Hiper-homocisteinemia como fator de risco para doença aterosclerótica coronariana em idosos

Abstract

M a i l i n g A d d r e s s : A r m ê n i o C o s t a G u i m a r ã e sThe level of homocysteine -a product of methionine demethylation -is regulated by intracellular remethylation and transsulfuration. Through remethylation homocysteine is converted back into methionine, and through transsulfuration it is converted into cystathionine, cysteine and sulfate, excreted by the kidneys. Folic acid is the substrate of the main remethylation pathway, which is catalyzed by methionine-synthase and methylenetetrahydrofolate reductase (MTHFR), and vitamin B12 (cyanocobalamin) is the cofactor. The other pathway, exclusively hepatic, is catalyzed by betainehomocysteine methyltransferase (BHMT). Transsulfuration is catalyzed by cystathionine beta-sinthase, and vitamin B6 (pyridoxine) is the cofactor. Under physiological conditions the remethylation cycle predominates, whereas under conditions of excess homocysteine an increase in the transsulfuration cycle occurs 1 .The hypothesis of hyperhomocysteinemia as a risk factor for atherosclerosis emerged from studies conducted in children with homozygotic homocystinuria, a rare genetic disorder that affects one in fi fty to two hundred thousand newborns 2 . These patients develop premature atherosclerosis (coronary, cerebral, and peripheral) and venous thromboembolic disease, dying before thirty years of age 2,3 .Other causes of hyperhomocysteinemia include the heterozygotic form of homocystinuria (one in one hundred individuals in the general population), MTHFR defi ciency (10 to 20% of the healthy population), and group B vitamin defi ciencies (folic acid, B6, B12), accounting for two thirds of the cases of hyperhomocysteinemia 1 . Causes of these defi ciencies include the use of drugs such as methotrexate, anticonvulsants (carmazepine, phenytoin, phenobarbital), theophylline, contraceptives, and smoking, alcoholism, and nutritional defi ciencies. These defi ciencies become more frequent in the elderly. This might have been a concurrent factor for the high prevalence of hyperhomocysteinemia (34%) in Taddei et al (Arq Bras Cardiol 2005;85:166-73 . A similar risk prediction occurs among coronary disease patients. In 587 coronary disease patients followed for four years, a 3.8% mortality was observed among those with homocysteinemia < 9µmol/l, and a 24.7% mortality among those with values >15µmol/l. For values between 5 and 20 µmol/L, the correlation with cardiovascular mortality increased, and was more intense for values above 15µmol/l 6 . Taddei et al's study adds important information related to the elderly (65 to 88 years of age), an age range poorly considered in clinical and epidemiological studies. The cases (84) with ≥ 70% coronary obstruction, mean age of 72.8 ± 0.46 years, presented homocysteinemia of 14.33 ± 6.84 µmol/l, whereas the control group presented levels of 11.99 ± 4.59 µmol/l, p = 0.015. In coronary obstruction cases, the mean value of homocysteinemia was close to the upper limit of the range considered normal (5 to 15 µmol/l), suggesting that it should be readj...

Homocysteine: validation and comparison of two methods using samples from patients with pulmonary hypertension

“…Homocysteine is a sulfur amino acid formed during the metabolism of methionine from diet or endogenous proteins degradation (10,18,22) . Published research hypothesized that increased plasma homocysteine levels favors the occurrence of diseases, such as acute myocardial infarction, thrombosis, and atherosclerosis disease (11,12,16,17) . Hyperhomocysteinemia can be inherited and/or acquired.…”