Article Figures & Data
- Figure 1
Mendelian randomisation results for genetically determined tHcy and risk of IAs. A, scatter plot for association of nine SNPs between tHcy and IAs. β, coefficient presented as the number of standard deviation of difference in homocysteine concentrations per allele; B, summary results for two-sample mendelian randomisation and sensitive analyses. MR pleiotropy residual sum and MR-PRESSO global tests indicated no sign of horizontal pleiotropy. Test for heterogeneity showed no strong heterogeneity between nine SNPs and the outcome of IAs. Abbreviations: SNPs and the outcome of IAs. Abbreviations: IAs, intracranial aneurysms; IVW, inverse variance weighted; MR-PRESSO, MR-Egger regression and MR Pleiotropy Residual Sum and Outlier; SNPs, single nucleotide polymorphisms; tHcy, total homocysteine.
- Figure 2
Flow diagram of patients inclusion. AVM, arteriovenous malformation; CHD, coronary heart disease; CTA, CT angiography; DSA, digital subtraction angiography; IAs, intracranial aneurysms; MRA,magnetic resonance angiography; PKD, polycystic kidneydisease; PSM, propensity score matching.
- Figure 3
Forest plot for subgroup analyses. IAs, intracranial aneurysms; tHcy, total homocysteine.
- Table 1
Baseline characteristics of patients before and after propensity score matching
Before matched After matched Non-IAs IAs P Non-IAs IAs P n=9831 n=5496 n=4951 n=4951 Sex, number (%) <0.001 0.063 Male 5693 (57.9) 2254 (41.0) 2264 (45.7) 2171 (43.8) Female 4138 (42.1) 3242 (59.0) 2687 (54.3) 2780 (56.2) Age, mean, (SD), years 63.9 (13.5) 57.8 (12.0) <0.001 58.0 (12.9) 58.4 (12.0) 0.072 Age class, number (%) <0.001 0.190 18–39 years 477 (4.9) 394 (7.2) 404 (8.16) 357 (7.21) 40–59 years 2981 (30.3) 2656 (48.3) 2215 (44.7) 2258 (45.6) ≥60 years 6373 (64.8) 2446 (44.5) 2332 (47.1) 2336 (47.2) BP class, mm Hg, SBP/DBP, number (%) <0.001 0.939 <140/<90 3449 (35.1) 2434 (44.3) 2174 (43.9) 2170 (43.8) 140~159/90~99 3404 (34.6) 1111 (20.2) 1094 (22.1) 1089 (22.0) 160~179/100~109 2065 (21.0) 888 (16.2) 872 (17.6) 859 (17.4) ≥180/≥110 913 (9.3) 1063 (19.3) 811 (16.4) 833 (16.8) Hyperlipidaemia, number (%) <0.001 0.431 No 4726 (48.1) 3060 (55.7) 2665 (53.8) 2705 (54.6) Yes 5105 (51.9) 2436 (44.3) 2286 (46.2) 2246 (45.4) Diabetes, type 1 and 2, number (%) <0.001 0.560 No 7098 (72.2) 4319 (78.6) 3879 (78.3) 3854 (77.8) Yes 2733 (27.8) 1177 (21.4) 1072 (21.7) 1097 (22.2) Smoke*, number (%) <0.001 0.291 No 7684 (78.2) 4778 (86.9) 4297 (86.8) 4260 (86.0) Yes 2147 (21.8) 718 (13.1) 654 (13.2) 691 (14.0) Alcohol use*, number (%) <0.001 0.125 No 7892 (90.0) 4775 (92.6) 4604 (93.0) 4563 (92.2) Yes 875 (10.0) 383 (7.4) 347 (7.0) 388 (7.8) *Missing data were imputed for 830 (5.4%) and 1402 (9.1%) patients about smoking and alcohol using by Multiple Imputation utilizing Mice package (3.14) for R (4.2.2).
BP, blood pressure; DBP, diastolic blood pressure; IAs, intracranial aneurysms; SBP, systolic blood pressure.
- Table 2
Distribution of tHcy among patients before and after propensity score matching
Before matched After matched Non-IAs IAs P Non-IAs IAs P n=9831 n=5496 n=4951 n=4951 tHcy* (SD), μmol/L 12.9 (6.3) 14.2 (9.8) <0.001* 11.7 (5.4) 14.4 (10.1) <0.001† Group tHcy, number (%) <0.001 <0.001 Low 7647 (77.8) 3905 (71.1) 4155 (83.9) 3464 (70.0) Moderate 1999 (20.3) 1405 (25.6) 739 (14.9) 1313 (26.5) High 185 (1.9) 186 (3.4) 57 (1.2) 174 (3.5) Moderate+high 2184 (22.2) 1591 (28.9) 796 (16.1) 1487 (30.0) *P value based on Mann-Whitney U-test.
†P value based on Wilcoxon test.
IAs, intracranial aneurysms; tHcy, total homocysteine.
- Table 3
Association between tHcy and intracranial aneurysm
Before matched After matched Crude OR Model 1* Model 2† Crude OR Model 1* Model 2† Adjusted OR Adjusted OR Adjusted OR Adjusted OR 95% CI P 95% CI P 95% CI P 95% CI P 95% CI P 95% CI P tHcy‡ (SD), μmol/L 1.23 (1.18 to 1.28) <0.001 1.50 (1.43 to 1.57) <0.001 1.50 (1.43 to 1.57) <0.001 1.82 (1.70 to 1.95) <0.001 1.99 (1.85 to 2.13) <0.001 1.98 (1.85 to 2.14) <0.001 tHcy§ 1.13 (1.11 to 1.16) <0.001 1.30 (1.24 to 1.33) <0.001 1.29 (1.25 to 1.33) <0.001 1.44 (1.38 to 1.50) <0.001 1.51 (1.45 to 1.59) <0.001 1.52 (1.45 to 1.59) <0.001 Group tHcy, number (%) <0.001¶ <0.001¶ <0.001¶ Low Reference. Reference. Reference. Reference. Reference. Reference. Moderate 1.38 (1.27 to 1.49) <0.001 1.72 (1.47 to 2.00) <0.001 1.71 (1.61 to 1.82) <0.001 2.13 (1.93 to 2.36) <0.001 2.70 (2.19 to 3.37) <0.001 1.80 (1.67 to 1.94) <0.001 High 1.97 (1.60 to 2.42) <0.001 0.94 (0.85 to 1.05) 0.281 2.06 (1.76 to 2.40) <0.001 3.66 (2.71 to 4.95) <0.001 0.90 (0.78 to 1.04) 0.200 2.69 (2.17 to 3.34) <0.001 Moderate+high 1.43 (1.32 to 1.54) <0.001 1.59 (1.50 to 1.69) <0.001 2.20 (2.02 to 2.39) <0.001 2.24 (2.03 to 2.47) <0.001 1.88 (1.75 to 2.02) <0.001 1.87 (1.74 to 2.00) <0.001 P-value for OR (odd ratios) was based on Wald tests.
*Adjusted for age, sex, hypertension and smoking.
†Adjusted for variables from Model 1 plus dyslipidaemia and diabetes.
‡: OR was estimated by one standard difference increase of tHcy (8.2 µmol/L).
§: OR was estimated by a increase of 5 µmol/L of tHcy.
¶: P value for trend.
tHcy, total homocysteine.
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