Electrophysiologic Substrate and Risk of Mortality in Incident Hemodialysis.

The single leading cause of mortality on hemodialysis is sudden cardiac death. Whether measures of electrophysiologic substrate independently associate with mortality is unknown. We examined measures of electrophysiologic substrate in a prospective cohort of 571 patients on incident hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease Study. A total of 358 participants completed both baseline 5-minute and 12-lead electrocardiogram recordings on a nondialysis day. Measures of electrophysiologic substrate included ventricular late potentials by the signal-averaged electrocardiogram and spatial mean QRS-T angle measured on the averaged beat recorded within a median of 106 days (interquartile range, 78-151 days) from dialysis initiation. The cohort was 59% men, and 73% were black, with a mean±SD age of 55±13 years. Transthoracic echocardiography revealed a mean±SD ejection fraction of 65.5%±12.0% and a mean±SD left ventricular mass index of 66.6±22.3 g/m2.7 During 864.6 person-years of follow-up, 77 patients died; 35 died from cardiovascular causes, of which 15 were sudden cardiac deaths. By Cox regression analysis, QRS-T angle ≥75° significantly associated with increased risk of cardiovascular mortality (hazard ratio, 2.99; 95% confidence interval, 1.31 to 6.82) and sudden cardiac death (hazard ratio, 4.52; 95% confidence interval, 1.17 to 17.40) after multivariable adjustment for demographic, cardiovascular, and dialysis factors. Abnormal signal-averaged electrocardiogram measures did not associate with mortality. In conclusion, spatial QRS-T angle but not abnormal signal-averaged electrocardiogram significantly associates with cardiovascular mortality and sudden cardiac death independent of traditional risk factors in patients starting hemodialysis.

SNP43 of CAPN10 and the risk of type 2 Diabetes in African-Americans: the Atherosclerosis Risk in Communities Study.

Recently, an A-to-G variant in intron 3 (SNP43) of the calcium-activated neutral protease 10 gene (CAPN10) was identified as a possible type 2 diabetes susceptibility gene through positional cloning in Mexican-Americans. We conducted cross-sectional and prospective studies to evaluate the relation between SNP43 and type 2 diabetes and related traits in middle-aged African-American participants of the Atherosclerosis Risk in Communities Study, a population-based longitudinal study. At baseline, 269 prevalent diabetes cases and 1,159 nondiabetic control subjects were studied. Those with the G/G genotype were more likely to have diabetes than those with the A/G or A/A genotype (odds ratio [OR] 1.41, 95% CI 1.00-1.99, P = 0.05). In the prospective study, 166 of the control subjects developed incident diabetes over 9 years of follow-up. The incidence of diabetes for individuals with the G/G genotype did not differ significantly from those with at least one copy of the A allele (23.3 vs. 19.5 per 1,000 person years, P = 0.29). Pooling prevalent and incident diabetic cases together, individuals with the G/G genotype were approximately 40% more likely to have diabetes than those without (OR 1.38, 95% CI 1.04-1.83, P = 0.03). Because of the high frequency of the G allele (0.88), approximately 25% of the susceptibility to type 2 diabetes in African-Americans may be attributed to the G/G genotype at SNP43 of CAPN10, although most of the subjects with the G/G genotype did not develop diabetes over the 9 years of follow-up. We conclude from this large prospective study that the G allele of SNP43 of CAPN10 or another allele or gene that is in linkage disequilibrium with it increases susceptibility to type 2 diabetes in African-Americans.

Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus.

BACKGROUND: In persons with diabetes, chronic hyperglycemia (assessed by glycosylated hemoglobin level) is related to the development of microvascular disease; however, the relation of glycosylated hemoglobin to macrovascular disease is less clear. PURPOSE: To conduct a meta-analysis of observational studies of the association between glycosylated hemoglobin and cardiovascular disease in diabetic persons. DATA SOURCES: Search of the MEDLINE database by using Medical Subject Heading search terms and key words related to glycosylated hemoglobin, diabetes, and cardiovascular disease. STUDY SELECTION: Prospective cohort studies with data on glycosylated hemoglobin levels and incident cardiovascular disease. DATA EXTRACTION: Relative risk estimates were derived or abstracted from each cohort study that met the inclusion criteria. DATA SYNTHESIS: Adjusted relative risk estimates for glycosylated hemoglobin (total glycosylated hemoglobin, hemoglobin A1, or hemoglobin A1c levels) and cardiovascular disease events (coronary heart disease and stroke) were pooled by using random-effects models. Three studies involved persons with type 1 diabetes (n = 1688), and 10 studies involved persons with type 2 diabetes (n = 7435). The pooled relative risk for cardiovascular disease was 1.18; this represented a 1-percentage point increase in glycosylated hemoglobin level (95% CI, 1.10 to 1.26) in persons with type 2 diabetes. Results in persons with type 1 diabetes were similar but had a wider CI (pooled relative risk, 1.15 [CI, 0.92 to 1.43]). LIMITATIONS: This review largely reflects the limitations of the literature. Important concerns were residual confounding, the possibility of publication bias, the small number of studies, and the heterogeneity of study results. CONCLUSIONS: Pending confirmation from large, ongoing clinical trials, this analysis shows that observational studies are consistent with limited clinical trial data and suggests that chronic hyperglycemia is associated with an increased risk for cardiovascular disease in persons with diabetes.