Biological age as a health index for mortality and major age-related disease incidence in Koreans: National Health Insurance Service – Health screening 11-year follow-up study

Figures & data

Table 1 Inclusion criteria for parameters

Parameters	Inclusion criteria
Age (year)	20.00	≤
HT (cm)	NA
WT (kg)	NA
BMI (kg/m^2)	15.00	∼	30.00
WC (cm)	60.00	∼	105.00
SBP (mmHg)	80.00	∼	160.00
DBP (mmHg)	50.00	∼	100.00
FBS (mmol/L)	2.78	∼	7.77
TC (mmol/L)	1.30	∼	6.73
TG (mmol/L)	0.57	∼	4.52
HDL-C (mmol/L)	0.52	∼	2.33
LDL-C (mmol/L)		<	4.92
Hgb (g/L)	100.00	∼	180.00
u-Prot (negative, trace, + ∼ ++++)	Negative	∼	++
Cr (µmol/L)	35.36	∼	176.80
AST (IU/L)		<	60.00
ALT (IU/L)		<	80.00
r-GTP (IU/L)		<	120.00

Notes: SI conversion factors: to convert FBS to mmol/L, multiply by 0.0555; TC, HDL-C and LDL-C to mmol/L, multiply by 0.0259; triglyceride to mmol/L, multiply by 0.0113; Hgb to g/L, multiply by 10.0; creatinine to µmol/L, multiply by 88.4.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; Cr, creatinine; DBP, diastolic blood pressure; FBS, fasting blood sugar; HDL-C, high-density lipoprotein cholesterol; Hgb, hemoglobin; HT, height; LDL-C, low-density lipoprotein cholesterol; NA, not available; r-GTP, gamma glutamyl transpeptidase; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride; u-Prot, urine protein; WC, waist circumference; WT, weight.

Table 2 General characteristics of the biological age model subjects

Parameters	Sexes combined (n=484,724)	Men (n=260,315)	Women (n=224,409)
Age (years)	50.75±14.11	50.12±13.92	51.48±14.29
HT (cm)	163.25±9.12	169.37±6.39	156.15±6.19
WT (kg)	62.76±10.33	68.36±9.16	56.26±7.38
BMI (kg/m^2)	23.47±2.72	23.79±2.60	23.09±2.81
WC (cm)	80.02±8.19	83.14±7.08	76.39±7.89
SBP (mmHg)	121.18±13.18	123.00±12.29	119.05±13.85
DBP (mmHg)	75.34±8.81	76.74±8.40	73.72±9.00
FBS (mmol/L)	5.24±0.71	5.30±0.74	5.16±0.67
TC (mmol/L)	4.96±0.80	4.92±0.80	5.01±0.80
TG (mmol/L)	1.42±0.72	1.53±0.77	1.28±0.64
HDL-C (mmol/L)	1.39±0.32	1.33±0.30	1.46±0.32
LDL-C (mmol/L)	2.92±0.75	2.89±0.75	2.95±0.75
Hgb (g/L)	139.25±14.74	148.40±11.63	128.63±10.14
u-Prot (negative, trace, + ∼ ++++)	1.05±0.27	1.05±0.27	1.05±0.27
Cr (µmol/L)	79.62±17.61	88.92±15.32	68.83±13.44
eGFR (mL/min/1.73 m^2)	102.27±29.35	87.69±19.76	119.20±29.57
AST (IU/L)	23.51±7.14	24.64±7.29	22.19±6.72
ALT (IU/L)	22.11±11.19	25.00±11.92	18.77±9.21
r-GTP (IU/L)	29.22±21.98	36.93±24.60	20.28±13.89

Notes: SI conversion factors: To convert FBS to mmol/L, multiply by 0.0555; TC, HDL-C and LDL-C to mmol/L, multiply by 0.0259; triglyceride to mmol/L, multiply by 0.0113; Hgb to g/L, multiply by 10.0; creatinine to µmol/L, multiply by 88.4.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; Cr, creatinine; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate, 186.3 × Cr (mg/dL)^−1.154 × Age^−0.203 × (0.742 in female); FBS, fasting blood sugar; HDL-C, high-density lipoprotein cholesterol; Hgb, hemoglobin; HT, height; LDL-C, low-density lipoprotein cholesterol; NA, not available; r-GTP, gamma glutamyl transpeptidase; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride; u-Prot, urine protein; WC, waist circumference; WT, weight.

Table 3 Pearson correlation coefficients between age and parameters

	Sexes combined (n=484,724)	Men (n=260,315)	Women (n=224,409)
HT (cm)	−0.387**	−0.478**	−0.549**
WT (kg)	−0.175**	−0.276**	−0.050**
BMI (kg/m^2)	0.129**	−0.014**	0.293**
WC (cm)	0.254**	0.169**	0.435**
SBP (mmHg)	0.272**	0.175**	0.391**
DBP (mmHg)	0.154**	0.076**	0.258**
FBS (mmol/L)	0.222**	0.212**	0.249**
TC (mmol/L)	0.126**	0.030**	0.229**
TG (mmol/L)	0.114**	0.006**	0.285**
HDL-C (mmol/L)	−0.125**	−0.068**	−0.214**
LDL-C (mmol/L)	0.134**	0.052**	0.223**
Hgb (g/L)	−0.180**	−0.321**	−0.042**
u-Prot (negative, trace, + ∼ ++++)	0.027**	0.040**	0.012**
Cr (µmol/L)	0.007**	0.005**	0.088**
eGFR (mL/min/1.73 m^2)	−0.207**	−0.243**	−0.309**
AST (IU/L)	0.186**	0.116**	0.297**
ALT (IU/L)	0.023**	−0.073**	0.201**
r-GTP (IU/L)	0.023**	0.006**	0.125**

Notes:

** p<0.001. SI conversion factors: To convert FBS to mmol/L, multiply by 0.0555; TC, HDL-C and LDL-C to mmol/L, multiply by 0.0259; triglyceride to mmol/L, multiply by 0.0113; Hgb to g/L, multiply by 10.0; creatinine to µmol/L, multiply by 88.4.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; Cr, creatinine; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate, 186.3 × Cr (mg/dL)^−1.154 × Age^−0.203 × (0.742 in female); FBS, fasting blood sugar; HDL-C, high-density lipoprotein cholesterol; Hgb, hemoglobin; HT, height; LDL-C, low-density lipoprotein cholesterol; NA, not available; r-GTP, gamma glutamyl transpeptidase; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride; u-Prot, urine protein; WC, waist circumference; WT, weight; WT (kg)/HT (m)².

Table 4 Principal component analysis

Parameters	First PCA loading
	Men		Women
Age (years)	0.844	–	0.799	–
HT (cm)	−0.617	−0.129	−0.553	−0.465
WC (cm)	0.282	0.653	0.631	0.643
SBP (mmHg)	0.373	0.597	0.561	0.559
FBS (mmol/L)	0.435	0.554	0.422	0.449
TC (mmol/L)	–	–	0.364	0.376
TG (mmol/L)	–	–	0.568	0.632
HDL-C (mmol/L)	–	–	−0.345	−0.364
Hgb (g/L)	−0.408	0.070	–	–
eGFR (mL/min/1.73 m^2)	−0.386	−0.347	−0.366	−0.334
AST (IU/L)	0.290	0.472	0.466	0.488
r-GTP (IU/L)	–	–	0.377	0.461
Eigenvalue	1.899	1.455	2.903	2.379
Total variance, %	23.743	20.785	26.394	23.789

Notes: SI conversion factors: To convert FBS to mmol/L, multiply by 0.0555; TC, HDL-C and LDL-C to mmol/L, multiply by 0.0259; triglyceride to mmol/L, multiply by 0.0113; Hgb to g/L, multiply by 10.0; creatinine to µmol/L, multiply by 88.4.

Abbreviations: AST, aspartate aminotransferase; eGFR, estimated glomerular filtration rate, 186.3 × Cr (mg/dL)^−1.154 × Age^−0.203 × (0.742 in female); FBS, fasting blood sugar; HDL-C, high-density lipoprotein cholesterol; Hgb, hemoglobin; HT, height; LDL-C, low-density lipoprotein cholesterol; r-GTP, gamma glutamyl transpeptidase; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride; u-Prot, urine protein; WC, waist circumference.

Table 5 Frequency of mortality and major age-related diseases

	Sexes combined						Men						Women
	Event				Total		Event				Total		Event				Total
	Yes		No		n	%	Yes		No		n	%	Yes		No		n	%
	n	%	n	%			n	%	n	%			n	%	n	%
Death	23,191	3.4	658,810	96.6	682,001	100.0	15,978	4.2	361,315	95.8	377,293	100.0	7,213	2.4	297,495	97.6	304,708	100.0
Hypertension	116,887	19.9	469,226	80.1	586,113	100.0	69,553	21.1	259,839	78.9	329,392	100.0	47,334	18.4	209,387	81.6	256,721	100.0
Diabetes mellitus	46,018	7.3	585,361	92.7	631,379	100.0	28,497	8.1	321,425	91.9	349,922	100.0	17,521	8.2	263,936	93.8	281,457	100.0
Heart diseases	39,829	5.9	635,471	94.1	675,300	100.0	23,220	6.2	350,727	93.8	373,947	100.0	16,609	5.5	284,744	94.5	301,353	100.0
Stroke	6,119	0.9	670,840	99.1	676,959	100.0	3,722	1.0	371,369	99.0	375,091	100.0	2,397	0.8	299,471	99.2	301,868	100.0
(Malignant) cancer	55,448	8.2	616,694	91.8	672,142	100.0	33,783	9.1	338,304	90.9	372,087	100.0	21,665	7.2	278,390	92.8	300,055	100.0

Table 6 Hazard ratios for all-cause mortality by BA difference

Age at baseline health checkup	Sexes combined*	Men**	Women**
All ages (years)	1.016 (1.015–1.016)	1.015 (1.014–1.016)	1.020 (1.018–1.021)
<50	1.027 (1.026–1.029)	1.027 (1.025–1.028)	1.034 (1.029–1.039)
50–59	1.019 (1.018–1.021)	1.018 (1.017–1.020)	1.025 (1.021–1.029)
60–69	1.014 (1.013–1.015)	1.013 (1.012–1.014)	1.020 (1.018–1.023)
70+	1.010 (1.008–1.011)	1.008 (1.006–1.009)	1.016 (1.014–1.019)

Notes:

* Adjusted for age and sex.

** Adjusted for age. Hazard ratios are for a 1-year increase in the difference between calculated BA and CA. All hazard ratios are p<0.001.

Abbreviations: BA, biological age; CA, chronological age.

Table 7 Hazard ratios for major age-related disease incidence by BA difference

	Age at baseline health checkup	Sexes combined*	Men**	Women**
Hypertension	All ages (years)	1.025 (1.025–1.026)	1.024 (1.024–1.024)	1.031 (1.030–1.032)
	<50	1.030 (1.030–1.030)	1.028 (1.028–1.028)	1.040 (1.039–1.040)
	50–59	1.023 (1.022–1.024)	1.022 (1.021–1.022)	1.029 (1.027–1.030)
	60–69	1.019 (1.018–1.020)	1.018 (1.017–1.018)	1.023 (1.022–1.024)
	70+	1.016 (1.015–1.018)	1.015 (1.013–1.017)	1.018 (1.015–1.020)
Diabetes mellitus	All ages (years)	1.042 (1.042–1.043)	1.040 (1.039–1.040)	1.050 (1.049–1.050)
	<50	1.047 (1.046–1.047)	1.044 (1.044–1.045)	1.058 (1.057–1.059)
	50–59	1.041 (1.040–1.042)	1.039 (1.038–1.039)	1.048 (1.047–1.049)
	60–69	1.034 (1.033–1.035)	1.031 (1.030–1.032)	1.041 (1.039–1.042)
	70+	1.032 (1.030–1.034)	1.029 (1.026–1.031)	1.038 (1.035–1.041)
Heart diseases	All ages (years)	1.013 (1.013–1.014)	1.012 (1.011–1.013)	1.017 (1.016–1.018)
	<50	1.017 (1.016–1.018)	1.016 (1.015–1.017)	1.025 (1.022–1.027)
	50–59	1.013 (1.012–1.014)	1.012 (1.010–1.013)	1.017 (1.016–1.019)
	60–69	1.008 (1.007–1.009)	1.007 (1.006–1.008)	1.011 (1.009–1.013)
	70+	1.007 (1.005–1.009)	1.006 (1.004–1.009)	1.009 (1.005–1.012)
Stroke	All ages (years)	1.016 (1.014–1.017)	1.015 (1.013–1.016)	1.019 (1.016–1.021)
	<50	1.020 (1.017–1.023)	1.019 (1.016–1.022)	1.027 (1.020–1.034)
	50–59	1.018 (1.016–1.021)	1.018 (1.015–1.021)	1.019 (1.013–1.025)
	60–69	1.012 (1.010–1.015)	1.010 (1.008–1.013)	1.018 (1.014–1.022)
	70+	1.008 (1.005–1.012)	1.008 (1.004–1.013)	1.008 (1.001–1.015)a
(Malignant) cancer	All ages (years)	1.004 (1.004–1.005)	1.004 (1.004–1.005)	1.004 (1.003–1.005)
	<50	1.006 (1.005–1.007)	1.006 (1.005–1.007)	1.003 (1.001–1.005)a
	50–59	1.004 (1.003–1.005)	1.004 (1.003–1.005)	1.003 (1.001–1.005)a
	60–69	1.002 (1.001–1.003)	1.002 (1.001–1.003)a	1.004 (1.002–1.006)
	70+	1.002 (1.000–1.003)b	1.000 (0.998–1.002)b	1.006 (1.003–1.010)a

Notes:

* Adjusted for age and sex.

** Adjusted for age. Hazard ratios are for a 1-year increase in the difference between calculated BA and CA. All hazard ratios are p<0.001 except,a,b where

a p<0.05 and

b p<0.05.

Abbreviations: BA, biological age; CA, chronological age.

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