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01-12-2017 | Original Article

Relationship of bone mineral density with valvular and annular calcification in community-dwelling older people: The Cardiovascular Health Study

Authors: Daniele Massera, Shuo Xu, Traci M. Bartz, Anna E. Bortnick, Joachim H. Ix, Michel Chonchol, David S. Owens, Eddy Barasch, Julius M. Gardin, John S. Gottdiener, John R. Robbins, David S. Siscovick, Jorge R. Kizer

Published in: Archives of Osteoporosis | Issue 1/2017

Abstract

Summary

Associations between bone mineral density and aortic valvular, aortic annular, and mitral annular calcification were investigated in a cross-sectional analysis of a population-based cohort of 1497 older adults. Although there was no association between continuous bone mineral density and outcomes, a significant association between osteoporosis and aortic valvular calcification in men was found.

Introduction

The process of cardiac calcification bears a resemblance to skeletal bone metabolism and its regulation. Experimental studies suggest that bone mineral density (BMD) and valvular calcification may be reciprocally related, but epidemiologic data are sparse.

Methods

We tested the hypothesis that BMD of the total hip and femoral neck measured by dual-energy X-ray absorptiometry (DXA) is inversely associated with prevalence of three echocardiographic measures of cardiac calcification in a cross-sectional analysis of 1497 older adults from the Cardiovascular Health Study. The adjusted association of BMD with aortic valve calcification (AVC), aortic annular calcification (AAC), and mitral annular calcification (MAC) was assessed with relative risk (RR) regression.

Results

Mean (SD) age was 76.2 (4.8) years; 58% were women. Cardiac calcification was highly prevalent in women and men: AVC, 59.5 and 71.0%; AAC 45.1 and 46.7%; MAC 42.8 and 39.5%, respectively. After limited and full adjustment for potential confounders, no statistically significant associations were detected between continuous BMD at either site and the three measures of calcification. Assessment of WHO BMD categories revealed a significant association between osteoporosis at the total hip and AVC in men (adjusted RR compared with normal BMD = 1.24 (1.01–1.53)). In graded sensitivity analyses, there were apparent inverse associations between femoral neck BMD and AVC with stenosis in men, and femoral neck BMD and moderate/severe MAC in women, but these were not significant.

Conclusion

These findings support further investigation of the sex-specific relationships between low BMD and cardiac calcification, and whether processes linking the two could be targeted for therapeutic ends.

Kizer JR, Wiebers DO, Whisnant JP, Galloway JM, Welty TK, Lee ET, Best LG, Resnick HE, Roman MJ, Devereux RB (2005) Mitral annular calcification, aortic valve sclerosis, and incident stroke in adults free of clinical cardiovascular disease: the Strong Heart Study. Stroke 36(12):2533–2537CrossRefPubMed

Barasch E, Gottdiener JS, Larsen EKM, Chaves PHM, Newman AB, Manolio TA (2006) Clinical significance of calcification of the fibrous skeleton of the heart and aortosclerosis in community dwelling elderly. The Cardiovascular Health Study (CHS). Am Heart J 151(1):39–47CrossRefPubMed

Barasch E, Gottdiener JS, Marino Larsen EK, Chaves PHM, Newman AB (2006) Cardiovascular morbidity and mortality in community-dwelling elderly individuals with calcification of the fibrous skeleton of the base of the heart and aortosclerosis (The Cardiovascular Health Study). Am J Cardiol 97(9):1281–1286CrossRefPubMed

Lindman BR, Clavel M-A, Mathieu P, Iung B, Lancellotti P, Otto CM, Pibarot P (2016) Calcific aortic stenosis. Nat Rev Dis Primer 2:16006CrossRef

Sud K, Agarwal S, Parashar A, Raza MQ, Patel K, Min D, Rodriguez LL, Krishnaswamy A, Mick SL, Gillinov AM, Tuzcu EM, Kapadia SR (2016) Degenerative mitral stenosis: unmet need for percutaneous interventions. Circulation 133(16):1594–1604CrossRefPubMed

Pawade TA, Newby DE, Dweck MR (2015) Calcification in aortic stenosis: the skeleton key. J Am Coll Cardiol 66(5):561–577CrossRefPubMed

Mohler ER, Gannon F, Reynolds C, Zimmerman R, Keane MG, Kaplan FS (2001) Bone formation and inflammation in cardiac valves. Circulation 103(11):1522–1528CrossRefPubMed

Rajamannan NM, Subramaniam M, Rickard D, Stock SR, Donovan J, Springett M, Orszulak T, Fullerton DA, Tajik AJ, Bonow RO, Spelsberg T (2003) Human aortic valve calcification is associated with an osteoblast phenotype. Circulation 107(17):2181–2184CrossRefPubMedPubMedCentral

Arounlangsy P, Sawabe M, Izumiyama N, Koike M (2004) Histopathogenesis of early-stage mitral annular calcification. J Med Dent Sci 51(1):35–44PubMed

10.

Hyder JA, Allison MA, Wong N, Papa A, Lang TF, Sirlin C, Gapstur SM, Ouyang P, Carr JJ, Criqui MH (2009) Association of coronary artery and aortic calcium with lumbar bone density: the MESA Abdominal Aortic Calcium Study. Am J Epidemiol 169(2):186–194CrossRefPubMed

11.

Chan JJ, Cupples LA, Kiel DP, O’Donnell CJ, Hoffmann U, Samelson EJ (2015) QCT volumetric bone mineral density and vascular and valvular calcification: The Framingham Study. J Bone Miner Res 30(10):1767–1774CrossRefPubMedPubMedCentral

12.

Kado DM, Browner WS, Blackwell T, Gore R, Cummings SR (2000) Rate of bone loss is associated with mortality in older women: a prospective study. J Bone Miner Res 15(10):1974–1980CrossRefPubMed

13.

Samelson EJ, Kiel DP, Broe KE, Zhang Y, Cupples LA, Hannan MT, Wilson PWF, Levy D, Williams SA, Vaccarino V (2004) Metacarpal cortical area and risk of coronary heart disease: The Framingham Study. Am J Epidemiol 159(6):589–595CrossRefPubMed

14.

Farhat GN, Newman AB, Sutton-Tyrrell K, Matthews KA, Boudreau R, Schwartz AV, Harris T, Tylavsky F, Visser M, Cauley JA, Health ABC Study (2007) The association of bone mineral density measures with incident cardiovascular disease in older adults. Osteoporos Int 18(7):999–1008CrossRefPubMed

15.

Sugihara N, Matsuzaki M (1993) The influence of severe bone loss on mitral annular calcification in postmenopausal osteoporosis of elderly Japanese women. Jpn Circ J 57(1):14–26CrossRefPubMed

16.

Davutoglu V, Yilmaz M, Soydinc S, Celen Z, Turkmen S, Sezen Y, Akcay M, Akdemir I, Aksoy M (2004) Mitral annular calcification is associated with osteoporosis in women. Am Heart J 147(6):1113–1116CrossRefPubMed

17.

Aksoy Y, Yagmur C, Tekin GO, Yagmur J, Topal E, Kekilli E, Turhan H, Kosar F, Yetkin E (2005) Aortic valve calcification: association with bone mineral density and cardiovascular risk factors. Coron Artery Dis 16(6):379–383CrossRefPubMed

18.

Choi HS, Rhee Y, Hur NW, Chung N, Lee EJ, Lim S-K (2009) Association between low bone mass and aortic valve sclerosis in Koreans. Clin Endocrinol 71(6):792–797CrossRef

19.

Pfister R, Michels G, Sharp SJ, Luben R, Wareham NJ, Khaw K-T (2015) Inverse association between bone mineral density and risk of aortic stenosis in men and women in EPIC-Norfolk prospective study. Int J Cardiol 178:29–30CrossRefPubMed

20.

Fried LP, Borhani NO, Enright P, Furberg CD, Gardin JM, Kronmal RA, Kuller LH, Manolio TA, Mittelmark MB, Newman A (1991) The Cardiovascular Health Study: design and rationale. Ann Epidemiol 1(3):263–276CrossRefPubMed

21.

Ives DG, Fitzpatrick AL, Bild DE, Psaty BM, Kuller LH, Crowley PM, Cruise RG, Theroux S (1995) Surveillance and ascertainment of cardiovascular events. The Cardiovascular Health Study. Ann Epidemiol 5(4):278–285CrossRefPubMed

22.

Cushman M, Cornell ES, Howard PR, Bovill EG, Tracy RP (1995) Laboratory methods and quality assurance in the Cardiovascular Health Study. Clin Chem 41(2):264–270PubMed

23.

Virtanen JK, Mozaffarian D, Cauley JA, Mukamal KJ, Robbins J, Siscovick DS (2010) Fish consumption, bone mineral density, and risk of hip fracture among older adults: the cardiovascular health study. J Bone Miner Res 25(9):1972–1979CrossRefPubMedPubMedCentral

24.

Robbins J, Hirsch C, Whitmer R, Cauley J, Harris T (2001) The association of bone mineral density and depression in an older population. J Am Geriatr Soc 49(6):732–736CrossRefPubMed

25.

Looker AC, Borrud LG, Hughes JP, Fan B, Shepherd JA, Melton LJ (2012) Lumbar spine and proximal femur bone mineral density, bone mineral content, and bone area: United States, 2005-2008. Vital Health Stat 11(251):1–132

26.

Gardin JM, Wong ND, Bommer W, Klopfenstein HS, Smith VE, Tabatznik B, Siscovick D, Lobodzinski S, Anton-Culver H, Manolio TA (1992) Echocardiographic design of a multicenter investigation of free-living elderly subjects: the Cardiovascular Health Study. J Am Soc Echocardiogr 5(1):63–72CrossRefPubMed

27.

Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS (1999) Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Engl J Med 341(3):142–147CrossRefPubMed

28.

American Diabetes Association (2014) Standards of medical care in diabetes—2014. Diabetes Care 37(Suppl 1):S14–S80CrossRef

29.

Newman DJ, Thakkar H, Edwards RG, Wilkie M, White T, Grubb AO, Price CP (1995) Serum cystatin C measured by automated immunoassay: a more sensitive marker of changes in GFR than serum creatinine. Kidney Int 47(1):312–318CrossRefPubMed

30.

Psaty BM, Kuller LH, Bild D, Burke GL, Kittner SJ, Mittelmark M, Price TR, Rautaharju PM, Robbins J (1995) Methods of assessing prevalent cardiovascular disease in the Cardiovascular Health Study. Ann Epidemiol 5(4):270–277CrossRefPubMed

31.

Hannan MT, Felson DT, Anderson JJ (1992) Bone mineral density in elderly men and women: results from the Framingham Osteoporosis Study. J Bone Miner Res 7(5):547–553CrossRefPubMed

32.

Bortnick AE, Bartz TM, Ix JH, Chonchol M, Reiner A, Cushman M, Owens D, Barasch E, Siscovick DS, Gottdiener JS, Kizer JR (2016) Association of inflammatory, lipid and mineral markers with cardiac calcification in older adults. Heart 102(22):1826–1834CrossRef

33.

Thanassoulis G, Campbell CY, Owens DS, Smith JG, Smith AV, Peloso GM, Kerr KF, Pechlivanis S, Budoff MJ, Harris TB, Malhotra R, O’Brien KD, Kamstrup PR, Nordestgaard BG, Tybjaerg-Hansen A, Allison MA, Aspelund T, Criqui MH, Heckbert SR, Hwang S-J, Liu Y, Sjogren M, van der Pals J, Kälsch H, Mühleisen TW, Nöthen MM, Cupples LA, Caslake M, Di Angelantonio E, Danesh J, Rotter JI, Sigurdsson S, Wong Q, Erbel R, Kathiresan S, Melander O, Gudnason V, O’Donnell CJ, Post WS, CHARGE Extracoronary Calcium Working Group (2013) Genetic associations with valvular calcification and aortic stenosis. N Engl J Med 368(6):503–512CrossRefPubMedPubMedCentral

34.

Henzell S, Dhaliwal S, Pontifex R, Gill F, Price R, Retallack R, Prince R (2000) Precision error of fan-beam dual X-ray absorptiometry scans at the spine, hip, and forearm. J Clin Densitom 3(4):359–364CrossRefPubMed

35.

Dweck MR, Khaw HJ, Sng GKZ, Luo ELC, Baird A, Williams MC, Makiello P, Mirsadraee S, Joshi NV, van Beek EJR, Boon NA, Rudd JHF, Newby DE (2013) Aortic stenosis, atherosclerosis, and skeletal bone: is there a common link with calcification and inflammation? Eur Heart J 34(21):1567–1574CrossRefPubMed

36.

Ortlepp JR (2001) The vitamin D receptor genotype predisposes to the development of calcific aortic valve stenosis. Heart 85:635–638CrossRefPubMedPubMedCentral

37.

Schmitz F, Ewering S, Zerres K, Klomfass S, Hoffmann R, Ortlepp JR (2009) Parathyroid hormone gene variant and calcific aortic stenosis. J Heart Valve Dis 18(3):262–267PubMed

38.

Iwata S, Walker MD, Di Tullio MR, Hyodo E, Jin Z, Liu R, Sacco RL, Homma S, Silverberg SJ (2012) Aortic valve calcification in mild primary hyperparathyroidism. J Clin Endocrinol Metab 97(1):132–137CrossRefPubMed

39.

Linefsky JP, O’Brien KD, Katz R, de Boer IH, Barasch E, Jenny NS, Siscovick DS, Kestenbaum B (2011) Association of serum phosphate levels with aortic valve sclerosis and annular calcification: the cardiovascular health study. J Am Coll Cardiol 58(3):291–297CrossRefPubMedPubMedCentral

40.

Parhami F, Morrow AD, Balucan J, Leitinger N, Watson AD, Tintut Y, Berliner JA, Demer LL (1997) Lipid oxidation products have opposite effects on calcifying vascular cell and bone cell differentiation. A possible explanation for the paradox of arterial calcification in osteoporotic patients. Arterioscler Thromb Vasc Biol 17(4):680–687CrossRefPubMed

41.

Elmariah S, Delaney JAC, O’Brien KD, Budoff MJ, Vogel-Claussen J, Fuster V, Kronmal RA, Halperin JL (2010) Bisphosphonate use and prevalence of valvular and vascular calcification in women: The Multi-Ethnic Study of Atherosclerosis. J Am Coll Cardiol 56(21):1752–1759CrossRefPubMedPubMedCentral

42.

Aksoy O, Cam A, Goel SS, Houghtaling PL, Williams S, Ruiz-Rodriguez E, Menon V, Kapadia SR, Tuzcu EM, Blackstone EH, Griffin BP (2012) Do bisphosphonates slow the progression of aortic stenosis? J Am Coll Cardiol 59(16):1452–1459CrossRefPubMed

43.

Hekimian G, Boutten A, Flamant M, Duval X, Dehoux M, Benessiano J, Huart V, Dupré T, Berjeb N, Tubach F, Iung B, Vahanian A, Messika-Zeitoun D (2013) Progression of aortic valve stenosis is associated with bone remodelling and secondary hyperparathyroidism in elderly patients—the COFRASA study. Eur Heart J 34(25):1915–1922CrossRefPubMed

44.

Umana E, Ahmed W, Alpert MA (2003) Valvular and perivalvular abnormalities in end-stage renal disease. Am J Med Sci 325(4):237–242CrossRefPubMed

45.

Asselbergs FW, Mozaffarian D, Katz R, Kestenbaum B, Fried LF, Gottdiener JS, Shlipak MG, Siscovick DS (2009) Association of renal function with cardiac calcifications in older adults: the cardiovascular health study. Nephrol Dial Transplant 24(3):834–840CrossRefPubMed

Title: Relationship of bone mineral density with valvular and annular calcification in community-dwelling older people: The Cardiovascular Health Study
Authors: Daniele Massera
Shuo Xu
Traci M. Bartz
Anna E. Bortnick
Joachim H. Ix
Michel Chonchol
David S. Owens
Eddy Barasch
Julius M. Gardin
John S. Gottdiener
John R. Robbins
David S. Siscovick
Jorge R. Kizer
Publication date: 01-12-2017
Publisher: Springer London
Published in: Archives of Osteoporosis / Issue 1/2017
Print ISSN: 1862-3522
Electronic ISSN: 1862-3514
DOI: https://doi.org/10.1007/s11657-017-0347-y

At a glance: The STEP trials

Springer Medicine

Relationship of bone mineral density with valvular and annular calcification in community-dwelling older people: The Cardiovascular Health Study

Abstract

Summary

Introduction

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusion

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