ST-elevation myocardial infarction (STEMI) as a serious type of coronary artery disease (CAD)and stands as a leading cause of mortality and disability. Although percutaneous coronary intervention (PCI) has emerged as a critical intervention for acute myocardial infarction (AMI). Nevertheless, more than 6% of Asian AMI patients still face major adverse cardiovascular events (MACEs) within two years post-PCI1. Studies indicated a close relationship between insulin resistance and the onset and progression of atherosclerotic plaque, alongside factors like diabetes, obesity, and dyslipidemia, substantiating insulin resistance as a significant risk factor for CAD2,3. Insulin resistance disrupts the glucose and lipid metabolism balance, where chronic hyperglycemia from glucose metabolism disorders triggers oxidative stress and inflammation, culminating in cellular damage. Dysregulated lipid metabolism results in abnormal lipid profiles, such as elevated plasma triglycerides, reduced high-density lipoprotein (HDL-C) levels, and the formation of small, dense low-density lipoprotein particles, fostering atherosclerotic plaques’ development2.
Glycosylated hemoglobin A1c (HbA1c) serves as a long-term marker of blood glucose control, minimally affected by acute stress or glucose management, and elevated HbA1c is associated with increased risk of cardiovascular disease4. Irrespective of diabetes status, HbA1c emerges as a pivotal predictor of coronary artery stenosis severity in AMI patient5. Apolipoprotein A1 (ApoA1), the primary apolipoprotein of HDL-C, exerts anti-atherosclerotic effects, with lowered ApoA1 concentrations associated with an escalated risk of atherosclerotic cardiovascular disease6. Glycosylated hemoglobin A1c/Apolipoprotein (A1HbA1c/ApoA-1), an indirect marker of insulin resistance, serves as an accessible atherosclerosis indicator. This ratio also exhibits promise as a cardiovascular risk assessor in acute coronary syndrome (ACS) patients7,8.
Nonetheless, the full extent of HbA1c/ApoA-1’s role in STEMI patient prognosis post-PCI remains unclear. Thus, this study explores the correlation between HbA1c/ApoA-1 and short-term prognosis in STEMI patients following PCI. Notably, HbA1c/ApoA-1 emerges as an independent risk factor for short-term MACEs in STEMI patients post-PCI, offering valuable predictive capabilities for early MACEs identification and mitigation.
Results left ventricular ejection fraction(LVEF), left ventricular end-diastolic diameter, left ventricular end-systolic diameter (LVESD), and comprehensive venous blood analyses upon hospital admission covering blood tests, amino terminal brain natriuretic peptide precursor(pro-BNP),
Baseline characteristics of the two groups in the study cohort
The baseline characteristics of the two groups enrolled in current study were shown in Table 1. Of the 182 patients studied, there were 152 males and 30 females, with an average age of 60.1 ± 12.1 years. Patients in the MACEs group were older than those in the non-MACEs group. The MACEs group exhibited a higher prevalence of diabetes, Killip grades III to IV, multi-vessel coronary artery disease, left ventricular end-diastolic diameter, left ventricular end-systolic diameter (LVESD), amino terminal brain natriuretic peptide precursor(pro-BNP), γ-glutamyl transferase, fasting plasma glucose, HbA1c, and HbA1c/ApoA-1 compared to the non-MACEs group. Conversely, the MACEs group had lower admission left ventricular ejection fraction (LVEF), hemoglobin, hematocrit, and serum albumin levels than the non-MACEs group. Furthermore, a higher proportion of patients in the MACEs group were using β-blockers, angiotensin receptor-neprilysin inhibitor or renin-angiotensin system inhibitor (ARNI/RASi), and sodium-glucose transporter inhibitors (SGLT2) during hospitalization compared to the non-MACEs group (all P < 0.05, Table 1).
Table 1
Baseline characteristics of the two groups enrolled in current study.
|
NO-MACEs
(n = 132)
|
MACEs
(n = 50)
|
Tor χ2
|
P
|
Male, n (%)
|
112 (84.8)
|
40 (80.0)
|
0.619
|
0.431
|
Age, years
Medical history, n (%)
|
57.67 ± 11.60
|
62.70 ± 12.62
|
-2.550
|
0.012
|
Hypertension
|
68 (51.5)
|
26 (52.0)
|
0.003
|
0.953
|
Diabetes
|
37 (28.0)
|
29 (58.0)
|
14.092
|
< .001
|
Cerebral infarction
|
5 (3.8)
|
6 (12.0)
|
2.982
|
0.084
|
Prior PCI
|
15 (11.4)
|
8 (16.3)
|
0.793
|
0.373
|
Smoking
|
66 (50.0)
|
26 (52.0)
|
0.058
|
0.810
|
Drinking
|
38 (28.8)
|
13 (26.0)
|
0.049
|
0.894
|
Killip grade, n (%)
|
|
|
|
|
Grade I
|
91 (68.9)
|
20 (40.0)
|
24.598
|
< .001
|
Grade II
|
37 (28.0)
|
18 (36.0)
|
Grade III
|
4 (3.03)
|
10 (20.0)
|
Grade IV
|
0 (0.0)
|
2 (4.0)
|
TIMI grade, n (%)
|
|
|
|
|
Grade 0
|
43 (32.6)
|
24 (48.0)
|
5.402
|
0.148
|
Grade I
|
7 (5.3)
|
4 (8.0)
|
Grade II
|
13 (9.8)
|
2 (4.0)
|
Grade III
|
69 (52.3)
|
20 (40.0)
|
Artery lesions, n (%)
Multiple
Single
|
81 (61.36)
51 (38.64)
|
48 (96.00)
2 (4.00)
|
21.08
|
< .001
|
Systolic BP, mmHg
|
128.64 ± 23.13
|
123.680 ± 22.18
|
1.307
|
0.193
|
Diastolic BP, mmHg
|
76.12 ± 14.50
|
74.14 ± 13.40
|
0.832
|
0.407
|
LVEF, %
|
59.74 ± 9.59
|
51.72 ± 9.71
|
5.013
|
< .001
|
LVEDD, mm
|
52.72 ± 9.53
|
54.65 ± 8.87
|
-1.243
|
0.216
|
LVESD, mm
Laboratory tests
|
35.71 ± 7.90
|
39.39 ± 8.38
|
-2.760
|
0.006
|
HB, g/L
|
141.01 ± 18.76
|
133.28 ± 17.43
|
2.525
|
0.012
|
HCT, %
|
42.21 ± 5.15
|
40.17 ± 5.00
|
2.395
|
0.018
|
TNT-hs, pg/ml
Probnp, pg/ml
|
362.70(120.100,1828.0)
642.90(181.05,1772.00)
|
527.00(127.00,1892.00)
1382.00(331.52,3352.7)
|
-0.588
-2.178
|
0.556
0.029
|
TP, g/L
|
64.35 ± 5.32
|
63.59 ± 6.07
|
0.821
|
0.413
|
ALB, g/L
|
41.08 ± 3.81
|
38.84 ± 3.97
|
3.479
|
< .001
|
GLB, g/L
|
23.392 = ± 4.09
|
24.74 ± 4.16
|
-1.963
|
0.051
|
γ-GT, U/L
|
25.50 (17.00, 38.75)
|
29.00 (20.00, 67.00)
|
-2.07
|
0.038
|
ALP, IU/L
|
85.50 (72.00, 103.00)
|
88.00 (75.00, 97.00)
|
-0.19
|
0.851
|
UREA, mmol/L
|
5.34 ± 2.13
|
6.022 ± 1.92
|
-1.956
|
0.052
|
Cr, µmol/l
|
72.50 (63.67, 85.10)
|
73.350(65.57, 87.07)
|
-0.544
|
0.587
|
eGFR,mL/min/1.73m2
|
94.12 (82.75, 103.23)
|
90.35 (75.25, 101.53)
|
-1.45
|
0.148
|
CysC, mg/L
|
1.43 ± 4.65
|
1.07 ± 0.25
|
0.553
|
0.581
|
TC, mmol/l
|
4.08 ± 1.16
|
4.36 ± 1.10
|
-1.489
|
0.138
|
TG, mmol/L
|
1.73 ± 1.46
|
1.78 ± 1.08
|
-0.212
|
0.833
|
HDL-C, mmol/L
|
1.04 ± 0.22
|
1.06 ± 0.23
|
-0.370
|
0.712
|
LDL-C, mmol/l
|
2.52 ± 0.98
|
2.76 ± 1.03
|
-1.437
|
0.152
|
VLD, mmol/L
|
0.52 ± 0.48
|
0.610 ± 0.56
|
-1.063
|
0.289
|
ApoA-l, g/L
|
1.09 ± 0.17
|
1.14 ± 0.17
|
-1.574
|
0.117
|
ApoB, g/L
|
0.92 ± 0.30
|
0.99 ± 0.29
|
-1.489
|
0.138
|
Apoa, mg/dL
|
13.40 (6.25, 31.30)
|
13.60 (6.40, 27.80)
|
-0.11
|
0.912
|
FPG, mmol/l
|
6.13 ± 2.21
|
7.94 ± 3.01
|
-3.868
|
< .001
|
HbA1c, %
HbA1c/ApoA-1
Medications, n (%)
|
6.81 ± 1.77
6.31 ± 1.97
|
8.39 ± 2.29
7.45 ± 2.07
|
-4.403
-3.446
|
< .001
< .001
|
Aspirin
|
129 (97.7)
|
49 (98.0)
|
0.000
|
1.000
|
Clopidogrel
|
77 (58.3)
|
33 (66.0)
|
0.891
|
0.345
|
Tigrillo
|
50 (37.8)
|
17 (34.0)
|
0.235
|
0.628
|
Statins
|
129 (97.7)
|
49 (98.0)
|
0.000
|
1.000
|
Anticoagulants
|
34(87.2%)
|
73(81.1%)
|
1.163
|
0.603
|
Beta-blockers
|
64 (48.5)
|
33 (66.0)
|
4.469
|
0.035
|
ARNI/RASi
|
60 (45.4)
|
32 (64.0)
|
4.990
|
0.026
|
nicorandil
|
61 (46.2)
|
19 (38.0)
|
0.993
|
0.319
|
SGLT2i
|
38(28.8)
|
24(48.0)
|
5.959
|
0.015
|
Ivabradine
|
17(12.9)
|
11(22)
|
2.318
|
0.128
|
Multi-factor Logistic regression analysis of MACEs influencing factors of STEMI patients after PCI
Multivariate Logistic regression analysis revealed that HbA1c/ApoA-1 served as an independent risk factor for MACEs in STMEI patients post-PCI. Additionally, other independent predictors encompassed Killip grade III, multivessel coronary artery disease, decreased LVEF, increased of LVESD and γ-glutamyl transferase, and previous history of hypertension, diabetes, cerebral infarction, beta-blockers, and ARNI/RASi therapy. The differences exhibited statistical significance (P < 0.05), as shown in Table 2.
Table 2
Multi-factor Logistic regression analysis of MACEs influencing factors of STEMI patients after PCI.
| β | S.E | Z | P | OR (95%CI) |
Hypertension | 1.42 | 0.54 | 2.61 | 0.009 | 4.14 (1.42 ~ 12.02) |
Diabetes | -0.99 | 0.48 | -2.05 | 0.040 | 0.37 (0.14 ~ 0.96) |
cerebral infarction | -2.49 | 0.98 | -2.54 | 0.011 | 0.08 (0.01 ~ 0.57) |
Multivessel disease | 3.84 | 0.98 | 3.91 | < .001 | 46.75 (6.80 ~ 321.68) |
Killip III | 2.58 | 0.86 | 3.01 | 0.003 | 13.26 (2.46 ~ 71.45) |
LVEF | -0.19 | 0.05 | -3.95 | < .001 | 0.82 (0.75 ~ 0.91) |
LVESD | -0.19 | 0.06 | -3.20 | 0.001 | 0.82 (0.73 ~ 0.93) |
γ-GT | 0.02 | 0.01 | 2.19 | 0.029 | 1.02 (1.01 ~ 1.03) |
HbA1c/ApoA-1 | 0.40 | 0.14 | 2.97 | 0.003 | 1.50 (1.15 ~ 1.95) |
Beta-blockers | -1.05 | 0.51 | -2.06 | 0.040 | 0.35 (0.13 ~ 0.95) |
ARNI/ RASi | -1.23 | 0.54 | -2.28 | 0.022 | 0.29 (0.10 ~ 0.84) |
Different models and Subgroup analysis confirmed the HbA1c/ApoA-1 ratio as an independent risk factor for MACEs
Different models showed a significant correlation between HbA1c/ApoA-1 and MACEs following PCI in Table 3. Model 1 was a crude model without adjusting for confounding variables. Model 2 adjusted for age and gender. Model 3 adjustments covered gender, age, hypertension, diabetes, cerebral infarction, PCI history, smoking, alcohol consumption, statin usage, and cardiac function classification, confirming the HbA1c/ApoA-1 ratio as an independent predictive marker for MACEs in STEMI patients post-PCI (OR:1.40 ;95%CI :1.13–1.73; P = 0.002) (in Table 3). Subgroup analysis revealed no significant interactions concerning gender, diabetes, smoking history, alcohol usage, Killip grade III, multi-vessel disease, and other subgroup variables (P interaction > 0.05), solidified the study’s result reliability (in Table 4).
Table 3
Different models analyzed the HbA1c/ApoA-1 was a predictor for MACEs.
| Model1 | | Model2 | | Model3 |
OR (95%CI) | P | OR (95%CI) | P | OR (95%CI) | P |
HbA1c/ApoA-1 | 1.45 (1.22 ~ 1.72) | < .001 | | 1.44 (1.20 ~ 1.72) | < .001 | | 1.40 (1.13 ~ 1.73) | 0.002 |
Table 4 Subgroup analysis and interaction.
|
OR (95%CI)
|
P
|
P interaction
|
gender
Male
female
Diabetes
Yes
No
Smoking
|
1.52 (1.23 ~ 1.87)
1.33 (0.97 ~ 1.82)
1.36 (1.08 ~ 1.71)
1.41 (1.07 ~ 1.86)
|
<.001
0.08
0.009
0.016
|
0.490
0.841
|
Yes
No
|
1.52 (1.15 ~ 1.99)
1.45 (1.15 ~ 1.83)
|
0.003
0.002
|
0.802
|
Drinking
Yes
No
|
1.80(1.16 ~ 2.80)
1.38(1.15~ 1.67)
|
0.009
<.001
|
0.506
|
Killip III
Yes
|
3.95(0.62~ 24.35)
|
0.130
|
0.309
|
No
multi-vessel disease
Yes
No
|
1.14(1.173~ 1.71)
1.13(0.48~ 2.65)
1.38(1.14~ 1.63)
|
<.001
0.138
<.001
|
0.646
|
Killip III, Killip cardiac function grade III. P<0.05 was considered as statistically significant. P interaction > 0.05 was considered as statistically significant.
The predictive value of HbA1c/ApoA-1 for MACEs
Receiver operating characteristic (ROC) curve analysis illustrated the robust predictive capacity of HbA1c/ApoA-1 for MACEs in STEMI patients post-PCI, with an area under curve (AUC) of 0.752 (95%CI: 0.68–0.86) and corresponding sensitivity and specificity values of 85.7% and 56.8%, respectively. HbA1c/ApoA-1 ratio remained a reliable predictor for MACEs occurrence in STMEI patients post-PCI. As shown in Table 5 and Fig. 1.
Table 5
Results of ROC curve analysis.
| AUC | 95%CI | Optimal cut-off value | sensitivity | specificity | Youden index | P-value |
HbA1c/ApoA-1 | 0.752 | 0.68–0.86 | 6.35 | 85.7% | 56.8% | 0.425 | < 0.001 |
Nonlinear relationship between HbA1c/ApoA-1 and MACEs
Restricted cubic spline (RCS) curve analysis showed a statistically significant nonlinear association (P nonlinearity = 0.023) between HbA1c/ApoA-1 and the occurrence of MACEs. The inflection point of the RCS curve was identified at HbA1c/ApoA-1 = 6.5. Subsequently, the dataset was stratified based on this inflection point, leading to the conduct of distinct logistic regression analyses for each segment. The results indicated that for HbA1c/ApoA-1 < 6.5, (OR: 3.95; 95%CI: 1.56–9.99, P = 0.004), Conversely, for HbA1c/ApoA-1 ≥ 6.5, (OR: 1.47; 95%CI: 0.96–2.26, P = 0.075). as shown in Fig. 2.