Operationalizing a frailty index using routine blood and urine tests

Figures & data

Table 1 Standard laboratory parameters used to construct the frailty index based on routine blood and urine tests (FI-Lab)

Standard laboratory parameter	Normal range/cutoff	AUC (95% CI) for 6-month mortality	P-value	AUC (95% CI) for 1-year mortality	P-value
Blood sample
White blood cells (number/µL)	4,000–10,000	0.592 (0.498–0.686)	0.045	0.589 (0.505–0.673)	0.03
Red blood cells (number/µL)	Men 4.5×10^6–5.9×10^6, women 3.9×10^6–5.1×10^6	0.53 (0.441–0.618)	0.519	0.546 (0.466–0.625)	0.269
Hemoglobin (g/dL)	Men 14–17.5, women 12.3–15.3	0.579 (0.496–0.662)	0.085	0.592 (0.518–0.666)	0.025
MCV (fL)	80–96	0.492 (0.402–0.582)	0.865	0.517 (0.435–0.599)	0.674
Hematocrit (%)	Men 40–52, women 35–47	0.613 (0.526–0.699)	0.014	0.614 (0.536–0.692)	0.006
Platelets (number/µL)	150,000–400,000	0.476 (0.379–0.572)	0.6	0.471 (0.384–0.558)	0.478
Quick value (%)	70–130	0.562 (0.469–0.654)	0.179	0.54 (0.458–0.622)	0.332
PTT (seconds)	25.1–36.5	0.597 (0.506–0.689)	0.034	0.589 (0.506–0.672)	0.032
Sodium (mval/L)	136–145	0.562 (0.47–0.655)	0.176	0.566 (0.483–0.649)	0.109
Potassium (mg/dL)	3.5–5.1	0.561 (0.466–0.656)	0.183	0.535 (0.452–0.618)	0.39
Calcium (mval/L)	4.3–5.2	0.647 (0.555–0.74)	0.001	0.617 (0.534–0.7)	0.005
Protein, total (g/dL)	6.4–8.7	0.548 (0.457–0.638)	0.305	0.568 (0.487–0.648)	0.103
Urea (mg/dL)	17–43	0.572 (0.483–0.661)	0.116	0.564 (0.483–0.644)	0.122
Creatinine (mg/dL)	Men 0.7–1.2, women 0.5–0.9	0.504 (0.415–0.594)	0.922	0.517 (0.436–0.597)	0.687
Bilirubin (mg/dL)	<1	0.558 (0.463–0.653)	0.207	0.548 (0.464–0.632)	0.248
AST (SGOT, U/L)	Men <35, women <31	0.571 (0.477–0.665)	0.123	0.573 (0.489–0.657)	0.076
ALT (SGPT, U/L)	Men <45, women <34	0.55 (0.456–0.644)	0.272	0.548 (0.464–0.631)	0.248
GGT (U/L)	Men <55, women <33	0.58 (0.495–0.665)	0.081	0.59 (0.513–0.666)	0.03
LDH (U/L)	Men <248, women <247	0.609 (0.52–0.699)	0.018	0.637 (0.559–0.716)	0.001
Albumin (g/dL)	3.97–4.94	0.612 (0.53–0.693)	0.015	0.606 (0.531–0.681)	0.01
CRP (mg/dL)	<0.5	0.623 (0.545–0.702)	0.007	0.601 (0.527–0.676)	0.014
TSH (µU/mL)	0.27–4.2	0.489 (0.4–0.578)	0.817	0.496 (0.415–0.576)	0.916
Spot urine
Protein, total (mg/dL)	<15 mg/dL	0.591 (0.495–0.686)	0.051	0.576 (0.492–0.661)	0.066

Abbreviations: AUC, area under the receiver-operating characteristic curve; CI, confidence interval; MCV, mean corpuscular volume; PTT, partial thromboplastin time; TSH, thyroid-stimulating hormone; AST, aspartate aminotransferase; SGOT, serum glutamic oxaloacetic transaminase; ALT, alanine aminotransferase; SGPT, serum glutamic pyruvic transaminase; GGT, gamma-glutamyl transferase; LDH, lactate dehydrogenase; CRP, C-reactive proteine.

Table 2 Clinical characteristics (baseline examination), 6-month mortality, and 1-year mortality of study participants according to frailty index based on routine blood and urine tests (FI-Lab) score

Clinical characteristic	Score 0 (n=2)	Score 0.001–0.1 (n=21)	Score 0.101–0.2 (n=33)	Score 0.201–0.3 (n=51)	Score 0.301–0.4 (n=89)	Score 0.401–0.5 (n=70)	Score 0.501–0.6 (n=28)	Score 0.601–0.7 (n=10)	Score >0.7 (n=2)	P-value
Age (years)	81±2.8	84.5±6.4	81.8±5.3	82.2±6.6	83±6.6	83.6±7	82.1±5.2	84±6.2	79.5±6.4	0.901
Female, % (n)	100 (2)	90.5 (19)	84.8 (28)	76.5 (39)	61.8 (55)	60 (42)	53.6 (15)	70 (7)	0	0.004
Height (cm)	159±5.7	159±8.1	162±7.1	163±8.7	164±9.5	164±11	165±12	159±11	172±5.7	0.404
Weight (kg)	79±21	72.3±13	70.4±16	70.4±15	75.6±17	71.9±15	79.9±19	65.1±11	88.2±13	0.216
BMI (kg/m^2)	31±6	28.6±5.3	26.7±5.2	26.6±5.5	28.1±6.1	26.9±5.4	29.4±5.8	25.7±1.6	29.7±2.3	0.437
Weight loss >4.5 kg in last year (unintentional), % (n)	0	28.6 (6)	12.1 (4)	15.7 (8)	20.2 (18)	40 (28)	39.3 (11)	40 (4)	0	0.011
MMSE (points)	28.5±0.7 (n=2)	26.5±3.8 (n=21)	26.3±2.7 (n=33)	25.5±4.6 (n=47)	25.9±4.6 (n=89)	24.8±4.5 (n=70)	25.2±4.2 (n=26)	21.3±9 (n=10)	26±0 (n=2)	0.005
GDS (points)	2.5±2.1 (n=2)	3.1±2.1 (n=21)	4.12±2.9 (n=33)	3.98±3.1 (n=47)	4.1±2.8 (n=89)	3.71±2.6 (n=68)	4.08±2.3 (n=26)	3.7±1.4 (n=10)	1.5±2.1 (n=2)	0.941
TUG >19 seconds or unable to perform TUG, % (n)	50 (1)	47.6 (10)	45.5 (15)	52.9 (27)	59.6 (53)	77.1 (54)	85.7 (24)	90 (9)	100 (2)	0.001
Barthel Index (points)	75±28	83.6±12	79.4±16	73.5±23	69.8±21	66.1±19	61.6±24	51±25	52.5±11	0.429
CIRS-G (points)	9±2.8	13.2±3.7	13.8±4.9	15.4±5	18.3±5.6	19.2±5	19.1±4.3	23.1±4.3	28.5±0.7	<0.001
Heart failure, % (n)	0	28.6 (6)	24.2 (8)	39.2 (20)	50.6 (45)	55.7 (39)	67.9 (19)	70 (7)	50 (1)	0.004
Myocardial infarction, % (n)	0	9.5 (2)	9.1 (3)	11.8 (6)	13.5 (12)	18.6 (13)	7.1 (2)	30 (3)	50 (1)	0.407
Peripheral vascular disease, % (n)	0	23.8 (5)	9.1 (3)	2 (1)	19.1 (17)	24.3 (17)	28.6 (8)	30 (3)	0	0.027
Stroke, % (n)	0	4.8 (1)	21.2 (7)	35.3 (18)	22.5 (20)	14.3 (10)	10.7 (3)	20 (2)	50 (1)	0.054
Cancer, % (n)	0	9.5 (2)	15.2 (5)	5.9 (3)	15.7 (14)	17.1 (12)	21.4 (6)	20 (2)	50 (1)	0.475
Diabetes mellitus, % (n)	50 (1)	28.6 (6)	27.3 (9)	29.4 (15)	39.3 (35)	48.6 (34)	42.9 (12)	30 (3)	50 (1)	0.415
Lung disease, % (n)	0	23.8 (5)	15.2 (5)	19.6 (10)	21.3 (19)	12.9 (9)	10.7 (3)	0	0	0.559
Kidney disease, % (n)	0	42.9 (9)	45.5 (15)	43.1 (22)	71.9 (64)	84.3 (59)	64.3 (18)	90 (9)	100 (2)	<0.001
Urinary incontinence or catheterized, % (n)	50 (1)	4.8 (1)	6.1 (2)	15.7 (8)	21.3 (19)	34.3 (24)	39.3 (11)	40 (4)	100 (2)	<0.001
Constipation, % (n)	50 (1)	28.6 (6)	21.2 (7)	39.2 (20)	19.1 (17)	42.9 (30)	42.9 (12)	30 (3)	50 (1)	0.044
>5 medications, % (n)	50 (1)	95.2 (20)	93.9 (31)	92.2 (47)	96.6 (86)	98.6 (69)	100 (28)	100 (10)	100 (2)	0.034
Institutionalized, % (n)	0	4.8 (1)	9.1 (3)	21.6 (11)	18 (16)	15.7 (11)	21.4 (6)	10 (1)	0	0.622
FI-Lab (−)	0±0	0.07±0	0.15±0	0.24±0	0.35±0	0.45±0	0.53±0	0.63±0	0.74±0	<0.001
FI-CGA (−)	0.25±0.2	0.29±0.1	0.29±0.1	0.34±0.1	0.39±0.1	0.44±0.1	0.49±0.1	0.51±0.1	0.57±0.1	0.015
FI-combined (−)	0.17±0.2	0.23±0.1	0.24±0.1	0.31±0.1	0.37±0.1	0.45±0.1	0.5±0.1	0.55±0.1	0.63±0	<0.001
Clinical Frailty Scale (category)	4.5±2.1	4.43±0.9	4.52±1.1	4.98±1.4	5.38±1.2	5.97±1.3	6.61±1.4	6.4±0.7	0.65±0.7	<0.001
Rule-based frailty definition (level)	1±1.4	1.05±1.2	1.03±1.1	1.25±1.2	1.63±1.2	1.99±0.9	2.21±0.9	2.5±1	2.5±0.7	0.001
Frail state (≥3 phenotypic components) according to frailty phenotype, % (n)	50 (1)	23.8 (5)	21.2 (7)	29.4 (15)	39.3 (35)	52.9 (37)	75 (21)	100 (10)	100 (2)	<0.001
Six-month mortality, % (n)	0	0	3 (1)	7.8 (4)	9 (8)	25.7 (18)	35.7 (10)	40 (4)	100 (2)	<0.001
One-year mortality, % (n)	0	0	3.1 (1)	13.7 (7)	12.5 (11)	32.9 (23)	46.3 (13)	50 (5)	100 (2)	<0.001

Note: The data are presented as mean ± standard deviation unless otherwise indicated.

Abbreviations: BMI, body mass index; CGA, comprehensive geriatric assessment; CIRS-G, Cumulative Illness Rating Scale – geriatric; GDS, Geriatric Depression Scale; MMSE, Mini-Mental State Examination; TUG, timed “up and go”.

Table 3 Ability of different frailty instruments and comparison of frailty index based on routine blood and urine tests (FI-Lab) with other frailty instruments to predict 6-month and 1-year mortality

Frailty instrument	AUC (95% CI) for 6-month mortality (n=306)	P-value	P-value, AUC 1 vs AUCs 2–7	AUC (95% CI) for 1-year mortality (n=304)	P-value	P-value, AUC 1 vs AUCs 2–7
FI-Lab	0.765 (0.694–0.836)	<0.001	–	0.769 (0.706–0.833)	<0.001	–
FI-CGA	0.834 (0.767–0.901)	<0.001	0.030	0.806 (0.744–0.867)	<0.001	0.139
FI-combined	0.853 (0.792–0.915)	<0.001	<0.001	0.832 (0.776–0.888)	<0.001	0.004
Clinical Frailty Scale	0.867 (0.807–0.926)	<0.001	0.002	0.852 (0.8–0.904)	<0.001	0.005
Rule-based frailty definition	0.716 (0.642–0.79)	<0.001	0.126	0.703 (0.638–0.769)	<0.001	0.040
Frailty phenotype	0.754 (0.687–0.82)	<0.001	0.391	0.724 (0.659–0.79)	<0.001	0.118

Abbreviations: AUC, area under the receiver-operating characteristic curve; CGA, comprehensive geriatric assessment; CI, confidence interval.

Table 4 HRs and adjusted (for age and sex) HRs for each increment in category or score of 0.01 of the different frailty instruments in relation to 6-month and 1-year mortality

Frailty instrument	HR (95% CI)	P-value	Adjusted HR (95% CI)	P-value
Six-month mortality
FI-Lab (per each 0.01 increment in score)	1.072 (1.048–1.096)	<0.001	1.072 (1.048–1.097)	<0.001
FI-CGA (per each 0.01 increment in score)	1.105 (1.076–1.135)	<0.001	1.102 (1.073–1.132)	<0.001
FI-combined (per each 0.01 increment in score)	1.134 (1.099–1.171)	<0.001	1.133 (1.098–1.17)	<0.001
Clinical Frailty Scale (per each increment in category [1–9])	2.614 (2.132–3.206)	<0.001	2.545 (2.055–3.15)	<0.001
Rule-based frailty definition (per each increment in level [0–3])	2.333 (1.613–3.373)	<0.001	2.259 (1.554–3.285)	<0.001
Frailty phenotype (per increase in category [robust/prefrail/frail])	6.063 (2.983–12.325)	<0.001	5.618 (2.754–11.46)	<0.001
One-year mortality
FI-Lab (per each 0.01 increment in score)	1.071 (1.05–1.092)	<0.001	1.071 (1.05–1.093)	<0.001
50-item FI-CGA (per each 0.01 increment in score)	1.089 (1.066–1.113)	<0.001	1.087 (1.064–1.112)	<0.001
FI-combined (per each 0.01 increment in score)	1.119 (1.09–1.148)	<0.001	1.118 (1.088–1.148)	<0.001
Clinical Frailty Scale (per each increment in category [1–9])	2.569 (2.128–3.1)	<0.001	2.515 (2.069–3.059)	<0.001
Rule-based frailty definition (per each increment in level [0–3])	2.189 (1.611–2.975)	<0.001	2.142 (1.567–2.929)	<0.001
Frailty phenotype (per increase in category [robust/prefrail/frail])	3.977 (2.389–6.622)	<0.001	3.744 (2.241–6.257)	<0.001

Abbreviations: CGA, comprehensive geriatric assessment; CI, confidence interval; FI-Lab, frailty index (based on routine blood and urine tests); HR, hazard ratio.

Table 5 Adjusted HRs for age, sex, and each increment in category/level or score of 0.01 of the frailty index based on FI-Lab, FI-CGA, rule-based frailty definition, and frailty phenotype in relation to 6-month and 1-year mortality

Variable	Adjusted HR (95% CI)	P-value
Six-month mortality
Age	1.026 (0.974–1.081)	0.329
Sex	0.747 (0.418–1.333)	0.324
FI-Lab (per each 0.01 increment in score)	1.046 (1.02–1.073)	0.001
Clinical Frailty Scale (per each increment in category [1–9])	2.287 (1.83–2.858)	<0.001
Age	1.046 (0.995–1.099)	0.077
Sex	0.711 (0.399–1.269)	0.249
FI-Lab (per each 0.01 increment in score)	1.041 (1.017–1.066)	0.001
FI-CGA (per each 0.01 increment in score)	1.087 (1.056–1.119)	<0.001
Age	1.064 (1.01–1.12)	0.019
Sex	0.693 (0.387–1.241)	0.217
FI-Lab (per each 0.01 increment in score)	1.054 (1.028–1.08)	<0.001
Rule-based frailty definition (per each increment in level [0–3])	3.562 (1.915–6.627)	<0.001
Age	1.052 (1.001–1.107)	0.047
Sex	0.716 (0.402–1.275)	0.257
FI-Lab (per each 0.01 increment in score)	1.051 (1.026–1.076)	<0.001
Frailty phenotype (per increase in category [robust/prefrail/frail])	3.869 (1.852–8.085)	<0.001
One-year mortality
Age	1.027 (0.974–1.082)	0.322
Sex	0.745 (0.417–1.33)	0.319
FI-Lab (per each 0.01 increment in score)	1.046 (1.02–1.073)	0.001
Clinical Frailty Scale (per each increment in category [1–9])	2.282 (1.826–2.852)	<0.001
Age	1.046 (0.995–1.099)	0.076
Sex	0.711 (0.398–1.268)	0.248
FI-Lab (per each 0.01 increment in score)	1.041 (1.017–1.066)	0.001
FI-CGA (per each 0.01 increment in score)	1.087 (1.056–1.119)	<0.001
Age	1.065 (1.011–1.121)	0.018
Sex	0.69 (0.385–1.236)	0.212
FI-Lab (per each 0.01 increment in score)	1.053 (1.027–1.079)	<0.001
Rule-based frailty definition (per each increment in level [0–3])	3.558 (1.913–6.616)	<0.001
Age	1.053 (1.001–1.108)	<0.045
Sex	0.713 (0.4–1.271)	0.251
FI-Lab (per each 0.01 increment in score)	1.05 (1.026–1.075)	<0.001
Frailty phenotype (per increase in category [robust/prefrail/frail])	3.828 (1.835–7.985)	<0.001

Abbreviations: CGA, comprehensive geriatric assessment; CI, confidence interval; FI-Lab, frailty index (based on routine blood and urine tests); HR, hazard ratio.