Stage 2 cardiovascular-kidney-metabolic syndrome and the risk of heart failure

Background

Stage 2 cardiovascular-kidney-metabolic (CKM) syndrome, defined as individuals with metabolic risk factors and/or chronic kidney disease (CKD), is characterized to precipitate the presentation of subclinical heart failure (HF). Yet, the optimal strategy for identifying individuals with an increased risk of HF remains unclear.

Purpose

Clinical background, the change in natriuretic peptides, and the risks of HF events and mortality were analysed to understand high-risk individuals with stage 2 CKM syndrome.

Methods

From anonymised medical records collected from 57 institutions across Japan, data from a total of 39,019 individuals aged ≥20 years with stage 2 CKM syndrome in January 2019 (i.e., baseline) were identified using ICD-10 codes for metabolic risk factors (i.e., hypertension, dyslipidaemia, diabetes, or metabolic syndrome) and/or CKD. Data from individuals with ICD codes for HF, atrial fibrillation, stroke, and atherosclerotic diseases at baseline were not included. Repeatedly measured brain natriuretic peptide (BNP) was analysed across components of risk factors (metabolic risk factors and/or CKD) and age groups from baseline. The risks of all-cause death and HF events, defined as newly assigned ICD codes for HF and elevated BNP (≥100 pg/mL) within a ±30-day window from an HF-ICD code assignment, were assessed.

Results

In a cohort of individuals (mean age 66 years, 52% female, 58% with ICD code for hypertension, 45% for diabetes, 43% for dyslipidaemia, 9.8% for CKD), 90.2% had metabolic risk factors only, 1.2% had CKD only, and 8.6% had both risk factors. 11,561 (30%) individuals had either BNP or N-terminal pro-BNP measurement at baseline.

In 7,979 (20.4%) individuals who had BNP measurement at baseline, compared to individuals with metabolic risk factors only, those with CKD only and both risk factors had a higher mean BNP (72.4 vs. 110 and 141 pg/mL, respectively). Similarly, older individuals had higher baseline BNP levels compared to younger individuals. Over the median follow-up of 5.1 years, increases in BNP levels were observed in all groups of risk factors (Figure 1A) and ages (Figure 1B), with particularly rapid increases observed in individuals with both risk factors and in the age group of 30-39.

Among the overall stage 2 CKM cohort, there were 1,399 (3.6%) individuals who experienced at least one HF event (incident rate of 0.77 per 100 person-years), and 1,652 (4.2%) deaths (0.90 per 100 person-years). The risk of HF events and deaths was higher in the elderly, compared to younger individuals, as well as those with CKD risk only and both risk factors, compared to those with metabolic risk only (Table 1).

Conclusions

In individuals with CKM stage 2, being elderly and having CKD involvement were associated with a heightened risk of HF events and mortality. CKM stage 2 involves younger individuals who experience a rapid increase in natriuretic peptide levels.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.