title: Associations of Macro- and Microvascular Endothelial Dysfunction With Subclinical Ventricular Dysfunction in End-Stage Renal Disease.
abstract: Patients with end-stage renal disease (ESRD) suffer high rates of heart failure and cardiovascular mortality, and we lack a thorough understanding of what, if any, modifiable factors contribute to cardiac dysfunction in these high-risk patients. To evaluate endothelial function as a potentially modifiable cause of cardiac dysfunction in ESRD, we investigated cross-sectional associations of macro- and microvascular dysfunction with left and right ventricular dysfunction in a well-controlled ESRD cohort. We performed comprehensive echocardiography, including tissue Doppler imaging and speckle-tracking echocardiography of the left and right ventricle, in 149 ESRD patients enrolled in an ongoing prospective, observational study. Of these participants, 123 also underwent endothelium-dependent flow-mediated dilation of the brachial artery (macrovascular function). Microvascular function was measured as the velocity time integral of hyperemic blood flow after cuff deflation. Impaired flow-mediated dilation was associated with higher left ventricular mass, independently of age and blood pressure: per 2-fold lower flow-mediated dilation, left ventricular mass was 4.1% higher (95% confidence interval, 0.49-7.7; P=0.03). After adjustment for demographics, blood pressure, comorbidities, and medications, a 2-fold lower velocity time integral was associated with 9.5% higher E/e' ratio (95% confidence interval, 1.0-16; P=0.03) and 6.7% lower absolute right ventricular longitudinal strain (95% confidence interval, 2.0-12; P=0.003). Endothelial dysfunction is a major correlate of cardiac dysfunction in ESRD, particularly diastolic and right ventricular dysfunction, in patients whose volume status is well controlled. Future investigations are needed to determine whether therapies targeting the vascular endothelium could improve cardiac outcomes in ESRD.
authors.affiliation: From the San Francisco VA Medical Center (R.F.D., I.G., A.A., R.S.) and Center for Vascular Excellence, Division of Cardiology, San Francisco General Hospital (C.M., C.D., P.G.), University of California, San Francisco; and Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (L.B., S.J.S.). ruth.dubin@ucsf.edu.
authors.forename: Ruth F
authors.initials: RF
authors.lastname: Dubin
authors.affiliation: From the San Francisco VA Medical Center (R.F.D., I.G., A.A., R.S.) and Center for Vascular Excellence, Division of Cardiology, San Francisco General Hospital (C.M., C.D., P.G.), University of California, San Francisco; and Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (L.B., S.J.S.).
authors.forename: Isabella
authors.initials: I
authors.lastname: Guajardo
authors.affiliation: From the San Francisco VA Medical Center (R.F.D., I.G., A.A., R.S.) and Center for Vascular Excellence, Division of Cardiology, San Francisco General Hospital (C.M., C.D., P.G.), University of California, San Francisco; and Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (L.B., S.J.S.).
authors.forename: Amrita
authors.initials: A
authors.lastname: Ayer
authors.affiliation: From the San Francisco VA Medical Center (R.F.D., I.G., A.A., R.S.) and Center for Vascular Excellence, Division of Cardiology, San Francisco General Hospital (C.M., C.D., P.G.), University of California, San Francisco; and Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (L.B., S.J.S.).
authors.forename: Claire
authors.initials: C
authors.lastname: Mills
authors.affiliation: From the San Francisco VA Medical Center (R.F.D., I.G., A.A., R.S.) and Center for Vascular Excellence, Division of Cardiology, San Francisco General Hospital (C.M., C.D., P.G.), University of California, San Francisco; and Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (L.B., S.J.S.).
authors.forename: Catherine
authors.initials: C
authors.lastname: Donovan
authors.affiliation: From the San Francisco VA Medical Center (R.F.D., I.G., A.A., R.S.) and Center for Vascular Excellence, Division of Cardiology, San Francisco General Hospital (C.M., C.D., P.G.), University of California, San Francisco; and Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (L.B., S.J.S.).
authors.forename: Lauren
authors.initials: L
authors.lastname: Beussink
authors.affiliation: From the San Francisco VA Medical Center (R.F.D., I.G., A.A., R.S.) and Center for Vascular Excellence, Division of Cardiology, San Francisco General Hospital (C.M., C.D., P.G.), University of California, San Francisco; and Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (L.B., S.J.S.).
authors.forename: Rebecca
authors.initials: R
authors.lastname: Scherzer
authors.affiliation: From the San Francisco VA Medical Center (R.F.D., I.G., A.A., R.S.) and Center for Vascular Excellence, Division of Cardiology, San Francisco General Hospital (C.M., C.D., P.G.), University of California, San Francisco; and Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (L.B., S.J.S.).
authors.forename: Peter
authors.initials: P
authors.lastname: Ganz
authors.affiliation: From the San Francisco VA Medical Center (R.F.D., I.G., A.A., R.S.) and Center for Vascular Excellence, Division of Cardiology, San Francisco General Hospital (C.M., C.D., P.G.), University of California, San Francisco; and Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (L.B., S.J.S.).
authors.forename: Sanjiv J
authors.initials: SJ
authors.lastname: Shah
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001795:Blood Pressure Determination; D001916:Brachial Artery / Q000503:physiopathology*; D002140:California; D002199:Capillary Permeability / Q000502:physiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D015150:Echocardiography, Doppler / Q000379:methods; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000175:diagnosis / Q000628:therapy*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010530:Peritoneal Dialysis / Q000379:methods; D011446:Prospective Studies; D006435:Renal Dialysis / Q000379:methods; D018570:Risk Assessment; D012720:Severity of Illness Index; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology*
keywords: cardiovascular disease; echocardiography; heart failure