2. Results

The mean age at study entry was 73 years, 84% of the par- ticipants were white, and 54% were women (Table 1). Demo- graphic characteristics, overall health and functional status,

Years of life and years of healthy life differed by TAFI pro- moter genotypes among white men (Table 3), but there was little association of TAFI genotype with longevity in women (Table 4). The association with years of life in men remained significant in analyses that also adjusted for baseline socioe- conomic (P = 0.007) or health-related variables (P = 0.003); similar results were seen for years of healthy life (P = 0.01 after adjustment for socioeconomic variables; P = 0.02 after adjustment for health-related variables). During 10 years of − follow-up, men carrying the TAFI 438 A/A genotype had 0.9 additional years of life (95% CI 0.2–1.9 years) or 1.1 additional years of healthy life (95% CI 0.2–2.1 years) rel- − ative to men carrying at least one common TAFI 438 G allele.

Selected baseline characteristics of study participants

Characteristics n (%) or mean±S.D. (range) Age, years (range) 73.4±5.5 (64–94) White race 1954 (84) Female sex 1253 (54) Very good or excellent health 830 (36) Obesitya 682 (29) Current smoker 273 (12) Diabetes 727 (32) Hypertension 1097 (47) Prevalent cardiovascular diseaseb 727 (31) Previous diagnosis of cancer 321 (14) Anti-inflammatory medication usec 1161 (50)

Years of life and years of healthy life differed slightly, − but not significantly, by PAI-1 675 4G/5G genotype among whites (Tables 3 and 4), albeit in opposite directions among men and women (interaction P = 0.10 for years of life, and P = 0.01 for years of healthy life). There was little asso-  ciation between the interleukin-6 or -fibrinogen promoter

b Self-reported myocardial infarction, stroke, angina, transient ischemic attack, claudication, or re-vascularization procedure. c Baseline use of any of the following: aspirin, NSAIDs, ACE inhibitors, or statins.

A.P. Reiner et al. / Atherosclerosis 181 (2005) 175–183

Estimated genotype frequency distributions and tests of Hardy–Weinberg equilibrium, by race

Gene and SNP Genotype Whites (n=1874) Blacks (n=350) Observeda # (%) Expected # P Observeda # (%) Expected # P TAFI −438 GG 1070 (58) 1047 0.004 176 (52) 167 0.02 GA 643 (35) 690 133 (39) 141 AA 137 (7) 114 29 (8) 30 PAI-1 −675 4G/4G 487 (26) 510 0.03 37 (11) 32 0.19 4G/5G 974 (52) 928 136 (39) 146 5G/5G 399 (21) 422 173 (50) 168 IL6 −174 GG 712 (38) 693 0.06 288 (83) 289 0.61 GC 843 (45) 881 58 (17) 56 CC 299 (16) 280 2 (0.4) 3 (cid:1)-Fibrinogen −455 GG 1161 (63) 1158 0.63 312 (91) 312 0.81 GA 602 (33) 611 31 (9) 31 AA 84 (5) 81 1 (0.3) 1

A small number of participants (<2%) have missing genotype data because of genotyping assay failure. Hardy–Weinberg equilibrium was assessed using Pearson’s Chi-squared test. a Becausetheavailabledatawerederivedfromacase–controlsampleofthetotalCHScohort,weadjustedtheobservedgenotypedistributionsbythesampling probability of each participant, as described under Section 2.

polymorphisms and longevity (Table 3). Among blacks, there were no significant associations between the PAI-1 and TAFI  genotypes and longevity; the interleukin-6 or -fibrinogen promoter polymorphisms were too uncommon in blacks to assess genotype–longevity associations.

The overall mortality risk in men associated with the TAFI promoter polymorphism did not appear to differ by

Differences in the average number of years of life or years of healthy life according to inflammation and thrombosis gene promoter genotype in men, by racea

Genotype Years of life (95% CI) P Years of healthy life (95% CI) P White men (n=893) TAFI −438 0.003 G/G 0 (referent) 0 (referent) G/A +0.01 (−0.40, +0.41) 0.99 +0.09 (−0.47, +0.65) A/A +0.87 (+0.33, +1.41) 0.002 +1.08 (+0.26, +1.91) PAI-1 −675 0.04 4G/4G +0.53 (+0.07, +0.98) 0.02 +0.53 (−0.06, +1.12) 4G/5G 0 (referent) 0 (referent) 5G/5G +0.52 (+0.02, +1.02) 0.04 +0.54 (−0.13, +1.21) Interleukin-6 −174 0.60 G/G 0 (referent) 0 (referent) G/C +0.12 (−0.35, +0.59) 0.61 +0.10 (−0.50, +0.71) C/C +0.30 (−0.29, +0.90) 0.32 +0.51 (− 0.27, +1.29) Fibrinogen −455 0.56 G/G 0 (referent) 0 (referent) G/A −0.22 (−0.70, +0.25) 0.36 +0.03 (−0.53, +0.58) A/A +0.11 (−0.52, +0.75) 0.72 +0.33 (−0.64, +1.30) Black men (n=133) TAFI −438 0.26 G/G 0 (referent) 0 (referent) G/A +0.94 (−0.20, +2.08) 0.11 +0.73 (−0.68, +2.15) A/A +0.89 (−1.65, +3.43) 0.49 +1.57 (−1.69, +4.84) PAI-1 −675 0.51 4G/4G −0.81 (−2.83, +1.21) 0.43 −0.69 (−2.84, +1.47) 4G/5G 0 (referent) 0 (referent) 5G/5G −0.65 (−1.97, +0.67) 0.33 −0.34 (−1.95, +1.27)

a Adjusted for age at baseline and clinic site. Shown in bold are the adjusted P-values for the composite genotype test of association at each locus. are the adjusted P-values for the individual genotypes.

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Differences in the average number of years of life or years of healthy life according to inflammation and thrombosis gene promoter genotype in women, by