Temporal prevalence and prognostic impact of diabetes mellitus and albuminuria in heart failure with preserved ejection fraction

BACKGROUND: Most patients with heart failure with preserved ejection fraction (HFpEF) have a metabolic phenotype in which comorbidities including diabetes mellitus play an important role. Factors related to impaired glucose metabolism, such as kidney disease, may contribute to adverse clinical events. Albuminuria is an early marker of kidney disease. We assessed the prevalence of impaired glucose metabolism and albuminuria in HFpEF over time, and evaluated its prognostic implications. METHODS: Consecutive patients referred to our outpatient clinic and diagnosed with HFpEF between March 2015-November 2023 were included in this study. Patients with type 1 diabetes were excluded. Patients were stratified according to baseline glucose metabolism status (DM + for prediabetes and diabetes, or DM-) and albuminuria status (ALB+ or ALB- for albuminuria > 3.0 mg/mmol and normoalbuminuria, respectively). The primary outcome was a composite of HF hospitalizations (HFH) and all-cause mortality, and was analysed using multivariable-adjusted Cox-regression models. RESULTS: Among 332 patients with HFpEF (median age 77 years; 67% female), 121 (36.4%) were classified as DM-/ALB-, 106 (31.9%) as DM+ /ALB-, 44 (13.3%) as DM-/ALB+, and 61 (18.4%) as DM+ /ALB+. Both baseline DM and ALB were independently associated with the primary outcome after approximately 3 years: adjusted hazard ratio (aHR) 1.93; 95% confidence interval (CI) 1.25-2.97 and 1.58; 95%CI 1.04-2.41, respectively. Patients in the DM+ /ALB+ group showed the highest risk (aHR 2.85; 95%CI 1.57-5.15). After one year, DM/ALB status was re-evaluated in 250 (75%) patients. New DM+ and ALB+ incidence was 3.9% and 22%in those at risk, respectively. Patients particularly changed ALB groups compared to baseline (n = 63, 25.2%); 27 (10.8%) patients recovered from albuminuria. At 3 years follow-up, the primary outcome mainly occurred in patients who consistently showed albuminuria (27.1%) or who recovered from albuminuria (22.2%), and less so in patients who developed albuminuria after one year (13.9%) or who remained free of albuminuria (8.6%) (p = 0.008). CONCLUSIONS: DM and albuminuria are prevalent in HFpEF at baseline, and re-evaluation one year later still reveals new diagnoses. Both factors are independently associated with adverse outcomes. Albuminuria at any time point remains predictive of adverse outcomes in HFpEF. RESEARCH INSIGHTS: WHAT IS CURRENTLY KNOWN ABOUT THIS TOPIC?: Diabetes mellitus is an important cardiovascular risk factor in patients with HFpEF, contributing to disease progression and worse outcomes. Albuminuria is a prognostic marker in heart failure patients and more prevalent in patients with diabetes WHAT IS THE KEY RESEARCH QUESTION?: What is prevalence of impaired glucose metabolism and albuminuria in HFpEF over time and how does this translate to prognosis? WHAT IS NEW?: Both DM and albuminuria each independently associated with worse prognosis in HFpEF. Screening 1 year after HFpEF diagnosis yielded incidence rates of 3.9% and 10.8% for DM and prediabetes, respectively, and 22% for albuminuria. Albuminuria at any time point appeared prognostic in HFpEF, also when albuminuria recovered HOW MIGHT THIS STUDY INFLUENCE CLINICAL PRACTICE?: Intermittent screening of HFpEF patients for abnormal glucose metabolism and albuminuria is warranted to optimize risk management.