Biochemical and genetic risk factors for atherosclerosis in systemic lupus erythematosus

Systemic lupus erythematosus [SLE] is associated with an increase in the risk of premature cardiovascular complications caused by accelerated atherosclerosis which significantly contributes to morbidity and mortality. Carotid ultrasonography is a very sensitive imaging tool to detect premature atherosclerosis and measurements of carotid intima-media thickness [IMT] assess the extent and the severity of systemic atherosclerosis. The pathogenesis of accelerated atherosclerosis in SLE is not clear; inflammation and endothelial dysfunction in addition to genetic risk factors represent important factors in the onset of atherosclerosis. To evaluate the relation between asymmetric dimethylarginine [ADMA], high sensitive C-reactive protein [hs-CRP], monocyte chemoattractant protein-1 [MCP-1] [both serum levels and the genotypes of the MCP-1 A-2518G polymorphism] with the development of carotid atherosclerosis in patients with SLE and their relation to disease activity. In the present study, 30 non-menopause SLE female patients and 20 healthy age-matched females were included. Both patients and controls were subjected to evaluation of body mass index [BMI], IMT, serum glucose, serum lipids, hs-CRP, ADMA, MCP-1 [both serum level and gene polymorphism]. Serum ADMA, hs-CRP, and MCP-1, levels were measured by enzyme-linked immunosorbent assay. MCP-1 genomic variants were detected by polymerase chain reaction followed by restriction enzyme-fragment analysis. Values for IMT, hs-CRP, ADMA and MCP-1 were significantly higher in patients with SLE than in healthy controls with more significant increase in SLE patients with IMT >/=1 mm than in those with IMT <1 mm. Carotid IMT was significantly positively correlated with all the studied variables except for age, BMI and FBS, but significantly negatively correlated with HDL-C in all SLE patients. G/G genotype of MCP-1 A-2518G gene was more frequent in SLE patients than controls. IMT, hs-CRP, ADMA and MCP-1 from patients with G/G phenotypes were markedly higher than those from patients with the A/A genotype. In multiple regression analysis, ADMA and MCP-1 were the strongest independent determinants of IMT in SLE patients. Assessment of high levels of ADMA, hs-CRP, MCP-1, in addition to the MCP-1 A-2518G polymorphism may play a role in the pathogenesis of accelerated atherosclerosis in SLE patients and would be useful in identifying the risk of developing cardiovascular disease. Development of a novel therapy targeting ADMA and MCP-1 may have a potential role in preventing the progression of increased IMT in SLE patients

Study of some biochemical and genetic risk factors for a therosclerosis in systemic lupus erythematososus patients

The aim of this study was to evaluate the relation between asymmetric dimethylarginine [ADMA], high sensitive C-reactive protein [hs-CRP], monocyte chemoattractant protein-1 [MCP-1] [both serum levels and the genotypes of the MCP-1 A-2518G polymorphism] with the development of carotid atherosclerosis in systemic lupus erythematosus patients [SLE]. Thirty non menopause SLE female patients and twenty healthy age-matched females were included. Both cases and controls were subjected to evaluation of body mass index [BMI], intimal-medial thickness [IMT], fasting blood sugar [FBS], serum lipids. Serum ADMA, hs-CRP, and MCP-1, levels were measured by ELISA. MCP-1 polymorphism was detected by PCR-RFLP. Our results showed that values foi IMT, hs-CRP, ADMA and MCP-1, were significantly higher in SLE patients than in healthy control with more significant increase in SLE patients with IMT >/= 1 mm than those with IMT <1 mm. Carotid IMT was significantly positively correlated with all the studied variables except for age, BMI and FBS, but significantly negatively correlated with HDL-C in all SLE patients. Genotype of MCP-1 [A-25 1 8G] showed that; GIG genotype was more frequent in SLE patients than controls. IMT, hs-CRP, ADMA and MCP-l from patients with G/G phenotypes were markedly higher than patients with the A/A or A/G genotype. In multiple regression analysis, ADMA and MCP-1 were the strongest independent determinants of IMT in SLE patients. In conclusion assessment of high levels of ADMA, hs-CRP, MPC-1, in addition to the MCP-l G allele may play a role in the pathogenesis of accelerated atherosclerosis in SLE patients and would be useful in identifying the risk of developing atherosclerosis

Doppler tissue imaging: a new approach to myocardial assessment in infants of diabetic mothers and correlation to maternal diabetic controls

The study included 30 newborn infants born to diabetic mothers in the Obstetrics Department and admitted to the Neonatal Care Unit in Tanta University Hospital. Their gestational age ranged from 31-40 weeks [mean 37.7 +/- 2.13] and birth weight 2.5-5.7 kg [mean 3.61 +/- 0.7 kg]. Ten healthy newborn infants of matched gestational age and sex, born to non-diabetic mothers were included as controls. The aims of the present study were: 1] to define cardiac morphology particularly septal hypertrophy with conventional echocardiography, 2] to use Doppler Tissue Imaging [TDI] echocardiography to detect early cardiomyopathic changes in infants of diabetic mothers, 3] to correlate these data to the parameters of glycemic control of maternal diabetes and 4] to follow up cases with affected myocardium so that their prognosis is determined. Full history and thorough clinical evaluation were done. Laboratory investigations included: cord blood glucose, cord blood insulin, cord blood C-peptide and fetal glycosylated hemoglobin [Hb F1c] as well as maternal glycosylated hemoglobin [Hb A1c]. Cardiac evaluation was done using conventional M-mode, 2-D, and Doppler transmitral flow velocities as well as by TDI to assess cardiac diastolic function. Septal myocardial hypertrophy was detected in 46.66% of the studied cases. Diastolic dysfunction was found in 33.3% by conventional transmitral Doppler flow studies and in 66.6% by TDI. None of the detected myocardial abnormalities were significantly correlated to parameters of maternal diabetes control such as maternal Hb A1c, cord blood insulin, cord blood C-peptide or cord blood Hb F1c. In cases of myocardial hypertrophy or diastolic dysfunction echo-Doppler and DTI studies were repeated till disappearance of myocardial abnormalities. Macrosomia was detected in 20% of the studied cases and did not correlate significantly to maternal diabetes control parameters nor to the myocardial abnormalities. There was no sign of outflow tract obstruction or myocardial systolic dysfunction in any of our studied cases, and myocardial hypertrophy or diastolic dysfunction resolved within 6 months of follow up. We conclude that macrosomia and non-obstructive cardiomyopathy are transient phenomena that still occur in IDM irrespective to the metabolic control of maternal glycemia and it is possible that other factors contribute to such manifestations. The new technique TDI could detect more cases of myocardial diastolic dysfunction in IDM than conventional echo Doppler method and it could be used for early detection and follow up of myocardial abnormalities in IDM