A total of 1,911 patients with SIHD without prior revascularization or heart failure at admission were analyzed, of which 771 patients (40.3%) had DM (Fig. 1). The distribution of CCS class 0, I or II, and III or IV at baseline was 40.1% and 48.6%, 11.3% and 30.9%, and 54.9% and 14.2% in patients with DM and those without DM, respectively (P < 0.001). Patients with DM were more likely to be male and to have comorbidities, such as hypertension, dyslipidemia, and CKD, and multivessel disease (Table 1).
Table 1
Baseline characteristics according to DM status
Characteristic
|
Patients with DM, N = 771
|
Patients without DM, N = 1,140
|
P value
|
Age (years)
|
69 (62, 75)
|
70 (63, 76)
|
0.058
|
Female (%)
|
144 (18.7%)
|
276 (24.3%)
|
0.004
|
BMI (kg/m2)
|
24.3 (22.3, 26.7)
|
23.9 (22.1, 26.0)
|
0.004
|
Hypertension (%)
|
641 (83.2%)
|
845 (74.5%)
|
< 0.001
|
Dyslipidemia (%)
|
538 (69.9%)
|
714 (63.0%)
|
0.002
|
CKD (%)
|
331 (44.3%)
|
396 (35.9%)
|
< 0.001
|
HFrEF (%)
|
19 (2.5%)
|
23 (2.0%)
|
0.5
|
PAD (%)
|
106 (13.7%)
|
136 (12.0%)
|
0.3
|
Past history of MI (%)
|
54 (7.0%)
|
66 (5.8%)
|
0.3
|
Past history of HF (%)
|
50 (6.5%)
|
41 (3.6%)
|
0.004
|
Number of antianginal drugs (%)
|
|
|
0.3
|
0
|
681 (88.3%)
|
981 (86.1%)
|
|
1
|
69 (8.9%)
|
123 (10.8%)
|
|
more than 1
|
21 (2.7%)
|
36 (3.2%)
|
|
Anginal severity (%)
|
|
|
< 0.001
|
CCS 0
|
309 (40.1%)
|
352 (30.9%)
|
|
CCS I
|
133 (17.3%)
|
200 (17.5%)
|
|
CCS II
|
242 (31.4%)
|
426 (37.4%)
|
|
CCS III or IV
|
87 (11.3%)
|
162 (14.2%)
|
|
Unprotected LMT lesion (%)
|
48 (6.2%)
|
60 (5.3%)
|
0.4
|
Proximal LAD lesion (%)
|
286 (37.1%)
|
413 (36.2%)
|
0.7
|
Number of diseased vessels (%)
|
|
|
< 0.001
|
1
|
353 (45.8%)
|
651 (57.1%)
|
|
2
|
271 (35.1%)
|
357 (31.3%)
|
|
3
|
147 (19.1%)
|
132 (11.6%)
|
|
Optimal medical therapy (%)
|
536 (69.6%)
|
838 (73.7%)
|
0.051
|
Aspirin at discharge (%)
|
754 (98.4%)
|
1,118 (98.6%)
|
0.8
|
P2Y12 inhibitors at discharge (%)
|
736 (95.5%)
|
1,087 (95.4%)
|
> 0.9
|
Statin at discharge (%)
|
561 (73.2%)
|
883 (77.9%)
|
0.019
|
Beta blockers at discharge (%)
|
405 (52.8%)
|
572 (50.4%)
|
0.3
|
RAASi at discharge (%)
|
453 (59.1%)
|
535 (47.1%)
|
< 0.001
|
Data presented as median [interquartile range (IQR)] or n (%). CKD was defined as estimated glomerular filtration rate of less than 60 ml/min/1.73 m². HFrEF was defined as ejection fraction of less than 40%. Optimal medical therapy was defined as dual antiplatelet therapy and statins at discharge. Abbreviations: BMI, body mass index; CKD, chronic kidney disease; HFrEF, heart failure with reduced ejection fraction; PAD, peripheral artery disease; MI, myocardial infarction; HF, heart failure; CCS, Canadian Cardiovascular Society functional classification; LMT, left main coronary trunk; LAD, left anterior descending; RAASi, renin-angiotensin-aldosterone system inhibitors
The prevalence of unprotected LMT lesions increased with angina severity regardless of DM status. Similarly, the prevalence of pLAD lesions increased with angina severity in those with DM, whereas no association was observed in those without DM. By contrast, the prevalence of multivessel disease was not associated with angina severity regardless of DM status (Fig. 2). In patients with DM, multivariable logistic regression analyses revealed that pLAD lesions were associated with severe angina (adjusted odds ratio [aOR] 1.68 [95% CI 1.06, 2.66]; P = 0.028). In those without DM, female sex (aOR 1.59 [95% CI 1.08, 2.33]; P = 0.018), absence of hypertension (aOR 0.65 [95% CI 0.45, 0.96]; P = 0.030 for hypertension), and presence of CKD (aOR 1.57 [95% CI 1.09, 2.26]; P = 0.015) were associated with severe angina. The interaction analysis demonstrated that the association of high-risk coronary anatomies with severe angina did not depend on the patient’s DM status (interaction P value > 0.05 for all high-risk coronary anatomies, Fig. 3).
The median follow-up duration was 1,028 (interquartile range [IQR], 847-1,223) days, and the follow-up compliance rate was 91.7%. The incidence rates of the primary outcome at 2 years did not differ by DM status (8.2% and 10% in patients without and with DM, respectively; P = 0.16 [log-rank test]); however, patients with SIHD and DM had higher rates of the secondary outcome components than did those without DM (3.3% and 5.6% in patients without and with DM, respectively; P = 0.014 [log-rank test]) (Fig. 4). Multivariable Cox regression models revealed that DM was not associated with the primary or secondary outcome (adjusted hazard ratio [aHR] 1.08 [95% CI 0.79, 1.48]; P = 0.63 and aHR 1.52 [95% CI 0.96, 2.42]; P = 0.075, for the primary and secondary outcomes, respectively).
Among patients with DM, severe angina was associated with a higher incidence of the primary outcome after 2 years (9.1%, 9.3%, and 17% for CCS classes 0, I or II, III or IV, respectively; P = 0.049 [log-rank test]), whereas no association was observed with the secondary outcome (4.9%, 5.7%, and 8.2% for CCS classes 0, I or II, III or IV, respectively; P = 0.49 [log-rank test]). By contrast, angina severity was not associated with the incidence of the primary or secondary outcome in those without DM (9.9%, 7.5%, and 7.4%; P = 0.38 and 3.2%, 3.6%, and 2.5%; P = 0.79 in CCS classes 0, I or II, III or IV for the primary and secondary outcomes, respectively) (Fig. 5). Multivariable Cox regression models revealed that severe angina was associated with the incidence of the primary outcome (aHR 1.93 [95% CI 1.01, 3.71]; P = 0.047), whereas angina severity was not associated with the incidence of the secondary outcome (aHR 1.71 [95% CI 0.68, 4.32]; P = 0.26) in patients with DM. In those without DM, the presence of severe angina was not associated with either the primary or secondary outcome (Table 2).
Table 2
Association of baseline angina severity with long-term outcome according to DM status
|
Primary outcome
|
|
Secondary outcome
|
|
Patients with DM
|
Patients without DM
|
|
Patients with DM
|
Patients without DM
|
Characteristic
|
HR
|
95% CI
|
P value
|
HR
|
95% CI
|
P value
|
|
HR
|
95% CI
|
P value
|
HR
|
95% CI
|
P value
|
Anginal severity
|
|
|
|
|
|
|
|
|
|
|
|
|
|
CCS 0
|
—
|
—
|
|
—
|
—
|
|
|
—
|
—
|
|
—
|
—
|
|
CCS I or II
|
0.96
|
0.57, 1.61
|
0.88
|
0.95
|
0.60, 1.49
|
0.81
|
|
1.05
|
0.52, 2.11
|
0.89
|
1.59
|
0.74, 3.42
|
0.23
|
CCS III or IV
|
1.93
|
1.01, 3.71
|
0.047
|
0.82
|
0.42, 1.59
|
0.55
|
|
1.71
|
0.68, 4.32
|
0.26
|
0.99
|
0.31, 3.22
|
0.99
|
Age (years)
|
1.03
|
1.00, 1.06
|
0.075
|
1.04
|
1.02, 1.07
|
0.002
|
|
1.01
|
0.97, 1.04
|
0.76
|
1.01
|
0.97, 1.05
|
0.52
|
Female
|
1
|
0.57, 1.74
|
0.99
|
0.73
|
0.44, 1.21
|
0.22
|
|
0.97
|
0.45, 2.08
|
0.94
|
1.24
|
0.54, 2.82
|
0.61
|
BMI (kg/m2)
|
0.96
|
0.89, 1.02
|
0.2
|
0.95
|
0.88, 1.02
|
0.13
|
|
0.92
|
0.83, 1.01
|
0.091
|
0.92
|
0.83, 1.03
|
0.15
|
CKD
|
2.35
|
1.41, 3.92
|
0.001
|
1.45
|
0.95, 2.22
|
0.083
|
|
2.4
|
1.21, 4.77
|
0.013
|
2.1
|
1.04, 4.24
|
0.039
|
Optimal medical therapy
|
0.57
|
0.36, 0.90
|
0.017
|
0.58
|
0.38, 0.90
|
0.014
|
|
0.84
|
0.44, 1.63
|
0.61
|
0.47
|
0.24, 0.94
|
0.032
|
Unprotected LMT lesion
|
2.3
|
1.20, 4.42
|
0.013
|
2.46
|
1.32, 4.58
|
0.004
|
|
2.68
|
1.13, 6.36
|
0.026
|
1.88
|
0.56, 6.28
|
0.31
|
Proximal LAD lesion
|
1.01
|
0.62, 1.63
|
0.98
|
1.24
|
0.81, 1.88
|
0.32
|
|
0.79
|
0.41, 1.55
|
0.5
|
0.48
|
0.22, 1.08
|
0.075
|
Multivessel lesion
|
1.2
|
0.75, 1.93
|
0.45
|
1.35
|
0.89, 2.04
|
0.16
|
|
1.07
|
0.57, 2.01
|
0.84
|
2.07
|
1.05, 4.09
|
0.037
|
The primary outcome was a composite of all-cause death, new-onset acute coronary syndrome, and non-fatal ischemic stroke within 2-year and the secondary outcome was a composite of cardiovascular death, new-onset acute coronary syndrome, and heart failure within 2-year. CKD was defined as estimated glomerular filtration rate of less than 60 ml/min/1.73 m². Optimal medical therapy was defined as dual antiplatelet therapy and statins at discharge. Abbreviations: CCS, Canadian Cardiovascular Society functional classification; BMI, body mass index; CKD, chronic kidney disease; LMT, left main coronary trunk; LAD, left anterior descending; HR, hazard ratio; CI, confidence interval