Background-Retrospective and case-control studies show that hyperhomocysteinemia is an independent risk factor for atherosclerosis in patients with end-stage renal disease. We studied prospectively the association between total homocysteine and cardiovascular outcomes. Methods and Results-In all, 167 patients (93 men, 74 women; mean age, 56.3Ϯ14.7 years) were followed for a mean duration of 17.4Ϯ6.4 months. Cardiovascular events and causes of mortality were related to total homocysteine values and other cardiovascular risk factors. Cox regression analysis was used to identify the independent predictors for cardiovascular events and mortality. Fifty-five patients (33%) developed cardiovascular events and 31 (19%) died, 12 (8%) of cardiovascular causes. Total plasma homocysteine values ranged between 7.9 and 315.0 mol/L. Levels were higher in patients who had cardiovascular events or died of cardiovascular causes (43.0Ϯ48.6 versus 26.9Ϯ14.9 mol/L, Pϭ.02).The relative risk (RR) for cardiovascular events, including death, increased 1% per mol/L increase in total homocysteine concentration (RR, 1.01; CI, 1.00 to 1.01; Pϭ.01). Conclusions-These prospective observations confirm that hyperhomocysteinemia is an independent risk factor for cardiovascular morbidity and mortality in end-stage renal disease, with an increased RR of 1% per mol/L increase in total homocysteine concentration. Interventional studies are needed to evaluate the possible effects of modifying this risk factor in these patients. (Circulation. 1998;97:138-141.)Key Words: homocysteine Ⅲ risk factors Ⅲ kidney Ⅲ artherosclerosis Ⅲ thrombosis T he 1-year mortality rate for patients on dialysis in the United States between 1991 and 1993 was 23%, with cardiovascular and cerebrovascular diseases accounting for Ϸ47% of these deaths.1 Case-control studies show that high total plasma homocysteine (tHcy) concentrations (Ͼ14.5 mol/L) increase the risk for vascular events in these patients independent of other known risk factors such as diabetes, hypertension, hypercholesterolemia, and smoking. [2][3][4] This study examines prospectively the association between tHcy and cardiovascular events in patients with end-stage renal disease (ESRD). Methods SubjectsWe studied 176 patients with ESRD on dialysis for at least 90 days. One hundred thirty were on hemodialysis and 46 on peritoneal dialysis. We previously reported the association between homocysteine values and vascular events in these patients by use of a case-control design. 4 Total Plasma HomocysteineBaseline predialysis tHcy values were determined between March and April 1995 by the method of Jacobsen et al. 5 Risk Factors for Vascular DiseaseTotal fasting cholesterol concentrations were measured on the same samples as used for measurement of homocysteine. Hypercholesterolemia, hypertension, diabetes mellitus, and smoking status were defined in our previous report. 4 Diagnostic Criteria for Vascular EventsAll vascular events that occurred after homocysteine concentrations were originally measured in this patie...

The abnormal activation sequence resulting from right ventricular pacing accounts for only part of the reduction in EF as mid-term pacing is associated with a lower EF than short-term pacing, and EF remains depressed after cessation of AV pacing. Changes in ventricular function induced by right ventricular pacing may account for some of its associated adverse effects.

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