Key result
Diabetes linked to ~170% greater incident HF risk, mediated by obesity, hyperglycemia, and cardiac strain.
Why the study?
Heart failure risk remains high in diabetic individuals despite tight glycemic control, requiring better elucidation of correlates and mediators using large cohorts, long follow-up, and biologically relevant biomarkers.
Does diabetes status increase the risk of incident heart failure in the general population?
Cohort (n=94,011)
Yes
Does diabetes status increase the risk of incident heart failure in the general population?
Hazard Ratio: 2.7 (95% CI 2.49–2.93)
Absolute Event Rate: 17% vs 6.1%
p-value: p=<0.001
Diabetes is strongly associated with incident heart failure, with the main mediators being obesity, hyperglycemia, and cardiac strain/volume overload, while conventional risk factors affect both diabetics and non-diabetics equally.
Obesity, hyperglycemia and NT-proBNP mediate >50% of diabetes-related HF risk; supports targeted prevention but leaves causal pathways open for trials.
Background: The risk of heart failure among diabetic individuals is high, even under tight glycemic control. The correlates and mediators of heart failure risk in individuals with diabetes need more elucidation in large population-based cohorts with long follow-up times and a wide panel of biologically relevant biomarkers. Methods: In a population-based sample of 3834 diabetic and 90,177 non-diabetic individuals, proportional hazards models and mediation analysis were used to assess the relation of conventional heart failure risk factors and biomarkers with incident heart failure. Results: Over a median follow-up of 13.8 years, a total of 652 (17.0%) and 5524 (6.1%) cases of incident heart failure were observed in participants with and without diabetes, respectively. 51.4% were women and the mean age at baseline was 48.7 (standard deviation [SD] 12.5) years. The multivariable-adjusted hazard ratio (HR) for heart failure among diabetic individuals was 2.70 (95% confidence interval, 2.49-2.93) compared to non-diabetic participants. In the multivariable-adjusted Cox models, conventional cardiovascular disease risk factors, such as smoking (diabetes: HR 2.07 [1.59-2.69]; non-diabetes: HR 1.85 [1.68-2.02]), BMI (diabetes: HR 1.30 [1.18-1.42]; non-diabetes: HR 1.40 [1.35-1.47]), baseline myocardial infarction (diabetes: HR 2.06 [1.55-2.75]; non-diabetes: HR 2.86 [2.50-3.28]), and baseline atrial fibrillation (diabetes: HR 1.51 [0.82-2.80]; non-diabetes: HR 2.97 [2.21-4.00]) had the strongest associations with incident heart failure. In addition, biomarkers for cardiac strain (represented by nT-proBNP, diabetes: HR 1.26 [1.19-1.34]; non-diabetes: HR 1.43 [1.39-1.47]), myocardial injury (hs-TnI, diabetes: HR 1.10 [1.04-1.16]; non-diabetes: HR 1.13 [1.10-1.16]), and inflammation (hs-CRP, diabetes: HR 1.13 [1.03-1.24]; non-diabetes: HR 1.29 [1.25-1.34]) were also associated with incident heart failure. In general, all these associations were equally strong in non-diabetic and diabetic individuals. However, the strongest mediators of heart failure in diabetes were the direct effect of diabetes status itself (relative effect share 43.1% [33.9-52.3] and indirect effects (effect share 56.9% [47.7-66.1]) mediated by obesity (BMI, 13.2% [10.3-16.2]), cardiac strain/volume overload (nT-proBNP, 8.4% [-0.7-17.4]), and hyperglycemia (glucose, 12.0% [4.2-19.9]). Conclusions: The findings suggest that the main mediators of heart failure in diabetes are obesity, hyperglycemia, and cardiac strain/volume overload. Conventional cardiovascular risk factors are strongly related to incident heart failure, but these associations are not stronger in diabetic than in non-diabetic individuals. Active measurement of relevant biomarkers could potentially be used to improve prevention and prediction of heart failure in high-risk diabetic patients.
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Bergdahl et al. (2021) conducted a cohort in Heart failure (n=94,011). Diabetes status vs. Non-diabetic individuals was evaluated on Incident heart failure (HR 2.70, 95% CI 2.49-2.93, p=<0.001). Diabetes was associated with a 2.70-fold increased risk of incident heart failure compared to non-diabetic individuals, with obesity, hyperglycemia, and cardiac strain acting as key mediators.
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