Cardiovascular

Predominantly L-shaped association between hemoglobin glycation index and all-cause mortality in hospitalized patients with heart failure.

Wu R, Dou J, Guo C, Wei J • Diabetes & vascular disease research • 2026

PubMed 42706657 DOI 10.1177/14791641261474039

TL;DR

HGI was independently associated with short-term and long-term all-cause mortality in hospitalized patients with HF, with a predominantly L-shaped pattern observed, and excess mortality risk mainly concentrated at low HGI values.

Key Findings

Results

Among 3,470 hospitalized heart failure patients, 24.1% died within 365 days after discharge.

Study drew from the MIMIC-IV database, a retrospective cohort of adult patients hospitalized with heart failure.
837 of 3,470 included patients died within 365 days after discharge.
The primary outcome was 365-day all-cause mortality; the secondary outcome was 30-day all-cause mortality.
Patients were categorized into quartiles based on their hemoglobin glycation index (HGI) values.

Results

Restricted cubic spline analysis demonstrated a predominantly L-shaped association between HGI and both 30-day and 365-day all-cause mortality.

The L-shaped pattern indicates that mortality risk was highest at low HGI values and decreased as HGI increased, with a plateau at higher values.
Excess mortality risk was 'mainly concentrated at low HGI values' for both short-term and long-term outcomes.
This nonlinear relationship was identified using restricted cubic spline modeling within multivariable Cox regression frameworks.
The same L-shaped pattern was observed for both the primary (365-day) and secondary (30-day) mortality outcomes.

Results

Higher HGI quartiles were associated with significantly lower risks of both short-term and long-term all-cause mortality compared to the lowest quartile.

Multivariable Cox regression models were used to evaluate associations between HGI quartiles and mortality.
Compared with the lowest quartile, all higher HGI quartiles showed significantly reduced mortality risk.
These findings supported 'the particular vulnerability of patients with extremely low HGI.'
Kaplan-Meier survival analysis was also performed and contributed to characterizing these associations.

Results

A significant interaction between HGI and diabetes status was observed for 365-day mortality.

Subgroup analyses were performed to evaluate the robustness of the findings across different patient subgroups.
Subgroup analyses 'generally supported the robustness of these findings.'
A significant interaction with diabetes status was specifically noted for the 365-day mortality outcome.
No mention was made of a significant interaction with diabetes status for the 30-day mortality outcome.

Conclusions

HGI was independently associated with both short-term and long-term all-cause mortality in hospitalized heart failure patients.

HGI is calculated as the difference between measured HbA1c and predicted HbA1c derived from fasting plasma glucose.
HGI reflects 'the discrepancy between observed and predicted glycated hemoglobin' and represents interindividual variation in glycation beyond conventional HbA1c.
The association remained significant after multivariable adjustment.
The authors conclude that 'HGI may serve as a simple and accessible marker for risk stratification in this population.'

What This Means

This research examined whether a measure called the Hemoglobin Glycation Index (HGI) — which captures how much a person's actual blood sugar marker (HbA1c) differs from what would be predicted based on their fasting blood glucose — is linked to survival in patients hospitalized for heart failure. Using data from over 3,400 hospitalized heart failure patients in a large medical database (MIMIC-IV), the researchers found that about one in four patients (24.1%) died within a year of discharge. Patients with the lowest HGI values had the highest mortality risk, and this risk dropped sharply as HGI increased before leveling off — creating an 'L-shaped' curve rather than a straight-line relationship. The findings suggest that patients with unusually low HGI — meaning their HbA1c is lower than expected given their blood sugar levels — are at particularly high risk of dying in both the short term (30 days) and longer term (365 days) after a heart failure hospitalization. This relationship held up even after accounting for other health factors, and was generally consistent across different subgroups of patients, though the strength of the association varied depending on whether patients had diabetes. This research suggests that HGI, which can be calculated using two commonly measured lab values (HbA1c and fasting blood glucose), could serve as a straightforward tool to help identify heart failure patients who are at elevated risk of death. Because both measurements are routinely collected in hospitalized patients, incorporating HGI into clinical assessments would require no additional testing. Further research is needed to understand why low HGI appears to predict worse outcomes and whether addressing low HGI could improve survival in this population.

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Citation

Wu R, Dou J, Guo C, Wei J. (2026). Predominantly L-shaped association between hemoglobin glycation index and all-cause mortality in hospitalized patients with heart failure.. Diabetes &amp; vascular disease research. https://doi.org/10.1177/14791641261474039

Key Findings

What This Means

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