1
Supplementary Table 2: Baseline characteristics of the study population (n=5388)
Characteristics / Value (*)Age, mean (SD), years / 55.8 (13.8)
Female, n / 3,353 (62.2%)
Arterial Hypertension, n / 1,848 (34.3%)
Systolic blood pressure, mean (SD), mmHg / 131.5 (18.1)
Diastolic blood pressure, mean (SD), mmHg / 80.1 (9.8)
Antihypertensive treatment, n / 1,621 (31.7%)
ACE inhibitor/AT receptor antagonist, n / 841 (16.4%)
Beta-blocker, n / 1,039 (20.3%)
Calcium channel blocker, n / 515 (10.1%)
Diuretics, n / 641 (12.5%)
Diabetes mellitus, n / 662 (12.3%)
Fasting plasma glucose, mean (SD), mg/dl / 99.5 (33.0)
Insulin treatment, n / 181 (3.5%)
Hyperlipidemia, n / 1,498 (27.8%)
Statins, n / 547 (10.7%)
other lipid lowering drugs, n / 149 (2.9%)
total cholesterol, mean (SD), mg/dl / 225.5 (42.0)
HDL cholesterol, mean (SD), mg/dl / 55.7 (18.5)
LDL cholesterol, mean (SD), mg/dl / 129.3 (33.2)
Current smoker, n / 1,052 (21.2%)
Ex-smoker, n / 1,209 (24.3%)
Family history of CAD, n / 770 (14.8%)
Hip to waist ratio, mean (SD) / 1.13 (0.13)
Body mass index, mean (SD), kg/m² / 26.9 (4.9)
eGFR (ml/min/1,73 m2) / 57.8 (10.9)
Biomarkers
Sensitive Troponin I (cTnI) ng/l / 10 (330)
hsCRP, mean (SD), mg/l / 4.3 (7.0)
NT-pro-BNP, mean (SD), ng/l / 122.3 (307.5)
(*) = All percentages refer to number of subjects with existing data
Abbreviations: n = number; SD = standard deviation; CAD = coronary artery disease; hsCRP = highsensitive C-reactive protein; NT-pro-BNP = N-terminal pro brain natriuretic peptide; cTnI = sensitive Troponin I ; eGFR = estimated glomerular filtration rate (Cockroft/Gault; Nephron 1976;16(1):31-41)
1
Supplementary Table 3 : Independent predictors of cTnI levels in the third tertile by multivariate regression model
univariate / multivariateOR (*) / 95 % CI / p value / OR (*) / 95 % CI / p value
Age ; mean (SD) / 2.96 / 2.54 - 3.46 / <0.001 / 1.59 / 1.15 , 2.22 / 0.006
Male gender / 2.31 / 1.84 - 2.89 / <0.001 / 2.93 / 1.87 , 4.61 / <0.001
Framingham – score predicted risk; %; mean / 1.88 / 1.68 - 2.10 / <0.001 / 1.21 / 0.91 , 1.60 / 0.195
Arterial Hypertension / 3.52 / 2.80 - 4.42 / <0.001 / 1.72 / 1.18 , 2.52 / 0.005
Systolic blood pressure; mmHg; mean / 1.68 / 1.51 - 1.87 / <0.001 / 0.98 / 0.77 , 1.24 / 0.857
Diastolic blood pressure; mmHg; mean / 1.16 / 1.04 - 1.28 / 0.006 / 0.88 / 0.73 , 1.07 / 0.193
Diabetes mellitus / 3.03 / 2.31 - 3.96 / <0.001 / 0.98 / 0.56 , 1.75 / 0.959
Insulin dependent diabetes mellitus / 2.64 / 1.62 - 4.33 / <0.001 / 1.22 / 0.55 , 2.71 / 0.617
HbA1c; % ; mean / 1.46 / 1.35 - 1.59 / <0.001 / 1.14 / 0.97 , 1.33 / 0.108
Hyperlipidemia / 1.65 / 1.31 - 2.09 / <0.001 / 1.02 / 0.72 , 1.46 / 0.908
LDL cholesterol; mg/dl; mean (SD) / 1.07 / 0.95 - 1.19 / 0.258 / 0.98 / 0.82 , 1.17 / 0.839
Triglyceride; mg/dl; mean (SD) / 1.14 / 1.05 - 1.25 / 0.003 / 1.02 / 0.90 , 1.16 / 0.750
Body mass index; kg/m2 ; mean (SD) / 1.30 / 1.18 - 1.43 / <0.001 / 1.20 / 1.02 , 1.41 / 0.025
Current smoker / 0.71 / 0.52 - 0.97 / 0.030 / 1.16 / 0.74 , 1.81 / 0.512
eGFR ; (ml/min/1,73 m2); mean (SD) / 0.69 / 0.60 , 0.79 / <0.001 / 0.78 / 0.64 , 0.95 / 0.013
hsCRP, mean (SD), mg/l / 1.09 / 0.99 , 1.20 / 0.095 / 1.02 / 0.87 , 1.18 / 0.837
NT-pro-BNP, mean (SD), ng/l / 2.72 / 2.06 , 3.59 / <0.001 / 1.75 / 1.38 , 2.22 / <0.001
Abbreviations: CI = Confidence interval; OR = Odds-Ratio; SD standard deviation ; cTnI = sensitive Troponin I ; eGFR = estimated glomerular filtration rate (Cockroft/Gault; Nephron 1976;16(1):31-41); hsCRP = highsensitive C-reactive protein; NT-pro-BNP = N-terminal pro brain natriuretic peptide; (*) = reference group is the group of participiants with cTnI concentrations under the detection level ; OR for increase of 1SD for metric cardiovascular risk factors
Supplementary Table 4: Hazard Ratios for death by all causes and for major adverse cardiovascular events (MACE) according to cTnI levels using study specific detection limit
Death by all causes / MACEHR (95% CI) / p value / HR (95% CI) / p value
crude
cTnI detecable (+) / 4.82 (3.45 - 6.74) / <0.001 / 4.59 (3.16 , 6.66) / <0.001
cTnI > optimal cut-off value (*) / 5.38 (3.69 , 7.86) / <0.001 / 7.84 (5.02 , 12.25) / <0.001
adjusted for age, gender and eGFR
cTnI detecable (+) / 2.09 (1.46 , 2.98) / <0.001 / 1.92 (1.23 , 2.98) / 0.004
cTnI > optimal cut-off value (*) / 2.41 (1.59 , 3.64) / <0.001 / 3.74 (2.29 , 6.10) / <0.001
adjusted for hs CRP and NT-pro-BNP (*)
cTnI detecable (+) / 3.50 (2.49 , 4.94) / <0.001 / 3.22 (2.19 , 4.73) / <0.001
cTnI > optimal cut-off value (*) / 3.77 (2.56 , 5.54) / <0.001 / 4.86 (3.00 , 7.87) / <0.001
adjusted for age,gender, eGFR and risk factors (**)
cTnI detecable (+) / 1.94 (1.35 , 2.79) / <0.001 / 1.78 (1.15 , 2.75) / 0.009
cTnI > optimal cut-off value (*) / 2.22 (1.46 , 3.36) / <0.001 / 3.38 (2.03 , 5.63) / <0.001
adjusted for age, gender,eGFR, hs CRP, NT-pro-BNP (*) and risk factors (**)
cTnI detecable (+) / 1.68 (1.16 , 2.43) / 0.006 / 1.48 (0.96 , 2.29) / 0.075
cTnI > optimal cut-off value (*) / 1.96 (1.29 , 2.99) / 0.002 / 2.61 (1.56 , 4.36) / <0.001
Abbreviations: CI = Confidence interval; HR = Hazard-Ratio; MACE = major adverse cardiovascular event; cTnI = sensitive Troponin I; hs CRP = high sensitive C-reactive protein; NT-pro-BNP = N-terminal pro-brain natriuretic peptide; ; eGFR = estimated glomerular filtration rate (Cockroft/Gault; Nephron 1976;16(1):31-41)
(+) cTnI over assay specific detection limit (> 6 ng/l)
(*) Over optimal DETECT-discriminatory cutoff value(=study-specific optimal cut-off derived from ROC analysis) : NT-pro-BNP: All-cause-death (> 85.85 ng/l); Major adverse cardiovascular event (> 121.9 ng/l); hs CRP: All-cause-death (> 1.43 mg/l); Major adverse cardiovascular event (> 1.4 mg/l); cTnI : All-cause-death (> 11 ng/l); Major adverse cardiovascular event (> 17 ng/l)
(**) = Data were adjusted for the following variables: hypertension (binary); hyperlipidemia (binary); diabetes (binary), familial predisposition (binary); smoking status (binary) and body mass index (continuous)
1