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Alexandra Lajoie MD, PGY3 University of Washington Department of Internal Medicine

Osteoporosis and Bone Mineral Density Are Associated with Aortic Valve Calcification: the Age, Gene-Environment Susceptibility (AGES)-Reykjavik Study. Alexandra Lajoie MD, PGY3 University of Washington Department of Internal Medicine. Who develops aortic valve calcification?.

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Alexandra Lajoie MD, PGY3 University of Washington Department of Internal Medicine

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  1. Osteoporosis and Bone Mineral Density Are Associated with Aortic Valve Calcification: the Age, Gene-Environment Susceptibility (AGES)-Reykjavik Study Alexandra Lajoie MD, PGY3 University of Washington Department of Internal Medicine

  2. Who develops aortic valve calcification? *25thvs 75th percentile Stewart BF, et al. JACC 1997; 29(3):630-4. Quizlet.com

  3. Markers of bone metabolism within valve lesions. • Bone morphogenic proteins • Receptor Activator of NFkB Ligand (RANKL) • Matrix metalloproteins • Osteopontin • Osteoblasts Kaden et al, J Mol Cell Cardiol. 2004;36(1):57-66 Mohleret al, Circulation 2001;103(11):1522-1528. O'Brien et al, Circulation 1995;92(8):2163-2168. O’Brien et al, ArteriosclerThrombVascBiol 1996.

  4. Systemic regulation of bone metabolism • Inverse relationship between BMD and vascular calcification in renal disease and diabetics. Braun et al., Am J Kidney Dis. 1996;27(3):394-401. Carr et al., Bone 2008;42(1):43-52. • RANK downregulated in AV lesions Kadenet al., J Mol Cell Cardiol 204; 36(1):57-66.

  5. Study Hypothesis We therefore hypothesize that there is a significant inverse relationship between baseline measures of bone mineral density and the presence, severity and progression of aortic valve calcium in the AGES-Reykjavik population.

  6. METHODS

  7. AGES-Reykjavik • Age, Gene/Environment Susceptibility (AGES) study • Follow up study of original Reykjavik Study (1967) • >30,000 subjects recruited initially, followed longitudinally • All subjects now >67 years of age. • Joint epidemiology project between: • U.S. National Institute on Aging • Icelandic Heart Association • To identify genetic and novel risk factors for diseases affecting the elderly. • Aortic valve and bone mineral density measured from serial computed tomography scans.

  8. AGES-R Study Flow Follow Up AVC Baseline AVC “Midlife” INCIDENCE n=1934 Prospective n=5171 PROGRESSION n=1215 2007- 2012 1967- 1996 2002- 2007 Median 5.3 years (range 2.6-9.2) Median 26 years (range 11-36)

  9. Quantification of AV calcification • Quantification of calcium severity using Agatstonmethod • Can not assess hemodynamics, which has limited its clinical utility. • Semi-quantitative grading of calcium burden. • Doppler is gold standard for hemodynamic assessment.

  10. BMD Measurement • Quantitative computed tomography • Thoracic trabecular bone in vertebrae L1 & L2. • T scores calculated from CT trabecular bone scores using NHANES reference standards. diabetesendocrinology.in

  11. Statistical Methods • Performed multivariable logistic and linear regression using BMD as a predictor variable, and presence and severity of AVC as outcome. • Adjustments for: age, gender, body size, activity level, and cardiovascular risk factors. • Exclusions: • vtBMDz-scores >5 • eGFR<15 ml/min/1.73 m2

  12. RESULTS

  13. BMD Scores Data presented as mean ± SD. Comparison performed with t-test. • Osteoporosis (T-score<-2.5) in 19% of women and 3% of men.

  14. Loss of height is associated with AV calcification. • Over 26 years, from midlife to age 76±6 • Each 1cm loss of height was associated with a 1.07 (95% CI: 1.02-1.12, p=0.001) increased odds of AVC and a 0.10 (95% CI: 0.06-0.14, p<0.0005) increase in AVC severity.

  15. Relationship between osteoporosis and AVCat exam 1. • After adjusting for age, gender, body size, activity level, and cardiovascular risk factors: • Osteoporosis was associated with 1.25 (95% CI: 1.03-1.53; p=0.03) higher odds of AVC. • Osteoporosis was not associated with AVC severity (p=0.44).

  16. Changes in AVC over time. AGES-II 2007-2011 Exam 2 N=3149 AGES-Reykjavik 2002-2006 Exam 1 N=5171 5.3 years Incident AVC 20.1% AVC Progression Med AgS = 10 AgU/year [IQR: 3.0, 30.7]

  17. Relationship between osteoporosis and AVC over time. • After full adjustments: • Baseline vertebral BMD T-scores were inversely associated with AVC progression over a median 5.3 year follow up among women (p=0.01) but not men (p=0.82).

  18. Conclusions

  19. Loss of height from midlife, a marker of osteoporosis, is associated with the presence and severity of AVC in older age. • Vertebral BMD is associated with AVC on both a cross-sectional and prospective basis. • These findings suggest a mechanistic link between bone calcium loss and valvularcalcification.

  20. Further Study • Relationship between change in BMD and AVC between exam 1 and exam 2 (5.3 years). • Perturbations in bone homeostasis, increased shear forces due to altered thoracic aorta geometry, or other potential mediators merit further investigation. • Etiology of gender differences. • Bisphosphonates: Use (n=133) was associated with lower vtBMD (p<0.0005), increased odds of incident AVC (OR: 1.67, p=0.03) and with increased AVC progression (p=0.03).

  21. Acknowledgements • David S. Owens, MD • Sigurdur Sigurdsson, GuðnýEiríksdóttir, Kevin D. O’BrienVilmundurGudnason • University of Washington Departments of Cardiology and Internal Medicine

  22. Sclerosis Stenosis Lesion Formation Progressive Calcification Genetics Susceptible Substrate Aging Shear forces Male gender CV risk factors Lp(a) Height/BMI Shear forces Mineral metabolism Bone homeostasis

  23. Methodology for quantifying AVC Valve Annulus Agatston Score Area (excludes annulus) Central Calcification Annular Extension

  24. Epidemiology of aortic valve stenosis UVAhealth.com Sood & Taub, European Heart Journal 2008 Quizlet.com HeartValveSurgery.com 11% 82% 6% The Euro Heart Survey on Valvular Heart Disease, 2003.

  25. Study Population Reykjavik Study 1967(born 1907-1935) n=30,750 19,201 Died 26 years 11, 549 Survivors 11,549 Survived AGES-Reykjavik 2002-2006 Exam 1 N=5764 5.3 years AGES-II 2007-2011 Exam 2 N=2973

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