# Cardiovascular–Kidney–Metabolic (CKM) Syndrome as Independent Risk Factor for Pneumococcal Pneumonia: Evidence from a Territory-Wide Study

## TL;DR

This study shows that higher stages of CKM syndrome are linked to worse outcomes in adults hospitalized for pneumococcal pneumonia.

## Contribution

The study is the first to identify CKM syndrome as an independent risk factor for severe outcomes in pneumococcal pneumonia.

## Key findings

- Higher CKM syndrome stages are associated with increased in-hospital mortality.
- Severe respiratory failure and acute kidney injury risks rise with CKM syndrome severity.
- Results are consistent regardless of pneumococcal vaccination status.

## Abstract

Cardiovascular–kidney–metabolic (CKM) syndrome is an increasingly recognized condition that highlights the interaction between three important medical co-morbidities. Whether the presence of CKM syndrome may increase the risk of in-hospital adverse outcomes in patients with pneumococcal pneumonia has not been investigated. We conducted a territory-wide retrospective study on adults hospitalized for pneumococcal pneumonia between 1 January 2016 and 31 December 2024 in Hong Kong. In-patient mortality, severe respiratory failure (SRF) and acute kidney injury (AKI) were compared among patients with cardiovascular–kidney–metabolic (CKM) syndrome at different stages. Subgroup analyses were performed in patients who have or have not received a pneumococcal vaccine. In total, 2192 patients were hospitalized for pneumococcal pneumonia in the study period, with 1005 (45.8%), 373 (17.0%), 684 (31.2%) and 130 (5.9%) at stage 0–1, 2–3, 4a and 4b CKM syndrome. A higher stage of CKM syndrome was associated with increased risks of death during index admission, SRF and AKI. The adjusted odds ratios (aOR) for CKM stage 4a and 4b for death during index admission were 1.82 (95% CI 1.25–2.64) and 10.92 (95% CI 6.82–17.49) respectively (p = 0.002 and <0.001). The aOR for SRF for CKM stage 2–3, 4a and 4b were 1.43 (95% CI 1.01–2.03), 1.88 (95% CI 1.39–2.54) and 28.42 (95% CI 16.92–47.74) respectively (p = 0.042, <0.001 and <0.001). The aOR for AKI for CKM syndrome stage 2–3, 4a and 4b were 2.25 (95% CI 1.53–3.29), 3.00 (95% CI 2.14–4.22) and 4.30 (95% CI 2.69–6.88) (p < 0.001 for all). Subgroup analysis showed consistent results among those who have or have not received a pneumococcal vaccine within the 12 months preceding the index admission date. CKM syndrome, especially at a higher stage, constitutes an independent risk factor for severe in-hospital outcomes in adults hospitalized for pneumococcal pneumonia.