New Study Links Endothelial Dysfunction to LV Dysfunction

Scientific Updates Sponsored by Endothelix Inc.
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Hypertension. 2016 Aug 22

Associations of Macro- and Microvascular Endothelial Dysfunction With Subclinical Ventricular Dysfunction in End-Stage Renal Disease.

Dubin RF1, Guajardo I2, Ayer A2, Mills C2, Donovan C2, Beussink L2, Scherzer R2, Ganz P2, Shah SJ2.

  • 1From 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.
  • 2From 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.).

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).

Conclusions
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.


J Pediatr. 2016 Aug 18

Endothelial Function in Youth: A Biomarker Modulated by Adiposity-Related Insulin Resistance.

Tomsa A1, Klinepeter Bartz S1, Krishnamurthy R2, Krishnamurthy R2, Bacha F3.

  • 1US Department of Agriculture/Agricultural Research Service Children’s Nutrition Research Center, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX; Division of Pediatric Endocrinology and Diabetes, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX.
  • 2Department of Radiology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX.
  • 3US Department of Agriculture/Agricultural Research Service Children’s Nutrition Research Center, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX; Division of Pediatric Endocrinology and Diabetes, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX. Electronic address: fbacha@bcm.edu.

Abstract

OBJECTIVE: To investigate the physical and metabolic determinants of endothelial dysfunction, an early marker of subclinical atherosclerosis, in normal weight and overweight adolescents with and without type 2 diabetes mellitus. STUDY DESIGN: A cross-sectional study of 81 adolescents: 21 normal weight, 25 overweight with normal glucose tolerance, 19 overweight with impaired glucose regulation, and 16 with type 2 diabetes mellitus underwent evaluation of reactive hyperemia index (RHI) and augmentation index (AIx) at heart rate 75 bpm by peripheral arterial tonometry; oral glucose tolerance test, lipid profile, and hyperinsulinemic-euglycemic clamp to measure insulin sensitivity; and dual energy X-ray absorptiometry scan and abdominal magnetic resonance imaging for percentage of body fat and abdominal fat partitioning. RESULTS:Participants across tertiles of RHI (1.2 ± 0.02, 1.5 ± 0.02, and 2.0 ± 0.05, P  .001) had similar age, sex, race, lipid profile, and blood pressure. Body mass index z-score, percentage body fat, abdominal fat, and hemoglobin A1c decreased, and insulin sensitivity increased from the first to third tertile. RHI was inversely related to percentage body fat (r = -0.29, P = .008), total (r = -0.37, P = .004), subcutaneous (r = -0.39, P = .003), and visceral (r = -0.26, P = .04) abdominal fat. AIx at heart rate 75 bpm was higher (worse) in the lower RHI tertiles (P = .04), was positively related to percentage body fat (r = 0.26, P = .021), and inversely related to age, insulin sensitivity, and inflammatory markers (tumor necrosis factor-α and plasminogen activator inhibition-1).

CONCLUSIONS:

Childhood obesity, particularly abdominal adiposity, is associated with endothelial dysfunction manifested by worse reactive hyperemia and higher AIx. Insulin resistance appears to mediate this relationship.

 Scientific Updates Sponsored by Endothelix Inc.

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