healthmedicinet

CAD is a multifactorial disease, and these factors are called risk factors include a large number of traditional cardiovascular disease risk factors such as smoking, elder age, male, hypertension, lipid metabolism disorders (hyperlipidemia), glucose metabolism disorders (diabetes mellitus and insulin resistance), overweight and obesity, and some newly risk factors such as HHcy and inflammatory markers. Our previous study found that elevated serum myeloperoxidase activities are significantly associated with the prevalence of acute coronary syndrome (AMI and UAP) and high LDL-C levels in CAD patients, The interaction between multiple metabolic parameters, inflammatory markers and traditional cardiovascular risk factors promoted the occurrence and development of CAD [26]. This study revealed that high Hcy group in CAD patients were characterized by smoking, diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, low HDL-C and high LDL-C. These findings suggest that Hcy and traditional cardiovascular risk factors may be synergistically prompt the occurrence and development of CAD.

Vascular endothelium has important regulatory functions in the cardiovascular system and a pivotal role in regulating blood flow, mediating vasodilatation, coagulation reactions, platelet activation, leukocyte adhesion, and vascular muscle function [27]. During the last two decades, extensive experimental evidence, both in vitro and in vivo, indicates that Hcy is an independent risk factor for cardiovascular disease and elevated serum Hcy level is associated with CAD events [28–30]. Homocysteine Studies Collaboration research revealed that elevated approximately 3 ?mol/L Hcy will increase about 10% risk of cardiovascular events [31]. Humphrey et al. [32] analyzed has also demonstrated that increased 5 ?mol/L Hcy concentration will increase approximately 20% risk of CAD events.

In present study, AMI patients had the highest serum concentrations of Hcy, and UAP patients were a little lower than AMI but were the second highest, and SAP patients had the third higher level of Hcy, which were significantly higher than controls. Compared to SAP patients, patients with AMI and UAP had higher Hcy levels with approximately average elevated (4-5) ?mol/L, while SAP patients were approximately higher 8 ?mol/L than controls. CAD categories were positively correlated with Hcy, TC, TG, LDL-C, age, SBP, DBP, BMI, gender and smoking. Among them, Hcy showed the highest positively correlated with CAD categories. The prevalence of high Hcy progressively increased from controls, to SAP, to UAP, and to AMI. The present provide the valuable evidence that high concentrations of Hcy are significantly correlated with CAD categories. The more serious patients with CAD suffer, the more higher concentration their Hcy have.

Folic acid and vitamin B₁₂ as two vital regulators play an important role in regulating the metabolic process of Hcy [33, 34]. In biological cells, Hcy is derived from methionine after its utilization as a methyl group donor in biological methylation reactions. However, approximately 50% Hcy is produced to remethylate back to methionine by the transmethylation of methionine, while 50% Hcy metabolize via transsulfuration to cystathionine [35]. In this cycle, methionine is activated by condensation with adenosine triphosphate (ATP) to give the methyl donor, S-adenosylmethionine (SAM). SAM is transformed into S-adenosylhomocysteine (SAH) by donating its methyl group to the substrates of methylation reactions. Subsequently, SAH gives rise to Hcy in a reversible reaction that favors SAH over Hcy production [36]. Methyl-tetra-hydrofolic acid (MTHF) which derivate of folic acid provide methyl to remethylated of Hcy. Vitamin B₁₂ is agon of methionine synthetase that catalyzed this reaction and participate transfusion of methyl [13]. Folic acid deficiency will prevent remethylation of Hcy because of raw material deficiency. Moreover, Folic acid deficiency will also influence the production of MTHF through to affect activity of methylene tetrahydrofolate reductase (MTHFR) [37, 38].

We found that besides HDL-C, CAD categories were significantly negative correlated with folic acid, vitamin B₁₂. the levels of folic acid and vitamin B₁₂ in AMI and in UAP patients were obviously lower compared to those in SAP and controls. The prevalence of low folic acid and vitamin B₁₂ progressively increased from controls, to SAP, to UAP, and to AMI. Moreover, more than or close to half of the CAD patients with high Hcy had low folic acid or vitamin B₁₂ levels, 7 times or 5 times higher than that in CAD patients with normal-low Hcy concentrations, respectively. Hcy was strongly moderate negative correlation with folic acid and vitamin B₁₂. Our results confirmed that serum folic acid and vitamin B₁₂ influence Hcy metabolism as cosubstrate and cofactor, respectively. Low serum levels of folic acid and vitamin B₁₂ are also significantly correlated with CAD categories.