Associations of Serum Insulin-Like Growth Factor 1 with New Cardiovascular Events and Subsequent Death in Hemodialysis Patients: The DREAM Cohort

Abstract

Patients with chronic kidney disease (CKD) have elevated risk of death from cardiovascular disease (CVD).A low serum insulin-like growth factor 1 (IGF-1) level is known to predict higher risk for all-cause mortality in incident dialysis patients, although it is unknown whether IGF-1 predicts cardiovascular outcomes.Methods: This was a prospective cohort study of maintenance hemodialysis patients followed up for 5 years. Serum IGF-1 levels were measured at baseline, and patients were divided into IGF-1 tertiles. The key outcomes were all-cause mortality, a composite of new CVD, and death after new CVD events. Additional outcomes were hospitalization for infection and subsequent death. Association was analyzed using Cox proportional hazards models. Results:In the 516 patients that were analyzed, we identified 106 all-cause deaths, 190 new CVD events, and 61 subsequent deaths. In addition, there were 169 hospitalizations for infection and 47 subsequent deaths. The risk of all-cause death was the highest in the lowest IGF-1 tertile, and this association remained significant in multivariable-adjusted models. Regarding CVD outcomes, IGF-1 was not associated with new CVD events but significantly associated with subsequent death in adjusted models. Similarly, IGF-1 was not an independent predictor of hospitalization for infection, but it predicted subsequent death. Conclusions:A low IGF-1 level was not a significant predictor of new CVD events but an independent predictor of subsequent death in hemodialysis patients. Since similar associations with infection outcomes were observed, IGF-1 may be a biomarker of fragility or frailty in this population.(CVD) but also for death after CVD events 2) . These two factors synergistically increase the risk of cardiovascular death 3) .The elevated risk of CVD death in patients with chronic kidney disease (CKD), including those on hemodialysis, has been explained by the traditional and nontraditional risk factors 4) . Obesity is one of the Copyright©2021 Japan Atherosclerosis Society This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.

Differential associations of fetuin-A and calcification propensity with cardiovascular events and subsequent mortality in patients undergoing hemodialysis

“…This study was performed using data of the ‘DREAM’ (Dialysis-Related Endocrine and Metabolic changes affecting cardiovascular disease) cohort, which is a prospective, observational, and single-center study as previously registered at the UMIN-CTR (unique ID: UMIN000006168, http://www.umin.ac.jp/ctr/index.htm ). Some of the results of this cohort have been reported previously [ 24 , 25 ]. The DREAM cohort was composed of total 518 patients undergoing hemodialysis at Inoue Hospital, Suita, Osaka, Japan.…”

“…Use of VDRAs was associated with lower odds for incident CVD events whereas it was not associated with death after CVD events in hemodialysis patients [ 23 ]. Serum level of insulin-like growth factor I (IGF-I) was not independently associated with new CVD events, but a lower IGF-I was an independent predictor of death after CVD events in patients undergoing hemodialysis [ 24 ]. Thus, the findings of fetuin-A and T50 in the present study expanded the list of risk factors which predict the onset of CVD events and death after CVD events differently.…”

“…CVD events in the DREAM cohort were defined as the new occurrence of ischemic heart disease, ischemic stroke, hemorrhagic stroke, peripheral artery disease, pulmonary edema and cardiac valve disease as previously described [ 24 , 25 ]. Incident and recurrent CVD and interventions for CVD were included as CVD events whereas chest pain or transient ischemic attack with no evidence with images were excluded.…”

“…The cohort was followed-up for up to 5 years until the end of 2009. At the end of each year, primary physicians made up an annual follow-up sheet to report dates of death (cause of death), CVD events, kidney transplantation, switching to peritoneal dialysis and moving away to other dialysis unit, as previously reported [ 24 , 25 ].…”

Association of Reduced Free T3 to Free T4 Ratio with Lower Serum Creatinine in Japanese Hemodialysis Patients

“…The present study was conducted as a cross-sectional analysis of our prospective study cohort termed DREAM (Dialysis-Related Endocrine And Metabolic changes affecting cardiovascular disease) [11,16,17]. The total of 806 dialysis patients were treated at Inoue Hospital, Suita, Osaka, Japan, in December 2004.…”