{"doi":"10.1016/j.kint.2023.01.008","title":"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","abstract":"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. 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. Lay SummaryCardiovascular disease is very common in patients with chronic kidney disease (CKD). Although US hemodialysis patients are more likely to develop heart disease compared with Japanese patients, no direct comparison exists for non–dialysis-dependent CKD. Using patient data from the United States and Japan, we found that US patients with CKD had higher rates of heart failure and heart attack than Japanese patients. We then aimed to clarify how this happened. Our results revealed that the enlarged hearts of US patients and their weak contractility play important roles. These features explain most of the differences in","journal":"Kidney International","year":2023,"id":331262,"datarank":0.5101796072493234,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"self_citation_contribution":0.5101796072493234,"citation_network_contribution":0.0,"self_endowment_contribution":0.5101796072493234,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9497,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":776257,"name":"Naohiko Fujii","orcid":"0000-0002-6411-8599","position":1,"is_corresponding":false},{"id":271633,"name":"Takayuki Hamano","orcid":"0000-0002-2100-9106","position":2,"is_corresponding":false},{"id":281084,"name":"Wei Yang","orcid":"0000-0001-8984-4389","position":3,"is_corresponding":false},{"id":677137,"name":"Masataka Taguri","orcid":"0000-0001-8902-0056","position":4,"is_corresponding":false},{"id":332044,"name":"Mayank Kansal","orcid":"0000-0003-2552-8744","position":5,"is_corresponding":false},{"id":298709,"name":"Rupal Mehta","orcid":"0000-0001-5848-4325","position":6,"is_corresponding":false},{"id":298710,"name":"Tariq Shafi","orcid":"0000-0002-7222-4666","position":7,"is_corresponding":false},{"id":303936,"name":"Jonathan J. Taliercio","orcid":"0000-0003-4320-7151","position":8,"is_corresponding":false},{"id":249669,"name":"Alan S. Go","orcid":"0000-0001-9109-0811","position":9,"is_corresponding":false},{"id":277170,"name":"Panduranga S. Rao","orcid":"0000-0002-4699-5395","position":10,"is_corresponding":false},{"id":279729,"name":"L. Lee Hamm","orcid":null,"position":11,"is_corresponding":false},{"id":108266,"name":"Rajat Deo","orcid":"0000-0002-8250-2607","position":12,"is_corresponding":false},{"id":776258,"name":"Shoichi Maruyama","orcid":"0000-0002-8858-632X","position":13,"is_corresponding":false},{"id":470072,"name":"Masafumi Fukagawa","orcid":"0000-0002-7832-2339","position":14,"is_corresponding":false},{"id":58429,"name":"Harold I. Feldman","orcid":"0000-0003-4572-2608","position":15,"is_corresponding":false},{"id":277163,"name":"Lawrence J. Appel","orcid":"0000-0002-0673-6823","position":16,"is_corresponding":false},{"id":275444,"name":"Jing Chen","orcid":"0000-0003-0676-1794","position":17,"is_corresponding":false},{"id":283063,"name":"Debbie L. Cohen","orcid":"0000-0002-1325-315X","position":18,"is_corresponding":false},{"id":277166,"name":"James P. Lash","orcid":"0000-0002-6580-4080","position":19,"is_corresponding":false},{"id":68431,"name":"Robert G. Nelson","orcid":"0000-0001-7307-3786","position":20,"is_corresponding":false},{"id":277171,"name":"Mahboob Rahman","orcid":"0000-0001-9025-7413","position":22,"is_corresponding":false},{"id":277172,"name":"Vallabh O. Shah","orcid":"0000-0002-3584-4057","position":23,"is_corresponding":false},{"id":277173,"name":"Mark L. 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