Letter Regarding Article, “Glucose Levels Predict Hospitalization for Congestive Heart Failure in Patients at High Cardiovascular Risk”
To the Editor:
We applaud Held et al1 for their efforts to link the effects of glycemic control and hospitalizations for congestive heart failure. Their study demonstrates that after adjustment for age and sex, a 1-mmol/L higher fasting plasma glucose was associated with a 1.10-fold increased risk of congestive heart failure hospitalization (95% confidence interval 1.08 to 1.12, P<0.0001). The association persisted after adjustment for age, sex, smoking, previous myocardial infarction, hypertension, waist-to-hip ratio, creatinine, diabetes mellitus (DM), and use of aspirin, β-blockers, or statins (hazard ratio 1.05, 95% confidence interval 1.02 to 1.08, P<0.001).1 However, they have not evaluated the incidence of atrial fibrillation (AF) or atrial flutter in this specific group of congestive heart failure patients on the basis of fasting glucose levels. Fasting glucose levels are of significant relevance given the epidemiological and pathophysiological links between DM and AF, as well as the role of deranged glucose metabolism in the risk of new-onset AF.2–4
Of note, previous studies that used stepwise models demonstrated that high fasting plasma glucose levels were associated with AF,2 and the Framingham study found that DM was a significant independent risk factor for AF, with an odds ratio (OR) of 1.4; interestingly, levels of blood glucose per se were more important predictors than the diagnosis of DM.3 In a recent large-scale study that took place over a 10-year period, AF occurred in 43 674 patients with DM (14.9%) versus 57 077 (10.3%) in the control group (P<0.0001).4 Atrial flutter occurred in 11 852 patients with DM (4%) versus 13 554 (2.5%) of the control group (P<0.0001). After multivariate analysis, DM remained independently associated with AF, with an OR of 2.13 (95% confidence interval 2.10 to 2.16, P<0.0001), and with atrial flutter (OR 2.20, 95% confidence interval 2.15 to 2.26, P<0.0001).4
Hence, DM independently contributes to the risk of new-onset AF, and this effect is further exaggerated in patients with increasing body mass index.5 As an illustrative example, although the risk of obesity with AF is recognized, Dublin et al5 demonstrated that in a population-based case-control study that included 425 subjects with new-onset AF and 707 controls, the obesity-AF link was mediated in part by DM and only minimally by other cardiovascular risk factors. Therefore, it would be pertinent to analyze the results of the study by Held et al1 from this perspective of new-onset AF. The question remains whether fasting glucose levels directly caused congestive heart failure or whether it was an effect of AF, and this merits further evaluation.
Held C, Gerstein HC, Yusuf S, Zhao F, Hilbrich L, Anderson C, Sleight P, Teo K Glucose levels predict hospitalization for congestive heart failure in patients at high cardiovascular risk. Circulation. 2007; 115: 1371–1375.
Psaty BM, Manolio TA, Kuller LH, Kronmal RA, Cushman M, Fried LP, White R, Furberg CD, Rautaharju PM. Incidence of and risk factors for atrial fibrillation in older adults. Circulation. 1997; 96: 2455–2461.