The relation of low levels of bone mineral density with coronary artery calcium and mortality
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.
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.
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.
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).
The lower BMD levels are independently associated with the severity of CAC that predicts mortality.
KeywordsBone mineral density Computed tomography Coronary artery calcium Coronary artery disease Outcome
Compliance with ethical standards
Conflicts of interest
Matthew Budoff is a speaker bureau of GE. All other authors have no disclosures pertaining this manuscript.
- 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 79:102–111CrossRefPubMedGoogle 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 CardiolGoogle 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 149:82–85CrossRefPubMedGoogle 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 16:1263–1271CrossRefGoogle 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):A11080Google Scholar
- 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 53:2186–2196CrossRefPubMedGoogle 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 207:13–19CrossRefPubMedGoogle 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
- 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 42:71–77CrossRefPubMedGoogle 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): A11064Google Scholar