@article {7464, title = {eGFR and Albuminuria in Relation to Risk of Incident Atrial Fibrillation: A Meta-Analysis of the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study.}, journal = {Clin J Am Soc Nephrol}, volume = {12}, year = {2017}, month = {2017 Sep 07}, pages = {1386-1398}, abstract = {

BACKGROUND AND OBJECTIVES: The incidence of atrial fibrillation is high in ESRD, but limited data are available on the incidence of atrial fibrillation across a broad range of kidney function. Thus, we examined the association of eGFR and urine albumin-to-creatinine ratio with risk of incident atrial fibrillation.

DESIGN, SETTING, PARTICIPANTS, \& MEASUREMENTS: We meta-analyzed three prospective cohorts: the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study. Cox regression models were performed examining the association of eGFR and urine albumin-to-creatinine ratio with incident atrial fibrillation adjusting for demographics and comorbidity. In additional analyses, we adjusted for measures of subclinical cardiovascular disease (by electrocardiogram and cardiac imaging) and interim heart failure and myocardial infarction events.

RESULTS: In the meta-analyzed study population of 16,769 participants without prevalent atrial fibrillation, across categories of decreasing eGFR (eGFR>90 [reference], 60-89, 45-59, 30-44, and <30 ml/min per 1.73 m(2)), there was a stepwise increase in the adjusted risk of incident atrial fibrillation: hazard ratios (95\% confidence intervals) were 1.00, 1.09 (0.97 to 1.24), 1.17 (1.00 to 1.38), 1.59 (1.28 to 1.98), and 2.03 (1.40 to 2.96), respectively. There was a stepwise increase in the adjusted risk of incident atrial fibrillation across categories of increasing urine albumin-to-creatinine ratio (urine albumin-to-creatinine ratio <15 [reference], 15-29, 30-299, and >=300 mg/g): hazard ratios (95\% confidence intervals) were 1.00, 1.04 (0.83 to 1.30), 1.47 (1.20 to 1.79), and 1.76 (1.18 to 2.62), respectively. The associations were consistent after adjustment for subclinical cardiovascular disease measures and interim heart failure and myocardial infarction events.

CONCLUSIONS: In this meta-analysis of three cohorts, reduced eGFR and elevated urine albumin-to-creatinine ratio were significantly associated with greater risk of incident atrial fibrillation, highlighting the need for further studies to understand mechanisms linking kidney disease with atrial fibrillation.

}, issn = {1555-905X}, doi = {10.2215/CJN.01860217}, author = {Bansal, Nisha and Zelnick, Leila R and Alonso, Alvaro and Benjamin, Emelia J and de Boer, Ian H and Deo, Rajat and Katz, Ronit and Kestenbaum, Bryan and Mathew, Jehu and Robinson-Cohen, Cassianne and Sarnak, Mark J and Shlipak, Michael G and Sotoodehnia, Nona and Young, Bessie and Heckbert, Susan R} } @article {9482, title = {Evaluation of plasma sphingolipids as mediators of the relationship between kidney disease and cardiovascular events.}, journal = {EBioMedicine}, volume = {95}, year = {2023}, month = {2023 Aug 24}, pages = {104765}, abstract = {

BACKGROUND: Sphingolipids are a family of circulating lipids with regulatory and signaling roles that are strongly associated with both eGFR and cardiovascular disease. Patients with chronic kidney disease (CKD) are at high risk for cardiovascular events, and have different plasma concentrations of certain plasma sphingolipids compared to patients with normal kidney function. We hypothesize that circulating sphingolipids partially mediate the associations between eGFR and cardiovascular events.

METHODS: We measured the circulating concentrations of 8 sphingolipids, including 4 ceramides and 4 sphingomyelins with the fatty acids 16:0, 20:0, 22:0, and 24:0, in plasma from 3,463 participants in a population-based cohort (Cardiovascular Health Study) without prevalent cardiovascular disease. We tested the adjusted mediation effects by these sphingolipids of the associations between eGFR and incident cardiovascular disease via quasi-Bayesian Monte Carlo method with 2,000 simulations, using a Bonferroni correction for significance.

FINDINGS: The mean ({\textpm}SD) eGFR was 70 ({\textpm}16) mL/min/1.73~m; 62\% of participants were women. Lower eGFR was associated with higher plasma ceramide-16:0 and sphingomyelin-16:0, and lower ceramides and sphingomyelins-20:0 and -22:0. Lower eGFR was associated with risk of incident heart failure and ischemic stroke, but not myocardial infarction. Five of eight sphingolipids partially mediated the association between eGFR and heart failure. The sphingolipids associated with the greatest proportion mediated were ceramide-16:0 (proportion mediated 13\%, 95\% CI 8-22\%) and sphingomyelin-16:0 (proportion mediated 10\%, 95\% CI 5-17\%). No sphingolipids mediated the association between eGFR and ischemic stroke.

INTERPRETATION: Plasma sphingolipids partially mediated the association between lower eGFR and incident heart failure. Altered sphingolipids metabolism may be a novel mechanism for heart failure in patients with CKD.

FUNDING: This study was supported by T32 DK007467 and a KidneyCure Ben J. Lipps Research Fellowship (Dr.~Lidgard). Sphingolipid measurements were supported by R01 HL128575 (Dr. Lemaitre) and R01 HL111375 (Dr.~Hoofnagle) from the National Heart, Lung, and Blood Institute (NHLBI).

}, issn = {2352-3964}, doi = {10.1016/j.ebiom.2023.104765}, author = {Lidgard, Benjamin and Bansal, Nisha and Zelnick, Leila R and Hoofnagle, Andrew N and Fretts, Amanda M and Longstreth, William T and Shlipak, Michael G and Siscovick, David S and Umans, Jason G and Lemaitre, Rozenn N} }