Characteristics of the patients
A total of 242 AIS patients with AF (118 men; 124 females) were included in this study, their mean AF duration was 67.7 months. Of all patients, 85 had paroxysmal AF and 157 had persistent AF. 57 (23.6%) patients received anticoagulants, and 40(16.5%) patients received antiplatelets. 106 (43.8%) were assigned to the prestroke statins use group. The baseline characteristics of patients in the no prestroke statins use group (136) and prestroke statins use group (106) were compared (Table 1). At baseline, patients with prestroke statins use showed a significantly higher prevalence of hyperlipidemia than that in patients with no prestroke statins use (P<0.001). Patients with statins use showed significantly lower NIHSS score and Ox-LDL levels than patients with no statins use (P<0.005).
At discharge, all the patients were prescribed statins; 110 patients were prescribed direct oral anticoagulants, 61 in no prestroke statins group and 49 in prestroke statins group; 85 patients were prescribed warfarin, 46 in no prestroke statins group and 39 in prestroke statins group; 35 patients were prescribed antiplatelets, 25 in no prestroke statins group and 15 in prestroke statins group. 7 patients had intracranial hemorrhage conversion and 5 patients had gastrointestinal bleeding, who did not receive the anticoagulants and antiplatalets at discharge. After 4-8 weeks, 5 patients were prescribed direct oral anticoagulant, and 7 patients were prescribed antiplatelet therapy. No bleeding complications occurred during the follow-up period, and no patients stopped taking anticoagulants or antiplatelet drugs. There was no difference in direct oral anticoagulants, warfarin and antiplatelets between two groups(P>0.05). During the 3-month follow-up period, no patients were denied follow-up, and no patients had adverse reactions of statins.
Table 1. Comparison of baseline characteristics between patients with no prestroke statins use prestroke statins use groups.
|
No prestroke statins use group (136)
|
Prestroke Statins use group (106)
|
OR(95% CI)
|
P*
|
Age, y (Mean SD)
|
66.1±10.5
|
67.2±9.9
|
|
0.303
|
NIHSS score, median (IQR)
|
11 (7-14)
|
8(6-12)
|
|
0.041
|
Mean AF duration, m(Mean SD)
|
67.7±10.0
|
67.8±11.3
|
|
0.915
|
CHA2DS2-VASc, median (IQR)
|
4(3-5)
|
4(3-5)
|
|
0.090
|
Females, n (%)
|
66 (48.5%)
|
58 (54.7%)
|
1.29 (0.77-2.13)
|
0.339
|
Men, n (%)
|
70 (51.5%
|
48 (45.3%)
|
1.29 (0.77-2.13)
|
0.339
|
BMI≥24 kg/m, n (%)
|
36 (26.5%)
|
37 (34.9%)
|
1.50 (0.86-2.59)
|
0.156
|
Hypertension, patients, n (%)
|
90 (66.8%)
|
79 (74.5%)
|
1.50 (0.85-2.63)
|
0.160
|
Current Smoking, n (%)
|
46 (33.8%)
|
30 (28.3%)
|
0.77 (0.45-1.34)
|
0.359
|
Current alcohol consumption, n (%)
|
41 (30.2%)
|
24 (22.6%)
|
0.67 (0.38-1.22)
|
0.191
|
Diabetes, n (%)
|
37 (27.2%)
|
31 (29.2%)
|
1.11 (0.63-1.94)
|
0.736
|
Hyperlipidemia, n (%)
|
40 (29.4%)
|
79 (74.5%)
|
7.02 (3.96-12.4)
|
<0.001
|
AF Type
|
|
|
|
|
Paroxysmal, n (%)
|
47(34.6)
|
38(35.8)
|
0.95(0.56-1.61)
|
0.835
|
Permanent, n (%)
|
89(65.4)
|
68(64.2)
|
0.95(0.56-1.61)
|
0.835
|
Family history of stroke, n (%)
|
28 (20.6%)
|
23 (21.7%)
|
1.07 (0.57-1.99)
|
0.834
|
Ox-LDL,U/L (Mean SD)
|
37.6±5.1
|
33.5±5.5
|
|
<0.001
|
Medication use
|
|
|
|
|
Warfarin, n (%)
|
20 (14.7%)
|
19 (17.9%)
|
1.27 (0.64-2.52)
|
0.499
|
direct oral anticoagulants, n (%)
|
10(7.4%)
|
8(7.5%)
|
1.03(0.39-2.70)
|
0.954
|
antiplatelets, n (%)
|
25(18.4)
|
15(14.2)
|
0.73(0.36-1.45)
|
0.379
|
Antihypertensive, n (%)
|
76 (55.9%)
|
58 ((54.7%)
|
0.95 (0.57-1.59)
|
0.856
|
Bold indicates P-values less than 0.05.
*Comparison between no prestroke statins use and prestroke statins use groups. The data are presented as median values (interquartile range [IQR]), numbers (%), or mean values (±standard deviation). Categorical variables are expressed as frequency (percent) for P values. Pearson χ2 test, Fisher exact 2-sided test, Student’s t test, distributions of continuous variables were determined by the Kolmogorov–Smirnov test, Mann–Whitney two sample test was applied in case of non-normal distributions.
Plasma Ox-LDL levels in the prestroke statins use and no prestroke statins use groups
Plasma Ox-LDL levels were significantly lower in the prestroke statins use group on admission (33.5±5.5 vs 37.6±5.1, P<0.001). Compared with the baseline, Ox-LDL levels of the 3-month treatment period decreased both in two groups, the prestroke statins use group had lower Ox-LDL level (24.4±7.6 vs 29.3±6.0, P<0.001). Ox-LDL levels decreased about 27.1% in the prestroke statins use group, 22.1% in the no prestroke statin use group. The data showed significantly different Ox-LDL levels in the two groups at different time points.
Association Between Plasma Ox-LDL levels and Prognosis
We also analyzed whether the plasma Ox-LDL levels had effect on outcomes. 70 (70/242, 28.9%) patients had died during follow-up, and 86 patients had major disability at 3 months. Compared with the surviving patients, the patients who died had higher Ox-LDL levels (37.9±5.6 vs 35.0±5.5, P<0.001) on admission, and at 3 months (28.8±4.7 vs 26.5±7.3, P=0.039). Patients with major disability had higher Ox-LDL levels than patients with good prognosis on admission (36.4±6.0vs 33.6±4.6, P=0.004), there was no significant difference between two groups at 3 months (27.6±6.4 vs 25.4±8.0, P = 0.099). In the multivariable logistic regression model, adjusting for age, baseline NIHSS score, mean AF duration, CHA2DS2-VASc score, sex, BMI, hypertension, current smoking, current alcohol consumption, diabetes, hyperlipidemia, AF type, family history of stroke, prestroke statins use, and use of antihypertensive, warfarin, direct oral anticoagulants, antiplatelets, baseline plasma Ox-LDL levels were associated with increased risk of 3-month mortality(adjusted OR, 1.05; 95% CI, 0.99-1.12; P=0.047), there was no association between baseline plasma Ox-LDL levels and major disability (adjusted OR, 1.04; 95% CI, 0.96-1.12; P=0.335), and composite outcome (adjusted OR, 1.07; 95% CI, 0.99-1.14; P=0.072); similarly, 3-month plasma Ox-LDL levels were not associated with mortality (adjusted OR, 1.05; 95% CI, 0.99-1.10; P=0.096), major disability (adjusted OR, 1.04; 95% CI, 0.99-1.10; P=0.182), and composite outcome (adjusted OR, 1.04; 95% CI, 0.98-1.09 ; P=0.146).
Multivariable Models on the Association Between prestroke statins use and Death/Major disability
70 patients had died, and they had a significantly higher NIHSS score (13.4±6.4 vs 9.1±4.1, P<0.001), older age (68.6±11.3 vs 65.7±9.7, P=0.022), and lower percentage of prestroke statins use [32.9% (23/70) vs 48.3% (83/172); OR, 0.53 (95% CI, 0.30-0.94); P=0.029] on admission. In the multivariable logistic regression model, after adjustment for all confounders, prestroke statins use was associated with decreased risk of 3-month mortality(adjusted OR, 0.38; 95% CI, 0.16-0.91; P=0.031),and higher NIHSS score was associated with increased risk of mortality at 3 months(adjusted OR, 1.18; 95% CI, 1.11-1.27; P<0.001); 3-month plasma Ox-LDL levels were entered into multivariate logistic regression, prestroke statins use was associated with decreased risk of 3-month mortality(adjusted OR, 0.36; 95% CI, 0.15-0.84; P=0.019),and higher NIHSS score was associated with increased risk of mortality at 3 months(adjusted OR, 1.18; 95% CI, 1.10-1.26; P<0.001).
In addition to the 70 deaths, of the remaining 172 patients, 83 patients were in the prestroke statins use group, 32 (32/83, 38.6%) patients had a major disability, which was lower percentage than that in patients with no prestroke statins use (54/89, 60.7%); patients with 3-month major disability had a significantly higher NIHSS at admission (10.3±4.2 vs 8.0±3.7, P<0.001) than that in patients with a good prognosis.
In the multivariable logistic regression model, after adjusting for all confounders, prestroke statins use was associated with decreased risk of 3-month major disability (adjusted OR, 0.38; 95% CI, 0.15–0.99; P=0.047) and composite outcome (adjusted OR, 0.31; 95% CI, 0.17-0.74; P=0.009), and higher NIHSS score was associated with increased risk of 3-month major disability (adjusted OR, 1.17; 95% CI, 1.06–1.30; P=0.003) and composite outcome (adjusted OR, 1.20; 95% CI, 1.10-1.29; P<0.001); 3-month plasma Ox-LDL levels were entered into multivariate logistic regression, prestroke statins use was associated with decreased risk of 3-month major disability (adjusted OR, 0.38; 95% CI, 0.15–0.95; P=0.038) and composite outcome (adjusted OR, 0.27; 95% CI, 0.11-0.64; P=0.003), and higher NIHSS score was associated with increased risk of 3-month major disability (adjusted OR, 1.17; 95% CI, 1.06–1.30; P=0.003) and composite outcome (adjusted OR, 1.19; 95% CI, 0.10-1.29; P<0.001).
Table 2 Multivariable Models Showing Association Between prestroke Statins use and Prognosis
|
OR (95% CI)
|
P*
|
Death
|
0.38(0.16-0.91)
|
0.031
|
Major disability (mRs3-5)
|
0.38 (0.15-0.99)
|
0.047
|
Major disability (mRs3-5)+ death
|
0.31(0.17-0.74)
|
0.009
|
Bold indicates P-values less than 0.05.
*Multivariable adjusted for age, baseline NIHSS score, mean AF duration, CHA2DS2-VASc score, sex, BMI, hypertension, current smoking, current alcohol consumption, diabetes, hyperlipidemia, AF type, family history of stroke, prestroke statins use, baseline Ox-LDL levels and use of antihypertensive, warfarin, direct oral anticoagulants, antiplatelets.