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1Department of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
2Department of Cardiology, Dong-A University Hospital, Busan, Korea
3Department of Biostatistics, Korea University College of Medicine, Seoul, Korea
© 2023, Korean Society of Epidemiology
This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
CONFLICT OF INTEREST
The authors have no conflicts of interest to declare for this study.
FUNDING
This research was supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (2018R1D1A3B07043344).
AUTHOR CONTRIBUTIONS
Conceptualization: Park S, Park GM. Data curation: Park S, Han S, Park GM. Formal analysis: Park S, Han S. Funding acquisition: Park GM. Methodology: Park S, Han S, Park GM. Project administration: Kim SJ, Park GM. Visualization: Park S, Han S. Writing – original draft: Park S. Writing – review & editing: Park S, Kim YG, Ann SH, Cho YR, Kim SJ, Han S, Park GM.
Variables |
β coefficient |
|
---|---|---|
Men | Women | |
Age1 | 0.07605 | 0.09741 |
Current smoker2 | 0.63699 | 0.89538 |
Diabetes mellitus2 | 0.21904 | 0.29067 |
Systolic blood pressure1 | 0.01540 | 0.01353 |
Hypertension on medication2 | 0.25527 | 0.36764 |
Systolic blood pressure1 × Hypertension on medication2 | -0.00921 | -0.00634 |
Ln total cholesterol | 0.82618 | 0.27455 |
Ln high-density lipoprotein cholesterol | -0.42561 | -0.21176 |
Triglyceride1 | 0.00034 | - |
Hyperlipidemia on medication2 | - | -5.03538 |
Ln total cholesterol × Hyperlipidemia on medication2 | - | 0.90851 |
Urine protein1,3 | 0.20974 | 0.28333 |
Baseline survival S0(10) | 0.9995927 | 0.9986538 |
ASCVD, atherosclerotic cardiovascular disease; K-CVD, Korean atherosclerotic cardiovascular disease risk prediction; Ln, natural logarithm.
1 Centered variables; Each variable was centered at the following values (age of 40 years old, systolic blood pressure of 120 mmHg, triglyceride level of 150 mg/dL, urine protein of ≥1), respectively.
2 Binary variables where the reference value (i.e., 0) corresponds to not having that condition.
3 The urine protein level was based on dipstick urinalysis; Urine protein results of negative, trace, ≥1, ≥2, ≥3, and ≥4 were treated as corresponding ordinal variable values of 1 to 6, respectively.
Variables | Development dataset | Validation dataset | |
---|---|---|---|
Total (n) | 260,747 | 65,187 | |
Actual events (n) | 3,436 | 931 | |
K-CVD model | |||
C statistic (95% CI) | 0.823 (0.813, 0.833) | 0.815 (0.796, 0.834) | |
Time-dependent AUC (95% CI) | 0.846 (0.828, 0.864) | 0.846 (0.828, 0.864) | |
Calibration χ2 1 | 3.19 | 4.73 | |
p-value1 | 0.527 | 0.317 | |
Brier score | 0.013 | 0.013 | |
Framingham risk score | |||
C statistic (95% CI) | 0.804 (0.795, 0.814) | 0.797 (0.778, 0.816) | |
Time-dependent AUC (95% CI) | 0.820 (0.801, 0.839) | 0.826 (0.808, 0.845) | |
Calibration χ2 1 | 92,588.23 | 20,912.41 | |
p-value1 | <0.001 | <0.001 | |
Brier score | 0.021 | 0.021 | |
Pooled cohort equation | |||
C statistic (95% CI) | 0.819 (0.809, 0.829) | 0.813 (0.794, 0.832) | |
Time-dependent AUC (95% CI) | 0.841 (0.823, 0.859) | 0.846 (0.828, 0.864) | |
Calibration χ2 1 | 24,310.07 | 5,249.56 | |
p-value1 | <0.001 | <0.001 | |
Brier score | 0.016 | 0.017 |
Age (yr) |
Predicted 10-year ASCVD risk, % |
|||||
---|---|---|---|---|---|---|
Men |
Women |
|||||
Optimal RF2 | Intermediate RF3 | High RF4 | Optimal RF2 | Intermediate RF3 | High RF4 | |
20 | 0.07 | 0.29 | 0.97 | 0.02 | 0.08 | 0.36 |
25 | 0.10 | 0.42 | 1.42 | 0.03 | 0.13 | 0.58 |
30 | 0.15 | 0.62 | 2.07 | 0.05 | 0.21 | 0.94 |
35 | 0.21 | 0.91 | 3.02 | 0.08 | 0.34 | 1.52 |
40 | 0.31 | 1.32 | 4.38 | 0.13 | 0.55 | 2.47 |
45 | 0.45 | 1.93 | 6.34 | 0.20 | 0.89 | 3.98 |
50 | 0.66 | 2.81 | 9.14 | 0.33 | 1.45 | 6.40 |
55 | 0.97 | 4.08 | 13.07 | 0.54 | 2.35 | 10.21 |
60 | 1.41 | 5.91 | 18.53 | 0.87 | 3.79 | 16.08 |
65 | 2.06 | 8.53 | 25.90 | 1.42 | 6.09 | 24.82 |
70 | 3.00 | 12.22 | 35.50 | 2.30 | 9.73 | 37.14 |
75 | 4.36 | 17.36 | 47.34 | 3.72 | 15.34 | 53.03 |
80 | 6.31 | 24.34 | 60.86 | 5.98 | 23.75 | 70.77 |
ASCVD, atherosclerotic cardiovascular disease; RF, risk factor; HDL, high-density lipoprotein.
1 Estimated 10-year ASCVD risks for example cases with various RF profiles are shown; The definitions of the example cases are as follows.
2 Subjects with an optimal RF profile: non-smoker, absence of diabetes, systolic blood pressure of 115 mmHg, total cholesterol level of 170 mg/dL, HDL cholesterol level of 55 mg/dL, triglyceride level of 125 mg/dL, no treatment for hypertension or hyperlipidemia, negative urine protein.
3 Subjects with an intermediate RF profile: current smoker, absence of diabetes, systolic blood pressure of 150 mmHg, total cholesterol level of 200 mg/dL, HDL cholesterol level of 40 mg/dL, triglyceride level of 150 mg/dL, no treatment for hypertension or hyperlipidemia, negative urine protein.
4 Subjects with a high RF profile: current smoker, diabetes, systolic blood pressure of 160 mmHg, total cholesterol level of 250 mg/dL, HDL cholesterol level of 30 mg/dL, triglyceride level of 200 mg/dL, treatment for hypertension, no treatment for hyperlipidemia, urine protein ≥2.
Characteristics | Overall | Men (n=168,785) | Women (n=157,149) |
---|---|---|---|
Percentage of total cohort | 100 | 51.8 | 48.2 |
Age (yr) | 46.8±13.5 | 45.8±13.2 | 48.0±13.7 |
Body mass index (kg/m2) | 23.7±6.4 | 24.2 ±3.1 | 23.1±8.6 |
Waist circumference (cm) | 79.9±9.1 | 83.6±7.8 | 75.9±8.8 |
Systolic blood pressure (mmHg) | 121.9±15.0 | 124.5±14.1 | 119.1±15.5 |
Diastolic blood pressure (mmHg) | 76.0±10.1 | 78.0±9.7 | 73.9±10.1 |
Hypertension | 93,800 (28.8) | 49,042 (29.1) | 44,758 (28.5) |
Hypertension on medication | 53,198 (16.3) | 24,606 (14.6) | 28,592 (18.2) |
Diabetes mellitus | 39,554 (12.1) | 22,115 (13.1) | 17,439 (11.1) |
Hyperlipidemia | 77,210 (23.7) | 37,384 (22.1) | 39,826 (25.3) |
Hyperlipidemia on medication | 19,300 (5.9) | 8,520 (5.0) | 10,780 (6.9) |
Family history of heart disease | 10,017 (3.1) | 4,740 (2.8) | 5,277 (3.4) |
Family history of stroke | 18,240 (5.6) | 9,08 (5.4) | 9,157 (5.8) |
Current smoker | 81,177 (25.0) | 75,634 (45.0) | 5,543 (3.5) |
Hemoglobin (g/dL) | 13.9±1.6 | 15.0±1.2 | 12.8±1.2 |
Fasting glucose (mg/dL) | 96.9±23.3 | 99.1±25.5 | 94.6±20.4 |
Total cholesterol (mg/dL) | 195.8±40.6 | 195.4±40.4 | 196.2±40.7 |
High-density lipoprotein cholesterol (mg/dL) | 56.7±30.9 | 53.6±29.7 | 59.9±31.9 |
Triglyceride (mg/dL) | 133.7±107.4 | 155.1±122.4 | 110.7±82.5 |
Creatinine (mg/dL) | 1.1±1.3 | 1.2±1.5 | 0.9±0.9 |
eGFR (mL/min/1.73 m2) | 88.8±25.1 | 92.1±26.3 | 85.2±23.3 |
Urine protein | |||
Negative | 309,905 (95.4) | 160,391 (95.2) | 149,514 (95.5) |
Trace | 7,282 (2.2) | 3,816 (2.3) | 3,466 (2.2) |
1+ | 5,258 (1.6) | 2,811 (1.7) | 2,447 (1.6) |
2+ | 1,890 (0.6) | 1,044 (0.6) | 846 (0.5) |
3+ | 472 (0.1) | 267 (0.2) | 205 (0.1) |
4+ | 98 (0.0) | 61 (0.0) | 37 (0.0) |
Follow-up duration, median (IQR) | 10.1 (9.5-10.5) | 10.2 (9.5-10.5) | 10.1 (9.4-10.4) |
Incident clinical outcomes | |||
Cardiovascular death, MI, and stroke | 4,367 (1.3) | 2,807 (1.7) | 1,560 (1.0) |
Cardiovascular death | 1,805 (0.6) | 1,151 (0.7) | 654 (0.4) |
MI | 1,743 (0.5) | 1,344 (0.8) | 399 (0.3) |
Stroke | 1,074 (0.3) | 480 (0.3) | 594 (0.4) |
Variables | β coefficient |
|
---|---|---|
Men | Women | |
Age |
0.07605 | 0.09741 |
Current smoker |
0.63699 | 0.89538 |
Diabetes mellitus |
0.21904 | 0.29067 |
Systolic blood pressure |
0.01540 | 0.01353 |
Hypertension on medication |
0.25527 | 0.36764 |
Systolic blood pressure |
-0.00921 | -0.00634 |
Ln total cholesterol | 0.82618 | 0.27455 |
Ln high-density lipoprotein cholesterol | -0.42561 | -0.21176 |
Triglyceride |
0.00034 | - |
Hyperlipidemia on medication |
- | -5.03538 |
Ln total cholesterol × Hyperlipidemia on medication |
- | 0.90851 |
Urine protein |
0.20974 | 0.28333 |
Baseline survival S0(10) | 0.9995927 | 0.9986538 |
Variables | Development dataset | Validation dataset | |
---|---|---|---|
Total (n) | 260,747 | 65,187 | |
Actual events (n) | 3,436 | 931 | |
K-CVD model | |||
C statistic (95% CI) | 0.823 (0.813, 0.833) | 0.815 (0.796, 0.834) | |
Time-dependent AUC (95% CI) | 0.846 (0.828, 0.864) | 0.846 (0.828, 0.864) | |
Calibration χ2 |
3.19 | 4.73 | |
p-value |
0.527 | 0.317 | |
Brier score | 0.013 | 0.013 | |
Framingham risk score | |||
C statistic (95% CI) | 0.804 (0.795, 0.814) | 0.797 (0.778, 0.816) | |
Time-dependent AUC (95% CI) | 0.820 (0.801, 0.839) | 0.826 (0.808, 0.845) | |
Calibration χ2 |
92,588.23 | 20,912.41 | |
p-value |
<0.001 | <0.001 | |
Brier score | 0.021 | 0.021 | |
Pooled cohort equation | |||
C statistic (95% CI) | 0.819 (0.809, 0.829) | 0.813 (0.794, 0.832) | |
Time-dependent AUC (95% CI) | 0.841 (0.823, 0.859) | 0.846 (0.828, 0.864) | |
Calibration χ2 |
24,310.07 | 5,249.56 | |
p-value |
<0.001 | <0.001 | |
Brier score | 0.016 | 0.017 |
Age (yr) | Predicted 10-year ASCVD risk, % |
|||||
---|---|---|---|---|---|---|
Men |
Women |
|||||
Optimal RF |
Intermediate RF |
High RF |
Optimal RF |
Intermediate RF |
High RF |
|
20 | 0.07 | 0.29 | 0.97 | 0.02 | 0.08 | 0.36 |
25 | 0.10 | 0.42 | 1.42 | 0.03 | 0.13 | 0.58 |
30 | 0.15 | 0.62 | 2.07 | 0.05 | 0.21 | 0.94 |
35 | 0.21 | 0.91 | 3.02 | 0.08 | 0.34 | 1.52 |
40 | 0.31 | 1.32 | 4.38 | 0.13 | 0.55 | 2.47 |
45 | 0.45 | 1.93 | 6.34 | 0.20 | 0.89 | 3.98 |
50 | 0.66 | 2.81 | 9.14 | 0.33 | 1.45 | 6.40 |
55 | 0.97 | 4.08 | 13.07 | 0.54 | 2.35 | 10.21 |
60 | 1.41 | 5.91 | 18.53 | 0.87 | 3.79 | 16.08 |
65 | 2.06 | 8.53 | 25.90 | 1.42 | 6.09 | 24.82 |
70 | 3.00 | 12.22 | 35.50 | 2.30 | 9.73 | 37.14 |
75 | 4.36 | 17.36 | 47.34 | 3.72 | 15.34 | 53.03 |
80 | 6.31 | 24.34 | 60.86 | 5.98 | 23.75 | 70.77 |
Values are presented as mean±standard deviation or number (%). eGFR, estimated glomerular filtration rate; IQR, interquartile range; MI, myocardial infarction.
ASCVD, atherosclerotic cardiovascular disease; K-CVD, Korean atherosclerotic cardiovascular disease risk prediction; Ln, natural logarithm. Centered variables; Each variable was centered at the following values (age of 40 years old, systolic blood pressure of 120 mmHg, triglyceride level of 150 mg/dL, urine protein of ≥1), respectively. Binary variables where the reference value (i.e., 0) corresponds to not having that condition. The urine protein level was based on dipstick urinalysis; Urine protein results of negative, trace, ≥1, ≥2, ≥3, and ≥4 were treated as corresponding ordinal variable values of 1 to 6, respectively.
ASCVD, atherosclerotic cardiovascular disease; AUC, area under the curve; CI, confidence interval; K-CVD, Korean atherosclerotic cardiovascular disease risk prediction. Calibration χ2 and goodness-of-fit p-values were based on 5 specific predicted risk categories.
ASCVD, atherosclerotic cardiovascular disease; RF, risk factor; HDL, high-density lipoprotein. Estimated 10-year ASCVD risks for example cases with various RF profiles are shown; The definitions of the example cases are as follows. Subjects with an optimal RF profile: non-smoker, absence of diabetes, systolic blood pressure of 115 mmHg, total cholesterol level of 170 mg/dL, HDL cholesterol level of 55 mg/dL, triglyceride level of 125 mg/dL, no treatment for hypertension or hyperlipidemia, negative urine protein. Subjects with an intermediate RF profile: current smoker, absence of diabetes, systolic blood pressure of 150 mmHg, total cholesterol level of 200 mg/dL, HDL cholesterol level of 40 mg/dL, triglyceride level of 150 mg/dL, no treatment for hypertension or hyperlipidemia, negative urine protein. Subjects with a high RF profile: current smoker, diabetes, systolic blood pressure of 160 mmHg, total cholesterol level of 250 mg/dL, HDL cholesterol level of 30 mg/dL, triglyceride level of 200 mg/dL, treatment for hypertension, no treatment for hyperlipidemia, urine protein ≥2.