TY - JOUR
T1 - Excess risk of cardiovascular events in patients in the United States vs. Japan with chronic kidney disease is mediated mainly by left ventricular structure and function
AU - the CRIC Study Investigators
AU - Imaizumi, Takahiro
AU - Fujii, Naohiko
AU - Hamano, Takayuki
AU - Yang, Wei
AU - Taguri, Masataka
AU - Kansal, Mayank
AU - Mehta, Rupal
AU - Shafi, Tariq
AU - Taliercio, Jonathan
AU - Go, Alan
AU - Rao, Panduranga
AU - Hamm, L. Lee
AU - Deo, Rajat
AU - Maruyama, Shoichi
AU - Fukagawa, Masafumi
AU - Feldman, Harold I.
AU - Appel, Lawrence J.
AU - Chen, Jing
AU - Cohen, Debbie L.
AU - Lash, James P.
AU - Nelson, Robert G.
AU - Rao, Panduranga S.
AU - Rahman, Mahboob
AU - Shah, Vallabh O.
AU - Unruh, Mark L.
N1 - Publisher Copyright:
© 2023 International Society of Nephrology
PY - 2023/5
Y1 - 2023/5
N2 - While patients receiving dialysis therapy in the United States are more likely to develop cardiovascular disease (CVD) than those in Japan, direct comparisons of patients with predialysis chronic kidney disease (CKD) are rare. To study this, we compared various outcomes in patients with predialysis CKD using data from the Chronic Renal Insufficiency Cohort (CRIC) and CKD Japan Cohort (CKD-JAC) studies and determined mediators of any differences. Candidate mediators included left ventricular (LV) indices assessed by echocardiography. Among 3125 CRIC and 1097 CKD-JAC participants, the mean LV mass index (LVMI) and ejection fraction (EF) were 55.7 and 46.6 g/m2 and 54% and 65%, respectively (both significant). The difference in body mass index (32 and 24 kg/m2, respectively) largely accounted for the differences in LVMI and C-reactive protein levels across cohorts. Low EF and high LVMI were significantly associated with subsequent CVD in both cohorts. During a median follow-up of five years, CRIC participants were at higher risk for CVD (adjusted hazard ratio [95% confidence interval]: 3.66 [2.74–4.89]) and death (4.69 [3.05–7.19]). A three-fold higher C-reactive protein concentration and higher phosphate levels in the United States cohort were moderately strong mediators of the differences in CVD. However, echocardiographic parameters were stronger mediators than these laboratory measures. LVMI, EF and their combination mediated the observed difference in CVD (27%, 50%, and 57%, respectively) and congestive heart failure (33%, 62%, and 70%, respectively). Thus, higher LV mass and lower EF, even in the normal range, were found to be predictive of CVD in CKD.
AB - While patients receiving dialysis therapy in the United States are more likely to develop cardiovascular disease (CVD) than those in Japan, direct comparisons of patients with predialysis chronic kidney disease (CKD) are rare. To study this, we compared various outcomes in patients with predialysis CKD using data from the Chronic Renal Insufficiency Cohort (CRIC) and CKD Japan Cohort (CKD-JAC) studies and determined mediators of any differences. Candidate mediators included left ventricular (LV) indices assessed by echocardiography. Among 3125 CRIC and 1097 CKD-JAC participants, the mean LV mass index (LVMI) and ejection fraction (EF) were 55.7 and 46.6 g/m2 and 54% and 65%, respectively (both significant). The difference in body mass index (32 and 24 kg/m2, respectively) largely accounted for the differences in LVMI and C-reactive protein levels across cohorts. Low EF and high LVMI were significantly associated with subsequent CVD in both cohorts. During a median follow-up of five years, CRIC participants were at higher risk for CVD (adjusted hazard ratio [95% confidence interval]: 3.66 [2.74–4.89]) and death (4.69 [3.05–7.19]). A three-fold higher C-reactive protein concentration and higher phosphate levels in the United States cohort were moderately strong mediators of the differences in CVD. However, echocardiographic parameters were stronger mediators than these laboratory measures. LVMI, EF and their combination mediated the observed difference in CVD (27%, 50%, and 57%, respectively) and congestive heart failure (33%, 62%, and 70%, respectively). Thus, higher LV mass and lower EF, even in the normal range, were found to be predictive of CVD in CKD.
KW - cardiovascular disease
KW - chronic kidney disease
KW - left ventricular hypertrophy
KW - mediation analysis
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U2 - 10.1016/j.kint.2023.01.008
DO - 10.1016/j.kint.2023.01.008
M3 - Article
C2 - 36738890
AN - SCOPUS:85149981627
SN - 0085-2538
VL - 103
SP - 949
EP - 961
JO - Kidney international
JF - Kidney international
IS - 5
ER -