Study population and demographic characteristics
A total of 5503 patients were registered in Swedvasc during the period Jan 1st, 2009 - Dec 31st, 2015 with a carotid intervention. Out of these 5503 patients 1341 patients (24.4%) had T2D. The majority of the patients were treated for symptomatic CAS (88.6% patients without T2D vs. 89% T2D patients) and CEA was the most common intervention (95.9% patients without T2D vs. 94.6% T2D patients).
All baseline demographic characteristics of the patients studied are presented in Table 1. Mean age was 72 (SD 8) years in both groups, with a larger proportion of females among patients without T2D (33.0%) compared to T2D patients (28.2%). The majority of the patients were treated for a high-grade stenosis (70-99% NASCET), a small proportion of patients with repeated symptoms were treated for a stenosis of less than 50%, 6% of the patients had a contralateral stenosis in both groups. Patients without T2D were more likely to smoke compared to T2D patients (25.8% vs. 20.1%). In contrast, it was more common that T2D patients had a history of cardiovascular comorbidities compared to patients without T2D (Table 1). Lipid lowering drugs were used by 79.1% of the T2D patients, and by 63.0% among patients without T2D. Also, antiplatelet drugs were more frequently used in T2D patients; acetylsalicylic acid 66.9% vs. 60.5%, and clopidogrel 21.8% vs. 18.2%, respectively. Patients without T2D had a higher education level and an increased socioeconomic level than T2D patients (Table 1). There were no differences in the degree of ipsilateral or contralateral degree of carotid stenosis between groups (Table 1). Glycemic control and diabetes duration in T2D patients were HbA1c 55.6 (SD 14.2) mmol/mol (HbA1c 7.2%) and 10.5 (SD 7.9) years, respectively.
Table 1. Baseline characteristics of individuals (without 2 diabetes [Non-T2D] vs. type 2 diabetes [T2D]) undergoing carotid intervention.
|
Non-T2D
|
T2D
|
P-value
|
SMD
|
n
|
4162
|
1341
|
|
|
Age, mean (SD)
|
72.21 (8.30)
|
72.42 (7.72)
|
0.416
|
0.026
|
Female, n (%)
|
1372 (33.0)
|
378 (28.2)
|
0.010
|
0.104
|
Smoking, n (%)
|
875 (25.8)
|
248 (20.1)
|
<0.001
|
0.134
|
History of comorbidities, n (%)
|
|
|
|
|
Cardiovascular disease (%)
|
2265 (54.4)
|
851 (63.5)
|
<0.001
|
0.185
|
Stroke
|
1989 (47.8)
|
743 (55.4)
|
<0.001
|
0.153
|
Myocardial infarction
|
483 (11.6)
|
243 (18.1)
|
<0.001
|
0.184
|
Coronary heart disease
|
1119 (26.9)
|
539 (40.2)
|
<0.001
|
0.285
|
Heart failure
|
243 (5.8)
|
138 (10.3)
|
<0.001
|
0.164
|
Atrial fibrillation
|
460 (11.1)
|
216 (16.1)
|
<0.001
|
0.148
|
Kidney disease
|
150 (3.6)
|
86 (6.4)
|
<0.001
|
0.129
|
Cancer disease
|
450 (10.8)
|
137 (10.2)
|
0.573
|
0.019
|
Gastric bypass
|
2 (0.0)
|
2 (0.1)
|
0.541
|
0.032
|
Psychiatric disorder
|
156 (3.7)
|
41 (3.1)
|
0.272
|
0.038
|
Dementia
|
17 (0.4)
|
5 (0.4)
|
1.00
|
0.006
|
Degree of ipsilateral carotid stenosis, n (%)*
|
|
|
0.52
|
0.036
|
≤50%
|
229 (5.5)
|
82 (6.1)
|
|
|
50-69%
|
1194 (28.7)
|
397 (29.6)
|
|
|
70-99%
|
2737 (65.8)
|
862 (64.3)
|
|
|
Degree of contralateral carotid stenosis, n (%)*
|
|
|
0.19
|
0.068
|
≤50%
|
3105 (74.7)
|
966 (72.0)
|
|
|
50-69%
|
454 (10.9)
|
163 (12.2)
|
|
|
70-99%
|
349 (8.4)
|
132 (9.8)
|
|
|
Occlusion
|
251 (6.0)
|
80 (6.0)
|
|
|
Symptomatic stenosis, n (%)
|
3686 (88.6)
|
1194 (89.0)
|
0.669
|
0.015
|
Carotid endarterectomy, n (%)
|
3993 (95.9)
|
1269 (94.6)
|
0.050
|
0.062
|
Peripheral arterial disease (%)
|
175 (4.2)
|
101 (7.5)
|
<0.001
|
0.142
|
Medication, n (%)
|
|
|
|
|
Lipid lowering drug
|
2623 (63.0)
|
1061 (79.1)
|
<0.001
|
0.361
|
Antihypertensive drug
|
3192 (76.7)
|
1222 (91.1)
|
<0.001
|
0.401
|
ACE inhibitor
|
1154 (27.7)
|
533 (39.7)
|
<0.001
|
0.256
|
Angiotensin II receptor blocker
|
755 (18.1)
|
331 (24.7)
|
<0.001
|
0.160
|
Beta blocker
|
1740 (41.8)
|
777 (57.9)
|
<0.001
|
0.327
|
Calcium chanel blocker
|
1379 (33.1)
|
640 (47.7)
|
<0.001
|
0.301
|
Anticoagulant therapy†
|
1434 (34.5)
|
542 (40.4)
|
<0.001
|
0.123
|
Acetylsalicylic acid
|
2517 (60.5)
|
897 (66.9)
|
<0.001
|
0.134
|
P2Y12 inhibitor (Clopidogrel)
|
757 (18.2)
|
293 (21.8)
|
0.003
|
0.092
|
Antihyperglycaemic agent, n (%)
|
|
|
|
|
Metformin
|
0 (0.0)
|
744 (55.5)
|
<0.001
|
1.579
|
Sodium-glucose-transport-2 inhibitor
|
0 (0.0)
|
4 (0.3)
|
<0.001
|
0.077
|
Incretin‡
|
0 (0.0)
|
74 (5.5)
|
<0.001
|
0.342
|
Insulin
|
0 (0.0)
|
492 (36.7)
|
<0.001
|
1.077
|
Disposable income per month after tax, USD
|
2078.3 (2609)
|
1875.8 (204)
|
0.009
|
0.086
|
Educational level, n (%)
|
|
|
0.012
|
0.096
|
Compulsory school
|
1658 (40.3)
|
567 (42.8)
|
|
|
Upper secondary
|
1707 (41.5)
|
562 (42.4)
|
|
|
College/University
|
753 (18.3)
|
196 (14.8)
|
|
|
Civil status, n (%)
|
|
|
0.092
|
0.079
|
Single
|
385 (9.3)
|
132 (9.9)
|
|
|
Married
|
2294 (55.2)
|
712 (53.1)
|
|
|
Divorced
|
822 (19.8)
|
303 (22.6)
|
|
|
Widowed
|
657 (15.8)
|
193 (14.4)
|
|
|
Origin, n (%)
|
|
|
0.015
|
0.088
|
Sweden
|
3574 (85.9)
|
1112 (82.9)
|
|
|
Europe except Sweden
|
298 (7.2)
|
106 (7.9)
|
|
|
Rest of the world
|
290 (7.0)
|
123 (9.2)
|
|
|
*Definition accordingly to The North American Symptomatic Carotid Endarterectomy Trial. †Anticoagulant therapy
includes Heparin, Low molecular Heparin, Non-Vitamin K antagonist and Vitamin K antagonists. ‡Incretin, includes
dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1. SMD, Standardised mean difference. SD, Standard deviation.
Categorical variables are presented as number (%) and continuous variables are presented as mean (SD).
Early (within 30-days) complication rates
The perioperative (within 30-days) complication rate for stroke was 3.7% (95% CI 2.7% - 4.7%) compared to 2.3% (95% CI 1.8 % - 2.7%) for patients without T2D. There was no difference in rates of perioperative death between groups: T2D patients 0.7% (95% CI 0.5% - 1.0%) vs. patients without T2D 0.7% (95% CI 0.3% - 1.2%), respectively. Corresponding early crude HRs (95% CI) for stroke was 1.65 (1.17-2.32) in T2D patients compared to patients without T2D, whereas early crude risk for death was similar 1.00 (0.49-2.04) in both groups.
Long-term outcome events and crude incidence rate between groups after carotid intervention
Median follow up time 4.3 (IQR 2.9-6.0) years for T2D patients and 4.6 (IQR 3.1-6.3) years for patients without T2D with a maximum follow-up time of 8.0 years (both groups). Kaplan-Meier estimated survival curves demonstrating the cumulative number of patients at risk and the proportions for the outcomes, i.e., stroke, death, and MACE are shown in Figure 1A-C. Numbers of event and crude incidence rate for the studied outcomes were all increased in T2D patients compared to patients without T2D (Table 2).
Table 2. Total number of events and incidence rate with exact 95% Poisson confidence interval for the outcomes of individuals without type 2 diabetes (Non-T2D) and individuals with type 2 diabetes (T2D), respectively, undergoing carotid intervention.
|
Non-T2D
(n=4162)
|
T2D
(n=1341)
|
Outcome
|
Events
(n)
|
Incidence rate
(per 1000 patients)
|
Events
(n)
|
Incidence rate
(per 1000 patients)
|
Stroke
|
453
|
25.1 (22.8 - 27.5)
|
193
|
35.7 (30.8 - 41.1)
|
Ischemic stroke
|
380
|
20.8 (18.8 - 23.0)
|
166
|
30.3 (25.9 - 35.3)
|
Hemorrhagic stroke
|
68
|
3.5 (2.7 - 4.5)
|
20
|
3.4 (2.1 - 5.2)
|
Death
|
725
|
37.4 (34.7 - 40.2)
|
324
|
54.5 (48.7 - 60.7)
|
Cardiovascular death
|
161
|
8.3 (7.1 - 9.7)
|
89
|
15.0 (12.0 - 18.4)
|
MACE
|
1248
|
82.7 (78.2 - 87.4)
|
551
|
135 (123.4 - 146.1)
|
HR, Hazard Ratio; MACE, Major adverse cardiovascular events, i.e. Non-fatal myocardial infarction, non-fatal stroke and cardiovascular death.
Propensity score matched risk of long-term outcomes between groups after carotid intervention
After propensity score matching the groups were well balanced concerning all covariates and demographic characteristics (Table S2). HRs (95% CI) for stroke, death, cardiovascular death, and MACE were all increased in patients with T2D: 1.27 (1.05-1.54), 1.27 (1.10-1.47), 1.60 (1.20-2.12), and 1.21 (1.08-1.35), respectively, compared to patients without T2D (Table 3).
Table 3. Cox-regression estimates (crude and after adjustments using inverse probability of treatment weighting [IPTW]) for individuals with type 2 diabetes compared with individuals without type 2 diabetes with asymptomatic and symptomatic carotid stenosis undergoing any carotid intervention.
Outcome
|
Crude
HR (95% CI)
|
P-value
|
IPTW adjustment*
HR (95% CI)
|
P-value
|
Stroke
|
1.38 (1.17 - 1.64)
|
<0.001
|
1.27 (1.05 - 1.54)
|
0.012
|
Ischemic stroke
|
1.41 (1.18 - 1.69)
|
<0.001
|
1.30 (1.06 - 1.60)
|
0.011
|
Hemorrhagic stroke
|
0.95 (0.58 - 1.56)
|
0.834
|
1.29 (1.06 - 1.55)
|
0.009
|
Death
|
1.48 (1.30 - 1.68)
|
<0.001
|
1.27 (1.10 - 1.47)
|
0.001
|
Cardiovascular death
|
1.79 (1.38 - 2.32)
|
<0.001
|
1.60 (1.20 - 2.12)
|
0.001
|
MACE
|
1.52 (1.37 - 1.68)
|
<0.001
|
1.21 (1.08 - 1.35)
|
0.001
|
CI, Confidence interval. HR, Hazard Ratio; MACE, Major adverse cardiovascular events. i.e. Non-fatal myocardial infarction, non-fatal stroke and cardiovascular death. IPTW, Inverse probability of treatment weighting. *Adjusted for all variables in Table S1 (Supplemental Material).
The corresponding numbers of the HRs for the outcomes, after dividing groups in symptomatic vs. asymptomatic carotid stenosis, and CEA vs. CAS procedures, are shown in Table S3 and Table S4, respectively. The proportion of events for CAS and asymptomatic stenosis compared to CEA and symptomatic stenosis were small (Table S3 and Table S4)