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Background: Mild hyperhomocysteinemia, a risk factor for vascular disease, is common in the general population. Offspring of hypertensive parents, have been reported to have endothelial dysfunction compared with the offspring of normotensive parents. This does not occur simply as a consequence of increased blood pressure but may rather be a cause of the condition. Carotid intima-media thickness (CIMT) is the second valid marker of generalized atherosclerosis.Objectives: To study the relation of sonographically determined carotid & femoral intima-media wall thickness and enothelial function to serum homocysteine (Hcy) concentrations in offspring of hypertensive parents.Methods: Plasma homocysteine levels were measured in normotensive siblings for hypertensive patients (n=78) and normotensive controls (n=30). All subjects were non-diabetic, had no past history of myocardial infarction, stroke or peripheral vascular disease and had normal renal functions. Brachial artery flow-mediated (FMD) and nitroglcerine-mediated vasodilatation (NTGMD) were measured to assess endothelial function. Also carotid and femoral intima-media thickness that reflect vascular disease were examined.Results: Hcy level was found to be significantly higher in normotensive siblings when compared to controls (13.7 ± 4.5 versus 7.8 ± 2.7 micromol/L, p<0.001). CIMT and femoral IMT were significantly increased in siblings in comparison to control (0.72 ± 0.6 mm versus 0.58±0.6 mm, P<0.01 and 0.71± 0.07 versus 0.54±0.06 mm, P<0.001 respectively). ΔFMD and FMD% that reflect endothelial dysfunction but not ΔNTGMD & NTGMD% were significantly lower in siblings compared with control(0.69 ± 0.42 mm versus 1.7 ± 0.27 mm and 20% versus 55% respectively, P<0.01 for each).Conclusion: Plasma homocysteine levels are significantly elevated in normotensive siblings for parents with essential hypertension. Increased carotid and femoral IMT in addition to endothelial dysfunction may serve as results of hyperhomocysteinemia that create the potential cardiovascular risk.