Elevated Fasting Total Plasma Homocysteine Levels and Cardiovascular Disease Outcomes in Maintenance Dialysis Patients

Abstract

There is an excess prevalence of hyperhomocysteinemia in dialysis-dependent end-stage renal disease (ESRD) patients. Cross-sectional studies of the relationship between elevated total homocysteine (tHcy) levels and prevalent cardiovascular disease (CVD) in this patient population suffer from severe methodologic limitations. No prospective investigations examining the association between tHcy levels and the subsequent development of arteriosclerotic CVD outcomes among maintenance dialysis patients have been reported. To assess whether elevated plasma tHcy is an independent risk factor for incident CVD in dialysis-dependent ESRD patients, we studied 73 maintenance peritoneal dialysis or hemodialysis patients who received a baseline examination between March and December 1994, with follow-up through April 1, 1996. We determined the incidence of nonfatal and fatal CVD events, which included all validated coronary heart disease, cerebrovascular disease, and abdominal aortic/lower-extremity arterial disease outcomes. After a median follow-up of 17.0 months, 16 individuals experienced at least one arteriosclerotic CVD event. Cox proportional-hazards regression analyses, unadjusted and individually adjusted for creatinine, albumin, and total cholesterol levels, total/HDL cholesterol ratio, dialysis adequacy/residual renal function, baseline CVD, and the established CVD risk factors (ie, age, sex, smoking, hypertension, diabetes/glucose intolerance, and dyslipidemia) revealed that tHcy levels in the upper quartile (> or = 27.0 mumol/L) versus the lower three quartiles (< 27.0 mumol/L) were associated with relative risk estimates (hazards ratios, with 95% confidence intervals for the occurrence of (pooled) nonfatal and fatal CVD ranging from 3.0 to 4.4; 95% confidence intervals (1.1-8.1) to (1.6-12.2). We conclude that the markedly elevated fasting tHcy levels found in dialysis-dependent ESRD patients may contribute independently to their excess incidence of fatal and nonfatal CVD outcomes.

A Low, Rather than a High, Total Plasma Homocysteine Is an Indicator of Poor Outcome in Hemodialysis Patients

“…Association between tHcy and hospitalization frequency, i.e., total number of hospital admissions, over the 12-month follow-up period, as reflected by hospitalization rate ratios (RR) and 95% confidence intervals a Moreover, in the aforementioned study, neither serum albumin nor CRP predicted mortality, whereas our study did. Hence, the reason that our current study and three other recent studies (10 -12) found the opposite association as compared with a few others (7,9,42) could be due to differences in race or ethnicity, comorbidities, the prevalence of diabetes, and/or study designs. Moreover, publication bias may have handicapped or delayed reporting such paradoxical findings in dialysis patients, because the investigators' first impression upon encountering results with inverse association between tHcy and mortality may be to consider them erroneous or flawed and hence to avoid reporting them (15,43,44).…”

“…This possibly flawed reasoning is known in epidemiology as ecological fallacy, in that inferences are based on comparing populations rather than individuals (41). However, a few stud- ies indeed have shown a positive correlation between tHcy and poor outcome (7,9,42), but they are subject to restrictions. For instance, in the study by Mallamaci et al (7), although tHcy was found to be positively associated with cardiovascular outcome in 175 MHD patients who were followed for an average of 29 mo, it failed to independently predict survival.…”

Randomized Trial of Folic Acid for Prevention of Cardiovascular Events in End-Stage Renal Disease

“…In ESRD, mean total homocysteine levels (tHcy) are commonly elevated, and the role of homocysteine as risk factor has been suggested in some small prospective studies (3)(4)(5). However, some studies in ESRD have observed an inverse relationship between tHcy and cardiovascular disease (6,7).…”

To Analyse the Pattern of Lipid Profile in Patients of Chronic Kidney Disease

“…All these abnormalities have been identified to be a sole risk factor for atherosclerosis, [12][13][14][15] with poor results with dialysis treatment. [16] An increased plasma homocysteine concentration is more among hemodialysis patients, [17,18] and also considered to be risk factor for atherosclerotic complications of ESRD. [19][20][21][22] CKD is associated with increase in triglyceride level, due to increase in VLDL, chylomicrons, and its remnants.…”