Ischemia-modified albumin as a marker of vascular dysfunction and subclinical atherosclerosis in β-thalassemia major

Figures & data

Table 1. Laboratory and radiological data of the studied patients with β-TM and healthy controls.

Variable	β-TM (n = 45)	Healthy controls (n = 30)	p value
WBC count (×10^9/l), median (IQR)	10.7 (8.1–17.5)	7.1 (5.3–8.6)	<0.001
Hemoglobin (g/dl), mean ± SD	7.62 ± 1.14	12.4 ± 3.4	<0.001
HbF (%), median (IQR)	62.0 (27.3–80.0)	0.6 (0.4–0.9)	<0.001
Serum albumin (mg/dl), mean ± SD	3.97 ± 0.45	4.5 ± 0.51	<0.001
Total bilirubin (mg/dl), mean ± SD	1.34 ± 0.62	0.6 ± 0.15	<0.001
Indirect bilirubin (mg/dl), median (IQR)	0.8 (0.5–1.0)	0.4 (0.3–0.5)	0.002
ALT(IU/l), median (IQR)	33 (20–65)	21 (13–30)	<0.001
AST(IU/l), median (IQR)	38 (30–65)	18 (10–35)	<0.001
Lactate dehydrogenase (IU/l), median (IQR)	446 (195–604)	330 (280–410)	0.01
Serum ferritin (µg/l), median (IQR)	2291 (1263–4045)	45 (27–60)	<0.001
IMA (U/ml), median (IQR)	18 (13–40)	4 (3–5)	<0.001
MDA (nmol/ml), median (IQR)	30 (20–45)	10 (7–15)	<0.001
EF (%), mean ± SD	64.5 ± 4.5	–	–
FS (%), mean ± SD	35.2 ± 3.3	–	–
LVESD (mm), mean ± SD	3.0 ± 0.47	–	–
LVEDD (mm), mean ± SD	4.58 ± 0.64	–	–
TRV (m/s), mean ± SD	2.48 ± 0.42	–	–
Mean CIMT (mm), mean ± SD	0.47 ± 0.1	0.33 ± 0.02	<0.001

β-TM: β-thalassemia major; WBC: white blood cell; Hb: hemoglobin; ALT: alanine aminotransferase; AST: aspartate aminotransferase; IMA: ischemia-modified albumin; MDA: malondialdehyde; EF: ejection fraction; FS: fractional shortening; LVESD: left ventricle end systolic diameter; LVEDD: left ventricle end diastolic diameter; TRV: tricuspid regurgitant jet velocity; CIMT: carotid intima media thickness; IQR: interquartile range.

Table 2. Clinical and radiological data of β-TM patients with mean serum ferritin above or lower than 2500 µg/l.

Variable	Ferritin <2500 (µg/l) (n = 24)	Ferritin ≥2500 (µg/l) (n = 21)	p value
Age (years)	14.8 ± 1.9	13.7 ± 3.6	0.055
Sex, n (%)
Males	14 (58.3)	11 (52.4)	0.688
Females	10 (41.7)	10 (47.6)
BMI SDS	0.32 (0.13–0.56)	0.28 (0.17–0.39)	0.581
Transfusion index (ml/kg/year)	320 (240–480)	470 (380–530)	0.012
Disease duration (years)	13.6 ± 2.7	12.2 ± 3.7	0.168
EF (%)	66.7 ± 4.5	60.0 ± 4.3	0.009
FS (%)	36.0 ± 3.9	34.6 ± 2.6	0.208
LVESD	3.06 ± 0.50	2.91 ± 0.42	0.373
LVEDD	4.64 ± 0.59	4.51 ± 0.71	0.578
TRV (m/s)	2.33 ± 0.42	2.58 ± 0.4	0.047
Mean CIMT (mm)	0.45 ± 0.09	0.49 ± 0.11	0.023

BMI: body mass index; SDS: standard deviation score; EF: ejection fraction; FS: fractional shortening; LVESD: left ventricle end systolic diameter; LVEDD: left ventricle end diastolic diameter; TRV: tricuspid regurgitant jet velocity; CIMT: carotid intima media thickness. Data were expressed as mean ± SD using Student’s t test for comparisons or as median (IQR) using Mann–Whitney test for comparisons unless specified as number (percentage) where Chi-square test (χ²) was used.

Figure 1. Ischemia modified albumin (IMA) and malondialdehyde (MDA) levels in patients with β-thalassemia major and controls.

Table 3. IMA and MDA levels in relation to clinical characteristics of β-TM patients.

Variable	Patients number	IMA (U/ml)		MDA (nmol/ml)
		Median (IQR)	p value	Median (IQR)	p value
Sex
Male	25 (55.6)	15 (12.5–25)	0.081	30 (20–50)	0.918
Female	20 (44.4)	17.5 (15–60)		30 (20–45)
Family history
Positive	27 (60)	17.5 (15–80)	0.232	30 (20–55)	0.675
Negative	18 (40)	16.25 (12.5–30)		30 (15–45)
Puberty
Delayed	30 (66.7)	18.75 (15–80)	0.064	32.5 (20–60)	0.344
Appropriate	15 (33.3)	15 (12.5–17.5)		25 (20–35)
Splenectomy
Positive	24 (53.3)	17.5 (15–77.5)	0.097	30 (20–45)	0.982
Negative	21 (46.7)	15 (1.5–20)		30 (20–45)
Viral hepatitis
Positive	23 (51.1)	17.5 (13.75–80)	0.231	32.5 (25–55)	0.081
Negative	22 (48.9)	17.5 (12.5–20)		23 (18–40)
Heart disease
Positive	9 (20)	17.5 (15.0–77.5)	0.017	30 (20–50)	0.385
Negative	36 (80)	12.5 (12.5–17.5)		23 (20–45)
PH risk
Positive	10 (22.2)	80 (17.5–100)	<0.001	30 (20–65)	0.913
Negative	35 (77.8)	15 (12.5–20)		27.5 (20–45)
Serum ferritin (µg/l)
≥2500	24 (53.3)	60 (2–90)	0.001	40 (30–65)	0.001
<2500	21 (64.7)	15 (12.5–17.5)		20 (16.5–35)
Compliance to chelation
Good	18 (40)	15 (12.5–17.5)	0.009	20 (20–35)	0.02
Poor	27 (60)	20 (12.5–80)		40 (25–65)

β-TM: β-thalassemia major; PH risk: pulmonary hypertension risk. Data were expressed as median (IQR) using Mann–Whitney test for comparisons.

Figure 2. Receiver operating characteristic (ROC) curve analysis of the cut off value of IMA for detection of PH risk (A) and for heart disease (B) among patients with β-thalassemia major.

Figure 3. Correlation between IMA and serum ferritin (A) and MDA levels (B) among patients with β-thalassemia major.

Figure 4. Correlation between IMA echocardiographic parameters among patients with β-thalassemia major. (A) IMA and ejection fraction. (B) IMA and tricuspid regurgitant jet velocity.

Figure 5. Correlation between IMA and MDA and carotid intima media thickness among patients with β-thalassemia major.

Table 4. Quadratic non-linear regression analysis for variables related to increased IMA levels in patients with β-thalassemia major.

Variable	Unstandardized		Standardized	p value
	Coefficients		Coefficients
	B	Standard Error	Beta
Disease duration (year)	1.135	8.242	0.107	0.891
WBC (×10^9/l)	1.803	0.603	1.396	0.005
ALT (IU/l)	0.236	0.207	0.483	0.261
AST (IU/l)	0.433	0.287	1.007	0.144
Serum ferritin (µg/l)	0.016	0.002	1.844	<0.001
MDA (nmol/ml)	0.891	0.396	0.665	0.03
EF (%)	−70.374	23.004	−8.485	0.004
TRV (m/s)	317.218	215.864	2.988	0.164
Mean CIMT (mm)	647.511	141.315	1.670	0.023

WBC: white blood cell; ALT: alanine aminotransferase; AST: aspartate aminotransferase; MDA: malondialdehyde; EF: ejection fraction; TRV: tricuspid regurgitant jet velocity; CIMT: carotid intima media thickness.