Appendicular Skeletal Muscle Mass Associated with Sarcopenia as a Predictor of Poor Functional Outcomes in Ischemic Stroke

Figures & data

Figure 1 Flow diagram for the inclusion and exclusion criteria.

Figure 2 A representative dual-energy X-ray absorptiometry image used for skeletal muscle mass measurement.

Table 1 Baseline Characteristics of Study Participants

	Patients with Poor Functional Outcome	Patients Without Poor Functional Outcome	P-value
N	89	564
Age (years)	74.0±12.4	64.6±13.0	<0.001
Sex (female, %)	48 (53.9%)	202 (35.8%)	0.001
Previous stroke, n (%)	14 (15.7%)	65 (11.5%)	0.258
Hypertension, n (%)	61 (68.5%)	365 (64.7%)	0.482
Diabetes, n (%)	42 (47.2%)	198 (35.1%)	0.028
AF, n (%)	24 (27.0%)	83 (14.7%)	0.004
CAD, n (%)	8 (9.0%)	44 (7.8%)	0.701
CHF, n (%)	5 (5.6%)	14 (2.5%)	0.162
PAD, n (%)	1 (1.1%)	7 (1.2%)	1.000
Onset-to-admission time (h)	13.8 [5.1, 26.3]	10.1 [2.2, 26.6]	0.172
Admission to DEXA scan (days)	2 [1, 4]	1 [1, 2]	0.007
Initial NIHSS	7 [4, 12]	2 [1, 5]	<0.001
Thrombolysis, n (%)	13 (14.6%)	65 (11.5%)	0.405
Territorial ischemic lesion, n (%)	6 (6.7%)	24 (4.3%)	0.280
Symptomatic ICH, n (%)	3 (3.4%)	2 (0.2%)	0.009
Craniectomy, n (%)	1 (1.1%)	0 (0%)	0.136
In-hospital infection, n (%)	16 (18.0%)	30 (5.3%)	<0.001
TOAST classification			0.047
LAA, n (%)	20 (22.5%)	126 (22.3%)
CE, n (%)	20 (22.5%)	84 (14.9%)
SVO, n (%)	16 (18.0%)	185 (32.8%)
Others, n (%)	7 (7.9%)	40 (7.1%)
Undetermined, n (%)	26 (29.2%)	129 (22.9%)
Height-adjusted ASM (kg/m^2)	6.2±1.1	7.1±1.2	<0.001
Height-adjusted ASM group			<0.001
Q1, n (%)	8 (9%)	155 (27.5%)
Q2, n (%)	15 (16.9%)	148 (26.2%)
Q3, n (%)	18 (20.2%)	145 (25.7%)
Q4, n (%)	48 (53.9%)	116 (20.6%)
Sarcopenia (EWGSOP2), n (%)	47 (52.8%)	167 (29.6%)	<0.001
Sarcopenia (AWGS), n (%)	41 (46.1%)	133 (23.6%)	<0.001

Note: Data are presented as mean±SD or median [interquartile range] according to normal distribution.

Abbreviations: AF, atrial fibrillation; CAD, coronary artery disease; CHF, congestive heart failure; PAD, peripheral artery disease; DEXA, dual-energy absorptiometry; LDL, low-density lipoprotein; NIHSS, National Institutes of Health Stroke Scale; ICH, intracerebral hemorrhage; TOAST, Trial of ORG 10172 in Acute Stroke Treatment; LAA, large-artery atherosclerosis; CE, cardioembolism; SVO, small vessel occlusion; ASM, appendicular skeletal muscle mass; EWGSOP2, European Working Group for Sarcopenia in Older People; AWGS, Asian Working Group for Sarcopenia.

Table 2 Body Scales, Laboratory Findings, and Medications of Study Participants

	Patients with Poor Functional Outcome	Patients Without Poor Functional Outcome	P-value
BMI (kg/m^2)	23.6±3.9	24.5±3.4	0.017
MUAC (cm)	28.7±8.4	30.1±6.8	0.093
TC (cm)	44.6±7.8	47.8±8.9	0.002
Hand grip test	13.0±8.0	20.1±12.3	<0.001
Laboratory findings
White blood cells (×10^3/mm^3)	9.14±3.23	8.02±3.22	0.002
Hemoglobin (g/dL)	13.5 [12.4, 14.6]	14.2 [13, 15.3]	0.001
Platelet count (×10^3/μL)	234 [207, 292]	229 [192, 272]	0.243
Initial glucose (mg/dL)	132±29	146±42	0.040
Fasting glucose (mg/dL)	124.2±38.8	117.0±42.4	0.140
HbA1c (%)	6.1 [5.7, 7.3]	6 [5.6, 6.8]	0.273
hs-CRP (ng/mL)	0.69 [0.14, 2.31]	0.13 [0.05, 0.34]	<0.001
Total cholesterol (mg/dL)	157[136, 182]	167 [140, 194]	0.065
Triglycerides (mg/dL)	112.5±40.7	134.4±86.4	<0.001
HDL cholesterol (mg/dL)	41 [35, 51]	44 [36, 54]	0.081
LDL cholesterol (mg/dL)	106.4±40.1	112.1±54.2	0.345
eGFR (mL/min/1.73 m^2)	74.6±24.6	89.7±27.9	<0.001
Homocysteine (IU/L)	12.8 [9.7, 15.3]	10.9 [8.6, 13.8]	0.008
Discharge medication
Statins			0.006
No medication, n (%)	12 (13.5%)	32 (5.7%)
Withdrawal, n (%)	4 (4.5%)	9 (1.6%)
Add-on, n (%)	55 (61.8%)	427 (75.7%)
Continuous usage, n (%)	18 (20.2%)	96 (17.0%)
Anti-platelet agents, n (%)	65 (73.0%)	494 (87.6%)	<0.001
Anticoagulants, n (%)	26 (29.2%)	85 (15.1%)	0.001

Note: Data are presented as mean±SD or median [interquartile range] according to normal distribution.

Abbreviations: BMI, body mass index; MUAC, mid-upper arm circumference; TC, thigh circumference; hs-CRP, C-reactive protein; eGFR, estimated glomerular filtration rate; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; LDL, low-density lipoprotein.

Figure 3 (A and B) Modified Rankin Scale scores at 90 days according to the diagnosis of sarcopenia. The distribution of scores on the modified Rankin Scale is shown. Scores ranged from 0 to 6, with 0 indicating no symptoms, 1 indicating no clinically significant disability, 2 indicating slight disability (patient is able to handle own affairs without assistance but unable to carry out all previous activities), 3 indicating moderate disability (patient requires some help but is able to walk unassisted), 4 indicating moderately severe disability (patient is unable to attend to bodily needs without assistance and is unable to walk unassisted), 5 indicating severe disability (patient requires constant nursing care and attention), and 6 indicating death. (C) Modified Rankin Scale scores at 90 days according to the quartiles of height-adjusted ASM. Categorical variables were divided into four groups (Q1–4) based on the quartiles of height-adjusted ASM. Q1 implied the highest value of height-adjusted ASM and Q4 implied the lowest value.

Abbreviations: AWGS, Asian Working Group for Sarcopenia; EWGSOP2, European Working Group on Sarcopenia in Older People; ASM, appendicular skeletal muscle mass.

Table 3 Univariable and Multivariable Analyses for Poor Functional Outcome

	Crude OR (95% CI)	P-value	Adjusted OR (95% CI)^a	P-value
Height-adjusted ASM per 1 increase	0.50 (0.40–0.62)	<0.001	0.61 (0.40–0.91)	0.016
Height-adjusted ASM category		<0.001		0.056
Q1	Reference		Reference
Q2	1.96 (0.81–4.77)	0.136	0.92 (0.32–2.60)	0.868
Q3	2.41 (1.01–5.70)	0.046	1.05 (0.36–3.08)	0.924
Q4	8.02 (3.65–17.60)	<0.001	2.98 (0.85–10.49)	0.089
Sarcopenia per EWGSOP2	2.66 (1.69–4.19)	<0.001	-	-
Sarcopenia per AWGS	2.77 (1.75–4.38)	<0.001	-	-

Notes: Q1 implied the highest value of height-adjusted ASM and Q4 implied the lowest value. Multivariable models were adjusted for covariates in univariate analyses (P < 0.05) and were performed using the backward elimination method. ^aAdjusted for age, sex, BMI, WBC, Hb, hs-CRP, TG, eGFR, homocysteine, hand grip test, NIHSS, DM, AF, discharge statins, discharge antiplatelet agents, discharge anticoagulants, TOAST, symptomatic ICH, in-hospital infection, and time from admission to DEXA scan.

Abbreviations: OR, odds ratio; ASM, appendicular skeletal muscle mass; EWGS, European Working Group for Sarcopenia in Older People; AWGS, Asian Working Group for Sarcopenia; CI, confidence interval; BMI, body mass index; WBC, white blood cells; AF, atrial fibrillation; DM, diabetes mellitus; DEXA, dual-energy absorptiometry; hs-CRP, C-reactive protein; TG, triglyceride; eGFR, estimated glomerular filtration rate; Hb, hemoglobin; NIHSS, National Institutes of Health Stroke Scale; ICH, intracerebral hemorrhage; TOAST, Trial of ORG 10172 in Acute Stroke Treatment.

Figure 4 Restricted cubic spline models for the relationship between clinical outcome (poor function and mortality) and height-adjusted ASM. (A) Poor functional outcome in relation to height adjusted ASM (P = 0.008). (B) Mortality in relation to height-adjusted ASM (P = 0.860). The adjusted ORs are represented by solid lines and the 95% confidence intervals of the adjusted ORs are represented by shaded areas. The restricted cubic spline model was adjusted for age; sex; body mass index; white blood cell count; hemoglobin levels; high-sensitivity C-reactive protein level; TG; estimated glomerular filtration rate; homocysteine level; National Institute of Health Stroke Scale score; DM; AF; use of statins, antiplatelet agents, and anticoagulants; the Trial of ORG 10172 in Acute Stroke Treatment classification; symptomatic ICH; in-hospital infection; and time from admission to the dual-energy X-ray absorptiometry scan.

Abbreviations: OR, odds ratio; ASM, appendicular skeletal muscle mass.