ABSTRACT
BACKGROUND: Cardiovascular complications are common in beta-thalassemia major (beta-TM), mainly attributed to increased cardiac iron depositions. Early cardiovascular involvement in patients without cardiac symptoms and without cardiac iron overload has not been adequately investigated. METHODS: Twenty six patients (11 males) with beta-TM, on chelation therapy, age 23+/-4 years without cardiac iron overload (measured by magnetic resonance imaging), and 30 age and gender matched healthy controls were included in the study. Carotid-femoral and carotid-radial pulse wave velocity (PWVc-f and PWVc-r) and augmentation index (AI) were measured by SphygmoCor device; carotid intima-media thickness; left ventricular (LV) dimensions and function; left atrial (LA) volume and function were assessed by echocardiography. RESULTS: Patients with beta-TM had higher PWVc-f (8.4+/-1.4 vs 7.2+/-1.1 m/s, p=0.002) and augmentation index (21.7+/-10.9 vs 14.7+/-9.7%, p=0.04) indicating decreased aortic elastic properties; greater LV mass index (72.0+/-13.3 vs 63.8+/-11.5 g/m(2), p=0.04) and greater LA volumes. Multivariate logistic regression analysis revealed that higher PWVc-f was independently associated with higher LV mass [OR 1.74 95%CI (1.09-2.88), p=0.026]; and greater LA dimensions [OR 1.68 95%CI (1.04-2.72), p=0.035]. CONCLUSIONS: In the absence of cardiac iron overload, asymptomatic patients with beta-TM demonstrated aortic stiffening associated with increased LV mass and LA enlargement. These alterations may represent signs of early cardiovascular involvement.
Subject(s)
Aortic Diseases , Hypertrophy, Left Ventricular , beta-Thalassemia/complications , Adult , Aorta/diagnostic imaging , Aorta/pathology , Aortic Diseases/diagnostic imaging , Aortic Diseases/etiology , Aortic Diseases/pathology , Blood Flow Velocity , Brachial Artery/diagnostic imaging , Brachial Artery/pathology , Carotid Arteries/diagnostic imaging , Carotid Arteries/pathology , Echocardiography , Elasticity , Female , Humans , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/etiology , Hypertrophy, Left Ventricular/pathology , Iron Overload , Linear Models , Logistic Models , Magnetic Resonance Imaging , Male , Multivariate Analysis , Pulsatile Flow , Radial Artery/diagnostic imaging , Radial Artery/pathology , Young AdultABSTRACT
Matrix metalloproteinases (MMPs) appear to play a central role in atherosclerotic plaque remodeling; however, the relationship of increased MMP levels in inducing carotid plaque instability remains controversial. We investigated whether gelatinases (MMP-2 and MMP-9) are implicated in carotid intraplaque hemorrhage and whether their serum levels may predict local carotid events. Nineteen carotid specimens obtained by endarterectomy of 18 patients were studied. The presence of gross intraplaque hemorrhage was recorded before plaque removal and quantification of MMP-2, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) in extracts from (1) the more stenotic area of the plaque, (2) the periphery of the plaque, and (3) serum was performed by enzyme-linked immunosorbent assay. MMP-9 levels measured in extracts from the most stenotic area were significantly higher in patients with intraplaque hemorrhage (p = 0.007); however, serum levels showed no difference, while those taken from the periphery of the lesion were also increased but did not reach a statistically significant level (p = 0.06). An increase in MMP-2 values was observed in the periphery of the lesion (p = 0.04) in patients with intraplaque hemorrhage. TIMP-1 levels showed no difference between the two groups regardless of the presence or absence of intraplaque hemorrhage. No significant differences in MMP levels were observed between symptomatic and asymptomatic patients. Increased levels of MMPs, particularly MMP-9, have been implicated in carotid intraplaque hemorrhage without their serum levels being predictive of local events.