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  • Lower eGFR Predicts Increased Risk of MACE in Young Adults: Large Canadian Database Analysis

    Lower estimated glomerular filtration rates (eGFRs) were associated with an increased risk for major adverse cardiovascular events (MACEs) and MACE plus heart failure (MACE+) in young adults between the ages of 18 and 39, a new study shows.

    These data were reported by Junayd Hussain, BSc, of the University of Ottawa, Ontario, and colleagues, in a manuscript published Monday online and in the Sept. 26 issue of the Journal of the American College of Cardiology.

    Early cardiovascular (CV) risk factor detection has become increasingly important as more young adults experience increased rates of obesity, diabetes and hypertension. The American College of Cardiology and the American Heart Association noted chronic kidney disease (CKD) as a silent risk factor for cardiovascular disease (CVD). Measurement of eGFR allows investigators to examine structural damage to the kidneys.

    The investigators in this study sought to determine age-specific associations in subclinical eGFR levels in young adults who experience MACEs or MACE+. A total of 8.7 million participants were included in this study (mean age=41.3±13.6 years, 52.3% female, median follow-up duration=9.2 years, 90.3% urban living), gathered by several health care data sets from Ontario between January 2008 and March 2021.

    The association of categorized eGFR with MACE and MACE+ was analyzed using Cox models. These data were stratified according to age (18-39, 40-49 and 50-65 years old; mean eGFR=104.2 mL/min/1.73 m2). The primary outcome of this study was time to MACE (composite outcome defined by the first occurrence of CV mortality, acute coronary syndrome and ischemic stroke).

    In young adults, the relative risk of both MACE and MACE+ showed a stepwise increase after eGFR <80 mL/min/1.73 m2. For example, with the main outcome, MACE, there were 2.37 events per 1,000 person-years (hazard ratio [HR]=1.31; 95% confidence interval [CI]=1.27-1.40) in young adults. In adults ages 40-49 years, there were 6.26 events per 1,000 person-years (HR=1.07; 95% CI=1.06-1.12), and in adults ages 50-65 years there were 14.9 events per 1,000 person-years (HR=1.07; 95% CI=1.05-1.08).

    The results were consistent for each component of MACE, as well as for MACE+, upon further analysis. Past CV disease, albuminuria at index and repeated eGFR measures stratified the MACE component analyses.

    The authors noted several limitations in this study. First, the primary outcome was defined using previously validated codes for MACE and MACE+, and no external committee was used to validate these codes. Second, there may have been confounding explanations for the observed associations, but the large cohort size provided some consistency. In addition, the mechanism of eGFR function nor the subtypes of CV outcomes were included in the study.

    The investigators concluded that younger adults (age 18-39 years) who had an eGFR measure below a healthy age-specific mean had a greater risk for CV events, and this risk was associated with higher eGFR levels compared with the middle-aged and older adult cohorts. The pattern was the same after adjusting for repeated kidney function measures, interactions with albuminuria at index and a history of CV disease.

    In an accompanying editorial, Daniel A. Duprez, MD, and David R. Jacobs Jr., PhD, of the University of Minnesota, discussed the importance of early detection of CV risk factors and symptoms. They noted that a new epidemic of CVD in young people is expected to take a toll.

    The editorialists applauded the large sample size and the evidence for expanding CVD prevention guidelines and concluded that screening young people for CVD will become increasingly important.

    “Strategic health programs considering integrative aspects of socioeconomic factors and multiple disease conditions should be developed and implemented to promote and expand access to kidney screening and clinical care, ultimately reducing the burden of severe kidney disease, CVD, and mortality,” Duprez and Jacobs concluded.


    Hussain J, Imsirovic H, Canney M, et al. Impaired Renal Function and Major Cardiovascular Events in Young Adults. J Am Coll Cardiol. 2023;82:1316-1327.

    Duprez DA, Jacobs DR, Jr. Time to Routinely Measure eGFR and Albuminuria in Young and Middle-Aged Adults. J Am Coll Cardiol. 2023;82:1328-1330.

    Image Credit: lovelyday12 –

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