HIGH PREVALENCE OF HYPERHOMOCYSTEINEMIA AND ASYMPTOMATIC VASCULAR-DISEASE IN SIBLINGS OF YOUNG-PATIENTS WITH VASCULAR-DISEASE AND HYPERHOMOCYSTEINEMIA

Hyperhomocysteinemia (HHC) is associated with an increased risk of ath erosclerotic vascular disease and may be inherited. Fasting and postme thionine HHC are independent risk factors that overlap to a limited ex tent. To study the familial occurrence of HHC, we investigated the pre valence of HHC (both fasting and after methionine) among 450 siblings of 167 consecutive young patients with vascular disease and postmethio nine HHC. Furthermore, all subjects with postmethionine HHC (n=125) we re invited for noninvasive vascular testing; 101 (80.8%) agreed. Of th ose with a normal postmethionine plasma level (n=325), we randomly sel ected 73 subjects for further studies; 53 agreed (72.6%). Thus, a tota l of 154 siblings underwent ultrasonography of the carotid arteries, m easurement of ankle-brachial pressure indices at rest and after a trea dmill 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 w ere 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 conclusio n, we found a high prevalence of HHC and asymptomatic vascular disease in siblings of young patients with vascular (mainly peripheral arteri al) disease and HHC. Our data raise the possibility that homocysteine does not play a major role in the early, asymptomatic phases of vascul ar disease, at least among siblings of young patients with vascular di sease.