Age-stratified profiles and outcomes of patients with heart failure with preserved ejection fraction

Abstract

Aims: This study aimed to elucidate age-stratified clinical profiles and outcomes in patients with heart failure (HF) with preserved left ventricular ejection fraction (LVEF) (HFpEF).

Methods and results: The Chronic Heart Failure Registry and Analysis in the Tohoku District-2 (CHART-2) Study included 2824 consecutive HFpEF patients with LVEF ≥ 50% (mean age 69.0 ± 12.3 years; 67.7% male) with a median follow-up of 9.8 years. We stratified them into five age groups: ≤54 (N = 349, 12.4%), 55-64 (N = 529, 18.7%), 65-74 (N = 891, 31.6%), 75-84 (N = 853, 30.2%), and ≥85 years (N = 202, 7.2%), and we categorized these age groups into younger (≤64 years) and older (≥65 years) groups. We compared the clinical profiles and outcomes of HFpEF patients across age groups. Younger HFpEF groups exhibited a male predominance, elevated body mass index (BMI), and poorly controlled diabetes (haemoglobin A1c > 7.0%). Older HFpEF groups were more likely to be female with multiple comorbidities, including coronary artery disease, hypertension, renal impairment, and atrial fibrillation. The positive association between elevated BMI and HFpEF was more pronounced with lower classes of age from ≥85 to ≤54 years, especially in males. With higher classes of age from ≤54 to ≥85 years, mortality rates increased, and HF death became proportionally more prevalent (P_trend < 0.001), whereas sudden cardiac death (SCD) exhibited the opposite trend (P_trend = 0.002). Poorly controlled diabetes emerged as the only predictor of SCD in the younger groups (adjusted hazard ratio 4.26; 95% confidence interval 1.45-12.5; P = 0.008). Multiple comorbidities were significantly associated with an increased risk of HF-related mortality in the older groups.

Conclusions: Younger HFpEF patients (≤64 years) exhibit a male predominance, elevated BMI, and poorly controlled diabetes, highlighting the importance of glycaemic control in reducing SCD risk. Older HFpEF patients (≥65 years) are more likely to be female, with multiple comorbidities linked to an increased risk of HF-related mortality. These findings underscore the need for physicians to recognize age-related, distinct HFpEF phenotypes for personalized patient management.

Keywords: Age; Diabetes; HFpEF; Obesity; Sex; Sudden death.

Figure 1

(A) Baseline clinical characteristics associated with younger and older HFpEF patients. In binomial logistic regression analysis, age‐related differences in clinical characteristics among HFpEF patients were examined. The following variables were included for multivariable adjustment: sex, BMI, CAD, hypertension, diabetes, CKD, AF, NYHA class, LVEF, and BNP. Well‐controlled diabetes status was defined as HbA1c ≤ 7.0%, and poorly controlled diabetes status was defined as HbA1c > 7.0%. (B) Sex differences in age‐related trends of the relevance of BMI to HFpEF. In multinomial logistic regression analysis, sex differences in age‐related trends in the relevance of BMI to HFpEF were examined. The following variables were included for multivariable adjustment: sex, BMI, CAD, hypertension, diabetes, CKD, AF, NYHA class, LVEF, and BNP. OR, odds ratio. Other abbreviations are in Table 1 .

Figure 2

Age‐related differences in causes of death in heart failure (HF) with preserved ejection fraction patients. AMI, acute myocardial infarction; CV, cardiovascular; NCV, non‐cardiovascular; NS, not significant.