Relationship Between Diastolic Dysfunction and Atherosclerosis and Vascular Calcification in Hemodialysis Patients: Diagnostic Potential of the Cardio-Ankle Vascular Index.

Diastolic dysfunction (DD) commonly causes heart failure with preserved ejection fraction (EF). Here, we examine associations between DD severity and atherosclerosis/vascular calcification in hemodialysis patients. Echocardiography was performed on 101 patients undergoing hemodialysis therapy. Twelve patients (EF < 50% or chronic atrial fibrillation) were excluded; DD of the remaining 89 patients was classified into four grades. We then investigated the relationship between their DD grades and the cardio-ankle vascular index (CAVI), ankle-brachial pressure index (ABI), toe-brachial pressure index (TBI), and aortic calcification area index (ACAI). Seventy-seven patients (86.5%) with EF ≥ 50% had DD. Associations with advanced age and comorbid diabetes mellitus and cardiovascular disease were observed. The CAVI, TBI, and ACAI, but not ABI, increased proportionally with DD grades. Thus, many hemodialysis patients developed DD, with systolic function maintained. Strong associations between DD grades and progression of both atherosclerosis and vascular calcification could be inferred.

Serum level of macrophage colony-stimulating factor and atherosclerosis in hemodialysis patients.

BACKGROUND/AIMS: Atherosclerosis and its related complications are the leading causes of death in the hemodialysis (HD) population. Aortic calcification index (ACI), intima-media thickness (IMT) in common carotid arteries, and electrocardiogram (ECG) are atherosclerotic parameters that are available in usual clinical outpatient settings. Macrophage colony-stimulating factor (MCSF) and monocyte chemoattractant protein-1 (MCP-1) play important roles in atherosclerosis. METHODS: We performed a cross-sectional study of 133 outpatients on maintenance HD in a single HD outpatient center. We measured serum levels of MCSF and MCP-1, determined the ACI using computed tomography scan and the IMT using high-sensitivity ultrasound B-mode imaging, and performed ECGs. RESULTS: Stepwise multivariate regression analysis revealed that the MCSF level correlated with age-adjusted mean and maximum IMT (F = 10.811, p = 0.001, and F = 6.784, p = 0.010, respectively) as well as with the diastolic blood pressure. Age and MCSF level (F = 4.866, p = 0.029) were independently related to an increased ACI. High-sensitivity C-reactive protein (hsCRP) was not related to IMT and ACI. The hsCRP level (chi2 = 5.002, p = 0.025) correlated with ECG changes followed by MCSF (chi2 = 3.940, p = 0.047). MCP-1 was not related to the above atherosclerotic parameters. CONCLUSION: A head-to-head comparison between MCSF and hsCRP revealed that MCSF was more closely associated with IMT and ACI in HD patients.

Methylenetetrahydrofolate reductase genotype, vitamin B12, and folate influence plasma homocysteine in hemodialysis patients.

Hyperhomocysteinemia, a well-recognized cardiovascular risk factor, is frequent in hemodialysis (HD) patients. A common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, C-->T substitution at nucleotide 677, is associated with homocysteine (Hcy) level elevation. We examined whether three factors involved in the methionine cycle could influence plasma Hcy concentrations in HD patients: MTHFR polymorphism; vitamin B12, an essential cofactor; and folate, the substrate. In a cross-sectional study, serum vitamin B12, folate, and plasma Hcy were measured and MTHFR genotyping was performed in 534 HD patients. Effects of MTHFR genotypes, vitamin B12, and folate on plasma Hcy levels were examined in 450 HD patients not administered vitamin B12 or folate. To examine the effect of vitamin B12 on plasma Hcy concentrations, we compared plasma Hcy concentrations in HD patients with and without vitamin B12 supplementation. To examine whether functional vitamin B12 deficiency exists even in HD patients with normal vitamin B12 concentrations, 15 HD patients (serum vitamin B12 concentrations, 250 to 2,100 pg/mL) were treated with vitamin B12 (mecobalamin, 1.5 mg/d) for 8 weeks. Serum concentrations of methylmalonic acid (MMA) and vitamin B12 were measured. Hcy levels were higher and folate levels were lower in patients with the TT and CT genotypes compared with patients with the CC genotype. Analysis of covariance to determine independent predictors of high Hcy levels identified low serum vitamin B12 and folate levels and high albumin (Alb) levels in CC-genotype patients, low folate levels and high Alb levels in CT-genotype patients, and low folate levels in TT-genotype patients. Plasma Hcy levels were lower in CC- and CT-genotype patients with vitamin B12 supplementation than in those without supplementation. Vitamin B12 supplementation for 8 weeks significantly reduced MMA concentrations in HD patients with normal serum vitamin B12 concentrations. These results indicate that MTHFR genotype influences the correlation of Hcy level with vitamin B12 and folate levels in HD patients. Functional vitamin B12 deficiency may exist, even in HD patients with normal vitamin B12 concentrations. The efficacy of vitamin B12 and folate supplementation on plasma Hcy levels may depend on MTHFR genotype.