syndrome; apoA-I: apolipoprotein A-I; BMI: body mass index; BP: blood pressure; DM: diabetes mellitus; HbA1c: hemoglobin A1c; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; LVEF: left ventricular ejection fraction.

In the whole population, 213 patients had multivessel lesions, while 255 patients had a single-vessel lesion. HbA1c was higher in patients with multivessel lesions ( vs. , ). However, apoA-I is lower in patients with multivessel lesions than a single-vessel lesion ( vs. , ).

In the non-DM subgroup, 165 and 149 patients had multi- and single-vessel lesions, respectively. HbA1c was unaltered between patients with different numbers of affected vessels, whereas apoA-I was decreased in patients with multivessel lesions compared to those with a single-vessel lesion ( vs. , ).

In the DM subgroup, 90 and 64 patients had multi- and single-vessel lesions, respectively. HbA1c was in patients with multiple-vessel lesions, which is significantly higher than that in patients with a single-vessel lesion (, ). Moreover, the HDL-C/apoA-I ratio was higher in multivessel lesion DM patients than in single-vessel lesion DM patients ( vs. , ).

3.3. Association between HDL-C/apoA-I and Severity of Coronary Artery Stenosis

The severity of coronary artery stenosis was evaluated by the number of affected vessels suffering from coronary artery stenosis as described. Simple linear regression analysis demonstrated that the HDL-C/apoA-I ratio was positively correlated with the severity of coronary artery stenosis in DM ACS patients (, ). However, the HDL-C/apoA-I ratio was not associated with the severity of coronary artery stenosis in non-DM ACS patients (Figure 2).

Multiregression analysis was then performed to further determine the risk factors regarding the severity of coronary artery stenosis (Table 3). Consistently, the HDL-C/apoA-I ratio was only found to be significantly positively correlated to the severity of coronary artery stenosis in diabetic ACS patients (95% CI 0.235 to 3.368, ).


VariableCoefficient95% CI value

Non-DM
 Age0.012-0.002 to 0.025ns
 BMI (kg/m2)0.006-0.033 to 0.045ns
 HDL-C/apoA-I (mmol/g)-0.091-1.263 to 1.080ns
 apoA-I (g/L)-0.299-0.986 to 0.387ns
 HbA1c (%)0.178-0.166 to 0.521ns
DM
 Age-0.019-0.038 to 0.000ns
 BMI (kg/m2)0.005-0.044 to 0.054ns
 HDL-C/apoA-I (mmol/g)1.8010.235 to 3.368<0.05
 apoA-I (g/L)-0.317-1.252 to 0.618ns
 HbA1c (%)0.052-0.057 to 0.162ns

Data are the and number (%). apoA-I: apolipoprotein A-I; BMI: body mass index; BP: blood pressure; DM: diabetes mellitus; HbA1c: hemoglobin A1c; HDL-C: high-density lipoprotein cholesterol.
3.4. Comparison of Characteristics between Patients with Different HDL-C/apoA-I Levels

Patients were divided into 3 groups based on HDL-C/apoA-I tertiles, and the comparison of various characteristics is shown in Table 4. In the whole population, age, HDL-C, LDL-C, and apoA-I were significantly increased in uprising HDL-C/apoA-I levels (). On the contrary, BMI was stepwise decreased based on HDL-C/apoA-I levels (). Patients with the middle level of HDL-C/apoA-I had the highest level of HbA1c compared to those with low and high levels of HDL-C/apoA-I ( vs. vs. , ). No difference in gender, HR, BP, LVEF, and the number of stenotic coronary arteries was found in this comparison. Similar trends of all these characteristics were found in the non-DM ACS patients.


CharacteristicsHDL/apoA value
<0.770.77-0.89>0.89

All
 Patient number152161155
 Age<0.001
 Male, (%)121 (79.6)125 (77.6)119 (76.8)ns
 BMI (kg/m2)<0.01
 HR (bpm)ns
 Systolic BP (mmHg)ns
 Diastolic BP (mmHg)ns
 LVEF (%)ns
 Creatine (μmol/L)ns
 HDL-C (mmol/L)<0.001
 LDL-C (mmol/L)<0.01
 Triglyceride (mmol/L)<0.001
 Lipoprotein A (mg/L)<0.05
 apoA-I (g/L)<0.01
 HbA1c (%)<0.01
 HDL-C/apoA-I (mmol/g)<0.001
 Affected vesselsns
Non-DM
 Patient number92103110
 Age<0.001
 Male, (%)75 (81.5)84 (81.6)90 (75.6)ns
 BMI (kg/m2)<0.001
 HR (bpm)ns
 Systolic BP (mmHg)ns
 Diastolic BP (mmHg)ns
 LVEF (%)ns
 Creatine (μmol/L)ns
 HDL-C (mmol/L)<0.001
 LDL-C (mmol/L)ns
 Triglyceride (mmol/L)<0.001
 Lipoprotein A (mg/L)<0.01
 apoA-I (g/L)<0.05
 HbA1c (%)ns
 HDL-C/apoA-I (mmol/g)<0.001
 Affected vesselsns
DM
 Patient number605836
 Age<0.05
 Male, (%)46 (76.7)41 (70.7)29 (80.6)ns
 BMI (kg/m2)ns
 HR (bpm)ns
 Systolic BP (mmHg)ns
 Diastolic BP (mmHg)ns
 LVEF (%)ns
 Creatine (μmol/L)ns
 HDL-C (mmol/L)<0.001
 LDL-C (mmol/L)ns
 Triglyceride (mmol/L)<0.001
 Lipoprotein A (mg/L)ns
 apoA-I (g/L)ns
 HbA1c (%)ns
 HDL-C/apoA-I (mmol/g)<0.05
 Affected vessels