Supplementary Online Content McEvoy JW, Chen Y, Ndumele CE, et al. Six-year change in high-sensitivity cardiac troponin T and risk of subsequent coronary heart disease, heart failure, and death. JAMA Cardiol. Published online June 8, 2016. doi:10.1001/jamacardio.2016.0765. etable 1. Study Population for the Primary Analysis Evaluating the Association of hs-ctnt Change Between ARIC Visit 2 and Visit 4 With subsequent CHD, HF, or Death Occurring After Visit 4 etable 2. Crude Incidence Rates (per 1000 Person-years) and Adjusted* Hazard Ratios (95% CIs) for Incident Coronary Heart Disease, Heart Failure Hospitalization, or Death According To Sex-Specific Categories of 6-Year Change in High-Sensitivity Cardiac Troponin T (hs-ctnt) (N=8838) etable 3. Adjusted* Hazard Ratios (95% CIs) for Incident Coronary Heart Disease, Heart Failure, or Death According to Categories of 6-Year Change in High-Sensitivity Cardiac Troponin T (hs-ctnt) With and Without Further Adjustment for Either Change in NT-proBNP or Visit 4 hs-ctnt etable 4. Crude Incidence Rates (per 1000 Person-years) and Adjusted* Hazard Ratios (95% CIs) for Incident Coronary Heart Disease, Heart Failure Hospitalization, or Death According to 25% Relative Change of 6-Year Change in hs-ctnt etable 5. Net Reclassification Improvement for Coronary Heart Disease, Heart Failure and Death With the Addition of the First and Second hs-ctnt Values to a Traditional Risk Factor Prediction Model etable 6. Adjusted* Hazard Ratios (95% CIs) for Heart Failure Subtypes (HFrEF and HFpEF) Adjudicated After 2005 According to Categories of 6-Year Change in High-Sensitivity Cardiac Troponin T (hs-ctnt): Full Model With and Without Further Adjustment for 6-Year Change in NT-proBNP efigure 1. Cumulative Survival Free of Coronary Heart Disease, Heart Failure Hospitalization, or Death Stratified by Categories of Change in High-Sensitivity Cardiac Troponin T (hs-ctnt) During 6 Years (Incident Detectable, Incident Elevated, or Percent Relative Change*) efigure 2. Restricted Cubic Splines for Adjusted* Hazard Ratios (95% CIs) of Incident Coronary Heart Disease (CHD), Heart Failure (HF) Hospitalization, or Death According to Absolute 6-Year Change in High-Sensitivity Cardiac Troponin T (hs-ctnt) (per Unit Increase in ng/l) efigure 3. Restricted Cubic Splines for Adjusted* Hazard Ratios (95% CIs) of (a) Incident Coronary Heart Disease (CHD) (B) Heart Failure (HF) Hospitalization, or (C) Death According to Absolute 6-Year Change in High-Sensitivity Cardiac Troponin T (hs-ctnt) (per Unit Increase in ng/l) and Stratified by Visit 2 Concentration Groups (<5 ng/l, 5-13 ng/l, and 14 ng/l) efigure 4. Restricted Cubic Splines for Adjusted* Hazard Ratios (95% CIs) of Incident HFrEF or HFpEF according to Absolute 6-Year Change in High-Sensitivity Cardiac Troponin T (hs-ctnt) (per Unit Increase in ng/l) This supplementary material has been provided by the authors to give readers additional information about their work.
etable 1. Study Population for the Primary Analysis Evaluating the Association of hs-ctnt Change Between ARIC Visit 2 and Visit 4 With subsequent CHD, HF, or Death Occurring After Visit 4 Exclusion Process Exclusion Population Participates at visit 4 11656 Prevalent CHD and HF at or prior to visit 4 1308 10348 Missing model covariates at visit 4 576 9772 Missing hs-ctnt data at either visit 2 or visit 4 748 9024 Missing follow-up information for events after visit 4 123 8901 Non black or white, race-center exclusion 63 8838 Study population 8838
etable 2. Crude Incidence Rates (per 1000 Person-years) and Adjusted* Hazard Ratios (95% CIs) for Incident Coronary Heart Disease, Heart Failure Hospitalization, or Death According To Sex-Specific Categories of 6-Year Change in High-Sensitivity Cardiac Troponin T (hs-ctnt) (N=8838) Outcomes Absolute hs-ctnt change according to Gender MEN Incident Elevated (Baseline <24ng/L, Follow-up 24ng/L) WOMEN Incident Elevated (Baseline <14ng/L, Follow-up 14ng/L) No (N=3500) Yes (N=83) No (N=5040) Yes (N=108) Heart Failure n=367 n=31 n=489 n=41 Incidence Rate 8.3 (7.5-9.2) 40.1 (28.2-57.0) 7.4 (6.8-8.1) 39.3 (29.0-53.4) Demographic Model* 4.11 4.28 (2.83-5.96) (3.10-5.90) 2.60 2.56 (1.77-3.82) (1.81-3.63) Coronary Heart Disease n=652 n=29 n=416 n=23 Incidence Rate 15.9(14.7-17.2) 39.4 (27.4-56.7) 6.3 (5.7-7.0) 20.8 (13.8-31.3) Demographic Model* 2.32 2.77 (1.59-3.37) (1.81-4.24) 1.71 2.08 (1.16-2.51) (1.33-3.25) Death n=870 n=45 n=791 n=53 Incidence Rate 19.2(18.0-20.6) 52.4 (39.1-70.2) 11.6 (10.8-12.4) 43.9 (33.5-57.5) Demographic Model* 2.32 3.08 (1.72-3.14) (2.33-4.08) 1.93 2.26 (1.42-2.62) (1.68-3.05) * Demographic Model- Adjusted for age, race-center; Full Model- Adjusted for age,, race-center, body mass index (kg/m3), C-reactive protein (mg/l), smoking (current; former; never), drinking (current; former; never), systolic blood pressure (mmhg), current use of blood pressure-lowering medication (yes or no), diagnosed diabetes (yes or no), LDL-cholesterol (mg/dl), HDL-cholesterol (mg/dl), triglycerides (mg/dl), and current use of cholesterollowering medication (yes or no), estimated GFR (ml/min/1.73m2), and left ventricular hypertrophy (yes or no, by Cornell criteria).
etable 3. Adjusted* Hazard Ratios (95% CIs) for Incident Coronary Heart Disease, Heart Failure, or Death According to Categories of 6-Year Change in High-Sensitivity Cardiac Troponin T (hs-ctnt) With and Without Further Adjustment for Either Change in NT-proBNP or Visit 4 hs-ctnt Outcomes Absolute hs-ctnt change among all participants Incident Detectable (Baseline <5ng/L, Follow-up 5ng/L) No (N=3888) Yes (N=2152) Incident Elevated (Baseline <14ng/L, Follow-up 14ng/L) No (N=8155) Relative change among persons with measurable hs-ctnt values >50% Decrease Change 50% >50% Increase Yes (N=443) (N=74) (N=2227) (N=1147) Heart Failure n=235 n=260 n=761 n=134 n=10 n=309 n=234 Additional adjustments Coronary Heart Disease Additional adjustments 1.96 (1.62-2.37) 1.86 (1.53-2.25) 2.78 (2.27-3.40) 2.54 (2.07-3.13) 0.49 (0.23-1.01) 0.94 (0.49-1.77) 1.60 (1.35-1.91) 1.34 (1.12-1.60) n=330 n=301 n=969 n=119 n=9 n=374 n=239 1.38 (1.16-1.63) 1.37 (1.16-1.63) 1.75 (1.43-2.15) 1.68 (1.36-2.06) 0.47 (0.22-1.03) 0.79 (0.41-1.53) 1.28 (1.09-1.52) 1.14 (0.96-1.35) Death n=508 n=486 n=1496 n=209 n=17 n=584 n=392 Additional adjustments 1.50 (1.31-1.72) 1.46 (1.28-2.10 (1.80-2.46) 1.97 (1.69-2.31) 0.57 (0.33-0.99) 0.89 (0.55-1.39 (1.22-1.59) 1.23 (1.08-1.41) 1.68) 1.46) * Full Model- Adjusted for age, sex, race-center, body mass index (kg/m3), C-reactive protein (mg/l), smoking (current; former; never), drinking (current; former; never), systolic blood pressure (mmhg), current use of blood pressure-lowering medication (yes or no), diagnosed diabetes (yes or no), LDL-cholesterol (mg/dl), HDL-cholesterol (mg/dl), triglycerides (mg/dl), and current use of cholesterol-lowering medication (yes or no), estimated GFR (ml/min/1.73m2), and left ventricular hypertrophy (yes or no, by Cornell criteria). Sample (N=3448) includes only those who have measurable hs-ctnt values ( 3 ng/l) at both visits. Relative change is calculated as a percent of baseline hs-ctnt. The full model for this relative change exposure is further adjusted for visit 2 hsctnt. Additional adjustment is for 1) continuous absolute change in NT-proBNP (in pg/ml) between visits 2 and 4 for the incident detectable and incident elevated models and 2) both adjusting for absolute change in NT-proBNP and for visit 4 hs-ctnt instead of visit 2 hs-ctnt for the relative change model.
etable 4. Crude Incidence Rates (per 1000 Person-years) and Adjusted* Hazard Ratios (95% CIs) for Incident Coronary Heart Disease, Heart Failure Hospitalization, or Death According to 25% Relative Change of 6-Year Change in hs-ctnt Outcomes Relative change among persons with measurable hs-ctnt values >25% Decrease Change 25% >25% Increase (N=414) (N=1377) (N=1657) Heart Failure n=50 n=185 n=318 Incidence Rate 9.5 10.7 16.5 Demographic Model* 0.88 (0.65-1.21) 1.53 (1.28-1.84) 0.83 (0.60-1.16) 1.54 (1.28-1.86) Coronary Heart Disease n=69 n=226 n=327 Incidence Rate 13.7 13.5 17.6 Demographic Model* 1.07 (0.81-1.40) 1.24 (1.05-1.47) 1.04 (0.78-1.39) 1.21 (1.02-1.44) Death n=96 n=357 n=540 Incidence Rate 17.6 19.8 26.4 Demographic Model* 0.93 (0.74-1.17) 1.29 (1.13-1.47) 0.86 (0.68-1.09) 1.29 (1.13-1.48) * Demographic Model- Adjusted for age, sex, race-center; Full Model- Adjusted for age, sex, race-center, body mass index (kg/m3), C-reactive protein (mg/l), smoking (current; former; never), drinking (current; former; never), systolic blood pressure (mmhg), current use of blood pressure-lowering medication (yes or no), diagnosed diabetes (yes or no), LDL-cholesterol (mg/dl), HDL-cholesterol (mg/dl), triglycerides (mg/dl), and current use of cholesterol-lowering medication (yes or no), estimated GFR (ml/min/1.73m2), left ventricular hypertrophy (yes or no, by Cornell criteria) and visit 2 hs-ctnt. Relative change sample (N=3448) only includes those who have measurable hs-ctnt values ( 3 ng/l) at both visits. Relative change is calculated as a percent of baseline hs-ctnt.
etable 5. Net Reclassification Improvement for Coronary Heart Disease, Heart Failure and Death With the Addition of the First and Second hs-ctnt Values to a Traditional Risk Factor Prediction Model Continuous NRI Coronary heart disease Heart failure All-cause mortality Model Overall NRI p value Overall NRI p value Overall NRI p value Model 1 (vs. base model*) -2% 0.538-7% 0.077 +4% 0.245 Model 2 (vs. model 1) +7% 0.050 +16% 0.006 +11% 0.001 *Base model is adjusted for age, sex, race-center, smoking (current; former; never), systolic blood pressure (mmhg), current use of blood pressure-lowering medication (yes or no), diagnosed diabetes (yes or no), LDLcholesterol (mg/dl), HDL-cholesterol (mg/dl) *Model 1 is base model + v4 hs-ctnt. *Model 2 is base model + v4 hs-ctnt +v2 hs-ctnt.
etable 6. Adjusted* Hazard Ratios (95% CIs) for Heart Failure Subtypes (HFrEF and HFpEF) Adjudicated After 2005 According to Categories of 6-Year Change in High-Sensitivity Cardiac Troponin T (hs-ctnt): Full Model With and Without Further Adjustment for 6-Year Change in NT-proBNP Heart Failure Subtypes Absolute hs-ctnt change among all participants Incident Detectable (Baseline <5ng/L, Follow-up 5ng/L) No (n=3599) Yes (n=1867) Incident Elevated (Baseline <14ng/L, Follow-up 14ng/L) No (n=7306) Relative change among persons with measurable hs-ctnt values >50% Decrease Change 50% >50% Increase Yes (n=286) (n=71) (n=2038) (n=996) HFrEF n=88 n=72 n=256 n=30 n=5 n=121 n=77 Additional adjustment for 6-year change in NT-proBNP 1.54 (1.10-2.16) 1.43 (1.02-2.02) 2.43 (1.62-3.65) 2.31 (1.54-3.47) 0.85 (0.31-2.31) 0.87 (0.32-2.38) 1.26 (0.94-1.69) 1.24 (0.93-1.66) HFpEF n=69 n=67 n=199 n=17 n=3 n=76 n=46 Additional adjustment for 6-year change in NT-proBNP 1.72 (1.20-2.47) 1.68 (1.17-2.41) 1.80 (1.06-3.05) 1.70 (1.01-2.89) 1.06 (0.32-3.51) 1.10 (0.33-3.65) 1.16 (0.80-1.69) 1.09 (0.74-1.59) * Demographic Model- Adjusted for age, sex, race-center; Full Model- Adjusted for age, sex, race-center, body mass index (kg/m3), C-reactive protein (mg/l), smoking (current; former; never), drinking (current; former; never), systolic blood pressure (mmhg), current use of blood pressure-lowering medication (yes or no), diagnosed diabetes (yes or no), LDL-cholesterol (mg/dl), HDL-cholesterol (mg/dl), triglycerides (mg/dl), and current use of cholesterol-lowering medication (yes or no), estimated GFR (ml/min/1.73m2), and left ventricular hypertrophy (yes or no, by Cornell criteria). Sample (N=3448) only includes those who have measurable hs-ctnt values ( 3 ng/l) at both visits. Relative change is calculated as a percent of baseline hs-ctnt. The full model for this exposure is further adjusted for visit 2 hs-ctnt.
efigure 1. Cumulative Survival Free of Coronary Heart Disease, Heart Failure Hospitalization, or Death Stratified by Categories of Change in High-Sensitivity Cardiac Troponin T (hs-ctnt) During 6 Years (Incident Detectable, Incident Elevated, or Percent Relative Change*)
*Incident Detectable=Baseline <5ng/L, Follow-up 5ng/L; Incident Elevated=Baseline <14ng/L, Follow-up 14ng/L. Percent relative change sample (N=3448) only includes those who have measurable hs-ctnt values ( 3 ng/l) at both visits. Relative change is calculated as a percent of baseline hs-ctnt
efigure 2. Restricted Cubic Splines for Adjusted* Hazard Ratios (95% CIs) of Incident Coronary Heart Disease (CHD), Heart Failure (HF) Hospitalization, or Death According to Absolute 6-Year Change in High-Sensitivity Cardiac Troponin T (hs-ctnt) (per Unit Increase in ng/l) *Adjusted for age, sex, race-center, body mass index (kg/m3), C-reactive protein (mg/l), smoking (current; former; never), drinking (current; former; never), systolic blood pressure (mmhg), current use of blood pressure-lowering medication (yes or no), diagnosed diabetes (yes or no), LDL-cholesterol (mg/dl), HDL-cholesterol (mg/dl), triglycerides (mg/dl), and current use of cholesterol-lowering medication (yes or no), estimated GFR (ml/min/1.73m2), left ventricular hypertrophy (yes or no, by Cornell criteria), and visit 2 hs-ctnt (ng/l). Sample (N=3448) only includes those who have measurable hs-ctnt values ( 3 ng/l) at both visits. Background histogram displays the frequency distribution of hs-ctnt change in the sample. Splines are centered at the median of hs-ctnt change and are truncated at the 1 st and 99 th percentile.
efigure 3. Restricted Cubic Splines for Adjusted* Hazard Ratios (95% CIs) of (a) Incident Coronary Heart Disease (CHD) (B) Heart Failure (HF) Hospitalization, or (C) Death According to Absolute 6-Year Change in High- Sensitivity Cardiac Troponin T (hs-ctnt) (per Unit Increase in ng/l) and Stratified by Visit 2 Concentration Groups (<5 ng/l, 5-13 ng/l, and 14 ng/l) A- CHD
B- Heart Failure
C- Death (All-cause Mortality) *Adjusted for age, sex, race-center, body mass index (kg/m3), C-reactive protein (mg/l), smoking (current; former; never), drinking (current; former; never), systolic blood pressure (mmhg), current use of blood pressure-lowering medication (yes or no), diagnosed diabetes (yes or no), LDL-cholesterol (mg/dl), HDL-cholesterol (mg/dl), triglycerides (mg/dl), and current use of cholesterol-lowering medication (yes or no), estimated GFR (ml/min/1.73m2), and left ventricular hypertrophy (yes or no, by Cornell criteria). Sample (N=3448) only includes those who have measurable hs-ctnt values ( 3 ng/l) at both visits. Background histogram displays the frequency distribution of hs-ctnt change in the sample. Splines are centered at the median of hs-ctnt change and are truncated at the 1 st and 99 th percentile.
efigure 4. Restricted Cubic Splines for Adjusted* Hazard Ratios (95% CIs) of Incident HFrEF or HFpEF according to Absolute 6-Year Change in High-Sensitivity Cardiac Troponin T (hs-ctnt) (per Unit Increase in ng/l) - HFREF - HFPEF *Adjusted for age, sex, race-center, body mass index (kg/m3), C-reactive protein (mg/l), smoking (current; former; never), drinking (current; former; never), systolic blood pressure (mmhg), current use of blood pressure-lowering medication (yes or no), diagnosed diabetes (yes or no), LDL-cholesterol (mg/dl), HDL-cholesterol (mg/dl), triglycerides (mg/dl), and current use of cholesterol-lowering medication (yes or no), estimated GFR (ml/min/1.73m2), left ventricular hypertrophy (yes or no, by Cornell criteria), and visit 2 hs-ctnt (ng/l). Sample (N=3448) only includes those who have measurable hs-ctnt values ( 3 ng/l) at both visits. Background histogram displays the frequency distribution of hs-ctnt change in the sample. Splines are centered at the median of hs-ctnt change and are truncated at the 1 st and 99 th percentile.