Left ventricular diastolic abnormalities other than valvular heart disease in antiphospholipid syndrome: An echocardiographic study.

BACKGROUND: Antiphospholipid syndrome (APS) can be primary or secondary to other autoimmune disorders. Besides valvular heart disease (VHD) and coronary artery disease (CAD), little is known about the impact of APS on left ventricular (LV) function. METHODS: After excluding CAD, relevant VHD and heart failure, 69 patients (mean age = 43.9 years, 40 with primary and 29 with secondary APS) were assessed by echo-Doppler. Sixty-nine heathy controls, matched for age and sex, formed the control group. APS was diagnosed in presence of at least one clinical criteria and one confirmed laboratory criteria, including lupus anticoagulant (LA) titre. The adjusted global APS score (aGAPSS), derived from the combination of risk factors for thrombosis and autoimmune-antibody profile was calculated. RESULTS: Patients had similar blood pressure and heart rate, but higher body mass index (BMI) than controls. LV mass index (p = 0.007) and left atrial volume index (p < 0.01) were greater, while early diastolic velocity (e') was lower (p = 0.003) and E/e' higher (p = 0.007) in APS. Primary APS patients had lower E/A and e' compared to both controls and secondary APS, while E/e' was higher in secondary APS than in controls. APS patients with diastolic dysfunction were older but did not differ for risk factors prevalence from those with normal/indeterminate diastolic function. In the pooled APS, LA positivity was independently associated with e' and E/e' after adjusting for age, BMI and aGAPSS in separate multivariate models. CONCLUSION: In APS, LV diastolic abnormalities are detectable. They are more pronounced in primary APS and independently associated with LA positivity.

Cyclic supplementation of 5-MTHF is effective for the correction of hyperhomocysteinemia.

Folic acid supplementation is the mainstay treatment of hyperhomocysteinemia (HHcy). However, no recommendations are currently available in regard to the optimal replacement therapy. Therefore, this prospective study hypothesized that a cyclic schedule (1 month of therapy followed by 2 months of withdrawal) of 5-methyltetrahydrofolate (5-MTHF) would reduce plasma levels of fasting total homocysteine (tHcy) in patients with mild/moderate HHcy. Patients with a new diagnosis of mild/moderate HHcy were evaluated for the methylenetetrahydrofolate reductase genotype and the presence of major features of metabolic syndrome. All enrolled subjects received a cyclic 5-MTHF oral supplementation and were reevaluated after each treatment cycle for a total of 2 years. In the 246 enrolled subjects, a significant reduction of tHcy levels occurred after the first cycle of treatment (from 31.6 ± 13.6 to 14.4 ± 5.77 µmol/L, P < .001) and during the whole 2-year follow-up (from 31.6 ± 13.6 to 12.18 ± 3.03 µmol/L, P < .001). The values of tHcy returned to reference range in 117 subjects (51.3%) after the first cycle and in 198 (86.8%) during the follow-up. The risk of failure in tHcy level normalization was increased in patients with metabolic syndrome (hazard ratio [HR], 3.49; 95% confidence interval [CI], 1.46-8.36), higher baseline tHcy levels (HR, 1.045; 95% CI, 1.018-1.073), or methylenetetrahydrofolate reductase homozygous mutation (HR, 6.59; 95% CI, 2.64-16.4). This study clearly shows that a cyclic schedule (1 month of therapy followed by 2 months of withdrawal) of 5-MTHF supplementation is able to significantly reduce tHcy levels in patients with mild/moderate HHcy.

Risk factors and recurrent thrombotic episodes in patients with cerebral venous thrombosis.

BACKGROUND: The prevalence of thrombophilic abnormalities in patients with cerebral vein thrombosis has been reported to be similar to that in patients with deep vein thrombosis of the lower limb. The role of gender-specific risk factors (pregnancy, oral contraceptives) is well established, whereas that of other acquired risk conditions is debated. MATERIALS AND METHODS: We screened 56 patients with cerebral vein thrombosis and 184 age- and sex-matched apparently healthy controls for prothrombin (factor II, FII) G20210A and factor V Leiden polymorphisms; protein S, protein C, and antithrombin deficiency; anticardiolipin antibodies; hyperhomocysteinaemia and other putative risk factors. RESULTS: The G20210A polymorphism was found in 29.1% of patients and in 5.7% of controls (odds ratio [OR] 7.1; P<0.0001; adjusted OR 12.67, P<0.0001). Frequencies of factor V Leiden and hyperhomocysteinaemia were not significantly different in patients and controls, nor were the other thrombophilic tests and some established cardiovascular risk factors, such as smoking, obesity or overweight and arterial hypertension. Conversely, 53.7% of the women who developed cerebral vein thrombosis did so while assuming oral contraceptives (OR 6.12; P<0.0001), with a further increase of risk in FII G20210A carriers (OR 48.533). Some associated diseases (onco-haematological disorders and infections) also had a significant role. Over a median 7-year follow-up, irrespective of the duration of antithrombotic treatment, 9/56 (16%) patients had further episodes of venous/arterial thrombosis. No significant risk factor for recurrent thrombosis was identified. DISCUSSION: In spite of the limitations of the sample size, our data confirm the role of FII G20210A mutation in this setting and its interactions with acquired risk factors such as oral contraceptives, also highlighting the risk of recurrent thrombosis in cerebral vein thrombosis patients.