The baseline characteristics of the study participants (3,136 men and 3,517 women) stratified by the baseline presence of diabetes are shown in . A total of 820 participants had baseline diabetes including 7 individuals with type 1 diabetes (use of insulin at the time of initial diagnosis of diabetes and age at diabetes diagnosis <40 years). The MESA cohort demonstrated substantial variability in the distributions of major CVD risk factors. In the total MESA cohort, serum values of cystatin C and creatinine were 0.92 (standard deviation (SD), 0.27) mg/dL and 1.07 (SD, 0.32) mg/dL in men, respectively, and 0.87 (SD, 0.21) mg/dL and 0.85 (SD, 0.20) mg/dL in women, respectively. Serum cystatin C and creatinine were higher in men and women with diabetes compared with men and women without diabetes (). During 6 years of follow-up, 297 (9.5%) events occurred in men and 180 (5.1%) in women, with 122 events occurring in participants with baseline diabetes. The cardiovascular risk prediction models with FRSVs alone, FRSVs + cystatin C, and FRSVs + creatinine levels are shown in . When added to the FRSVs, cystatin C was independently associated with occurrence of incident events in both men and women, while creatinine was a significant predictor only in men. The interaction term between cystatin C and diabetes on CVD risk was not significant for men (P = 0.27) or women (P = 0.46). However, the interaction term between diabetes and serum creatinine on CVD risk was significant among men (P = 0.02) but not among women (P = 0.45). Interaction terms between age greater than 65 years and cystatin C and serum creatinine and between race/ethnicity and cystatin C and serum creatinine on CVD risk did not reach statistical significance. Among participants with baseline diabetes, cystatin C (P < 0.0001) and serum creatinine (P = 0.005) were significantly associated with incident CVD among men when added to the FRSVs but were not significant among women (P = 0.17 for cystatin C and P = 0.39 for creatinine).
Baseline Characteristics of Participants by Baseline Presence of Diabetes Mellitus and Gender, The Multi-Ethnic Study of Atherosclerosis, 2000–2002a
Transformed Variables and Beta Coefficients in the 3 Risk Models, The Multi-Ethnic Study of Atherosclerosis, 2000–2008
Comparisons of overall model fitness for the 3 models stratified by sex and by baseline diabetes are shown in . In the total cohort, the addition of cystatin C modestly improved all measures of risk prediction (C statistic, −2 log likelihood ratios, the Akaike Information Criterion, and the Bayes Information Criterion) in men, and modest improvement in the C statistic was noted among women with the addition of cystatin C to FRSVs (). In contrast, the addition of serum creatinine to FRSVs did not change the overall prediction of incident CVD risk in men or women in the total cohort (). Among male participants with baseline diabetes, the C statistic improved substantially with the addition of cystatin C to FRSVs compared with the FRSVs-alone model (). Among women, no substantial change in the C statistic was noted with the addition of cystatin C to the FRSVs compared with the model with FRSVs alone regardless of diabetes status. The addition of serum creatinine to FRSVs actually decreased the C statistic by 0.16 among women without baseline diabetes ().
Measures of Model Fit in the Total Cohort, The Multi-Ethnic Study of Atherosclerosis, 2000–2008
Measures of Model Fit Among Participants With Diabetes, The Multi-Ethnic Study of Atherosclerosis, 2000–2008
Measures of Model Fit Among Participants Without Diabetes, The Multi-Ethnic Study of Atherosclerosis, 2000–2008
and compare risk stratification between the FRSVs and FRSVs + cystatin C models, as well as the FRSVs and FRSVs + creatinine models, respectively. Calibration of the risk prediction models can be assessed by comparing the proportions of events in the margins of and with the corresponding row and column labels. Six-year event rates in low-, intermediate-, and high-risk groups were 1.6%, 5.9%, and 13.9%, respectively, in the model with the FRSVs alone and 1.8%, 5.1%, and 14.5%, respectively, in the model with FRSVs + cystatin C. In the model with FRSVs + creatinine, the 6-year event rates in low-, intermediate-, and high-risk groups were 1.6%, 5.9%, and 13.9%, respectively. Thus, the calibrations of the 3 models were very similar. Comparisons of the models with FRSVs alone, FRSVs + cystatin C, and FRSVs + creatinine led to 870 (13.1%) and 245 (3.7%) individuals stratified to other risk groups, respectively. Risk stratification capacity was similar across the models with FRSVs (72.6%), FRSVs + cystatin C (72.0%), and FRSVs + creatinine (72.1%) when judged by risk or when judged by classification accuracy (41.1%, 41.3%, and 40.4% in the FRSVs, FRSVs + cystatin C, and FRSVs + creatinine models, respectively) (). Net reclassification improvement was very small with the addition of cystatin C to FRSVs (0.016; P = 0.48) and slightly negative with the addition of serum creatinine to FRSVs (−0.009; P = 0.49) (). The addition of cystatin C or serum creatinine to FRSVs did not substantially impact risk stratification in MESA participants with or without baseline diabetes. The net reclassification improvement was less than 1% for FRSVs + cystatin C and for FRSVs + creatinine in the cohort with baseline diabetes. No meaningful impact on CVD risk prediction was noted after the addition of cystatin C or creatinine to FRSVs in racial/ethnic subgroups ().
Risk Stratification Table of Framingham Risk Score Variables Alone Versus Those With Cystatin C, The Multi-Ethnic Study of Atherosclerosis, 2000–2008
Risk Stratification Table of Framingham Risk Score Variables Alone Versus Those Without Serum Creatinine, The Multi-Ethnic Study of Atherosclerosis, 2000–2008
Reclassification Measures in the Total Cohort, Participants With Diabetes, and Participants in Racial/Ethnic Subgroups, The Multi-Ethnic Study of Atherosclerosis, 2000–2008