Key result
Higher HbA1c/HDL-C ratio shows borderline link to increased mortality in AF.
Why the study?
Is a higher baseline HbA1c/HDL-C ratio associated with increased all-cause mortality in ICU patients with atrial fibrillation?
Cohort (n=2,573)
No
Is a higher baseline HbA1c/HDL-C ratio associated with increased all-cause mortality in ICU patients with atrial fibrillation?
In ICU patients with atrial fibrillation, the HbA1c/HDL-C ratio shows only a borderline independent association with all-cause mortality and offers minimal incremental prognostic value beyond conventional clinical risk factors.
Should not yet inform mortality risk assessment in AF; leaves open whether the ratio adds prognostic value beyond standard factors.
Background Atrial fibrillation (AF) is one of the most prevalent cardiac arrhythmias worldwide, with its incidence continuing to rise. The ratio of glycated hemoglobin to high-density lipoprotein cholesterol (HbA1c/HDL-C ratio, HHR) is a novel composite biomarker that reflects the combined glucose–lipid metabolic status and has demonstrated prognostic value across a range of metabolic disorders. Leveraging the MIMIC-IV database, we investigated the association between the HHR and all-cause mortality in patients with AF. Methods We enrolled 2,573 patients with AF from the MIMIC-IV database with complete baseline HbA1c and HDL-C data. HHR was calculated as the HbA1c-to-HDL-C ratio. The primary outcome was all-cause mortality. In the primary analysis, HHR was modeled as a continuous variable scaled per interquartile range (IQR). Sequentially adjusted Cox proportional hazards models, restricted cubic spline (RCS) regression, subgroup interaction analyses and nested model comparisons were performed to characterize the association and its incremental prognostic value relative to conventional clinical risk factors. A data-driven dichotomized analysis was undertaken as an exploratory hypothesis-generating exercise, with bootstrap internal validation based on 1000 resampling replicates. Results After full adjustment for demographics, comorbidities and clinical laboratory variables, each IQR increment in HHR showed a borderline association with increased all-cause mortality (HR = 1.06, 95% CI: 0.998–1.124, P = 0.0595). Restricted cubic spline analysis revealed a threshold-type dose-response relationship. In an exploratory analysis using a data-driven cutoff of 3.33, elevated HHR was associated with higher mortality risk (HR = 1.46, 95% CI: 1.11–1.91, P = 0.006). Nested model comparisons further demonstrated that the incremental prognostic value of HHR beyond conventional clinical risk factors was limited. Conclusions Elevated HHR shows a borderline independent association with increased all-cause mortality in patients with AF, with a modest effect size and limited incremental prognostic gain over established clinical risk factors. Further external validation studies are warranted to confirm these findings and elucidate the underlying pathophysiological mechanisms. Clinical trial number Not applicable.
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Wang et al. (2026) conducted a cohort in Atrial fibrillation (n=2,573). HbA1c/HDL-C ratio (HHR) per interquartile range (IQR) increment vs. Lower HbA1c/HDL-C ratio (continuous per IQR; exploratory cutoff <=3.33) was evaluated on All-cause mortality (HR 1.06, 95% CI 0.998-1.124, p=0.0595). Each IQR increment in the HbA1c/HDL-C ratio showed a borderline association with increased all-cause mortality in atrial fibrillation patients after full adjustment (HR 1.06, 95% CI 0.998-1.124, P=0.0595).
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