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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2655-2662.)
© 1997 American Heart Association, Inc.

Articles

High Prevalence of Hyperhomocysteinemia and Asymptomatic Vascular Disease in Siblings of Young Patients With Vascular Disease and Hyperhomocysteinemia

Sylvia C. de Jong; Coen D. A. Stehouwer; Albert J. C. Mackaay; Michiel van den Berg; Ellen J. Bulterijs; Frans C. Visser; Jeroen Bax; ; Jan A. Rauwerda

From the Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, The Netherlands (S.C. de J., C.D.A.S., A.J.C.M., M. van den B., F.C.V., J.A.R.) and the Departments of Surgery, (S.C. de J., A.J.C.M., M. van den B., E.J.B., J.A.R.), Internal Medicine, (C.D.A.S.), Cardiology, (F.C.V., J.B.), Academisch Ziekenhuis Vrije Universiteit, Amsterdam, The Netherlands

Correspondence to Dr S.C. de Jong, Department of Surgery, Academisch Ziekenhuis Vrije Universiteit, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, The Netherlands.

Abstract Hyperhomocysteinemia (HHC) is associated with an increased risk of atherosclerotic vascular disease and may be inherited. Fasting and postmethionine HHC are independent risk factors that overlap to a limited extent. To study the familial occurrence of HHC, we investigated the prevalence of HHC (both fasting and after methionine) among 450 siblings of 167 consecutive young patients with vascular disease and postmethionine HHC. Furthermore, all subjects with postmethionine HHC (n=125) were invited for noninvasive vascular testing; 101 (80.8%) agreed. Of those with a normal postmethionine plasma level (n=325), we randomly selected 73 subjects for further studies; 53 agreed (72.6%). Thus, a total of 154 siblings underwent ultrasonography of the carotid arteries, measurement of ankle-brachial pressure indices at rest and after a treadmill exercise test, and exercise electrocardiographic stress testing. We observed HHC after methionine, fasting, or both, in 27.8% (95% CI, 23.7 to 31.9), 11.1% (CI, 8.2 to 14.0) and 8.7% (CI, 6.1 to 11.3) of the siblings. Abnormal peripheral, coronary, or carotid artery tests were observed in 35.7% (CI, 28.1 to 43.3), 7.1% (CI, 3.0 to 11.2), and 7.1% (CI, 3.0 to 11.2). Univariate and multivariate analyses revealed weak evidence of a relationship with homocysteine levels.

In conclusion, we found a high prevalence of HHC and asymptomatic vascular disease in siblings of young patients with vascular (mainly peripheral arterial) disease and HHC. Our data raise the possibility that homocysteine does not play a major role in the early, asymptomatic phases of vascular disease, at least among siblings of young patients with vascular disease.

Key Words: hyperhomocysteinemia • vascular testing • vascular disease

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