Incidence of major cardiovascular outcomes in patients with chronic kidney disease by severity: a United States population-based study using electronic medical records
Authors: Vora P , Costa A , Rossignol P , Wanner C , Wilson D , Japp S , Sandrak P , Tyl B 
Published: November 2023

Abstract

Background and Aims
Data on the incidence of cardiovascular (CV) events by stage of chronic kidney disease (CKD) and the effect of previous CV history on future events in CKD patients (pts) is limited. We aimed to analyze a large US electronic medical record (EMR) database and evaluate incidence of new major adverse CV events (MACE) per CKD stage over a 5-year follow-up.

Methods
A retrospective cohort study was conducted using IBM® Explorys EMR data (&gt;53 million patients) from Jan 2010 to Dec 2019. Two cohorts of CKD patients were created: Cohort 1 based on diagnostic codes (n = 810,987 pts), and Cohort 2 on KDIGO screening/staging criteria (n = 953,396). Sub-cohorts were created for each CKD stage (1-5). CKD classification was not mutually exclusive (individual pts could contribute to multiple main and sub-cohorts). Pts in Cohort 1 were required to have an ICD 9/10 code for a specific CKD stage while pts in Cohort 2 required two consecutives abnormal eGFR, uACR/uPCR results within 3-18 months to determine KDIGO CKD stage. Pts were required to have at least 12-months lookback period. Index date was the date of diagnosis or second abnormal test. We followed up each patient individually until the occurrence of a composite of MACE including death, coronary artery disease (CAD) events, any stroke, hospitalization for heart failure, or loss to follow-up, or for up to 5 years.

Results
Most patients in Cohort 1 (DxC) and 2 (KDIGO) were Caucasian and had stage 3 CKD at baseline. Mean age was 70y and 71y in Cohort 1 and 2 respectively, with 49% and 40% males. The prevalence of pre-existing CV diseases increased with CKD stage. The proportion of pts from Cohort 2 receiving a diagnosis of CKD at least once during their study period increased from 34% in stage 1 to 86% and 83% in stage 4 and 5, respectively. The 5-year incidence of the composite of MACE increased with stage in both cohorts: 40.3% to 66.0% in Cohort 1 and 25.1% to 65.8% in Cohort 2. These incidences were higher in pts with a CV history (Table 1). DxC pts tended to have a higher incidence of MACE, especially in the early stages. Death was the most frequent event at 5y in both cohorts across all stages (27.8% and 19.7% respectively at stage 3). It occurred in half of pts with a prior history of CV disease in both Cohorts in stages 4-5 CKD. Stroke was the most frequent event in the early stages (21.6% and 19.5% respectively at stage 3) and CAD events the most frequent in the late stages (27.6% and 29.5% respectively at stage 5).

Conclusion
CKD pts have a high risk of MACE at 5 years, with incidence 2-3 times higher in patients with pre-existing CV disease. There are differences in MACE incidences between CKD definitions, that were higher in coded diagnoses vs. lab results, especially in stages 1-3, warranting further investigation. Aggressive treatment of CV disease and risk factors should be considered for all CKD pts due to high 5-year MACE rates, regardless of CKD stage.Table 1.