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Supplementary Appendix

Contents

Table S1. Characteristics of study participants according to baseline metabolic health and

obesity status

Table S2. Risk of incident unhealthy metabolic status (≥ 2 risk factors) according to baseline

obesity status and number of risk factors

Table S3. Risks of CV events, CV mortality, and all-cause mortality in participants with

MHNO at baseline according to 2 year metabolic health and obesity status using the stable

MHNO group as a reference group

Table S4. Risks of CV events, CV mortality, and all-cause mortality in participants with

MHNO at baseline according to 2 year metabolic health and obesity status using the stable

MUNO group as a reference group

Table S5. Risks of CV events, CV mortality, and all-cause mortality in participants with

MHNO at baseline according to 2 year metabolic health and obesity status using the stable

MUO group as a reference group

Table S6. Risk of CV events, CV mortality, and all-cause mortality according to baseline

metabolic health and obesity status with MHO as a reference group

Table S7. Risks of CV events, CV mortality, and all-cause mortality in participants with

MHO at baseline according to 2 year metabolic health and obesity status using the MHO-

MHNO group as a reference group

Fig S1. Study design and participants. A: Selection of study participants. B: Study design.

NHIS-HEALS, National Health Insurance Service-Health Screening Cohort.

Table S1. Characteristics of study participants according to baseline metabolic health and obesity status

Baseline categoryBMIMetabolic health status

MHNO< 25 kg/m2

0–1 risk factors

MHO≥ 25 kg/m2

0–1 risk factors

MUNO< 25 kg/m2

≥ 2 risk factors

MUO≥ 25 kg/m2

≥ 2 risk factors

P value forBMI group

P value formetabolic health status

P value forinteraction

N 115,750 (31.9) 36,378 (10.0) 116,816 (32.2) 93,919 (25.9)

Sex (% men) 49.5 51.4 55.4 57.6 <.001 <.001 0.476

Age (yr) 57.5 ± 8.5 57.4 ± 7.9 60.5 ± 9.1 59.4 ± 8.5 0.006 <.001 <.001

BMI (kg/m2) 22.1 ± 1.9 26.8 ± 1.7 22.7 ± 1.7 27.3 ± 2.0 <.001 <.001 <.001

WC (cm) 77.2 ± 6.7 87.0 ± 6.4 80.5 ± 6.4 89.5 ± 6.6 <.001 <.001 <.001

Systolic BP (mmHg) 119.1 ± 13.5 123.1 ± 13.5 130.4 ± 14.8 132.7 ± 14.4 <.001 <.001 <.001

Diastolic BP (mmHg) 74.4 ± 9.1 76.8 ± 9.1 80.3 ± 9.8 82.0 ± 9.8 <.001 <.001 <.001

Smoking (%) <.001 <.001 <.001

Current smoker 16.3 13.5 19.8 17.6

Ex-smoker 15.5 18.4 18.1 21.6

Non-smoker 65.6 65.0 59.0 57.8

Drinking (%) <.001 <.001 <.001

None 60.0 57.6 56.1 53.4

Mild 18.7 17.9 16.1 15.9

Moderate 4.1 4.0 4.8 4.2

Heavy 15.1 18.1 20.6 24.0

Physical activity (%) <.001 <.001 <.001

None 26.8 27.3 29.3 29.4

1–2 times/week 22.4 23.0 21.6 23.4

3–4 times/week 21.5 21.2 20.7 20.7

≥ 5 times/week 27.5 26.4 26.3 24.3

Medical history (%) <.001 <.001 <.001

Type 2 diabetes 1.4 1.4 16.4 19.0 <.001 <.001 <.001

HTN 11.6 20.0 46.7 57.4 <.001 <.001 <.001

Dyslipidemia 4.4 5.1 29.9 35.4 <.001 <.001 <.001

FPG (mg/dl) 92.2 ± 13.8 93.0 ± 12.8 109.2 ± 30.3 111.0 ± 29.9 <.001 <.001 <.001

TG (mg/dl) 100.1 ± 169.1 112.7 ± 54.4 169.1 ± 103.4 190.3 ± 112.3 <.001 <.001 <.001

LDL-C (mg/dl) 120.4 ± 34.6 126.3 ± 34.2 120.9 ± 40.4 122.5 ± 41.8 <.001 <.001 <.001

HDL-C (mg/dl) 59.2 ± 26.3 56.5 ± 24.9 51.2 ± 26.5 49.1 ± 24.1 0.591 <.001 <.001

TC (mg/dl) 198.8 ± 33.6 204.4 ± 34.1 203.8 ± 40.0 207.1 ± 40.0 <.001 <.001 <.001

Results reported as means ± SD, unless otherwise indicated.

Abbreviations: BMI; body mass index, BP; blood pressure, FPG; fasting plasma glucose, HDL-C; high-density lipoprotein cholesterol, HTN;

hypertension, LDL-C; low-density lipoprotein cholesterol, TC; total cholesterol, TG; triglyceride, WC; waist circumference

Table S2. Risk of incident unhealthy metabolic status (≥ 2 risk factors) according to baseline obesity status and number of risk factors

Baseline category MHNO MHOBMIMetabolic health status

< 25 kg/m2

No risk factor< 25 kg/m2

1 risk factor≥ 25 kg/m2

No risk factor≥ 25 kg/m2

1 risk factorN 39,175 60,853 8,032 23,456Number of events (%) 6,370 (16.3) 22,434 (36.9) 2,068 (25.9) 11,397 (48.6)Incidence/1,00 person-years 81.7 185.5 130.0 244.2HR (95% CI) 1 (ref) 2.13 (2.07–2.19) 1.57 (1.49–1.65) 2.82 (2.74–2.91)Multivariate-adjusted HR (95% CI)a 1 (ref) 2.08 (2.02–2.14) 1.55 (1.47–1.62) 2.72 (2.64–2.81)

aAdjusted for baseline age, sex, smoking, alcohol drinking, physical activities, and LDL cholesterol level.

Table S3. Risks of CV events, CV mortality, and all-cause mortality in participants with MHNO at baseline according to 2 year metabolic

health and obesity status using the stable MHNO group as a reference group.

Baseline category MHNO

Follow-up category

Follow-up BMI

Follow-up metabolic health status

MHNO

Reference group

MHO

≥ 25 kg/m2

0–1 risk factors

MUNO

< 25 kg/m2

≥ 2 risk factors

MUO

≥ 25 kg/m2

≥ 2 risk factors

N (% of baseline MHNO) 67,168 (67.6) 3,764 (3.8) 25,531 (25.7) 2,874 (2.9)

CV event incidence

Number of events (%) 708 (1.1) 46 (1.2) 436 (1.7) 52 (1.8)

HR (95% CI) 1 (ref) 1.25 (0.93-1.69) 1.32 (1.17-1.49) 1.61 (1.21-2.13)

Multivariate-adjusted HR (95% CI)a 1 (ref) 1.27 (0.94-1.71) 1.30 (1.15-1.46) 1.60 (1.21-2.12)

N (% of baseline MHO)

CVD mortality

Number of events (%) 151 (0.22) 6 (0.16) 120 (0.46) 4 (0.14)

HR (95% CI) 1 (ref) 0.88 (0.39-1.98) 1.49 (1.17-1.89) 0.58 (0.21-1.56)

Multivariate-adjusted HR (95% CI)a 1 (ref) 0.88 (0.39-2.00) 1.48 (1.16-1.88) 0.59 (0.22-1.59)

Mortality

Number of events (%) 1,086 (1.61) 45 (1.19) 667 (2.58) 47 (1.61)

HR (95% CI) 1 (ref) 0.87 (0.64-1.17) 1.21 (1.10-1.33) 0.94 (0.70-1.26)

Multivariate-adjusted HR (95% CI)a 1 (ref) 0.92 (0.69-1.25) 1.24 (1.13-1.37) 1.01 (0.75-1.35)

aAdjusted for baseline age, sex, smoking, alcohol drinking, physical activities, and LDL-cholesterol level.

Table S4. Risks of CV events, CV mortality, and all-cause mortality in participants with MUNO at baseline according to 2 year metabolic

health and obesity status using the stable MUNO group as a reference group.

Baseline category MUNO

Follow-up category

Follow-up BMI

Follow-up metabolic health status

MHNO

< 25 kg/m2

0–1 risk factors

MHO

≥ 25 kg/m2

0–1 risk factors

MUNO

Reference group

MUO

≥ 25 kg/m2

≥ 2 risk factors

N (% of baseline MUNO) 22,236 (22.5) 1,544 (1.6) 66,921 (67.9) 7,912 (8.0)

CV event incidence

Number of events (%) 354 (1.59) 26 (1.68) 1,622 (2.42) 184 (2.33)

HR (95% CI) 0.73 (0.65-0.82) 0.82 (0.56-1.21) 1 (ref) 1.02 (0.87-1.18)

Multivariate-adjusted HR (95% CI)a 0.72 (0.64-0.81) 0.85 (0.58-1.25) 1 (ref) 1.03 (0.88-1.20)

N (% of baseline MUNO) 22,236 (22.5) 1,544 (1.6) 66,921 (67.9) 7,912 (8.0)

CVD mortality

Number of events (%) 87 (0.39) 4 (0.26) 371 (0.55) 37 (0.46)

HR (95% CI) 0.83 (0.66-1.05) 0.61 (0.23-1.63) 1 (ref) 0.95 (0.68-1.33)

Multivariate-adjusted HR (95% CI)a 0.80 (0.63-1.01) 0.64 (0.24-1.70) 1 (ref) 0.97 (0.69-1.36)

Mortality

Number of events (%) 589 (2.64) 25 (1.61) 2,028 (2.98) 197 (2.45)

HR (95% CI) 1.02 (0.93-1.12) 0.68 (0.46-1.01) 1 (ref) 0.91 (0.79-1.05)

Multivariate-adjusted HR (95% CI)a 0.98 (0.89-1.07) 0.71 (0.48-1.06) 1 (ref) 0.94 (0.81-1.09)

aAdjusted for baseline age, sex, smoking, alcohol drinking, physical activities, and LDL-cholesterol level.

Table S5. Risks of CV events, CV mortality, and all-cause mortality in participants with MUO at baseline according to 2 year metabolic

health and obesity status using the stable MUO group as a reference group.

Baseline category MUO

Follow-up category

Follow-up BMI

Follow-up metabolic health status

MHNO

< 25 kg/m2

0–1 risk factors

MHO

≥ 25 kg/m2

0–1 risk factors

MUNO

< 25 kg/m2

≥ 2 risk factors

MUO

Reference group

N (% of baseline MUO) 2,573 (3.17) 9,549 (11.78) 9,494 (11.71) 58,443 (72.11)

CV event incidence

Number of events (%) 43 (1.67) 160 (1.68) 238 (2.51) 1,227 (2.10)

HR (95% CI) 0.80 (0.59-1.08) 0.88 (0.75-1.04) 1.01 (0.88-1.16) 1 (ref)

Multivariate-adjusted HR (95% CI)a 0.79 (0.58-1.07) 0.89 (0.75-1.05) 1.01 (0.88-1.16) 1 (ref)

N (% of baseline MHO) 2,588 (3.19) 9,595 (11.84) 9,682 (11.95) 59,179 (73.02)

CVD mortality

Number of events (%) 7 (0.27) 21 (0.22) 60 (0.63) 225 (0.38)

HR (95% CI) 0.69 (0.33-1.47) 0.67 (0.43-1.05) 1.25 (0.94-1.66) 1 (ref)

Multivariate-adjusted HR (95% CI)a 0.66 (0.31-1.39) 0.67 (0.43-1.05) 1.25 (0.94-1.66) 1 (ref)

Mortality

Number of events (%) 58 (2.25) 119 (1.25) 300 (3.16) 1,109 (1.90)

HR (95% CI) 1.18 (0.91-1.54) 0.76 (0.63-0.92) 1.31 (1.15-1.49) 1 (ref)

Multivariate-adjusted HR (95% CI)a 1.17 (0.90-1.52) 0.77 (0.64-0.93) 1.31 (1.15-1.49) 1 (ref)

aAdjusted for baseline age, sex, smoking, alcohol drinking, physical activities, and LDL-cholesterol level.

Table S6. Risk of CV events, CV mortality, and all-cause mortality according to baseline metabolic health and obesity status with MHO as a

reference group.

Baseline category

BMI

Metabolic health status

MHNO

< 25 kg/m2

0–1 risk factors

MHO

≥ 25 kg/m2

0–1 risk factors

MUNO

< 25 kg/m2

≥ 2 risk factors

MUO

≥ 25 kg/m2

≥ 2 risk factors

N (% of total) 115,750 (31.9) 36,378 (10.0) 116,816 (32.2) 93,919 (25.9)

CV event incidence

Number of events (%) 2,416 (2.1) 804 (2.2) 4492 (3.9) 3,343 (3.6)

HR (95% CI) 0.91 (0.84-0.98) 1 (ref) 1.34 (1.24-1.45) 1.37 (1.27-1.48)

Multivariate-adjusted HR (95% CI)a 0.88 (0.81-0.95) 1 (ref) 1.29 (1.20-1.39) 1.35 (1.25-1.46)

CV mortality

Number of events (%) 459 (0.4) 97 (0.3) 876 (0.8) 510 (0.5)

HR (95% CI) 1.28 (1.03-1.60) 1 (ref) 1.69 (1.37-2.09) 1.54 (1.24-1.92)

Multivariate-adjusted HR (95% CI)a 1.17 (0.94-1.45) 1 (ref) 1.61 (1.31-1.99) 1.55 (1.24-1.92)

Mortality

Number of events (%) 3,186 (2.8) 689 (1.9) 5,095 (4.4) 2,562 (2.7)

HR (95% CI) 1.31 (1.20-1.42) 1 (ref) 1.50 (1.38-1.62) 1.13 (1.04-1.23)

Multivariate-adjusted HR (95% CI)a 1.16 (1.07-1.26) 1 (ref) 1.39 (1.28-1.51) 1.11 (1.02-1.21)

aAdjusted for baseline age, sex, smoking, alcohol drinking, physical activities, and LDL-cholesterol level.

Table S7. Risks of CV events, CV mortality, and all-cause mortality in participants with MHO at baseline according to 2 year metabolic

health and obesity status using the MHO-MHNO group as a reference group.

Baseline category MHO

Follow-up category

Follow-up BMI

Follow-up metabolic health status

MHNO

< 25 kg/m2

0–1 risk factors

MHO

≥ 25 kg/m2

0–1 risk factors

MUNO

< 25 kg/m2

≥ 2 risk factors

MUO

≥ 25 kg/m2

≥ 2 risk factors

N (% of baseline MHO) 3,642 (11.7) 14,318 (45.8) 1,837 (5.9) 11,468 (36.7)

CV event incidence

Number of events (%) 50 (1.4) 165 (1.2) 36 (2.0) 180 (1.6)

HR (95% CI) 1 (ref) 0.94 (0.68-1.29) 1.18 (0.77-1.81) 1.15 (0.84-1.57)

Multivariate-adjusted HR (95% CI)a 1 (ref) 0.96 (0.70-1.32) 1.19 (0.77-1.82) 1.16 (0.85-1.59)

N (% of baseline MHO) 3,658 (11.6) 14,365 (45.6) 1,876 (6.0) 11,589 (36.8)

CVD mortality

Number of events (%) 7 (0.2) 23 (0.2) 9 (0.5) 29 (0.3)

HR (95% CI) 1 (ref) 1.03 (0.44-2.40) 1.97 (0.73-5.30) 1.36 (0.60-3.11)

Multivariate-adjusted HR (95% CI)a 1 (ref) 1.03 (0.44-2.42) 1.95 (0.73-5.26) 1.36 (0.59-3.11)

Mortality

Number of events (%) 56 (1.5) 153 (1.1) 59 (3.1) 169 (1.5)

HR (95% CI) 1 (ref) 0.82 (0.61-1.12) 1.62 (1.12-2.34) 0.97 (0.72-1.31)

Multivariate-adjusted HR (95% CI)a 1 (ref) 0.86 (0.63-1.17) 1.68 (1.17-2.43) 1.02 (0.75-1.38)

aAdjusted for baseline age, sex, smoking, alcohol drinking, physical activities, and LDL-cholesterol level.

Fig S1. Study design and participants. A: Selection of study participants. B: Study design. NHIS-HEALS, National Health Insurance Service-Health Screening Cohort.