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The relation of low levels of bone mineral density with coronary artery calcium and mortality

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Abstract

Summary

Osteoporosis and atherosclerosis are two prevalent major healthcare concerns that frequently coexist. The clinical outcome of 5590 consecutive subjects who underwent coronary artery calcium (CAC) scanning and thoracic bone mineral density (BMD) measurement was assessed. A significant link between low BMD levels and CAC with increased risk of mortality in both genders across ethnicities noted.

Introduction

While a relation of CAC with lower levels of BMD reported previously; it is unclear whether low levels of BMD would be an independent risk factor for CAC and mortality. This study investigated the relation of BMD levels with CAC and mortality in both genders across ethnicities.

Methods

This study consisted of 5590 consecutive at-risk subjects without known coronary artery disease (CAD), age 57 ± 12, and 69% male, who underwent non-enhanced cardiac computed tomography, and were followed for mean of 8 years. The subjects’ CAC (Agatston score) and thoracic BMD levels (mg/cm3) were measured. CAC stratified based on the severity to CAC 0, 1–100, 101–400, and 400+. Low-BMD levels defined as BMD levels below median (180 mg/cm3). Physician verified that all-cause mortality was assessment hard-endpoint. Multivariate regression analysis, adjusted for age, gender, and other cardiovascular risk factors, was used to assess the relationship between BMD and CAC.

Results

The BMD levels were proportionally lowering with the severity of CAC in both genders, especially in postmenopausal women (p < 0.05). The risk of each standard deviation reduce in BMD levels increased with the severity of CAC, as compared to CAC = 0 across ethnicities (p < 0.05). Low BMD levels were an independent predictor of mortality and event-free survival rate decreased from 99% in those within normal BMD levels to 93% in those with low BMD levels (p = 0.0001). Furthermore, a significant link between low BMD levels and CAC > 0 with increased risk of mortality was noted (p = 0.0001). The relative risk of death was 2.8, 5.9, and 14.3-folds higher in CAC 1–100, 101–400, and 400+ with low BMD levels, compared to CAC = 0 and within normal BMD levels, respectively (p < 0.05).

Conclusions

The lower BMD levels are independently associated with the severity of CAC that predicts mortality.

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References

  1. Higgins CL, Marvel SA, Morrisett JD (2005) Quantification of calcification in atherosclerotic lesions. Arterioscler Thromb Vasc Biol 25:1567–1576

    Article  PubMed  CAS  Google Scholar 

  2. Farhat GN, Strotmeyer ES, Newman AB, Sutton-Tyrrell K, Bauer DC, Harris T, Johnson KC, Taaffe DR, Cauley JA (2006) Volumetric and areal bone mineral density measures are associated with cardiovascular disease in older men and women: the health, aging, and body composition study. Calcif Tissue Int 79:102–111

    Article  PubMed  CAS  Google Scholar 

  3. Varma R, Aronow WS, Basis Y, Singh T, Kalapatapu K, Weiss MB, Pucillo AL, Monsen CE (2008) Relation of bone mineral density to frequency of coronary heart disease. Am J Cardiol 101:1103–1104

    Article  PubMed  Google Scholar 

  4. Mangiafico RA, Russo E, Riccobene S, Pennisi P, Mangiafico M, D'Amico F, Fiore CE (2006) Increased prevalence of peripheral arterial disease in osteoporotic postmenopausal women. J Bone Miner Metab 24:125–131

    Article  PubMed  Google Scholar 

  5. Alexandersen P, Tanko LB, Bagger YZ, Jespersen J, Skouby SO, Christiansen C (2006) Associations between aortic calcification and components of body composition in elderly men. Obesity (Silver Spring) 14:1571–1578

    Article  Google Scholar 

  6. Nordstrom A, Eriksson M, Stegmayr B, Gustafson Y, Nordstrom P (2010) Low bone mineral density is an independent risk factor for stroke and death. Cerebrovasc Dis 29:130–136

    Article  PubMed  Google Scholar 

  7. QuX, HuangX, JinF, WangH, HaoY, TangT, DaiK (2011) Bone mineral density and all-cause, cardiovascular and stroke mortality: a meta-analysis of prospective cohort studies. Int J Cardiol

  8. von der Recke P, Hansen MA, Hassager C (1999) The association between low bone mass at the menopause and cardiovascular mortality. Am J Med 106:273–278

    Article  PubMed  Google Scholar 

  9. Jorgensen L, Joakimsen O, Rosvold Berntsen GK, Heuch I, Jacobsen BK (2004) Low bone mineral density is related to echogenic carotid artery plaques: a population-based study. Am J Epidemiol 160:549–556

    Article  PubMed  Google Scholar 

  10. Detrano R, Guerci AD, Carr JJ, Bild DE, Burke G, Folsom AR, Liu K, Shea S, Szklo M, Bluemke DA, O'Leary DH, Tracy R, Watson K, Wong ND, Kronmal RA (2008) Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med 358:1336–1345

    Article  PubMed  CAS  Google Scholar 

  11. Brown ER, Kronmal RA, Bluemke DA, Guerci AD, Carr JJ, Goldin J, Detrano R (2008) Coronary calcium coverage score: determination, correlates, and predictive accuracy in the Multi-Ethnic Study of Atherosclerosis. Radiology 247:669–675

    Article  PubMed  PubMed Central  Google Scholar 

  12. Parfitt AM (1988) Bone remodeling. Henry Ford Hosp Med J 36:143–144

    PubMed  CAS  Google Scholar 

  13. Lang TF, Li J, Harris ST, Genant HK (1999) Assessment of vertebral bone mineral density using volumetric quantitative CT. J Comput Assist Tomogr 23:130–137

    Article  PubMed  CAS  Google Scholar 

  14. Genant HK, Turski PA, Moss AA (1983) Advances in CT assessment of metabolic and endocrine disorders. Adv Intern Med 28:409–447

    PubMed  CAS  Google Scholar 

  15. Lenchik L, Shi R, Register TC, Beck SR, Langefeld CD, Carr JJ (2004) Measurement of trabecular bone mineral density in the thoracic spine using cardiac gated quantitative computed tomography. J Comput Assist Tomogr 28:134–139

    Article  PubMed  Google Scholar 

  16. Budoff MJ, Khairallah W, Li D, Gao YL, Ismaeel H, Flores F, Child J, Carson S, Mao SS (2012) Trabecular bone mineral density measurement using thoracic and lumbar quantitative computed tomography. Acad Radiol 19:179–183

    Article  PubMed  Google Scholar 

  17. Wong M, Papa A, Lang T, Hodis HN, Labree L, Detrano R (2005) Validation of thoracic quantitative computed tomography as a method to measure bone mineral density. Calcif Tissue Int 76:7–10

    PubMed  CAS  Google Scholar 

  18. Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB (1998) Prediction of coronary heart disease using risk factor categories. Circulation 97:1837–1847

    Article  PubMed  CAS  Google Scholar 

  19. Becker CR, Knez A, Jakobs TF, Aydemir S, Becker A, Schoepf UJ, Bruening R, Haberl R, Reiser MF (1999) Detection and quantification of coronary artery calcification with electron-beam and conventional CT. Eur Radiol 9:620–624

    Article  PubMed  CAS  Google Scholar 

  20. Budoff MJ, Hamirani YS, Gao YL, Ismaeel H, Flores FR, Child J, Carson S, Nee JN, Mao S (2010) Measurement of thoracic bone mineral density with quantitative CT. Radiology 257:434–440

    Article  PubMed  Google Scholar 

  21. McFarlane SI, Muniyappa R, Shin JJ, Bahtiyar G, Sowers JR (2004) Osteoporosis and cardiovascular disease: brittle bones and boned arteries, is there a link? Endocrine 23:1–10

    Article  PubMed  CAS  Google Scholar 

  22. Hyder JA, Allison MA, Barrett-Connor E, Detrano R, Wong ND, Sirlin C, Gapstur SM, Ouyang P, Carr JJ, Criqui MH (2010) Bone mineral density and atherosclerosis: the multi-ethnic study of atherosclerosis, abdominal aortic calcium study. Atherosclerosis 209:283–289

    Article  PubMed  CAS  Google Scholar 

  23. Yeboah J, Crouse JR, Hsu FC, Burke GL, Herrington DM (2007) Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study. Circulation 115:2390–2397

    Article  PubMed  Google Scholar 

  24. Kirma C, Akcakoyun M, Esen AM, Barutcu I, Karakaya O, Saglam M, Kargin R, Turkmen M, Boztosun B, Izgi A, Sonmez K (2007) Relationship between endothelial function and coronary risk factors in patients with stable coronary artery disease. Circ J 71:698–702

    Article  PubMed  Google Scholar 

  25. Quyyumi AA (2003) Prognostic value of endothelial function. Am J Cardiol 91:19H–24H

    Article  PubMed  CAS  Google Scholar 

  26. Libby P, Okamoto Y, Rocha VZ, Folco E (2010) Inflammation in atherosclerosis: transition from theory to practice. Circulation J: Off J Jpn Circ Soc 74:213–220

    Article  CAS  Google Scholar 

  27. Czerny B, Kaminski A, Kurzawski M, Kotrych D, Safranow K, Dziedziejko V, Bohatyrewicz A, Pawlik A (2010) The association of IL-1beta, IL-2, and IL-6 gene polymorphisms with bone mineral density and osteoporosis in postmenopausal women. Eur J Obstet Gynecol Reprod Biol 149:82–85

    Article  PubMed  CAS  Google Scholar 

  28. Koh JM, Khang YH, Jung CH, Bae S, Kim DJ, Chung YE, Kim GS (2005) Higher circulating hsCRP levels are associated with lower bone mineral density in healthy pre- and postmenopausal women: evidence for a link between systemic inflammation and osteoporosis. Osteoporos Int: J Established Result Coop Between Eur Found Osteoporos Nat Osteoporos Found USA 16:1263–1271

    Article  CAS  Google Scholar 

  29. Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N (1999) VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 5:623–628

    Article  PubMed  CAS  Google Scholar 

  30. Deckers MM, Karperien M, van der Bent C, Yamashita T, Papapoulos SE, Lowik CW (2000) Expression of vascular endothelial growth factors and their receptors during osteoblast differentiation. Endocrinology 141:1667–1674

    Article  PubMed  CAS  Google Scholar 

  31. Ahmadi N, Zughaib H, Patel N, Rathod A, Hajsadeghi F, Flores F, Ebrahimi R, Mao SS, Budoff M (2011) Relation of changes in coronary artery calcium, bone mineral density measured computed tomography and aged garlic extract. Circulation 124(Suppl 21):A11080

  32. Fraley AE, Schwartz GG, Olsson AG, Kinlay S, Szarek M, Rifai N, Libby P, Ganz P, Witztum JL, Tsimikas S (2009) Relationship of oxidized phospholipids and biomarkers of oxidized low-density lipoprotein with cardiovascular risk factors, inflammatory biomarkers, and effect of statin therapy in patients with acute coronary syndromes: results from the MIRACL (Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering) trial. J Am Coll Cardiol 53:2186–2196

    Article  PubMed  CAS  Google Scholar 

  33. Barengolts EI, Berman M, Kukreja SC, Kouznetsova T, Lin C, Chomka EV (1998) Osteoporosis and coronary atherosclerosis in asymptomatic postmenopausal women. Calcif Tissue Int 62:209–213

    Article  PubMed  CAS  Google Scholar 

  34. Lee SN, Cho JY, Eun YM, Song SW, Moon KW (2016) Associations between osteoporosis and coronary artery disease in postmenopausal women. Climacteric 19:458–462

    Article  PubMed  CAS  Google Scholar 

  35. Pierre-Louis B, Aronow WS, Yoon JH, Ahn C, DeLuca AJ (2009) Relation of bone mineral density to stress test-induced myocardial ischemia. Am J Cardiol 104:199–201

    Article  PubMed  Google Scholar 

  36. Kiel DP, Kauppila LI, Cupples LA, Hannan MT, O'Donnell CJ, Wilson PW (2001) Bone loss and the progression of abdominal aortic calcification over a 25 year period: the Framingham Heart Study. Calcif Tissue Int 68:271–276

    Article  PubMed  CAS  Google Scholar 

  37. Nicoll R, Wiklund U, Zhao Y, Diederichsen A, Mickley H, Ovrehus K, Zamorano P, Gueret P, Schmermund A, Maffei E, Cademartiri F, Budoff M, Henein M (2016) The coronary calcium score is a more accurate predictor of significant coronary stenosis than conventional risk factors in symptomatic patients: Euro-CCAD study. Int J Cardiol 207:13–19

    Article  PubMed  CAS  Google Scholar 

  38. Ceponiene I, Nakanishi R, Osawa K, Kanisawa M, Nezarat N, Rahmani S, Kissel K, Kim M, Jayawardena E, Broersen A, Kitslaar P, Budoff MJ (2017) Coronary artery calcium progression is associated with coronary plaque volume progression: results from a quantitative semiautomated coronary artery plaque analysis. JACC Cardiovasc Imaging. https://doi.org/10.1016/j.jcmg.2017.07.023

  39. Ostrom MP, Gopal A, Ahmadi N, Nasir K, Yang E, Kakadiaris I, Flores F, Mao SS, Budoff MJ (2008) Mortality incidence and the severity of coronary atherosclerosis assessed by computed tomography angiography. J Am Coll Cardiol 52:1335–1343

    Article  PubMed  Google Scholar 

  40. Minson CT, Wong BJ (2004) Reactive hyperemia as a test of endothelial or microvascular function? J Am Coll Cardiol 43:2147; author reply 2147-2148–2147; author reply 2148

    Article  PubMed  Google Scholar 

  41. Binggeli C, Spieker LE, Corti R, Sudano I, Stojanovic V, Hayoz D, Luscher TF, Noll G (2003) Statins enhance postischemic hyperemia in the skin circulation of hypercholesterolemic patients: a monitoring test of endothelial dysfunction for clinical practice? J Am Coll Cardiol 42:71–77

    Article  PubMed  CAS  Google Scholar 

  42. Ahmadi N, Mao S, Hajsadeghi F, Arnold B, GaoY, Flores F, Merz NB, Ebrahimi R, Azen S, Budoff M (2011) Bone mineral density is inversely related with coronary artery calcification independent of age, gender and ethnicity. Circulation 124(Suppl 21): A11064

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Correspondence to N. Ahmadi.

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Matthew Budoff is a speaker bureau of GE. All other authors have no disclosures pertaining this manuscript.

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Ahmadi, N., Mao, S.S., Hajsadeghi, F. et al. The relation of low levels of bone mineral density with coronary artery calcium and mortality. Osteoporos Int 29, 1609–1616 (2018). https://doi.org/10.1007/s00198-018-4524-7

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  • DOI: https://doi.org/10.1007/s00198-018-4524-7

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