Summary. Background: In recent years there has been a significant increase in the diagnosis of sudden sensorineural hearing loss (SSHL) in western, countries with an incidence of 20 of 100 000 people affected every year. No clear causes for this disease have been found thus far, but cochlear ischemia has been hypothesized in patients in whom an infectious episode or acoustic neurinoma have been excluded. Objectives: The aim of this case-control study was to investigate a number of acquired and inherited thrombophilic risk factors [antithrombin, protein C and S; factor V (FV) Leiden, FII polymorphism; lupus anticoagulant (LA); anticardiolipin (aCL) antibodies; fasting homocysteine (Hcy); lipoprotein(a) (Lp(a)); plasminogen activator inhibitor-1 (PAI-1)] in addition to cardiovascular risk factors in patients with idiopathic SSHL (ISSHL). Patients and methods: We investigated 155 patients (67 male/88 female; age: 55 (range 19-79 years) with a diagnosis of ISSHL within 30 days from the onset of symptoms, and 155 controls (67 male/ 88 female; age 54 (range 19-78 years). Fasting Hcy levels were significantly higher in patients than in controls [11.6 (6.7-60) lmol/L vs. 8.7 (5.0-24) lmol/L] as well as PAI-1 levels [19 (2-95) mg/dL vs. 14.5 (4.0-87) mg/dL]. Lupus anticoagulant was present in 13 of 155 (8.4%) patients; 20 patients (12.9%) had positivity of aCL (four IgM and 16 IgG). In no patient was a deficiency of physiological clotting inhibitors antithrombin, protein C and protein S found. No significant differences between patients and controls were observed for Lp(a) plasma levels [111 (1-1146) mg/L vs. 103 (11-695) mg/L] and for the presence of FV Leiden (4.5% vs. 4.5%) and FII variant G20210A (3.8% vs. 3.2%). Results and conclusions: Independent risk factors for ISSHL at the multivariate analysis (adjusted for age, sex and the traditional cardiovascular risk factors) were the positivity of aCL: OR 5.6 (95% CI 2.0-15.3); cholesterol levels within the second and third tertiles (with respect to the first tertile): T2 ¼ OR 4.8 (95% CI 1.9-12.6)/T3 ¼ OR 19 (95% CI 7-50.1); PAI-1 and Hcy levels within the third tertile (with respect to the first tertile): OR 20 (95% CI 7.8-78) and OR 4.0 (95% CI 2.0-8.1), respectively. These preliminary data suggest that hypercholesterolemia, hyperhomocysteinemia, elevated PAI-1 levels and anticardiolipin antibodies are associated with ISSHL, so indirectly supporting the hypothesis of a vascular occlusion in the pathogenesis of the disease.

SummaryFew and contrasting data are available on the prevalence of hemostatic risk factors in patients with central retinal vein occlusion (CRVO). Aim of this study was to investigate the metabolic and inherited risk factors for venous thrombosis in 100 CRVO patients (age: 59 yrs; range 18-77) and in 100 controls (age: 56 yrs; range 18-84). In patients homocysteine (Hcy) levels were significantly higher than in controls and were affected by the C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism (p <0.001). The prevalences of activated protein C resistance (APCR), factor V Leiden positivity, elevated PAI-1 and Lp(a) levels were significantly higher in patients with respect to controls. At multivariate analysis, only hyperhomocysteinemia (OR 11, 95% CI 3.6-36.2; p <0.0001) and elevated PAI-1 levels (OR 8.9, 95% CI 3.5-41.3; p <0.01), in addition to hypertension (OR 40.5, 95% CI 8.6-188.8; p <0.00001) and hypercholesterolemia (OR 3.1, 95% CI 1.6-20.5; p <0.05), were independent risk factors for CRVO. These data demonstrate a potential role of hemostatic risk factors in the pathophysiology of CRVO.

Complications of pregnancy have been found to be related with thrombophilic polymorphisms that explain about 30% of obstetric complications. We evaluated the angiotensin converting enzyme (ACE) and the angiotensin type 1 receptor (AT1R) gene polymorphisms in the renin-angiotensin system (RAS) as possible risk factors for fetal loss. Fifty-nine women with a history of three or more first-trimester fetal losses and 70 healthy women with a history of normal pregnancies were enrolled in this study. Thrombophilic factors, ACE insertion/deletion (I/D) and AT1R A1166C polymorphisms, prothrombin G20210A and factor V Leiden mutations were analyzed. At univariate and multivariate analysis, a significant association between ACE DD and AT1R CC genotype and fetal loss was observed. The effect of the ACE DD genotype on the risk of fetal loss was higher in AT1R C allele carriers. The prevalence of hyperhomocysteinemia (Hcy) (defined as baseline plasma levels higher than the 95% percentile; cut-off, 10.5 micromol/l per l) was significantly higher in women with fetal loss, and an association between Hcy and fetal loss was detected. All patients showed normal antithrombin, protein C, protein S, and plasminogen activator inhibitor-1 (PAI-1) values. The presence of one risk factor not associated with others was found in 33 out of 59 patients (56%); ACE DD genotype was the most prevalent risk factor. Our results identify new possible predictive markers for fetal loss in RAS polymorphisms and Hcy. Large-scale studies are warranted to attribute clinical relevance to these polymorphisms as risk factors for complicated pregnancies.