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Original article
Association of inflammatory, lipid and mineral markers with cardiac calcification in older adults
  1. Anna E Bortnick1,
  2. Traci M Bartz2,
  3. Joachim H Ix3,
  4. Michel Chonchol4,
  5. Alexander Reiner2,
  6. Mary Cushman5,
  7. David Owens2,
  8. Eddy Barasch6,
  9. David S Siscovick7,
  10. John S Gottdiener8,
  11. Jorge R Kizer1,9
  1. 1Cardiology Division, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA
  2. 2Department of Biostatistics, University of Washington, Seattle, Washington, USA
  3. 3Department of Medicine, and the Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California, and Nephrology Section, Veteran Affairs San Diego Health Care System, San Diego, California, USA
  4. 4Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Denver, Aurora, Colorado, USA
  5. 5Departments of Pathology and Biochemistry, University of Vermont, Burlington, Vermont, USA
  6. 6Department of Research and Education, St. Francis Hospital, The Heart Center, Roslyn, New York, USA
  7. 7New York Academy of Medicine, New York, New York, USA
  8. 8Division of Cardiovascular Medicine, Department of Cardiology, University of Maryland, Baltimore, Maryland, USA
  9. 9Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA
  1. Correspondence to Jorge R Kizer, MD, MSc, Cardiovascular Clinical Research Unit, 1300 Morris Park Ave, Bronx, NY 10461, USA; jorge.kizer{at}einstein.yu.edu

Abstract

Objective Calcification of the aortic valve and adjacent structures involves inflammatory, lipid and mineral metabolism pathways. We hypothesised that circulating biomarkers reflecting these pathways are associated with cardiac calcification in older adults.

Methods We investigated the associations of various biomarkers with valvular and annular calcification in the Cardiovascular Health Study. Of the 5888 participants, up to 3585 were eligible after exclusions for missing biomarker, covariate or echocardiographic data. We evaluated analytes reflecting lipid (lipoprotein (Lp) (a), Lp-associated phospholipase A2 (LpPLA2) mass and activity), inflammatory (interleukin-6, soluble (s) CD14) and mineral metabolism (fetuin-A, fibroblast growth factor (FGF)-23) pathways that were measured within 5 years of echocardiography. The relationships of plasma biomarkers with aortic valve calcification (AVC), aortic annular calcification (AAC) and mitral annular calcification (MAC) were assessed with relative risk (RR) regression.

Results Calcification was prevalent: AVC 59%, AAC 45% and MAC 41%. After adjustment, Lp(a), LpPLA2 mass and activity and sCD14 were positively associated with AVC. RRs for AVC per SD (95% CI) were as follows: Lp(a), 1.051 (1.022 to 1.081); LpPLA2 mass, 1.036 (1.006 to 1.066) and LpPLA2 activity, 1.037 (1.004 to 1.071); sCD14, 1.039 (1.005 to 1.073). FGF-23 was positively associated with MAC, 1.040 (1.004 to 1.078) and fetuin-A was negatively associated, 0.949 (0.911 to 0.989). No biomarkers were significantly associated with AAC.

Conclusion This study shows novel associations of circulating FGF-23 and fetuin-A with MAC, and LpPLA2 and sCD14 with AVC, confirming that previously reported for Lp(a). Further investigation of Lp and inflammatory pathways may provide added insight into the aetiology of AVC, while study of phosphate regulation may illuminate the pathogenesis of MAC.

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Footnotes

  • This work was presented, in part, at the American College of Cardiology Scientific Sessions, San Diego, California, 2015

  • Contributors Conception or design of the work: AEB and JRK. Data collection: MiC, JHI, MaC, AR, EB and JSG. Data analysis and interpretation: TMB, AEB, MiC, JHI, MaC, AR, DO, EB, JSG, DSS and JRK. Drafting the article: AEB and JRK. Critical revision of the article: AEB, TMB, MiC, JHI, MaC, AR, DO, EB, DSS, JSG and JRK. Final approval of the version to be published: AEB, TMB, MiC, JHI, MaC, AR, DO, EB, JSG, DSS and JRK.

  • Funding This work was supported by R01 HL-094555, as well as by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086 and grant U01HL080295 from the National Heart, Lung and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by R01AG023629 from the National Institute on Aging. AEB is supported by a fellowship from the Empire Clinical Research Investigator Program. A full list of principal Cardiovascular Health Study investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

  • Competing interests MC and JRK have received research funding from diaDexus (manufacturer of the LpPLA2 test). JRK reports ownership of stock in Pfizer and Gilead Sciences.

  • Ethics approval Institutional Review Board approval received at each participating institution.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement De-identified data from the Cardiovascular Health Study can be obtained from the USA National Institutes of Health (BioLINCC) by members of the research community.

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