Variable I/I I/D D/D (n=899) (n=844) (n=214) Mean (SE) p-value of ANOVA Lowest ankle-arm index (baseline) 1.030 (0.004) 1.021 (0.004) 1.034 (0.008) 0.1099 Lowest ankle-arm index (5th yr FU) 1.021 (0.005) 1.024 (0.005) 1.011 (0.010) 0.5342 Lowest ankle-arm index (% change at 5th yr FU) -0.997 (0.488) 0.343 (0.513) -2.266 (1.017) 0.0350 Age (year) 72.23 (0.18) 72.84 (0.18) 73.08 (0.37) 0.0212 2 BMI (kg/m ) 23.89 (0.11) 23.95 (0.12) 23.94 (0.24) 0.9488 PASE score 86.77 (1.11) 83.93 (1.14) 84.97 (2.27) 0.2010 Freq (%) p-value of Chi square Peripheral arterial diseases (ABI<0.9) (baseline) 70 (7.8%) 88 (10.4%) 18 (8.4%) 0.1484 Peripheral arterial diseases (ABI<0.9) (5th yr FU) 91 (12.6%) 84 (12.8%) 27 (16.2%) 0.4440 Diabetes 124 (13.8%) 126 (14.9%) 34 (15.9%) 0.6641 Heart disease (MI/ ANGINA/ CHF) 148 (16.5%) 145 (17.2%) 30 (14.0%) 0.5390 Hypertension 378 (42.1%) 383 (45.4%) 93 (43.5%) 0.3738 Stroke 29 (3.2%) 27 (3.2%) 9 (4.2%) 0.7467 Use of ACE inhibitor 66 (7.3%) 75 (8.9%) 16 (7.5%) 0.4722 Current smoker 13 (1.5%) 20 (2.4%) 4 (1.9%) 0.3741 Current alcohol use 28 (3.1%) 19 (2.3%) 4 (1.9%) 0.4106 Saturated fatty acids (g/day) <8.3 295 (32.9%) 275 (32.7%) 78 (36.5%) 0.7670 8.3-11.4 299 (33.3%) 284 (33.7%) 65 (30.4%) 11.5 or above 304 (33.9%) 283 (33.6%) 71 (33.2%) Monosaturated fatty acids (g/day) <14.2 302 (33.6%) 274 (32.5%) 76 (35.5%) 0.6691 14.2-19.3 302 (33.6%) 280 (33.3%) 69 (32.2%) 19.4 or above 294 (32.7%) 288 (34.2%) 69 (32.2%) Polyunsaturated fatty acids (g/day) <10.1 291 (32.4%) 294 (34.9%) 66 (30.8%) 0.8656 10.1-13.6 307 (34.2%) 263 (31.2%) 83 (38.8%) 13.7 or above 300 (33.4%) 285 (33.9%) 65 (30.4%) Vitamin C (mg/day) <116 313 (34.9%) 264 (31.4%) 72 (33.6%) 0.3681 116-169.5 293 (32.6%) 287 (34.1%) 70 (32.7%) 169.6 or above 292 (32.5%) 291 (34.6%) 72 (33.6%) Vitamin D (IU/day) <4.7 308 (34.3%) 269 (32.0%) 78 (36.5%) 0.2678 4.7-11.8 298 (33.2%) 286 (34.0%) 74 (34.6%) 11.9 or above 292 (32.5%) 287 (34.1%) 62 (29.0%) Vitamin K (mcg/day) <192.9 299 (33.3%) 288 (34.2%) 67 (31.3%) 0.7204 192.9-308.7 315 (35.1%) 256 (30.4%) 76 (35.5%) 308.8 or above 284 (31.6%) 298 (35.4%) 71 (33.2%) Iron (mg/day) <9.9 297 (33.1%) 276 (32.8%) 66 (30.8%) 0.6764 9.9-13.8 312 (34.7%) 270 (32.1%) 77 (36.0%) 13.9 or above 289 (32.2%) 296 (35.2%) 71 (33.2%) Cholesterol (mg/day) <103.3 302 (33.6%) 283 (33.6%) 71 (33.2%) 0.9751 103.3-167.5 294 (32.7%) 278 (33.0%) 75 (35.1%) 167.6 or above 302 (33.6%) 281 (33.4%) 68 (31.8%) Isoflavones (mg/day) <5.2 298 (33.2%) 289 (34.3%) 75 (35.1%) 0.8424 5.2-12.8 313 (34.9%) 266 (31.6%) 59 (27.6%) 12.9 or above 287 (32.0%) 287 (34.1%) 80 (37.4%) Fish (g/day) <42.9 295 (32.9%) 282 (33.5%) 70 (32.7%) 0.7879 42.9-81.3 293 (32.6%) 282 (33.5%) 78 (36.5%) 81.4 or above 310 (34.5%) 278 (33.0%) 66 (30.8%) Chinese tea (g/day) <35.7 282 (31.4%) 283 (33.6%) 63 (29.4%) 0.4307 35.7-501.4 285 (31.7%) 264 (31.4%) 70 (32.7%) 501.5 or above 331 (36.9%) 295 (35.0%) 81 (37.9%) Fruit (g/day) <169.9 296 (33.0%) 281 (33.4%) 72 (33.6%) 0.9038 169.9-271.4 305 (34.0%) 277 (32.9%) 64 (29.9%) 271.5 or above 297 (33.1%) 284 (33.7%) 78 (36.5%) Vegetable (g/day) <164.7 306 (34.1%) 284 (33.7%) 65 (30.4%) 0.2509 164.7-252.9 319 (35.5%) 256 (30.4%) 76 (35.5%) 253 or above 273 (30.4%) 302 (35.9%) 73 (34.1%) Tomato (g/day) <7.1 288 (32.1%) 282 (33.5%) 71 (33.2%) 0.9401 7.1-14.3 345 (38.4%) 303 (36.0%) 82 (38.3%)



Estimated mean (SE) of lowest ankle-arm index for subjects among different groups of ACE genotype, ANCOVA adjusted by

Mean (SE) p-value of ANCOVA Variable I/I I/D D/D Adjusted for potential confounders Male Lowest ankle-arm index (baseline) 1.077 (0.010) 1.074 (0.010) 1.080 (0.013) 0.8275 Lowest ankle-arm index (5th yr FU) 1.066 (0.011) 1.057 (0.011) 1.060 (0.015) 0.4056 Lowest ankle-arm index (% change at 5th yr FU) -0.979 (1.127) -1.386 (1.125) -2.438 (1.449) 0.4461 Female Lowest ankle-arm index (baseline) 1.004 (0.014) 0.998 (0.014) 1.013 (0.016) 0.1468 Lowest ankle-arm index (5th yr FU) 0.997 (0.019) 1.004 (0.019) 0.991 (0.021) 0.4205 Lowest ankle-arm index (% change at 5th yr FU) -2.408 (1.993) -0.903 (1.991) -3.567 (2.186) 0.0227





Bold: p<0.05; * potential confounders including age, BMI, PASE, diabetes, heart disease, hypertension, stroke, use of ACE inhibitors, smoking, alcohol, dietary intake of saturated fatty



Freq/ Total (%) p-value of Chi square Variable No. didn’t have disease I/I I/D D/D at baseline Male Incidence of disease Diabetes 1273 27/ 556 (4.9%) 23/ 601 (3.8%) 5/ 116 (4.3%) 0.6918 Stroke 1415 34/ 628 (5.4%) 27/ 658 (4.1%) 3/ 129 (2.3%) 0.2501 Hypertension 867 78/ 390 (20.0%) 86/ 398 (21.6%) 17/ 79 (21.5%) 0.8479 Myocardial infarct 1328 33/ 583 (5.7%) 41/ 623 (6.6%) 5/ 122 (4.1%) 0.5316 Angina 1337 26/ 585 (4.4%) 22/ 622 (3.5%) 6/ 130 (4.6%) 0.6837 Congestive heart failure 1426 18/ 620 (2.9%) 11/ 672 (1.6%) 3/ 134 (2.2%) 0.3167 Female Incidence of disease Diabetes 1335 38/ 635 (6.0%) 25/ 556 (4.5%) 8/ 144 (5.6%) 0.5187 Stroke 1500 20/ 701 (2.9%) 24/ 638 (3.8%) 5/ 161 (3.1%) 0.6432 Hypertension 871 87/ 421 (20.7%) 99/ 354 (28.0%) 27/ 96 (28.1%) 0.0429 Myocardial infarct 1414 29/ 661 (4.4%) 27/ 595 (4.5%) 15/ 158 (9.5%) 0.0284 Angina 1440 26/ 667 (3.9%) 27/ 612 (4.4%) 8/ 161 (5.0%) 0.7999



Variable Freq (%)/ mean (SD) HR (95% CI) Alive Dead Crude Age adj. Male ACE genotype I/I 688 (84.4%) 127 (15.6%) 1 1 I/D 704 (83.6%) 138 (16.4%) 1.08 (0.84, 1.37) 1.13 (0.88, 1.44) D/D 136 (73.9%) 48 (26.1%) 1.45 (1.04, 2.03) 1.54 (1.10, 2.16) Age (per 1 year) 71.71 (4.58) 75.16 (5.49) - 1.06 (1.04, 1.08) Female ACE genotype I/I 844 (93.9%) 55 (6.1%) 1 1 I/D 776 (91.9%) 68 (8.1%) 1.22 (0.85, 1.74) 1.23 (0.86, 1.76) D/D 203 (94.9%) 11 (5.1%) 0.73 (0.37, 1.45) 0.71 (0.36, 1.41)



without the protective effect of higher endogenous oestrogen levels are more susceptible to the effect of increase ACE