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. 2020 Jun 5;11(6):1510–1528. doi: 10.1093/advances/nmaa061

TABLE 3.

Subgroup analysis of the dietary intake of homocysteine metabolism-related B-vitamins and the risk of stroke1

Vitamin B-6 Folate Vitamin B-12
N RR (95% CI) I2 P 2 P 3 N RR (95% CI) I2 P 2 P 3 N RR (95% CI) I2 P 2 P 3
Overall 10 0.84 (0.73, 0.97) 48.8 0.041 16 0.85 (0.78, 0.94) 11.5 0.322 10 1.03 (0.94, 1.13) 0.4 0.434
Location 0.015 0.803 0.45
 USA 2 1.09 (0.58, 2.05) 56.8 0.128 6 0.85 (0.74, 0.97) 0 0.467 2 0.84 (0.56, 1.26) 33.1 0.221
 Europe 4 0.9 (0.81, 1.01) 0 0.566 7 0.88 (0.73, 1.06) 23.3 0.251 6 1.02 (0.51, 0.69) 0 0.946
 Asia 4 0.73 (0.64, 0.83) 0 0.429 3 0.86 (0.64, 1.17) 53.6 0.116 2 1.34 (0.96, 1.88) 5.6 0.303
Sex 0.067 0.203 0.67
 Male 7 0.91 (0.78, 1.07) 44.4 0.095 6 0.86 (0.74, 1) 24.7 0.249 6 1.04 (0.88, 1.22) 36.5 0.163
 Female 2 0.71 (0.60, 0.84) 0 0.615 3 0.96 (0.8, 1.16) 1.5 0.362 1 1.13 (0.71, 1.79) — —
Follow-up 0.266 0.371 0.84
 >10 y 9 0.86 (0.74, 0.99) 50.6 0.04 12 0.84 (0.77, 0.92) 2.7 0.418 7 1.04 (0.9, 1.2) 25.6 0.234
 ≤10 y 1 0.54 (0.25, 1.14) — — 4 0.96 (0.57, 1.6) 38.2 0.183 3 0.98 (0.64, 1.5) 0 0.705
Participants 0.004 0.05 0.10
 <50,000 6 0.94 (0.80, 1.11) 26.3 0.237 13 0.81 (0.74, 0.89) 0 0.511 8 1.00 (0.90, 1.10) 0 0.688
 >50,000 4 0.73 (0.64, 0.83) 0 0.429 3 0.98 (0.83, 1.15) 0 0.395 2 1.34 (0.96, 1.88) 5.6 0.303
Stroke subtype 0.43 0.978 0.62
 Ischemic stroke 2 1.08 (0.72, 1.64) 75.6 0.043 7 0.84 (0.73, 0.97) 33.9 0.169 3 0.94 (0.74, 1.19) 42.5 0.176
 Hemorrhagic stroke 2 0.87 (0.65, 1.17) 0 0.596 4 0.85 (0.61, 1.19) 11.1 0.338 3 1.05 (0.81, 1.37) 0 0.863
Mean age (y) 0.73 0.98 0.11
 ≥55 7 0.84 (0.73, 0.96) 28.4 0.212 10 0.88 (0.76, 1.01) 27.1 0.195 6 1.05 (0.95, 1.16) 0 0.695
 <55 3 0.91 (0.51, 1.49) 77.5 0.012 6 0.85 (0.74, 0.96) 0 0.467 4 0.84 (0.56, 1.26) 33.1 0.221
Exposure assessment 0.266 0.501 0.57
 FFQ 9 0.86 (0.74, 0.99) 50.6 0.04 14 0.87 (0.78, 0.97) 21.1 0.224 9 1.03 (0.92, 1.15) 5.8 0.387
 Non-FFQ 1 0.54 (0.25, 1.14) — — 2 0.80 (0.65, 0.98) 0 0.844 1 0.86 (0.47, 1.57) — —
Validation on B-vitamins 0.03 0.04 0.56
 Yes 5 0.96 (0.83, 1.10) 15.6 0.315 6 0.80 (0.71, 0.89) 0 0.519 5 1.00 (0.90, 1.11) 1.6 0.397
 No 4 0.73 (0.64, 0.83) 0 0.429 8 0.96 (0.83, 1.11) 11.3 0.342 4 1.29 (0.96, 1.71) 0 0.637
Exposure source 0.05 0.265 0.56
 Foods + supplements 7 0.80 (0.65, 0.99) 54.1 0.041 12 0.89 (0.78, 0.99) 11.9 0.328 6 1.07 (0.81, 1.42) 37.8 0.154
  Foods 3 0.91 (0.82, 1.02) 0 0.914 4 0.81 (0.71, 0.92) 6.9 0.359 4 1.02 (0.92, 1.13) 0 0.862
Quality 0.266 0.846 0.84
  <7 1 0.54 (0.25, 1.14) — — 3 0.80 (0.40, 1.59) 47.2 0.151 3 0.98 (0.64, 1.50) 0 0.705
  ≥7 9 0.86 (0.74, 0.99) 50.6 0.04 13 0.85 (0.78, 0.93) 8.5 0.36 7 1.04 (0.90, 1.20) 25.6 0.234
Adjustments4
 Age — 0.56 0.783
  Yes 10 0.84 (0.73, 0.97) 48.8 0.041 14 0.85 (0.78, 0.92) 1.9 0.428 8 1.03 (0.91, 1.16) 16.3 0.302
  No 0 — — — 2 0.56 (0.08, 3.76) 70.1 0.067 2 1.11 (0.61, 2.04) 0 0.552
 BMI 0.266 0.828 0.57
  Yes 9 0.86 (0.74, 0.99) 50.6 0.04 13 0.86 (0.78, 0.96) 25.1 0.19 9 1.03 (0.92, 1.15) 5.8 0.387
  No 1 0.54 (0.25, 1.14) — — 3 0.82 (0.63, 1.07) 0 0.646 1 0.86 (0.47, 1.57) — —
 Physical activity 0.503 0.36 0.84
  Yes 7 0.86 (0.74, 1.00) 56.8 0.031 9 0.84 (0.75, 0.93) 13.8 0.319 5 1.00 (0.90, 1.11) 1.6 0.397
  No 3 0.75 (0.50, 1.13) 38.4 0.197 7 0.9 (0.76, 1.08) 11.8 0.339 5 1.20 (0.92, 1.55) 0 0.545
 Alcohol 0.266 0.967 0.21
  Yes 9 0.86 (0.74, 0.99) 50.6 0.04 11 0.85 (0.77, 0.95) 19 0.263 7 1.04 (0.90, 1.20) 25.6 0.234
  No 1 0.54 (0.25, 1.14) — — 5 0.85 (0.65, 1.11) 12.9 0.332 3 0.98 (0.64, 1.50) 0 0.705
 Energy intake 0.512 0.78
  Yes 10 0.84 (0.73, 0.97) 48.8 0.041 — 13 0.85 (0.79, 0.92) 0 0.475 8 1.03 (0.91, 1.16) 16.3 0.302
  No 0 — — — 3 0.72 (0.36, 1.44) 58.9 0.088 2 1.11 (0.61, 2.04) 0 0.552
 Excluding pre-existing stroke 0.266 0.705 0.57
  Yes 9 0.86 (0.74, 0.99) 50.6 0.04 15 0.86 (0.78, 0.95) 16.7 0.267 9 1.03 (0.92, 1.15) 5.8 0.387
  No 1 0.54 (0.25, 1.14) — — 1 0.75 (0.38, 1.46) — — 1 0.86 (0.47, 1.57) — —
 Level of education 0.004 0.572 —
  Yes 2 0.72 (0.62, 0.82) 26.7 0.216 1 0.80 (0.64, 0.99) — — 0 — — —
  No 8 0.92 (0.79, 1.08) 48.8 0.041 15 0.87 (0.78, 0.96) 15.9 0.276 10 1.03 (0.94, 1.13) 0.4 0.434
 Level of income 0.004 — —
  Yes 2 0.72 (0.62, 0.82) 26.7 0.216 0 — — — 0 — — —
  No 8 0.92 (0.79, 1.08) 48.8 0.041 16 0.85 (0.78, 0.94) 11.5 0.322 10 1.03 (0.94, 1.13) 0.4 0.434
Adjustment model 0.517 0.565 0.763
  Basic 7 0.77 (0.65, 0.92) 74.3 <0.001 11 0.85 (0.76, 0.95) 32.2 0.141 7 1.10 (0.96, 1.25) 24.7 0.241
  Multivariable 7 0.82 (0.72, 0.93) 37.3 0.141 11 0.88 (0.78, 0.99) 30.2 0.158 7 1.05 (0.95, 1.16) 0 0.635
 Diabetes 0.266 0.705 0.57
  Yes 9 0.86 (0.74, 0.99) 50.6 0.04 15 0.86 (0.78, 0.95) 16.7 0.267 9 1.03 (0.92, 1.15) 5.8 0.387
  No 1 0.54 (0.25, 1.14) — — 1 0.75 (0.38, 1.46) — — 1 0.86 (0.47, 1.57) — —
 Hypertension/blood pressure 0.266 0.705 0.57
  Yes 9 0.86 (0.74, 0.99) 50.6 0.04 15 0.86 (0.78, 0.95) 16.7 0.267 9 1.03 (0.92, 1.15) 5.8 0.387
  No 1 0.54 (0.25, 1.14) — — 1 0.75 (0.38, 1.46) — — 1 0.86 (0.47, 1.57) — —
1

Pooled estimates were obtained using a random-effects model by comparing the highest category and lowest category.

2

P value for heterogeneity within each subgroup.

3

P value for heterogeneity between subgroups with meta-regression analysis.

4

Cigarette smoking was adjusted for in all studies; therefore, no stratified results by smoking are reported.