Characteristics of patients in the discrepancy group
A total of 7,762 patients were included in this study (Additional file 1: Figure S1). The mean age was 64.4 (±11.6) years, and males accounted for 68.8% of the study population. The mean hemoglobin level was 135.1 (± 21.3) g/L, and the mean eGFR was 81.7 (± 25.4) ml min-1 (1.73 m)-2. A total of 53.3% of patients were treated with at least one class of oral glucose-lowering drugs or insulin. The numbers of patients in the consistent group and the discrepancy group were 5,490 (70.7%) and 2,272 (29.3%), respectively. Patients in the discrepancy group were more likely to have lower eGFR (Additional file 1: Figure S2). In the discrepancy group, increased HbA1c but normal FPG accounted for 77.5% of the discrepancies (1,761/2,272), and increased FPG but normal HbA1c group accounted for 22.5% of the discrepancies (511/2,272). The baseline characteristics of patients in the increased HbA1c but normal FPG group and increased FPG but normal HbA1c group are shown in Table 1. Patients in the increased FPG but normal HbA1c group were more likely to have lower eGFR, higher heart rate, poorer heart function, STEMI and hypertension, and be treated with glucose-lowering agents.
Table 1. Characteristics of patients with discrepancy between HbA1c and FPG.
|
HbA1c ≥ 6.5% and FPG < 7.0 mmol/L
(n = 1761)
|
HbA1c < 6.5% and FPG ≥ 7.0 mmol/L
(n = 511)
|
P value
|
Age (years, mean [SD])
|
65.4(11.2)
|
65.4(10.9)
|
0.947
|
Male (n [%])
|
1184(67.2)
|
348(68.1)
|
0.713
|
Systolic blood pressure (mmHg, mean [SD])
|
135.0(22.8)
|
135.0(25.2)
|
0.895
|
Diastolic blood pressure (mmHg, median [IQR])
|
78.0(70.0, 87.0)
|
78.0(70.0, 89.0)
|
0.442
|
Heart rate (bpm. Median [IQR])
|
78.0(68.0, 87.0)
|
80.0(70.0, 90.0)
|
< 0.001
|
Current smoker (n [%])
|
508(28.8)
|
153(29.9)
|
0.047
|
Family history of CHD (n [%])
|
71(4.0)
|
21(4.1)
|
0.937
|
Hypertension (n [%])
|
1300(73.8)
|
403(78.9)
|
0.021
|
Previous acute myocardial infarction (n [%])
|
214(12.2)
|
58(11.4)
|
0.623
|
Previous coronary artery bypass grafting (n [%])
|
16(0.9)
|
4(0.8)
|
0.789
|
Atrial fibrillation history (n [%])
|
53(3.0)
|
14(2.7)
|
0.751
|
Heart failure history (n [%])
|
58(3.3)
|
19(3.7)
|
0.640
|
Cerebrovascular disease history (n [%])
|
185(10.5)
|
57(11.2)
|
0.675
|
Peripheral artery disease history (n [%])
|
31(1.8)
|
10(2.0)
|
0.769
|
Killip class (n [%])
|
|
|
0.289
|
I or II
|
1505(85.5)
|
427(83.6)
|
|
III or IV
|
256(14.5)
|
84(16.4)
|
|
Types of ACS (n [%])
|
|
|
< 0.001
|
STEMI
|
716(40.7)
|
276(54.0)
|
|
NSTE-ACS
|
1045(59.3)
|
235(46.0)
|
|
HbA1c (%, mean [SD])
|
8.2(14.7)
|
5.8(0.8)
|
< 0.001
|
FPG (mmol/L, mean [SD])/ (mg/dl, mean [SD])
|
5.6(1.2)/ 100.8(21.6)
|
9.5(2.6)/ 171.0(46.8)
|
< 0.001
|
eGFR (ml min-1 [1.73m]-2, mean [SD])
|
79.1(25.1)
|
76.4(27.3)
|
0.046
|
Hemoglobin (g/l, mean [SD])
|
132.1(20.4)
|
132.4(23.6)
|
0.192
|
Total cholesterol (mmol/L, median [IQR])/ (mg/dl, median [IQR])
|
4.3(3.5, 5.1)/ 166.2(135.3, 197.2)
|
4.3(3.5, 5.1)/ 166.2(135.3, 197.2)
|
0.721
|
HDL-cholesterol (mmol/L, median [IQR])/ (mg/dl, median [IQR])
|
1.0(0.8, 1.2)/ 38.7(30.9, 46.4)
|
1.0(0.8, 1.2) / 38.7(30.9, 46.4)
|
0.931
|
LDL-cholesterol (mmol/L, median [IQR])/ (mg/dl, median [IQR])
|
2.6(2.0, 3.2)/ 100.5(77.3, 123.7)
|
2.5(2.0, 3.2)/ 96.7(77.3, 123.7)
|
0.326
|
Triglyceride (mmol/L, median [IQR])/ (mg/dl, median [IQR])
|
1.6(1.1, 2.4)/ 141.8(97.5, 212.6)
|
1.5(1.0, 2.3)/ 132.9(88.6, 203.8)
|
0.027
|
Oral glucose-lowering agents or insulin use before admission (n [%])
|
809(45.9)
|
288(56.4)
|
< 0.001
|
Therapy during hospitalization (n [%])
|
|
|
|
Percutaneous coronary intervention
|
1170(66.4)
|
337(65.9)
|
0.836
|
Aspirin
|
1644(93.4)
|
482(94.3)
|
0.432
|
P2Y12 inhibitors
|
1603(91.0)
|
473(92.6)
|
0.276
|
Statins
|
1653(93.9)
|
477(93.3)
|
0.669
|
β-blockers
|
1146(65.1)
|
291(56.9)
|
0.001
|
ACE inhibitor/angiotensin receptor blocker
|
917(52.1)
|
248(48.5)
|
0.159
|
Patients with referral (n [%])
|
587(33.3)
|
172(33.7)
|
0.891
|
ACE, angiotensin-converting enzyme; ACS, acute coronary syndrome; CHD, coronary heart disease; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; HbA1c, glycosylated hemoglobin; HDL, high density lipoprotein; IQR, interquartile range; LDL, low density lipoprotein; NSTE-ACS, non-ST-segment elevation acute coronary syndrome; SD, standard deviation; STEMI, ST-segment elevation myocardial infarction.
The prevalence of the increased FPG but normal HbA1c discrepancy was higher in patients over 65 years of age, hemoglobin less than 120 g/L, eGFR less than 60 ml min-1 (1.73 m)-2, Killip class III or IV, and STEMI and who were treated with oral glucose-lowering drugs or insulin (Figure 1, Additional file 1: Table S2).
Type of discrepancy and in-hospital outcomes
The comparison of in-hospital outcomes between the increased HbA1c but normal FPG group and the increased FPG but normal HbA1c group is shown in Figure 2. The rates of all the in-hospital outcomes were higher in the increased FPG but normal HbA1c group than in the increased HbA1c but normal FPG group. A logistic regression model was performed to explore the relationship between the type of discrepancy and in-hospital outcomes, except for death from any cause because of the small event number. In univariate logistic regression analysis, a significantly higher risk of all the in-hospital outcomes was observed in patients with increased FPG but normal HbA1c (Table 2). After adjusting for confounders in the multivariate logistic regression model, patients in the increased FPG but normal HbA1c group had a significant 1.6-fold increased risk of heart failure (OR, 1.62; 95% CI, 1.08-2.44), a 1.6-fold increased risk of composite cardiovascular death and heart failure (OR, 1.63; 95% CI, 1.09-2.43), and a 1.6-fold increased risk of composite MACCEs and heart failure (OR, 1.56; 95% CI, 1.08-2.24) (Table 2). The effect on MACCEs was not significant (OR, 1.49; 95% CI, 0.85-2.63) (Table 2). Furthermore, in order to investigate the association between the severe discrepancy and in-hospital outcomes, we used the cut off values of HbA1c 7.5% and FPG 8.0mmol/L. Although the significant P values were not shown in logistic regression analysis, trends that patients in the increased FPG group had a higher risk of MACCEs, heart failure, composite cardiovascular dearth and heart failure, and composite MACCEs and heart failure were observed (Additional file 1: Table S3).
Table 2. Logistic regression analysis for in-hospital outcomes in increased FPG group compared with increased HbA1c group†.
|
Unadjusted OR (95% CI)
|
P value
|
Adjusted OR
(95% CI)*
|
P value
|
MACCE
|
1.94(1.13-3.34)
|
0.016
|
1.52(0.85-2.72)
|
0.158
|
Heart failure
|
2.09(1.42-3.07)
|
< 0.001
|
1.63(1.07-2.48)
|
0.024
|
Cardiovascular death or heart failure
|
2.11(1.44-3.07)
|
< 0.001
|
1.63(1.08-2.47)
|
0.021
|
MACCE or heart failure
|
1.98(1.41-2.79)
|
< 0.001
|
1.57(1.07-2.28)
|
0.020
|
† A categorized variable to compare increased FPG group with increased HbA1c group was used in logistic regression analysis.
* ORs were adjusted for age, gender, systolic blood pressure, heart rate, current smoker, hypertension, hemoglobin at admission, eGFR at admission, Killip class, type of acute coronary syndrome, and glucose-lowering drug use, and β-blocker use during hospitalization.
FPG, fasting plasma glucose; HbA1c, glycosylated hemoglobin; MACCE, major adverse cardiovascular and cerebrovascular event.
Subgroup analysis was performed based on age, sex, medical history, Killip class, hemoglobin, eGFR, type of ACS, and glucose-lowering drug use before hospitalization. A higher risk of all the in-hospital outcomes was observed in patients with increased FPG but normal HbA1c, which was consistent in all subgroups (all P for interaction > 0.05), except for the eGFR subgroup for MACCEs (Figure 3), which showed that increased FPG but normal HbA1c increased the risk of MACCEs to a greater extent in patients with eGFR ≥ 60 ml min-1 (1.73 m)-2.