The study initially enrolled 26,597 patients hospitalzed with ACS, and 6,978 participants fulfilled the inclusion criteria (Figure 1). The baseline characteristics according to diabetes status are summarized in Table 1. Compared with patients without diabetes, those with diabetes (n = 3989, 57.1%) were older, were more likely to be females, and had higher BMI and systolic blood pressures. Patients with diabetes were less likely to be current smokers and had low alcohol consumption compared with those without diabetes; however, they had more frequent comorbidities and more frequently used concomitant medications. The baseline characteristics of patients with and without diabetes stratified by BMI are summarized (Supplementary Table 1). Obese patients were more likely to be younger, males, and physically active, and current smokers and more frequently used medications than normal-weighted patients.
Table 1. Baseline characteristics by diabetes status
|
Without diabetes
(n = 2,989)
|
With diabetes
(n = 3,989)
|
P-value
|
Age, years
|
60.8 ± 9.7
|
64.4 ± 9.5
|
<0.001
|
Women, n (%)
|
1,038 (34.7)
|
1,528 (38.3)
|
0.002
|
Body mass index, kg/m2
|
24.2 ± 2.9
|
24.6 ± 3.1
|
<0.001
|
Systolic blood pressure, mmHg
|
130.1 ± 17.7
|
131.7 ± 17.9
|
<0.001
|
Diastolic blood pressure, mmHg
|
80.4 ± 11.3
|
80.0 ± 11.0
|
0.073
|
Total cholesterol, mg/dL
|
203.7 ± 40.1
|
201.5 ± 44.6
|
0.030
|
Fasting glucose, mg/dL
|
94.0 (86.0–102.0)
|
106.0 (92.0–131.0)
|
<0.001
|
Clinical diagnosis, n (%)
|
|
|
|
Myocardial infarction
|
1,565 (52.4)
|
1,946 (48.8)
|
0.003
|
Unstable angina
|
1,424 (47.6)
|
2,043 (51.2)
|
Smoking status, n (%)
|
|
|
|
Never
|
1,745 (58.4)
|
2,463 (61.7)
|
<0.001
|
Former
|
429 (14.3)
|
630 (15.8)
|
Current
|
815 (27.3)
|
896 (22.5)
|
Alcohol consumption, n (%)
|
|
|
|
Low
|
2,032 (68.0)
|
2,996 (75.1)
|
<0.001
|
Middle
|
874 (29.2)
|
904 (22.7)
|
High
|
83 (2.8)
|
89 (2.2)
|
Physical activity, n (%)
|
|
|
|
Low
|
1,007 (33.7)
|
1,066 (26.7)
|
<0.001
|
Middle
|
1,567 (52.4)
|
2,366 (59.3)
|
High
|
415 (13.9)
|
557 (14.0)
|
Household income, n (%)
|
|
|
|
Lower 30%
|
611 (20.4)
|
921 (23.1)
|
0.030
|
Mid 40%
|
996 (33.3)
|
1,283 (32.2)
|
Upper 30%
|
1,382 (46.2)
|
1,785 (44.7)
|
Comorbidities, n (%)
|
|
|
|
Heart failure
|
376 (12.6)
|
830 (20.8)
|
<0.001
|
Stroke
|
445 (14.9)
|
967 (24.2)
|
<0.001
|
Concurrent medication, n (%)
|
|
|
|
ACEi or ARB
|
2,166 (72.5)
|
3,377 (84.7)
|
<0.001
|
Beta-blockers
|
2,268 (75.9)
|
3,383 (84.8)
|
<0.001
|
Calcium channel blocker
|
2,120 (70.9)
|
3,229 (80.9)
|
<0.001
|
Statin
|
2,208 (73.9)
|
3,382 (84.8)
|
<0.001
|
Antiplatelet agents
|
2,056 (68.8)
|
3,204 (80.3)
|
<0.001
|
ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker
Association of diabetes with CV outcomes
During a mean follow-up of 5.4 ± 3.7 years (median, 4.9 years), 1,633 (23.4%) MACE and 1,023 (14.7%) deaths occurred. ACS patients with diabetes had a higher risk of MACE (event rates 5.81 vs. 4.01 per 100 person-years, HR 1.49, 95% CI 1.34–1.65) and its individual components than those without diabetes (CV death: HR 1.25, 95% CI 1.03–1.53; MI: HR 1.26, 95% CI 1.09–1.50; stroke: HR 2.06, 95% CI 1.75–2.42). These associations were attenuated after adjustment for confounding variables, and remained significant for MACE and stroke (MACE: HR 1.22, 95% CI 1.09–1.37; stroke: HR 1.50, 95% CI 1.26–1.79). Patients with diabetes also had higher event rates and risks of HHF and all-cause death than patients without diabetes (HHF: event rates 2.40 vs. 1.15, HR 2.13, 95% CI 1.79–2.55; all-cause death: event rates 3.05 vs. 2.25, HR 1.40, 95% CI 1.23–1.60). This association remained significant after adjustment for confounding variables (HHF: HR 1.47, 95% CI 1.22–1.78; all-cause death: HR 1.28, 95% CI 1.11–1.49) (Table 2).
Table 2. Hazard ratio of cardiovascular outcomes in patients with acute coronary syndrome by diabetes status
|
Without diabetes (n = 2,989)
|
|
With diabetes (n = 3,989)
|
Unadjusted HR (95% CI)
|
Adjusted HR (95% CI)*
|
Person-years
|
No. of events
|
Event rate (per 100 PY)
|
|
Person-years
|
No. of events
|
Event rate (per 100 PY)
|
MACE
|
13,057
|
524
|
4.01
|
|
19,096
|
1,109
|
5.81
|
1.49 (1.34–1.65)
|
1.22 (1.09–1.37)
|
Cardiovascular death
|
14,471
|
153
|
1.06
|
|
22,913
|
286
|
1.25
|
1.25 (1.03–1.53)
|
1.15 (0.92–1.43)
|
Myocardial infarction
|
13,542
|
272
|
2.01
|
|
20,734
|
500
|
2.41
|
1.26 (1.09–1.50)
|
1.05 (0.89–1.23)
|
Stroke
|
13,863
|
196
|
1.41
|
|
20,812
|
592
|
2.84
|
2.06 (1.75–2.42)
|
1.50 (1.26–1.79)
|
Hospitalization for heart failure
|
14,103
|
162
|
1.15
|
|
21,385
|
513
|
2.40
|
2.13 (1.79–2.55)
|
1.47 (1.22–1.78)
|
All-cause death
|
14,471
|
325
|
2.25
|
|
22,913
|
698
|
3.05
|
1.40 (1.23–1.60)
|
1.28 (1.11–1.49)
|
*Adjusted for sex, age, body mass index, systolic blood pressure, fasting glucose, total cholesterol, alcohol consumption, smoking status, physical activity, household income, concurrent medications, comorbidities, and index year.
CI, confidence interval; HR, hazard ratio; MACE, major adverse cardiovascular events; PY, person-years
Association of BMI and diabetes with CV outcomes
The risks of the CV outcomes by BMI and diabetes status in ACS patients are described in Figure 2. After adjustment for confounding variables, compared to normal-weight patients without diabetes (reference group), obese class I patients with and without diabetes had a lower risk of MACE, but only significant in patients without diabetes (with diabetes: HR 0.95, 95% CI 0.78–1.14; without diabetes: HR 0.78, 95% CI 0.62–0.97). Regarding individual components of MACE except for stroke, obese class I patients with and without diabetes tend to be a lower risk with no statistical significance. In terms of stroke, obese class I patient without diabetes was associated with a lower risk, on the other hand, those with diabetes were not (with diabetes: HR 1.11, 95% CI 0.84–1.47; without diabetes: HR 0.61, 95% CI 0.42–0.88). Among the secondary outcomes with HHF and all-cause death, obese patients showed similar results to the reference group, but obese class I patients without diabetes had a lower risk of HHF (HR 0.62, 95% CI 0.42–0.92) (Supplementary Figure 1).
In contrast, underweight patients with and without diabetes had a higher risk of MACE compared to the reference group, but only significant in patients with diabetes (with diabetes: HR 1.79, 95% CI 1.24–2.58; without diabetes: HR 1.23, 95% CI 0.77–1.97). In patients with diabetes, the underweight BMI was associated with a higher risk of individual components of MACE, but only significant for the risk of MI (HR 2.00. 95% CI 1.16–3.46). In patients without diabetes, underweight tend to increase the risk of those events except for CV death, with no statistical significance. In terms of all-cause death among secondary outcomes, underweight patients with and without diabetes had a significantly higher risk (with diabetes: HR 2.07, 95% CI 1.43–3.00; without diabetes: HR 2.07, 95% CI 1.40–3.07).
The subgroup analyses stratified by sex, age, smoking status, and clinical diagnosis were shown in Supplementary Figure 2. In all subgroups, obese I class patients without diabetes had a lower risk of MACE, but only significant in female, elderly (³ 65 years), and hospitalization for unstable angina patients. In contrast, underweight patients with diabetes had a higher risk of MACE, but only significant in male, younger (< 65 years), current smoker, and hospitalization for MI patients.