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Background and Objectives: There is only limited available evidence of a relationship between total plasma homocysteine (tHcy) levels and type 2 diabetes in hypertensive subjects.Methods and Study Design: A total of 5,935 Chinese essentially hypertensive subjects were recruited by cluster sampling from 60 communities. The cases had diabetes, whereas the controls did not. Anthropometric indices and biochemical parameters were assessed using standard procedures. A multivariable analysis was performed to analyze the association of tHcy and type 2 diabetes susceptibility in hypertensive subjects.Results: The 5,241 controls (women/men: 2,716/2,625) and 594 cases (women/men: 291/303) were recruited consecutively. The level of tHcy was dose- dependently associated with type 2 diabetes in the hypertensive women subjects. After controlling for corresponding confounding factors, a significant trend was only noted in the women subjects, with odds ratios per 5 μmol/L tHcy of 1.11 (95% confidence interval (CI), 1.07-1.16) in the crude model, 1.05 (95% CI, 1.01-1.11) in model 1, and 1.07 (95% CI, 1.02-1.13) in model 2. However, no significant result was found for levels of tHcy>or=15 μmol/L vs <15 μmol/L in the men, women and all hypertensive subjects.Conclusions: When the level of tHcy was divided into quartiles, tHcy was positively associated with type 2 diabetes in hypertensive women subjects. However, when the level of tHcy was separated into hyperhomocysteinemic (>or=15 μmol/L) and normal (<15 μmol/L), no significant results were observed. [ABSTRACT FROM AUTHOR]

Abstract: The methylenetetrahydrofolate reductase (MTHFR), cystathione-β-synthase (CBS) and methionine synthase (MTR) genes interact with each other and the environment. These interactions could influence homocysteine (Hcy) and diseases contingent thereon. We determined single nucleotide polymorphisms (SNPs) within these genes, their relationships and interactions with total Hcy concentrations within black South Africans to address the increased prevalence of diseases associated with Hcy. The MTHFR 677 TT and MTR 2756 AA genotypes were associated with higher Hcy concentrations (16.6 and 10.1μmol/L; p<0.05) compared to subjects harboring the MTHFR 677 CT/CC and the MTR 2756 AG genotypes (10.5, 9.7 and 9.5μmol/L, respectively). The investigated CBS genotypes did not influence Hcy. We demonstrated interactions between the area of residence and the CBS T833C/844ins68 genotypes (p=0.005) so that when harboring the wildtype allele, rural subjects had significantly higher Hcy than their urban counterparts, but when hosting the variant allele the environment made no difference to Hcy. Between the CBS T833C/844ins68 or G9276A and MTHFR C677T genotypes, there were two-way interactions (p=0.003 and=0.004, respectively), with regard to Hcy. Subjects harboring the MTHFR 677 TT genotype in combination with the CBS 833 TT/homozygous 844 non-insert or the MTHFR 677 TT genotype in combination with the CBS 9276 GA/GG displayed higher Hcy concentrations. Therefore, some of the investigated genotypes affected Hcy; residential area changed the way in which the CBS T833C/844ins68 SNPs influenced Hcy concentrations highlighting the importance of environmental factors; and gene–gene interactions allude to epistatic effects. [Copyright &y& Elsevier]

Background: Diabetic nephropathy, especially when advanced, is associated with high prevalence of atherosclerotic cardiovascular disease in which inflammation and coagulation may play pathogenic roles. We investigated the relationships between diabetic nephropathy and coagulation, fibrinolysis, or inflammation in patients with Type 2 diabetes. Methods: We evaluated markers of inflammation and coagulation in 105 Type 2 diabetic patients with various grades of nephropathy and 49 healthy control subjects, in association with plasma total homocysteine (tHcy) measurements. Results: Plasma tHcy concentrations were significantly higher in diabetic patients than in controls (8.96±3.04 vs. 6.92±1.36 μmol/l, P<0.0001). Plasma concentrations of interleukin (IL)-6 were significantly higher in diabetic patients than in control subjects (P<0.0001). In diabetic patients, plasma tHcy correlated positively with urinary albumin, fibrinogen, IL-6 and plasmin-α2-antiplasmin complex (PAP), while plasma tHcy correlated negatively with creatinine clearance (Ccr) and protein C activity. After adjustment for Ccr, IL-6 and protein C activity were significantly associated with plasma tHcy. Plasma tHcy concentrations were significantly higher in patients with overt albuminuria than in those with normoalbuminuria or microalbuminuria, as were plasma concentrations of fibrinogen, prothrombin F1+2, and interleukin-6. Conclusions: Diabetic nephropathy is associated with elevated markers for both coagulation and inflammation. High plasma homocysteine may be a link between diabetic nephropathy and both chronic inflammation and hypercoagulability, increasing cardiovascular risk. [Copyright &y& Elsevier]

: ObjectivesThe objective of this study was to evaluate the association of high plasma levels of either C-reactive protein (CRP), lipoprotein (a) (Lp[a]) or total homocysteine (tHCY) with the long-term prognosis after successful coronary stenting (CS): BackgroundHigh plasma levels of either CRP, Lp(a) or tHCY may have an impact in coronary artery disease. However, long-term prospective data after coronary stenting (CS) are limited.: MethodsFour-hundred and eighty-three consecutive patients with either stable or unstable coronary syndromes were followed for up to three years after successful CS. The composite of cardiac death, myocardial infarction or rehospitalization for rest unstable angina, whichever occurred first, was the prespecified primary end point. Moreover, the one-year incidence of clinical recurrence of symptoms, in-stent restenosis (ISR) and progression of atherosclerosis to a significant lesion (PTSL) were additionally evaluated. PTSL was defined as an increase by at least 25% in the luminal diameter stenosis of a known nonsignificant lesion (≤50% luminal diameter stenosis) that was located in a nonintervened vessel at restudy, resulting in an angiographically significant lesion (≥70% luminal diameter stenosis).: ResultsBy the end of the follow-up, high plasma levels of either CRP or Lp(a) but not tHCY were independently associated with the primary end point. In particular, CRP ≥0.68 mg/dl (p < 0.001) or Lp(a) ≥25 mg/dl (p = 0.003) conferred a significantly increased risk. By 1 year, a CRP ≥0.68 mg/dl conferred a significantly increased risk for clinical recurrence of symptoms (p < 0.001) or PTSL (p < 0.001). None of the studied biochemical markers was related to ISR.: ConclusionsHigh plasma levels of either CRP or Lp(a) but not tHCY may be associated with a higher incidence of late adverse events after successful CS. PTSL in vessels not previously intervened upon may play a significant role in the underlying pathophysiology as opposed to ISR. [Copyright &y& Elsevier]

: ObjectivesWe evaluated the effect of therapy with folic acid and cobalamin on coronary endothelial function, expressed as a change in volumetric coronary blood flow (CBF), in hyperhomocysteinemic patients with coronary artery disease (CAD).: BackgroundHyperhomocysteinemia is an independent risk factor for CAD. The mechanism responsible for this increased risk is unclear, but it is generally assumed that hyperhomocysteinemia causes endothelial dysfunction. It is unknown whether lowering plasma homocysteine levels with folic acid and cobalamin improves coronary endothelial function in patients with hyperhomocysteinemia and symptomatic CAD.: MethodsFifteen patients scheduled for elective percutaneous transluminal coronary angioplasty (PTCA) with plasma homocysteine levels of ≥16 μmol/l were randomized for six months of treatment with folic acid 5 mg and cobalamin 400 μg daily or placebo. Coronary endothelial function was evaluated in a non-PTCA vessel using acetylcholine infusion in dosages of 10−8 M, 10−7 M, and 10−6 M. Endothelium- dependent CBF is determined using intracoronary Doppler velocity and quantitative coronary angiography at baseline and after six months.: ResultsIn the folic acid/cobalamin treated group, CBF increased after acetylcholine infusion with 96% (standard deviation 54; 95% confidence interval [CI]: 44% to 154%) compared with a decrease of 16% (standard deviation 35; 95% CI: −20% to +30%) of the CBF in the placebo-treated group (p < 0.005).: ConclusionsThis is the first prospective randomized placebo-controlled intervention study evaluating coronary endothelial function in hyperhomocysteinemic patients with CAD. Our results suggest that coronary endothelial function improves after treatment with folic acid and cobalamin. [Copyright &y& Elsevier]