Elevated serum osteoprotegerin is associated with increased left ventricular mass index and myocardial stiffness.

Daisuke Kamimura, Takeki Suzuki, Anna L Furniss, Michael E Griswold, Iftikhar J Kullo, Merry L Lindsey, Michael D Winniford, Kenneth R Butler, Thomas H Mosley, Michael E Hall
Author Information
  1. Daisuke Kamimura: aDivision of CardiologybDepartment of Medicine, Center for Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, MississippicDivision of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MinnesotadDepartment of Physiology and Biophysics, Mississippi Center for Heart Research, University of Mississippi Medical CentereResearch Service, G.V. (Sonny) Montgomery Veterans Affairs Medical CenterfDivision of Geriatric Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.

Abstract

AIM: Osteoprotegerin (OPG) is associated with a poor prognosis in patients with heart failure with preserved ejection fraction (HFpEF). OPG has also been associated with fibrosis and collagen cross-linking, which increase arterial and left ventricle (LV) myocardial stiffness. Little is known about the relation of OPG and LV structure and function in African-Americans who are disproportionately affected by HFpEF.
METHODS AND RESULTS: Our analysis included 1172 participants with preserved LV ejection fraction (>50%) from the African-American cohort in the Genetic Epidemiology Network of Arteriopathy Study (mean age 63 years, 72% female). We used diastolic wall strain indicator measured by echocardiography to assess LV myocardial stiffness. Diastolic wall strain was calculated as (LV posterior thickness at end-systole - LV posterior thickness at end-diastole)/LV posterior thickness at end-systole. Associations between OPG levels and indices of arterial and LV structure and function were evaluated by using generalized linear mixed models and adjusted for possible confounders. OPG levels were correlated with age, female sex, presence of hypertension and diabetes, and lower estimated glomerular filtration rate (P < 0.05 for all). Multivariable analysis revealed that higher OPG levels were associated with greater LV mass index, increased LV myocardial stiffness, and higher N-terminal prohormone brain natriuretic peptide levels (P < 0.05 for all).
CONCLUSION: In African-Americans, higher OPG levels were associated with characteristics common in patients with HFpEF and were significantly associated with known precursors to HFpEF. These findings indicate a potential role for OPG in the pathophysiology of HFpEF in African-Americans.

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Grants

  1. M01 RR000585/NCRR NIH HHS
  2. K08 DK099415/NIDDK NIH HHS
  3. U01 HL054463/NHLBI NIH HHS
  4. P20 GM104357/NIGMS NIH HHS
  5. L30 DK099913/NIDDK NIH HHS

MeSH Term

Black or African American
Aged
Diabetes Complications
Echocardiography
Female
Heart Failure
Heart Ventricles
Humans
Hypertension
Linear Models
Male
Middle Aged
Mississippi
Multivariate Analysis
Myocardium
Osteoprotegerin
Stroke Volume
Vascular Stiffness
Ventricular Function, Left

Chemicals

Osteoprotegerin
TNFRSF11B protein, human

Word Cloud

Created with Highcharts 10.0.0OPGLVassociatedHFpEFlevelsmyocardialstiffnessAfrican-AmericansposteriorthicknesshigherpatientspreservedejectionfractionarterialleftknownstructurefunctionanalysisagefemalewallstrainP < 005massindexincreasedAIM:Osteoprotegerinpoorprognosisheartfailurealsofibrosiscollagencross-linkingincreaseventricleLittlerelationdisproportionatelyaffectedMETHODSANDRESULTS:included1172participants>50%African-AmericancohortGeneticEpidemiologyNetworkArteriopathyStudymean63years72%useddiastolicindicatormeasuredechocardiographyassessDiastoliccalculatedend-systole - LVend-diastole/LVend-systoleAssociationsindicesevaluatedusinggeneralizedlinearmixedmodelsadjustedpossibleconfounderscorrelatedsexpresencehypertensiondiabeteslowerestimatedglomerularfiltrationrateMultivariablerevealedgreaterN-terminalprohormonebrainnatriureticpeptideCONCLUSION:characteristicscommonsignificantlyprecursorsfindingsindicatepotentialrolepathophysiologyElevatedserumosteoprotegerinventricular

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