Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial occlusive disease.

Abstract

A micromethod adapted for automated determinations was used to measure basal plasma levels of homocyst(e)ine [H(e)J. These levels included the sum of free and bound forms of homocysteine, its disulfide oxidation product, homocystine, and the homocysteine-cysteinemixed disulfide. Two groups of subjects were studied: apparently healthy individuals (n = 103) and patients with peripheral arterial occlusive disease (PAOD) (n= 47). Because age in PAOD patients was higher than in control subjects, the control subjects were subdivided into younger and older groups (aged 60 years or less and more than 60 years, respectively). The H(e) levels in the younger groups were 11.18±3.58 (mean+SD, expressed as homocysteine) and 8.58 +2.82 nmol/ml in men and women, respectively; in the older groups, the levels were 10.74±2.16 and 9.04+2.16 nmol/ml in men and women, respectively. There was a positive correlation of H(e) levels with age in the younger control women (r=0.373; p <0.02); no significant correlations were present in the other three control groups. Levels of H(e) in PAOD patients (15.44±5.76 and 17.04±8.26 nmol/ml in men and women, respectively) were significantly higher than those indicated above in the older controls. Next, the PAOD patients were assigned to two subgroups: 1) those with normal levels of H(e) (within two standard deviations of the mean of the control values) and 2) those with elevated levels of H(e). Age, cholesterolemia, and the prevalence of smoking and diabetes were similar in both subgroups. These results suggest that elevated plasma H(e) is an independent risk factor for arterial occlusive disease. (Circulation 1989;79:1180-1188

Flow-Induced Constriction in Arterioles of Hyperhomocysteinemic Rats Is Due to Impaired Nitric Oxide and Enhanced Thromboxane A 2 Mediation

“…Our previous studies showed that plasma homocysteine concentrations in rats fed a methionine diet are increased by Ϸ3-fold, 10,11 reaching a concentration similar to that shown to be associated with an increased risk of vascular disease in humans. 1,4,5,18 In these studies, we demonstrated that acetylcholine and histamine-induced, NO-mediated endothelial dilations are reduced in skeletal muscle arterioles of HHcy rats. 10 In addition, bradykinin induces an enhanced constriction of HHcy arterioles via increased TXA 2 production in the endothelium.…”

“…Key Words: homocysteine Ⅲ arteriole Ⅲ flow-induced response Ⅲ endothelium Ⅲ nitric oxide Ⅲ thromboxane A 2 I ncreasing epidemiological and experimental evidence suggests that an elevated plasma level of homocysteine is associated with the development of peripheral arterial disease. [1][2][3][4][5] Homocysteine is a sulfur-containing amino acid that is formed during the metabolism of the essential amino acid methionine. 4 Plasma homocysteine concentration can be increased through alterations in genetic and nutritional factors, such as various enzyme (cystathione-␤-synthase, methyltetrahydrofolate reductase) abnormalities and deficiency of vitamins (folic acid, cyanocobalamin, pyridoxal phosphate), all of which participate in the metabolism of homocysteine and methionine (for further references, see Lentz et al 4 ).…”

Impaired Anticoagulant Response to Infusion of Thrombin in Atherosclerotic Monkeys Associated With Acquired Defects in the Protein C System

“…22,23 Total plasma cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were measured using methods established by the Lipid Research Centers and standardized by the Centers for Disease Control and Prevention, Atlanta, Ga. 24 …”

Polymorphism of the Methionine Synthase Gene

“…Key Words: homocysteine Ⅲ methionine synthase Ⅲ methylenetetrahydrofolate reductase Ⅲ genetics R ecent reports indicate that even modest increases in plasma homocyst(e)ine levels can lead to an increased risk of occlusive vascular disease. [1][2][3][4][5][6][7][8][9] Homocysteine is a sulfur amino acid generated as an intermediate product in methionine metabolism and occurs at the intersection of 2 metabolic pathways, remethylation and transsulfuration. These pathways are known to be regulated by 3 key enzymes: cystathionine ␤-synthase, 5-methyltetrahydrofolate:homocysteine methyltransferase (methionine synthase), and 5,10-methylenetetrahydrofolate reductase (MTHFR), as well as by the cofactors folate, vitamin B 6 , and vitamin B 12 .…”