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Relationship between age, osteoporosis and coronary artery calcification detected by high-definition computerized tomography in Chinese elderly men
Archives of Gerontology and Geriatrics 79 (2018) 8–12
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Relationship between age, osteoporosis and coronary artery calcification detected by high-definition computerized tomography in Chinese elderly men ⁎
T
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Yuan Liua, Shihui Fua,b, Yongyi Baia, , Leiming Luoa, , Ping Yea a Department of Geriatric Cardiology, National Clinical Research Center of Geriatrics Disease, Beijing Key Laboratory of Precision Medicine for Chronic Heart Failure, Chinese People’s Liberation Army General Hospital, Beijing, China b Department of Cardiology and Hainan Branch, Chinese People’s Liberation Army General Hospital, Beijing, China
A R T I C LE I N FO
A B S T R A C T
Keywords: Age Osteoporosis Elderly Coronary artery calcification High-definition computerized tomography
Background: Few studies have analyzed the relationship between bone mineral density (BMD) and coronary artery calcification (CAC) in older men, and it remains subject to debate. The present study was designed to evaluate the age-related acceleration of osteoporosis and CAC, as well as the relationship between BMD and CAC in Chinese elderly men. Methods: Participants included 120 men older than 60 years. CAC was measured with high-definition computerized tomography. It is a highly sensitive technique for detecting the CAC and provides the most accurate CAC scores up to date. Results: Mean (standard deviation) age was 73 (8.5) years. For osteoporosis, there was a strongly inverse correlation between age and BMD of all scanned body parts (p < 0.05 for all) except the lumbar spine 1–4 (p > 0.05 for all). For CAC, there was a moderately positive correlation of agatston, volume and mass scores with age. CAC was present in 67% of participants. There was no significant correlation between all kinds of CAC scores including agatston, volume and mass scores, and BMD of all scanned body parts including lumbar spine 1–4, femoral neck, femoral trochanter and total femur (p > 0.05 for all). BMD of all these body parts had no ability to identify the CAC (p > 0.05 for all). Furthermore, on multiple linear regression analysis, the relationship between CAC scores and BMD remained statistically non-significant. Conclusions: Age constituted an important factor common for loss of BMD and development of CAC detected by HDCT, and no direct relationship was observed between osteoporosis and CAC in Chinese elderly men.
1. Introduction Osteoporosis is a common feature among the elderly. It represents a major public health problem that affects both men and women, usually as they grow older. Coronary artery calcification (CAC) is also a highly prevalent condition among the elderly, and its development has been demonstrated to be associated with future cardiovascular risk (Watanabe, Lemos, Manfredi, Draibe, & Canziani, 2010). Until recently, several clinical data have reported a relationship between osteoporosis and vascular calcification, including carotid artery plaque, aortic calcification and arterial stiffness (Frost et al., 2008; Jorgensen, Joakimsen, Rosvold Berntsen, Heuch, & Jacobsen, 2004). More importantly, previous studies have realized that bone mineral density (BMD) is implicated with CAC. However, while most of these studies have considered osteoporosis as a disease of older women and specially
⁎
chosen older women as the study participants, it is an undeniable fact that accelerated osteoporosis also occurs in older men. Other studies have proved that there is a sex difference in terms of vascular calcification and osteoporosis acceleration in natural aging process (Lin, Liu, Chang, & Shen, 2011). Few studies have analyzed the relationship between BMD and CAC in older men, and it remains subject to debate (Choi et al., 2009). High-definition computerized tomography (HDCT) is a highly sensitive technique for detecting the CAC and provides the most accurate CAC scores up to date. In the study presented here, we aimed to evaluate the age-related acceleration of osteoporosis and CAC detected by HDCT, as well as the relationship between BMD and CAC in Chinese elderly men.
Corresponding authors at: Department of Geriatric Cardiology, Chinese PLA General Hospital, No. 28, Fuxing Road, Beijing, 100853, China. E-mail addresses: [email protected] (Y. Bai), [email protected] (L. Luo).
https://doi.org/10.1016/j.archger.2018.07.002 Received 20 July 2017; Received in revised form 30 June 2018; Accepted 2 July 2018 Available online 20 July 2018 0167-4943/ © 2018 Elsevier B.V. All rights reserved.
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Table 1 Baseline characteristics of participants grouped by age. Characteristics
Total (n = 120)
Age < 75 years (n = 66)
Age ≥75 years (n = 54)
P value
Age (year) History of smoking (%) Body mass index (kg/m2)
73 ± 8.5 15(25.0) 25.1 ± 2.8
67 ± 4.9 11(33.3) 24.7 ± 2.9
81 ± 3.5 4(14.8) 25.4 ± 2.8
< 0.001 0.099 0.354
Comorbidity Hypertension (%) Diabetes mellitus (%) Coronary artery disease (%)
44(73.3) 29(48.3) 44(73.3)
19(57.6) 17(51.5) 19(57.6)
25(92.6) 12(44.4) 25(92.6)
0.002 0.586 0.002
Clinical presentation MSBP (mmHg) MDBP (mmHg) Heart rate (bpm) LVEF (%)
126 ± 15.6 72 ± 10.8 72 ± 10.6 60 ± 4.8
122 ± 16.5 72 ± 10.9 74 ± 12.6 61 ± 4.0
129 ± 13.7 72 ± 11.0 69 ± 7.1 59 ± 5.5
0.087 0.821 0.110 0.209
Laboratory test Fasting blood glucose (mmol/L) Triglyceride (mmol/L) HDL-c (mmol/L) LDL-c (mmol/L) Serum calcium (mmol/L) Serum phosphorus (mmol/L)
5.33 1.46 1.15 2.45 2.27 1.12
5.31 1.49 1.18 2.47 2.29 1.12
5.36 1.43 1.11 2.42 2.25 1.11
0.780 0.707 0.349 0.820 0.290 0.884
Bone mineral density Lumbar spine 1–4 (g/cm2) Corresponding T score Left femoral neck (g/cm2) Corresponding T score Right femoral neck (g/cm2) Corresponding T score Left femoral trochanter (g/cm2) Corresponding T score Right femoral trochanter (g/cm2) Corresponding T score Left total femur (g/cm2) Corresponding T score Right total femur (g/cm2) Corresponding T score
1.183 ± 0.240 0.97 ± 1.70 0.876 ± 0.150 −0.78 ± 1.15 0.868 ± 0.158 −0.82 ± 1.20 0.821 ± 0.154 −0.03 ± 1.30 0.801 ± 0.160 −0.20 ± 1.35 0.975 ± 0.166 −0.10 ± 1.28 0.963 ± 0.173 −0.21 ± 1.34
1.190 ± 0.274 1.14 ± 1.77 0.916 ± 0.140 −0.50 ± 1.09 0.916 ± 0.137 −0.45 ± 1.01 0.857 ± 0.149 0.24 ± 1.24 0.844 ± 0.144 0.12 ± 1.21 1.012 ± 0.158 0.16 ± 1.21 1.005 ± 0.155 0.09 ± 1.19
1.174 ± 0.195 0.76 ± 1.63 0.827 ± 0.150 −1.13 ± 1.14 0.811 ± 0.166 −1.27 ± 1.27 0.777 ± 0.152 −0.36 ± 1.30 0.750 ± 0.166 −0.60 ± 1.43 0.930 ± 0.168 −0.41 ± 1.31 0.911 ± 0.184 −0.57 ± 1.44
0.808 0.395 0.020 0.033 0.010 0.007 0.046 0.071 0.023 0.037 0.056 0.086 0.037 0.055
CAC scores Agatston score Volume score Mass score
454 ± 861 172 ± 309 58 ± 105
264 ± 371 105 ± 137 35 ± 51
686 ± 1188 254 ± 425 85 ± 143
0.085 0.091 0.092
± ± ± ± ± ±
0.69 0.63 0.30 0.78 0.16 0.17
± ± ± ± ± ±
0.74 0.68 0.31 0.71 0.19 0.19
± ± ± ± ± ±
0.64 0.59 0.27 0.86 0.10 0.16
MSBP: mean systolic blood pressure; MDBP: mean diastolic blood pressure; LVEF: left ventricular ejection fraction; HDL-c: high density lipoprotein-cholesterol; LDLc: low density lipoprotein-cholesterol; CAC: coronary artery calcification.
2. Methods
10 min. Standard echocardiogram was performed and left ventricular ejection fraction was calculated.
2.1. Study participants 2.3. Bone mineral density Participants included 120 men older than 60 years who visited Chinese People’s Liberation Army General Hospital. Criteria for exclusion included: 1) patients receiving percutaneous coronary intervention, coronary artery bypass graft, cardiac valve replacement or cardiac pacemaker implantation; 2) patients with a disorder influencing bone and calcium metabolism, such as thyrotoxicosis, hyperparathyroidism, chronic renal failure, neoplastic or infectious diseases; and 3) patients consuming drugs interacting with bone and calcium metabolism, such as glucocorticosteroid, estrogen and bisphosphonate.
BMD was evaluated by dual energy X-ray absorptiometry (DEXA; Lunar Prodigy, GE Healthcare, Wisconsin, USA) with the software (enCORE 11.20.068) provided by the manufacturer in the lumbar spine (L1–L4) and femur (femoral neck, femoral trochanter and total femur). All analyses were performed according to the consensus of two observers blind to clinical aspect of participants. For DEXA measurements there was limited intra-observer variation, with observers being on average within 3.1% of the pooled mean value. Similarly, there was good interobserver agreement, with an average variation of 2.2%.
2.2. Physical examination 2.4. Coronary artery calcium scores Each participant underwent a complete physical evaluation by the well-trained staffs. Height was measured in the standing position using a wall-mounted measuring tape and body weight was measured with a digital scale wearing a standardized health check-up clothes. Body mass index (BMI) was calculated as weight in kilogram, divided by height in meter squared. Mean systolic and diastolic blood pressure (MSBP and MDBP) was measured using a standard mercury sphygmomanometer, with participants in a seated position after having rested quietly for
CAC was measured with HDCT (Discovery CT 750 HD, GE Healthcare, Wisconsin, USA). CAC scores were determined using the Agatston, volume and mass scoring systems on a three-dimensional workstation (Advantage Windows Workstation 4.5, GE Healthcare, Wisconsin, USA) with the software (Smart score 4.0, GE Healthcare, Wisconsin, USA) (Agatston et al., 1990; Horiguchi et al., 2009). Calculation formulas of CAC scores were as follows: 1) Agatston score = 9
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analyzer (Cobas® 6000, Roche, Basel, Switzerland).
Table 2 Age-related changes in older men. Characteristics
2.6. Determination of diseases
Age r value
p value
History of smoking (%) Body mass index (kg/m2)
−0.237 −0.055
0.068 0.677
Comorbidity Hypertension (%) Diabetes mellitus (%) Coronary artery disease (%)
0.355 < 0.001 0.427
0.005 0.994 0.001
Clinical presentation MSBP (mmHg) MDBP (mmHg) Heart rate (bpm) LVEF (%)
0.140 −0.214 −0.224 −0.189
0.284 0.100 0.085 0.149
Laboratory test Fasting blood glucose (mmol/L) Triglyceride (mmol/L) HDL-c (mmol/L) LDL-c (mmol/L) Serum calcium (mmol/L) Serum phosphorus (mmol/L)
0.067 −0.139 −0.101 −0.115 −0.210 −0.023
0.613 0.289 0.443 0.380 0.108 −0.861
Bone mineral density Lumbar spine 1–4 (g/cm2) Corresponding T score Left femoral neck (g/cm2) Corresponding T score Right femoral neck (g/cm2) Corresponding T score Left femoral trochanter (g/cm2) Corresponding T score Right femoral trochanter (g/cm2) Corresponding T score Left total femur (g/cm2) Corresponding T score Right total femur (g/cm2) Corresponding T score
−0.009 −0.087 −0.443 −0.415 −0.446 −0.447 −0.374 −0.358 −0.398 −0.382 −0.371 −0.354 −0.375 −0.360
0.944 0.510 < 0.001 0.001 < 0.001 < 0.001 0.003 0.005 0.002 0.003 0.004 0.005 0.003 0.005
CAC scores Agatston score Volume score Mass score
0.228 0.219 0.239
0.080 0.092 0.066
Hypertension was present when participants had MSBP ≥ 140 mmHg, MDBP ≥ 90 mmHg or received medications for the treatment of hypertension. Diabetes mellitus was present when participants had FBG ≥ 7 mmol/L or received oral hypoglycemic agent/insulin. Coronary artery disease was characterized by the presence of myocardial infarction and angina pectoris after positive diagnostic procedures including stress test, computed tomography, radionuclide image and coronary angiography. 2.7. Statistical analyses All data were expressed as mean and standard deviation for continuous variables with normal distribution and as numbers and percentages for categorical variables. To evaluate the age-related changes, the total participants were classified into two groups according to 75 years. Comparison for different groups was undertaken by Student’s ttest for continuous variables with normal distribution and Chi-squared test for categorical variables. Parameters related to age and CAC scores were assessed using Pearson (continuous data with normal distribution) and Spearman (categorical data) coefficients. In addition, stepwise multiple linear regression analysis was performed to evaluate the association between CAC scores as a continuous variable and BMD. Regression models were adjusted for age, sex, history of smoking, hypertension, diabetes mellitus, coronary artery disease, body mass index, blood pressure, heart rate, serum levels of fasting blood glucose, TG, HDL-C, LDL-C, uric acid, calcium and phosphorus. Statistical analyses were implemented using Statistical Package for the Social Sciences version 17 (SPSS, Inc, Chicago, IL, USA). All statistical tests were 2tailed and p < 0.05 was considered statistically significant. 3. Results 3.1. Clinical characteristics according to age distribution Mean (standard deviation) age of the total participants was 73 (8.5) years. As designed, all participants were men more than 60 years. Age range was 60–89 years. Compared with the subgroup younger than 75 years, BMD at the level of femur (femoral neck, femoral trochanter and total femur), but not lumbar spine 1–4, were strongly or marginally lower in the subgroup older than 75 years (Table 1). All kinds of CAC scores including Agatston, volume and mass scores in the subgroup older than 75 years were modestly higher than in the subgroup younger than 75 years.
MSBP: mean systolic blood pressure; MDBP: mean diastolic blood pressure; LVEF: left ventricular ejection fraction; HDL-c: high density lipoprotein-cholesterol; LDL-c: low density lipoprotein-cholesterol; CAC: coronary artery calcification.
slice increment/slice thickness × ∑(area × cofactor); 2) volume = ∑(area × slice increment); and 3) mass = ∑(area × slice increment × mean CT density) × calibration factor. CAC scores were calculated individually for the left main, left circumflex, left anterior descending, posterior descending and right coronary arteries. Scores were then summed to calculate the total CAC score. Score above zero was considered to identify the presence of calcium. Radiologists blind to clinical aspect of participants reviewed all the scans. Consensus of two radiologists with more than two years of experience was obtained as the final results.
3.2. Parameters associated with an age-related process Table 2 listed the factors related to age simultaneously. For osteoporosis, there was a strongly inverse correlation between age and BMD of all scanned body parts (femoral neck, femoral trochanter and total femur) (p < 0.05 for all) except the lumbar spine 1–4 (p > 0.05 for all). For CAC, there was a moderately positive correlation of Agatston, volume and mass scores with age.
2.5. Biochemical parameter test
3.3. Relationship between BMD and CAC scores
Blood samples were taken in the morning, after participants fasting for all night long, and then delivered to the central laboratory in Department of Biochemistry, Chinese People’s Liberation Army General Hospital. Lipid profiles, including triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) levels, were measured using the enzymatic method by an automatic analyzer (Cobas® 6000, Roche, Basel, Switzerland). Biochemistry levels, including fasting blood glucose (FBG), serum calcium and serum phosphorus, were determined by a biochemistry
Regardless of the kind of CAC scores, CAC was present in 67% of participants. There was no detectable difference in BMD of all scanned body parts (femoral neck, femoral trochanter and total femur) between participants with CAC and without CAC (p > 0.05 for all). As shown in Table 3, there was no significant correlation between all kinds of CAC scores including Agatston, volume and mass scores, and BMD of all scanned body parts including lumbar spine 1–4, femoral neck, femoral 10
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Table 3 Relationship of coronary artery calcium scores with body mineral density and other variables. Characteristics
Agatston score
Volume score
Mass score
r value
p value
r value
p value
r value
p value
Age (year) History of smoking (%) Body mass index (kg/m2)
0.228 0.179 0.327
0.080 0.171 0.011
0.219 0.183 0.333
0.092 0.161 0.009
0.239 0.180 0.304
0.066 0.169 0.018
Comorbidity Hypertension (%) Diabetes mellitus (%) Coronary artery disease (%)
0.032 0.020 0.205
0.807 0.882 0.116
0.054 0.012 0.201
0.680 0.929 0.124
0.042 0.022 0.202
0.749 0.870 0.122
Clinical presentation MSBP (mmHg) MDBP (mmHg) Heart rate (bpm) LVEF (%)
0.188 0.090 −0.204 −0.049
0.150 0.496 0.117 0.708
0.198 0.105 −0.208 −0.047
0.130 0.424 0.111 0.722
0.173 0.068 −0.206 −0.055
0.186 0.605 0.114 0.675
Laboratory test Fasting blood glucose (mmol/L) Triglyceride (mmol/L) HDL-c (mmol/L) LDL-c (mmol/L) Serum calcium (mmol/L) Serum phosphorus (mmol/L)
0.075 0.061 −0.061 −0.157 −0.103 0.083
0.569 0.643 0.643 0.230 0.432 0.529
0.085 0.056 −0.065 −0.152 −0.081 0.073
0.517 0.674 0.622 0.245 0.537 0.579
0.099 0.052 −0.058 −0.180 −0.117 0.065
0.452 0.692 0.659 0.170 0.373 0.619
Bone mineral density Lumbar spine 1–4 (g/cm2) Corresponding T score Left femoral neck (g/cm2) Corresponding T score Right femoral neck (g/cm2) Corresponding T score Left femoral trochanter (g/cm2) Corresponding T score Right femoral trochanter (g/cm2) Corresponding T score Left total femur (g/cm2) Corresponding T score Right total femur (g/cm2) Corresponding T score
−0.026 −0.045 −0.122 −0.122 −0.083 −0.094 −0.054 −0.035 −0.060 −0.040 −0.060 −0.040 −0.056 −0.037
0.843 0.732 0.355 0.352 0.527 0.477 0.684 0.793 0.651 0.763 0.646 0.762 0.673 0.776
−0.008 −0.029 −0.101 −0.102 −0.064 −0.075 −0.036 −0.018 −0.050 −0.032 −0.040 −0.021 −0.043 −0.026
0.950 0.829 0.442 0.436 0.626 0.567 0.787 0.891 0.704 0.809 0.761 0.875 0.746 0.845
−0.019 −0.032 −0.127 −0.129 −0.092 −0.104 −0.052 −0.034 −0.057 −0.038 −0.062 −0.041 −0.056 −0.037
0.885 0.806 0.333 0.325 0.485 0.428 0.693 0.799 0.665 0.774 0.638 0.756 0.669 0.776
MSBP: mean systolic blood pressure; MDBP: mean diastolic blood pressure; LVEF: left ventricular ejection fraction; HDL-c: high density lipoprotein-cholesterol; LDLc: low density lipoprotein-cholesterol; CAC: coronary artery calcification.
factor correlated with BMD indicating osteoporosis, as well as age in older males is a moderate factor correlated with CAC scores. In other words, it was testified that bone mass decreased progressively, but CAC increased sequentially, in age process in older males. Bone mineralization processes peak at age 25–35 years and thereafter, bone mineral content decreases gradually (Garraway, Stauffer, Kurland, & O’Fallon, 1979). CAC is thought to initiate around 25–35 years old and progress until death (Wexler et al., 1996). Therefore, aging is a key determinant for both conditions. Recent clinical researches have identified a relationship between osteoporosis and vascular calcification, including carotid artery plaque, aortic calcification and arterial stiffness (Frost et al., 2008; Jorgensen et al., 2004). More importantly, previous studies have discovered that BMD is implicated with CAC widely used as a clinical indicator of atherosclerosis and closely connected with future cardiovascular risk (Watanabe et al., 2010). However, while most of these studies have deemed osteoporosis as a disease of older females and specially selected older females as the study participants, it is an undeniable fact that accelerated osteoporosis also occurs in older males. Other studies have illustrated that there is a sex difference in terms of vascular calcification and osteoporosis acceleration in natural aging process (Lin et al., 2011). There have been few studies exploring the relationship between BMD and CAC in older men, and it remains a matter of debate (Choi et al., 2009). Recently, Lee et al. has found that there is an inverse correlation in females but not in males (Lee et al., 2013). What’s more, Kim et al. has reported age and male sex are independent factors determining CAC, but not BMD, in both older men and women (Kim et al., 2011).
trochanter and total femur (p > 0.05 for all). BMD of all these body parts had no ability to identify the CAC (p > 0.05 for all). On multiple linear regression analysis, the relationship between CAC scores and BMD remained statistically non-significant (p > 0.05 for all). 4. Discussion HDCT is a highly sensitive technique for detecting the CAC and provides the most accurate CAC scores up to date. The study presented here advocated that osteoporosis and CAC detected by HDCT were considered to be age-related process, and no direct relationship was found between BMD and CAC in Chinese elderly men. Osteoporosis is a change easily seen in the elderly, and CAC is also a highly frequent abnormality for the elderly. They both represent the public health problems that affect both men and women, usually as they grow older. Effect of advancing age on osteoporosis has been documented in previous reports for women (Looker et al., 1995; Siris et al., 2001). But to men, whether osteoporosis through bone metabolism is natural aging process has not been fully described. In the relationship between age and CAC, Newman et al. has suggested that the extent of CAC was strongly related with age through the ninth decade in men and women (Newman et al., 2001). In contrast, Yoon et al. has demonstrated that neither age nor sex was a significant predictor of calcium deposition in the coronary vessels (Yoon, Emerick, Hill, Gjertson, & Goldin, 2002). The study presented here excluded female participants from analyses due to sex difference in the relationship between osteoporosis and CAC, and observed that age in older men was a strong 11
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Although a shift of calcium from the skeleton towards the arterial wall could account for both osteoporosis and vascular calcification, the underlying pathophysiologic mechanisms identified in bone metabolism and vascular homoeostasis have not been defined. Previous hypotheses have implied estrogen deficiency and abnormalities of vitamin D metabolism in a common pathogenesis for these two conditions (Christian, Harrington, Edwards, Oberg, & Fitzpatrick, 2002; Watson et al., 1997). Sex difference in hormonal variation might be of some significance in explaining the phenomenon that relationship between BMD and CAC exists in women rather than men.
bone mineral density is associated with higher coronary calcification and coronary plaque burdens by multidetector row coronary computed tomography in pre- and postmenopausal women. Clinical Endocrinology (Oxford), 71, 644–651. Christian, R. C., Harrington, S., Edwards, W. D., Oberg, A. L., & Fitzpatrick, L. A. (2002). Estrogen status correlates with the calcium content of coronary atherosclerotic plaques in women. The Journal of Clinical Endocrinology and Metabolism, 87, 1062–1067. Frost, M. L., Grella, R., Millasseau, S. C., Jiang, B. Y., Hampson, G., Fogelman, I., et al. (2008). Relationship of calcification of atherosclerotic plaque and arterial stiffness to bone mineral density and osteoprotegerin in postmenopausal women referred for osteoporosis screening. Calcified Tissue International, 83, 112–120. Garraway, W. M., Stauffer, R. N., Kurland, L. T., & O’Fallon, W. M. (1979). Limb fractures in a defined population. I. Frequency and distribution. Mayo Clinic Proceedings, 54, 701–707. Horiguchi, J., Matsuura, N., Yamamoto, H., Kiguchi, M., Fujioka, C., Kitagawa, T., et al. (2009). Coronary artery calcium scoring on low-dose prospective electrocardiographically-triggered 64-slice CT. Academic Radiology, 16, 187–193. Jorgensen, L., Joakimsen, O., Rosvold Berntsen, G. K., Heuch, I., & Jacobsen, B. K. (2004). Low bone mineral density is related to echogenic carotid artery plaques: A population-based study. American Journal of Epidemiology, 160, 549–556. Kim, K. I., Suh, J. W., Choi, S. Y., Chang, H. J., Choi, D. J., Kim, C. H., et al. (2011). Is reduced bone mineral density independently associated with coronary artery calcification in subjects older than 50 years? Journal of Bone and Mineral Metabolism, 29, 369–376. Lee, D. H., Youn, H. J., Yi, J. E., Chin, J. Y., Kim, T. S., Jung, H. O., et al. (2013). Gender difference in osteoporosis and vascular calcification associated with age. Korean Circulation Journal, 43, 453–461. Lin, T., Liu, J. C., Chang, L. Y., & Shen, C. W. (2011). Association between coronary artery calcification using low-dose MDCT coronary angiography and bone mineral density in middle-aged men and women. Osteoporosis International, 22, 627–634. Looker, A. C., Johnston, C. C., Jr, Wahner, H. W., Dunn, W. L., Calvo, M. S., Harris, T. B., et al. (1995). Prevalence of low femoral bone density in older U.S. women from NHANES III. Journal of Bone and Mineral Research, 10, 796–802. Newman, A. B., Naydeck, B. L., Sutton-Tyrrell, K., Feldman, A., Edmundowicz, D., & Kuller, L. H. (2001). Coronary artery calcification in older adults to age 99: Prevalence and risk factors. Circulation, 104, 2679–2684. Siris, E. S., Miller, P. D., Barrett-Connor, E., Faulkner, K. G., Wehren, L. E., Abbott, T. A., et al. (2001). Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: Results from the National Osteoporosis Risk Assessment. JAMA, 286, 2815–2822. Watanabe, R., Lemos, M. M., Manfredi, S. R., Draibe, S. A., & Canziani, M. E. (2010). Impact of cardiovascular calcification in nondialyzed patients after 24 months of follow-up. Clinical Journal of the American Society of Nephrology, 5, 189–194. Watson, K. E., Abrolat, M. L., Malone, L. L., Hoeg, J. M., Doherty, T., Detrano, R., et al. (1997). Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation, 96, 1755–1760. Wexler, L., Brundage, B., Crouse, J., Detrano, R., Fuster, V., Maddahi, J., et al. (1996). Coronary artery calcification: Pathophysiology, epidemiology, imaging methods, and clinical implications. A statement for health professionals from the American Heart Association. Writing Group Circulation, 94, 1175–1192. Yoon, H. C., Emerick, A. M., Hill, J. A., Gjertson, D. W., & Goldin, J. G. (2002). Calcium begets calcium: Progression of coronary artery calcification in asymptomatic subjects. Radiology, 224, 236–241.
5. Conclusions Age constituted an important factor common for loss of BMD and development of CAC detected by HDCT, and no direct relationship was observed between osteoporosis and CAC in Chinese elderly men. Funding This work was supported by grants from Health Special Scientific Research Project of Chinese People’s Liberation Army (12BJZ34 and 14BJZ12) and Hainan Natural Science Foundation (20168356). Disclosure The authors declare that they have no conflict of interest. Acknowledgments The authors are grateful to all study participants for their participation in the study. This work was supported by grants from the National Key Basic Research Project (2012CB517503 and 2013CB530804) and Health Special Scientific Research Project of Chinese People’s Liberation Army (12BJZ34 and 14BJZ12). References Agatston, A. S., Janowitz, W. R., Hildner, F. J., Zusmer, N. R., Viamonte, M., Jr, & Detrano, R. (1990). Quantification of coronary artery calcium using ultrafast computed tomography. Journal of the American College of Cardiology, 15, 827–832. Choi, S. H., An, J. H., Lim, S., Koo, B. K., Park, S. E., Chang, H. J., et al. (2009). Lower
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Relationship between age, osteoporosis and coronary artery calcification detected by high-definition computerized tomography in Chinese elderly men ⁎
T
⁎
Yuan Liua, Shihui Fua,b, Yongyi Baia, , Leiming Luoa, , Ping Yea a Department of Geriatric Cardiology, National Clinical Research Center of Geriatrics Disease, Beijing Key Laboratory of Precision Medicine for Chronic Heart Failure, Chinese People’s Liberation Army General Hospital, Beijing, China b Department of Cardiology and Hainan Branch, Chinese People’s Liberation Army General Hospital, Beijing, China
A R T I C LE I N FO
A B S T R A C T
Keywords: Age Osteoporosis Elderly Coronary artery calcification High-definition computerized tomography
Background: Few studies have analyzed the relationship between bone mineral density (BMD) and coronary artery calcification (CAC) in older men, and it remains subject to debate. The present study was designed to evaluate the age-related acceleration of osteoporosis and CAC, as well as the relationship between BMD and CAC in Chinese elderly men. Methods: Participants included 120 men older than 60 years. CAC was measured with high-definition computerized tomography. It is a highly sensitive technique for detecting the CAC and provides the most accurate CAC scores up to date. Results: Mean (standard deviation) age was 73 (8.5) years. For osteoporosis, there was a strongly inverse correlation between age and BMD of all scanned body parts (p < 0.05 for all) except the lumbar spine 1–4 (p > 0.05 for all). For CAC, there was a moderately positive correlation of agatston, volume and mass scores with age. CAC was present in 67% of participants. There was no significant correlation between all kinds of CAC scores including agatston, volume and mass scores, and BMD of all scanned body parts including lumbar spine 1–4, femoral neck, femoral trochanter and total femur (p > 0.05 for all). BMD of all these body parts had no ability to identify the CAC (p > 0.05 for all). Furthermore, on multiple linear regression analysis, the relationship between CAC scores and BMD remained statistically non-significant. Conclusions: Age constituted an important factor common for loss of BMD and development of CAC detected by HDCT, and no direct relationship was observed between osteoporosis and CAC in Chinese elderly men.
1. Introduction Osteoporosis is a common feature among the elderly. It represents a major public health problem that affects both men and women, usually as they grow older. Coronary artery calcification (CAC) is also a highly prevalent condition among the elderly, and its development has been demonstrated to be associated with future cardiovascular risk (Watanabe, Lemos, Manfredi, Draibe, & Canziani, 2010). Until recently, several clinical data have reported a relationship between osteoporosis and vascular calcification, including carotid artery plaque, aortic calcification and arterial stiffness (Frost et al., 2008; Jorgensen, Joakimsen, Rosvold Berntsen, Heuch, & Jacobsen, 2004). More importantly, previous studies have realized that bone mineral density (BMD) is implicated with CAC. However, while most of these studies have considered osteoporosis as a disease of older women and specially
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chosen older women as the study participants, it is an undeniable fact that accelerated osteoporosis also occurs in older men. Other studies have proved that there is a sex difference in terms of vascular calcification and osteoporosis acceleration in natural aging process (Lin, Liu, Chang, & Shen, 2011). Few studies have analyzed the relationship between BMD and CAC in older men, and it remains subject to debate (Choi et al., 2009). High-definition computerized tomography (HDCT) is a highly sensitive technique for detecting the CAC and provides the most accurate CAC scores up to date. In the study presented here, we aimed to evaluate the age-related acceleration of osteoporosis and CAC detected by HDCT, as well as the relationship between BMD and CAC in Chinese elderly men.
Corresponding authors at: Department of Geriatric Cardiology, Chinese PLA General Hospital, No. 28, Fuxing Road, Beijing, 100853, China. E-mail addresses: [email protected] (Y. Bai), [email protected] (L. Luo).
https://doi.org/10.1016/j.archger.2018.07.002 Received 20 July 2017; Received in revised form 30 June 2018; Accepted 2 July 2018 Available online 20 July 2018 0167-4943/ © 2018 Elsevier B.V. All rights reserved.
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Table 1 Baseline characteristics of participants grouped by age. Characteristics
Total (n = 120)
Age < 75 years (n = 66)
Age ≥75 years (n = 54)
P value
Age (year) History of smoking (%) Body mass index (kg/m2)
73 ± 8.5 15(25.0) 25.1 ± 2.8
67 ± 4.9 11(33.3) 24.7 ± 2.9
81 ± 3.5 4(14.8) 25.4 ± 2.8
< 0.001 0.099 0.354
Comorbidity Hypertension (%) Diabetes mellitus (%) Coronary artery disease (%)
44(73.3) 29(48.3) 44(73.3)
19(57.6) 17(51.5) 19(57.6)
25(92.6) 12(44.4) 25(92.6)
0.002 0.586 0.002
Clinical presentation MSBP (mmHg) MDBP (mmHg) Heart rate (bpm) LVEF (%)
126 ± 15.6 72 ± 10.8 72 ± 10.6 60 ± 4.8
122 ± 16.5 72 ± 10.9 74 ± 12.6 61 ± 4.0
129 ± 13.7 72 ± 11.0 69 ± 7.1 59 ± 5.5
0.087 0.821 0.110 0.209
Laboratory test Fasting blood glucose (mmol/L) Triglyceride (mmol/L) HDL-c (mmol/L) LDL-c (mmol/L) Serum calcium (mmol/L) Serum phosphorus (mmol/L)
5.33 1.46 1.15 2.45 2.27 1.12
5.31 1.49 1.18 2.47 2.29 1.12
5.36 1.43 1.11 2.42 2.25 1.11
0.780 0.707 0.349 0.820 0.290 0.884
Bone mineral density Lumbar spine 1–4 (g/cm2) Corresponding T score Left femoral neck (g/cm2) Corresponding T score Right femoral neck (g/cm2) Corresponding T score Left femoral trochanter (g/cm2) Corresponding T score Right femoral trochanter (g/cm2) Corresponding T score Left total femur (g/cm2) Corresponding T score Right total femur (g/cm2) Corresponding T score
1.183 ± 0.240 0.97 ± 1.70 0.876 ± 0.150 −0.78 ± 1.15 0.868 ± 0.158 −0.82 ± 1.20 0.821 ± 0.154 −0.03 ± 1.30 0.801 ± 0.160 −0.20 ± 1.35 0.975 ± 0.166 −0.10 ± 1.28 0.963 ± 0.173 −0.21 ± 1.34
1.190 ± 0.274 1.14 ± 1.77 0.916 ± 0.140 −0.50 ± 1.09 0.916 ± 0.137 −0.45 ± 1.01 0.857 ± 0.149 0.24 ± 1.24 0.844 ± 0.144 0.12 ± 1.21 1.012 ± 0.158 0.16 ± 1.21 1.005 ± 0.155 0.09 ± 1.19
1.174 ± 0.195 0.76 ± 1.63 0.827 ± 0.150 −1.13 ± 1.14 0.811 ± 0.166 −1.27 ± 1.27 0.777 ± 0.152 −0.36 ± 1.30 0.750 ± 0.166 −0.60 ± 1.43 0.930 ± 0.168 −0.41 ± 1.31 0.911 ± 0.184 −0.57 ± 1.44
0.808 0.395 0.020 0.033 0.010 0.007 0.046 0.071 0.023 0.037 0.056 0.086 0.037 0.055
CAC scores Agatston score Volume score Mass score
454 ± 861 172 ± 309 58 ± 105
264 ± 371 105 ± 137 35 ± 51
686 ± 1188 254 ± 425 85 ± 143
0.085 0.091 0.092
± ± ± ± ± ±
0.69 0.63 0.30 0.78 0.16 0.17
± ± ± ± ± ±
0.74 0.68 0.31 0.71 0.19 0.19
± ± ± ± ± ±
0.64 0.59 0.27 0.86 0.10 0.16
MSBP: mean systolic blood pressure; MDBP: mean diastolic blood pressure; LVEF: left ventricular ejection fraction; HDL-c: high density lipoprotein-cholesterol; LDLc: low density lipoprotein-cholesterol; CAC: coronary artery calcification.
2. Methods
10 min. Standard echocardiogram was performed and left ventricular ejection fraction was calculated.
2.1. Study participants 2.3. Bone mineral density Participants included 120 men older than 60 years who visited Chinese People’s Liberation Army General Hospital. Criteria for exclusion included: 1) patients receiving percutaneous coronary intervention, coronary artery bypass graft, cardiac valve replacement or cardiac pacemaker implantation; 2) patients with a disorder influencing bone and calcium metabolism, such as thyrotoxicosis, hyperparathyroidism, chronic renal failure, neoplastic or infectious diseases; and 3) patients consuming drugs interacting with bone and calcium metabolism, such as glucocorticosteroid, estrogen and bisphosphonate.
BMD was evaluated by dual energy X-ray absorptiometry (DEXA; Lunar Prodigy, GE Healthcare, Wisconsin, USA) with the software (enCORE 11.20.068) provided by the manufacturer in the lumbar spine (L1–L4) and femur (femoral neck, femoral trochanter and total femur). All analyses were performed according to the consensus of two observers blind to clinical aspect of participants. For DEXA measurements there was limited intra-observer variation, with observers being on average within 3.1% of the pooled mean value. Similarly, there was good interobserver agreement, with an average variation of 2.2%.
2.2. Physical examination 2.4. Coronary artery calcium scores Each participant underwent a complete physical evaluation by the well-trained staffs. Height was measured in the standing position using a wall-mounted measuring tape and body weight was measured with a digital scale wearing a standardized health check-up clothes. Body mass index (BMI) was calculated as weight in kilogram, divided by height in meter squared. Mean systolic and diastolic blood pressure (MSBP and MDBP) was measured using a standard mercury sphygmomanometer, with participants in a seated position after having rested quietly for
CAC was measured with HDCT (Discovery CT 750 HD, GE Healthcare, Wisconsin, USA). CAC scores were determined using the Agatston, volume and mass scoring systems on a three-dimensional workstation (Advantage Windows Workstation 4.5, GE Healthcare, Wisconsin, USA) with the software (Smart score 4.0, GE Healthcare, Wisconsin, USA) (Agatston et al., 1990; Horiguchi et al., 2009). Calculation formulas of CAC scores were as follows: 1) Agatston score = 9
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analyzer (Cobas® 6000, Roche, Basel, Switzerland).
Table 2 Age-related changes in older men. Characteristics
2.6. Determination of diseases
Age r value
p value
History of smoking (%) Body mass index (kg/m2)
−0.237 −0.055
0.068 0.677
Comorbidity Hypertension (%) Diabetes mellitus (%) Coronary artery disease (%)
0.355 < 0.001 0.427
0.005 0.994 0.001
Clinical presentation MSBP (mmHg) MDBP (mmHg) Heart rate (bpm) LVEF (%)
0.140 −0.214 −0.224 −0.189
0.284 0.100 0.085 0.149
Laboratory test Fasting blood glucose (mmol/L) Triglyceride (mmol/L) HDL-c (mmol/L) LDL-c (mmol/L) Serum calcium (mmol/L) Serum phosphorus (mmol/L)
0.067 −0.139 −0.101 −0.115 −0.210 −0.023
0.613 0.289 0.443 0.380 0.108 −0.861
Bone mineral density Lumbar spine 1–4 (g/cm2) Corresponding T score Left femoral neck (g/cm2) Corresponding T score Right femoral neck (g/cm2) Corresponding T score Left femoral trochanter (g/cm2) Corresponding T score Right femoral trochanter (g/cm2) Corresponding T score Left total femur (g/cm2) Corresponding T score Right total femur (g/cm2) Corresponding T score
−0.009 −0.087 −0.443 −0.415 −0.446 −0.447 −0.374 −0.358 −0.398 −0.382 −0.371 −0.354 −0.375 −0.360
0.944 0.510 < 0.001 0.001 < 0.001 < 0.001 0.003 0.005 0.002 0.003 0.004 0.005 0.003 0.005
CAC scores Agatston score Volume score Mass score
0.228 0.219 0.239
0.080 0.092 0.066
Hypertension was present when participants had MSBP ≥ 140 mmHg, MDBP ≥ 90 mmHg or received medications for the treatment of hypertension. Diabetes mellitus was present when participants had FBG ≥ 7 mmol/L or received oral hypoglycemic agent/insulin. Coronary artery disease was characterized by the presence of myocardial infarction and angina pectoris after positive diagnostic procedures including stress test, computed tomography, radionuclide image and coronary angiography. 2.7. Statistical analyses All data were expressed as mean and standard deviation for continuous variables with normal distribution and as numbers and percentages for categorical variables. To evaluate the age-related changes, the total participants were classified into two groups according to 75 years. Comparison for different groups was undertaken by Student’s ttest for continuous variables with normal distribution and Chi-squared test for categorical variables. Parameters related to age and CAC scores were assessed using Pearson (continuous data with normal distribution) and Spearman (categorical data) coefficients. In addition, stepwise multiple linear regression analysis was performed to evaluate the association between CAC scores as a continuous variable and BMD. Regression models were adjusted for age, sex, history of smoking, hypertension, diabetes mellitus, coronary artery disease, body mass index, blood pressure, heart rate, serum levels of fasting blood glucose, TG, HDL-C, LDL-C, uric acid, calcium and phosphorus. Statistical analyses were implemented using Statistical Package for the Social Sciences version 17 (SPSS, Inc, Chicago, IL, USA). All statistical tests were 2tailed and p < 0.05 was considered statistically significant. 3. Results 3.1. Clinical characteristics according to age distribution Mean (standard deviation) age of the total participants was 73 (8.5) years. As designed, all participants were men more than 60 years. Age range was 60–89 years. Compared with the subgroup younger than 75 years, BMD at the level of femur (femoral neck, femoral trochanter and total femur), but not lumbar spine 1–4, were strongly or marginally lower in the subgroup older than 75 years (Table 1). All kinds of CAC scores including Agatston, volume and mass scores in the subgroup older than 75 years were modestly higher than in the subgroup younger than 75 years.
MSBP: mean systolic blood pressure; MDBP: mean diastolic blood pressure; LVEF: left ventricular ejection fraction; HDL-c: high density lipoprotein-cholesterol; LDL-c: low density lipoprotein-cholesterol; CAC: coronary artery calcification.
slice increment/slice thickness × ∑(area × cofactor); 2) volume = ∑(area × slice increment); and 3) mass = ∑(area × slice increment × mean CT density) × calibration factor. CAC scores were calculated individually for the left main, left circumflex, left anterior descending, posterior descending and right coronary arteries. Scores were then summed to calculate the total CAC score. Score above zero was considered to identify the presence of calcium. Radiologists blind to clinical aspect of participants reviewed all the scans. Consensus of two radiologists with more than two years of experience was obtained as the final results.
3.2. Parameters associated with an age-related process Table 2 listed the factors related to age simultaneously. For osteoporosis, there was a strongly inverse correlation between age and BMD of all scanned body parts (femoral neck, femoral trochanter and total femur) (p < 0.05 for all) except the lumbar spine 1–4 (p > 0.05 for all). For CAC, there was a moderately positive correlation of Agatston, volume and mass scores with age.
2.5. Biochemical parameter test
3.3. Relationship between BMD and CAC scores
Blood samples were taken in the morning, after participants fasting for all night long, and then delivered to the central laboratory in Department of Biochemistry, Chinese People’s Liberation Army General Hospital. Lipid profiles, including triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) levels, were measured using the enzymatic method by an automatic analyzer (Cobas® 6000, Roche, Basel, Switzerland). Biochemistry levels, including fasting blood glucose (FBG), serum calcium and serum phosphorus, were determined by a biochemistry
Regardless of the kind of CAC scores, CAC was present in 67% of participants. There was no detectable difference in BMD of all scanned body parts (femoral neck, femoral trochanter and total femur) between participants with CAC and without CAC (p > 0.05 for all). As shown in Table 3, there was no significant correlation between all kinds of CAC scores including Agatston, volume and mass scores, and BMD of all scanned body parts including lumbar spine 1–4, femoral neck, femoral 10
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Table 3 Relationship of coronary artery calcium scores with body mineral density and other variables. Characteristics
Agatston score
Volume score
Mass score
r value
p value
r value
p value
r value
p value
Age (year) History of smoking (%) Body mass index (kg/m2)
0.228 0.179 0.327
0.080 0.171 0.011
0.219 0.183 0.333
0.092 0.161 0.009
0.239 0.180 0.304
0.066 0.169 0.018
Comorbidity Hypertension (%) Diabetes mellitus (%) Coronary artery disease (%)
0.032 0.020 0.205
0.807 0.882 0.116
0.054 0.012 0.201
0.680 0.929 0.124
0.042 0.022 0.202
0.749 0.870 0.122
Clinical presentation MSBP (mmHg) MDBP (mmHg) Heart rate (bpm) LVEF (%)
0.188 0.090 −0.204 −0.049
0.150 0.496 0.117 0.708
0.198 0.105 −0.208 −0.047
0.130 0.424 0.111 0.722
0.173 0.068 −0.206 −0.055
0.186 0.605 0.114 0.675
Laboratory test Fasting blood glucose (mmol/L) Triglyceride (mmol/L) HDL-c (mmol/L) LDL-c (mmol/L) Serum calcium (mmol/L) Serum phosphorus (mmol/L)
0.075 0.061 −0.061 −0.157 −0.103 0.083
0.569 0.643 0.643 0.230 0.432 0.529
0.085 0.056 −0.065 −0.152 −0.081 0.073
0.517 0.674 0.622 0.245 0.537 0.579
0.099 0.052 −0.058 −0.180 −0.117 0.065
0.452 0.692 0.659 0.170 0.373 0.619
Bone mineral density Lumbar spine 1–4 (g/cm2) Corresponding T score Left femoral neck (g/cm2) Corresponding T score Right femoral neck (g/cm2) Corresponding T score Left femoral trochanter (g/cm2) Corresponding T score Right femoral trochanter (g/cm2) Corresponding T score Left total femur (g/cm2) Corresponding T score Right total femur (g/cm2) Corresponding T score
−0.026 −0.045 −0.122 −0.122 −0.083 −0.094 −0.054 −0.035 −0.060 −0.040 −0.060 −0.040 −0.056 −0.037
0.843 0.732 0.355 0.352 0.527 0.477 0.684 0.793 0.651 0.763 0.646 0.762 0.673 0.776
−0.008 −0.029 −0.101 −0.102 −0.064 −0.075 −0.036 −0.018 −0.050 −0.032 −0.040 −0.021 −0.043 −0.026
0.950 0.829 0.442 0.436 0.626 0.567 0.787 0.891 0.704 0.809 0.761 0.875 0.746 0.845
−0.019 −0.032 −0.127 −0.129 −0.092 −0.104 −0.052 −0.034 −0.057 −0.038 −0.062 −0.041 −0.056 −0.037
0.885 0.806 0.333 0.325 0.485 0.428 0.693 0.799 0.665 0.774 0.638 0.756 0.669 0.776
MSBP: mean systolic blood pressure; MDBP: mean diastolic blood pressure; LVEF: left ventricular ejection fraction; HDL-c: high density lipoprotein-cholesterol; LDLc: low density lipoprotein-cholesterol; CAC: coronary artery calcification.
factor correlated with BMD indicating osteoporosis, as well as age in older males is a moderate factor correlated with CAC scores. In other words, it was testified that bone mass decreased progressively, but CAC increased sequentially, in age process in older males. Bone mineralization processes peak at age 25–35 years and thereafter, bone mineral content decreases gradually (Garraway, Stauffer, Kurland, & O’Fallon, 1979). CAC is thought to initiate around 25–35 years old and progress until death (Wexler et al., 1996). Therefore, aging is a key determinant for both conditions. Recent clinical researches have identified a relationship between osteoporosis and vascular calcification, including carotid artery plaque, aortic calcification and arterial stiffness (Frost et al., 2008; Jorgensen et al., 2004). More importantly, previous studies have discovered that BMD is implicated with CAC widely used as a clinical indicator of atherosclerosis and closely connected with future cardiovascular risk (Watanabe et al., 2010). However, while most of these studies have deemed osteoporosis as a disease of older females and specially selected older females as the study participants, it is an undeniable fact that accelerated osteoporosis also occurs in older males. Other studies have illustrated that there is a sex difference in terms of vascular calcification and osteoporosis acceleration in natural aging process (Lin et al., 2011). There have been few studies exploring the relationship between BMD and CAC in older men, and it remains a matter of debate (Choi et al., 2009). Recently, Lee et al. has found that there is an inverse correlation in females but not in males (Lee et al., 2013). What’s more, Kim et al. has reported age and male sex are independent factors determining CAC, but not BMD, in both older men and women (Kim et al., 2011).
trochanter and total femur (p > 0.05 for all). BMD of all these body parts had no ability to identify the CAC (p > 0.05 for all). On multiple linear regression analysis, the relationship between CAC scores and BMD remained statistically non-significant (p > 0.05 for all). 4. Discussion HDCT is a highly sensitive technique for detecting the CAC and provides the most accurate CAC scores up to date. The study presented here advocated that osteoporosis and CAC detected by HDCT were considered to be age-related process, and no direct relationship was found between BMD and CAC in Chinese elderly men. Osteoporosis is a change easily seen in the elderly, and CAC is also a highly frequent abnormality for the elderly. They both represent the public health problems that affect both men and women, usually as they grow older. Effect of advancing age on osteoporosis has been documented in previous reports for women (Looker et al., 1995; Siris et al., 2001). But to men, whether osteoporosis through bone metabolism is natural aging process has not been fully described. In the relationship between age and CAC, Newman et al. has suggested that the extent of CAC was strongly related with age through the ninth decade in men and women (Newman et al., 2001). In contrast, Yoon et al. has demonstrated that neither age nor sex was a significant predictor of calcium deposition in the coronary vessels (Yoon, Emerick, Hill, Gjertson, & Goldin, 2002). The study presented here excluded female participants from analyses due to sex difference in the relationship between osteoporosis and CAC, and observed that age in older men was a strong 11
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Although a shift of calcium from the skeleton towards the arterial wall could account for both osteoporosis and vascular calcification, the underlying pathophysiologic mechanisms identified in bone metabolism and vascular homoeostasis have not been defined. Previous hypotheses have implied estrogen deficiency and abnormalities of vitamin D metabolism in a common pathogenesis for these two conditions (Christian, Harrington, Edwards, Oberg, & Fitzpatrick, 2002; Watson et al., 1997). Sex difference in hormonal variation might be of some significance in explaining the phenomenon that relationship between BMD and CAC exists in women rather than men.
bone mineral density is associated with higher coronary calcification and coronary plaque burdens by multidetector row coronary computed tomography in pre- and postmenopausal women. Clinical Endocrinology (Oxford), 71, 644–651. Christian, R. C., Harrington, S., Edwards, W. D., Oberg, A. L., & Fitzpatrick, L. A. (2002). Estrogen status correlates with the calcium content of coronary atherosclerotic plaques in women. The Journal of Clinical Endocrinology and Metabolism, 87, 1062–1067. Frost, M. L., Grella, R., Millasseau, S. C., Jiang, B. Y., Hampson, G., Fogelman, I., et al. (2008). Relationship of calcification of atherosclerotic plaque and arterial stiffness to bone mineral density and osteoprotegerin in postmenopausal women referred for osteoporosis screening. Calcified Tissue International, 83, 112–120. Garraway, W. M., Stauffer, R. N., Kurland, L. T., & O’Fallon, W. M. (1979). Limb fractures in a defined population. I. Frequency and distribution. Mayo Clinic Proceedings, 54, 701–707. Horiguchi, J., Matsuura, N., Yamamoto, H., Kiguchi, M., Fujioka, C., Kitagawa, T., et al. (2009). Coronary artery calcium scoring on low-dose prospective electrocardiographically-triggered 64-slice CT. Academic Radiology, 16, 187–193. Jorgensen, L., Joakimsen, O., Rosvold Berntsen, G. K., Heuch, I., & Jacobsen, B. K. (2004). Low bone mineral density is related to echogenic carotid artery plaques: A population-based study. American Journal of Epidemiology, 160, 549–556. Kim, K. I., Suh, J. W., Choi, S. Y., Chang, H. J., Choi, D. J., Kim, C. H., et al. (2011). Is reduced bone mineral density independently associated with coronary artery calcification in subjects older than 50 years? Journal of Bone and Mineral Metabolism, 29, 369–376. Lee, D. H., Youn, H. J., Yi, J. E., Chin, J. Y., Kim, T. S., Jung, H. O., et al. (2013). Gender difference in osteoporosis and vascular calcification associated with age. Korean Circulation Journal, 43, 453–461. Lin, T., Liu, J. C., Chang, L. Y., & Shen, C. W. (2011). Association between coronary artery calcification using low-dose MDCT coronary angiography and bone mineral density in middle-aged men and women. Osteoporosis International, 22, 627–634. Looker, A. C., Johnston, C. C., Jr, Wahner, H. W., Dunn, W. L., Calvo, M. S., Harris, T. B., et al. (1995). Prevalence of low femoral bone density in older U.S. women from NHANES III. Journal of Bone and Mineral Research, 10, 796–802. Newman, A. B., Naydeck, B. L., Sutton-Tyrrell, K., Feldman, A., Edmundowicz, D., & Kuller, L. H. (2001). Coronary artery calcification in older adults to age 99: Prevalence and risk factors. Circulation, 104, 2679–2684. Siris, E. S., Miller, P. D., Barrett-Connor, E., Faulkner, K. G., Wehren, L. E., Abbott, T. A., et al. (2001). Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: Results from the National Osteoporosis Risk Assessment. JAMA, 286, 2815–2822. Watanabe, R., Lemos, M. M., Manfredi, S. R., Draibe, S. A., & Canziani, M. E. (2010). Impact of cardiovascular calcification in nondialyzed patients after 24 months of follow-up. Clinical Journal of the American Society of Nephrology, 5, 189–194. Watson, K. E., Abrolat, M. L., Malone, L. L., Hoeg, J. M., Doherty, T., Detrano, R., et al. (1997). Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation, 96, 1755–1760. Wexler, L., Brundage, B., Crouse, J., Detrano, R., Fuster, V., Maddahi, J., et al. (1996). Coronary artery calcification: Pathophysiology, epidemiology, imaging methods, and clinical implications. A statement for health professionals from the American Heart Association. Writing Group Circulation, 94, 1175–1192. Yoon, H. C., Emerick, A. M., Hill, J. A., Gjertson, D. W., & Goldin, J. G. (2002). Calcium begets calcium: Progression of coronary artery calcification in asymptomatic subjects. Radiology, 224, 236–241.
5. Conclusions Age constituted an important factor common for loss of BMD and development of CAC detected by HDCT, and no direct relationship was observed between osteoporosis and CAC in Chinese elderly men. Funding This work was supported by grants from Health Special Scientific Research Project of Chinese People’s Liberation Army (12BJZ34 and 14BJZ12) and Hainan Natural Science Foundation (20168356). Disclosure The authors declare that they have no conflict of interest. Acknowledgments The authors are grateful to all study participants for their participation in the study. This work was supported by grants from the National Key Basic Research Project (2012CB517503 and 2013CB530804) and Health Special Scientific Research Project of Chinese People’s Liberation Army (12BJZ34 and 14BJZ12). References Agatston, A. S., Janowitz, W. R., Hildner, F. J., Zusmer, N. R., Viamonte, M., Jr, & Detrano, R. (1990). Quantification of coronary artery calcium using ultrafast computed tomography. Journal of the American College of Cardiology, 15, 827–832. Choi, S. H., An, J. H., Lim, S., Koo, B. K., Park, S. E., Chang, H. J., et al. (2009). Lower
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