4 Cardiology Research and Practice Table 1: Baseline characteristics of study participants in the MESA cohort at baseline (2000). Variables Total CKD−/MetS− CKD+/MetS− CKD−/MetS+ CKD+/MetS+ P value n 5163 3444 119 1455 145 Age, years 61.6 (10.1) 60.7 (10.1) 71.1 (9.7) 62.2 (9.6) 69.7 (9.3) 0.0001 Caucasian 2283 (44%) 1565(69%) 65 (3%) 581 (25%) 72 (3%) 0.0002 Chinese 363 (7%) 293 (81%) 5 (1%) 61 (17%) 4 (1%) 0.0001 African 1449 (28%) 953 (66%) 29 (2%) 428 (30%) 39 (3%) 0.0001 Hispanic 1068 (21%) 633 (59%) 20 (2%) 385 (36%) 30 (3%) 0.0001 Male, % 2722 (53%) 1872(69%) 74 (3%) 697 (26%) 79 (3%) 0.0001 Female, % 2441 (47%) 1572 (64%) 45 (2%) 758 (31%) 66 (3%) 0.0001 DM, % 572 (11%) 128 (4%) 2 (2%) 394 (27%) 48 (33%) 0.0001 Current smokers, % 741 (14%) 491 (14%) 19 (16%) 213 (15%) 18 (12%) 0.8 Current drinking, % 3576 (69%) 2494 (72%) 78 (66%) 919 (63%) 85 (59%) 0.0001 Physical activity, min/wk 1644 (2395) 1777 (2537) 1670 (2855) 1372 (2012) 1205 (1683) 0.0001 Total cholesterol, mg/dL 193 (35) 194 (34) 187 (38) 193 (36) 188 (39) 0.08 SBP, mmHg 126 (21) 122 (20) 130 (23) 133 (21) 137 (25) 0.0001 DBP, mmHg 72 (10) 72 (10) 71 (10) 74 (10) 72 (11) 0.0001 LDL-C, mg/dL 117 (31) 118 (31) 113 (32) 116 (33) 113 (31) 0.01 HDL-C, mg/dL 51 (15) 55 (15) 52 (14) 43 (10) 42 (11) 0.0001 TG, mg/dL 125 (65) 103 (49) 109 (43) 173 (72) 170 (67) 0.0001 Fasting glucose, mmHg 96 (27) 90 (19) 89 (9) 110 (40) 109 (33) 0.0001 eGFRcysC, mL/min/1.73m2 93 (22) 98 (20) 51 (9) 90 (19) 49 (10) 0.0001 MetS components, % HTN, % 2219 (43%) 1078 (31%) 70 (59%) 954 (66%) 117 (81%) 0.0001 Obesity, % 2763 (54%) 1319 (38%) 57 (48%) 1259 (87%) 128 (88%) 0.0001 Elevated TG, % 1457 (28%) 415 (12%) 13 (11%) 939 (66%) 90 (62%) 0.0001 Low HDL-C, % 1957 (38%) 736 (21%) 32 (27%) 1078 (74%) 111 (77%) 0.0001 Impaired Glucose, % 2062 (40%) 1037 (30%) 39 (33%) 892 (61%) 94 (65%) 0.0001 CVD events, % 283 (5%) 118 (3%) 10 (8%) 120 (8%) 35 (24%) 0.0001 P values obtained by one aay analysis of variance. Data presented in total numbers (percentages) and continuous measures presented as mean value (standard deviation). DM: diabetes mellitus; SBP: dystolic blood pressure, mmHg; DBP: diastolic blood pressure, mmHg; LDL-C: mg/dL low density lipoprotein cholesterol; HDL-C: mg/dL high density lipoprotein cholesterol; TG: mg/dL, triglyceride; eGFRcysC: mL/min/1.73 m2 glomerular ﬁltration rate estimated from cystatin C; CVD: cardiovascular events; MetS: metabolic syndrome; CKD: chronic kidney disease. Table 2: Unadjusted and multivariate-adjusted HRs of CVD events associated with CKD and MetS. Total participants (n = 5, 163) Participants without diabetes (n = 4, 591) Crude Adjusted Crude Adjusted CKD−/MetS− 1 (Reference) 1 (Reference) 1 (Reference) 1 (Reference) CKD+/MetS− 2.70 (1.32−4.88) 1.43 (0.70−2.62) 2.90 (1.42−5.26) 1.41 (0.69−2.61) CKD−/MetS+ 2.51 (1.94−3.23) 2.40 (1.85−3.11) 2.17 (1.60−2.91) 2.08 (1.54−2.81) CKD+/MetS+ 8.46 (5.72−12.20) 5.56 (3.72−8.12) 7.27 (4.33−11.54) 4.43 (2.60−7.15) Hazard ratios (95% CI) adjusted for age, ethnicity, gender, study site, education, income, smoking, alcohol use, physical activity, and total and LDL cholesterol. HR: hazard ratio; CI: conﬁdence interval; CVD: cardiovascular events; CKD: chronic kidney disease; MetS: metabolic syndrome. Furthermore, even when compared with the CKD+/MetS− group or with the CKD−/MetS+ group, the risk of CVD events was signiﬁcantly higher in the CKD+/MetS+ group in the multivariate model (versus CKD+/MetS− group: HR 3.13, 95% CI 1.48–7.03, P = 0.03; versus CKD−/MetS+ group: HR 2.13, 95% CI 1.23–3.49, P = 0.01). Finally, when interaction was tested between CKD and MetS, no multiplicative interaction was demonstrated (CKD × MetS, P = 0.2). When formal tests for additive interaction such as relative excess risk due to interaction (RERI), attributable portion (AP), and synergy index (SI) were performed, there was presence of signiﬁcant additive interaction as shown in Table 3 and Appendix. RERI (95% CI) was estimated at 2.73 (0.57–4.85, P = 0.02), AP (95% CI) was estimated at 0.49 (0.24–0.74), and SI (95% CI) was estimated at 2.49 (1.24–4.98). According to the