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(Stroke. 1997;28:1730-1732.)
© 1997 American Heart Association, Inc.

Articles

Bone Changes and Carotid Atherosclerosis in Postmenopausal Women

Osamu Uyama, MD, PhD; Yoshio Yoshimoto, MD, PhD; Yukiko Yamamoto, MSc; Abi Kawai, MSN

From the Division of Pathobiology, College of Nursing Art and Science Hyogo, Akashi, Japan.

Correspondence to Osamu Uyama, MD, College of Nursing Art and Science Hyogo, 13-71 Kitaoji-cho, Akashi 673, Japan. E-mail uyama{at}kh.rim.or.jp

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose Because of increased life expectancy, most postmenopausal women today suffer from osteoporosis and atherosclerotic diseases, which are currently considered unrelated diseases. Our study was aimed at analyzing relations between bone mineral density (BMD) and ultrasonographic assessment of carotid wall characteristics.

Methods The relation of carotid atherosclerosis to BMD was examined in 30 postmenopausal women aged 67 to 85 years. High-resolution B-mode ultrasonography was performed, and the severity of carotid atherosclerosis was determined by plaque score. BMD was measured by dual-energy x-ray absorptiometry.

Results The correlation of plaque score with low total BMD was r=.549 (P<.002). Multiple linear regression analysis indicated significant correlation of plaque score with total cholesterol level and low total BMD.

Conclusions Our results suggest a relation between carotid atherosclerosis, one of the major causes of ischemic cerebrovascular diseases, and osteoporosis.

Key Words: : • atherosclerosis • bone density • carotid artery diseases • osteoporosis • ultrasonics

	Introduction

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Atherosclerosis and osteoporosis are currently considered unrelated diseases. As age advances, osteoporosis is more frequently found in women than men; atherosclerosis is an illness predominantly affecting men. A parallel relation has been noted between spinal osteoporosis and aortic calcification due to atherosclerosis.^{1 2} (Pathological calcification of the arterial wall is an underlying feature of atherosclerosis.) Because of increased life expectancy, many postmenopausal women today suffer from osteoporosis and atherosclerotic diseases, such as coronary heart disease and cerebrovascular disease.

Extracranial carotid atherosclerosis is one of the major causes of cerebrovascular diseases.³ In our present investigation, we performed high-resolution real-time B-mode ultrasonography to determine the extent of carotid atherosclerosis and quantified the results by use of a scoring system. We then evaluated the relation between osteoporosis and carotid atherosclerosis.

	Subjects and Methods

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Subjects
The study surveys, which were ultrasonographic assessments of the carotid arteries and evaluations of BMD, were carried out from July 1994 to April 1995. Thirty postmenopausal women aged 67 to 85 (mean±SD, 75.3±5.5) years from a private, upper-middle-class senior citizens residence participated in this study. All subjects underwent a health examination to screen for age-related diseases (arteriosclerotic disease, hypertension, diabetes mellitus, hypercholesterolemia, and heart diseases). None of the subjects had diseases that interfered with the activities of normal daily life. Informed consent was obtained from each subject.

Carotid Examination
In all subjects, carotid B-mode imaging was performed with a 7.5-MHz transducer with an axial resolution of less than 0.4 mm (EUB-555, Hitachi, Japan). The subject was seated comfortably, and scanning of the extracranial carotid arteries in the neck was performed bilaterally in three different longitudinal projections and in the transverse projection. Severity of carotid atherosclerosis was evaluated by plaque score. This score, through use of the scoring system method of Handa and colleagues,³ was computed by summing the maximum thickness (in millimeters) of the intima-media complex (plaque thickness) of both sides of the carotid arteries. All ultrasound examinations were performed by a single sonographer (O.U.), who was blinded to the BMD readings. The mean coefficient of variation for the difference between plaque scores obtained in repeated examinations performed by the same examiner was less than 8%.

Bone Examination
Total BMD, defined as the total BMC divided by the area (g/cm²), was measured by use of dual-energy x-ray absorptiometry (XR-26 x-ray bone densitometer, Norland). Lumbar spine BMD (L2-L4) was also measured.

Statistical Analysis
Data are expressed as mean±SD. The relation between the plaque score and BMD was evaluated by linear regression analysis. Multiple linear regression analysis was used to assess the correlation among BMD, carotid lesion, and risk factors (age, hypertension, and hypercholesterolemia).

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Subjects were considered hypertensive if they were taking antihypertensive agents or if blood pressure measured in our institute was >160 mm Hg systolic or >95 mm Hg diastolic (n=12). Subjects were considered diabetic if they were being treated for diabetes with oral hypoglycemic agents or insulin or if the glycosylated hemoglobin (HbA_1c) level was >7.0% (n=1). Subjects were considered hypercholesterolemic if they were taking antihypercholesterolemic agents or their serum cholesterol level was >220 mg/dL (n=13). The atherogenic index was calculated as the ratio of (total cholesterol-HDL cholesterol) to HDL cholesterol. Only one subject was a moderate drinker (up to 10 g alcohol per day) or a smoker. The characteristics of subjects are shown in Table 1.

View this table: [in this window] [in a new window]   Table 1. Demographic and Clinical Characteristics of 30 Subjects

As shown in the Figure, there was a significant linear correlation (r=.549; P<.002) between plaque score and low total BMD. Lumbar spine BMD was not significantly associated with plaque score. We also examined the associations among plaque score, age, hypertension, total cholesterol, atherogenic index, and total BMD. Multiple linear regression analysis indicated significant correlation of plaque score with age, total cholesterol level, and low total BMD. Hypertension and atherogenic index were not significantly associated with carotid atherosclerosis in the postmenopausal women in our study (Table 2).

View larger version (13K): [in this window] [in a new window]   Figure 1. Scatterplot of correlation between total BMD and plaque score in 30 postmenopausal women. Note that the horizontal axis has been reversed.

View this table: [in this window] [in a new window]   Table 2. Predictors of Plaque Score by Multiple Regression Analysis

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Some studies^{1 2} have suggested a relation between spinal osteoporosis and aortic calcification due to atherosclerosis. The mechanism of this apparent calcium shift from bone to soft tissue remains to be elucidated. Osteoporosis has been ascribed to prolonged calcium deficiency leading to secondary hyperparathyroidism. The increase in atherosclerosis among women as they develop osteoporosis suggests that the two illnesses may be more closely related than previously realized. It has been suggested⁴ that the use of vitamin D as a food supplement coincides with epidemic onsets of atherosclerosis and osteoporosis and that excess vitamin D induces both conditions in humans and laboratory animals. Nordin et al⁵ studied the effects of six different treatment regimens on 95 postmenopausal women with unequivocally wedged or compressed vertebrae. Three treatments (calcium, estrogens, and 1-OHD₃ plus hormones) appear to be useful. Vitamin D (10 000 to 50 000 IU/d) and 1-OHD₃ (1 to 2 µg/d) resulted in increased bone calcium resorption. The amount of vitamin D that may increase the incidence of cardiovascular degeneration was estimated in one epidemiological study to be 30 µg (1200 IU)/d.⁶ Fifteen patients in our study had been treated with 1-OHD₃ (0.25 to 1.0 µg/d). There were no significant differences in plaque score and total BMD between the untreated and treated patients (plaque score, 3.38±3.08 versus 3.34±4.59; total BMD, 0.740±0.084 versus 0.739±0.075 g/cm²).

Laroche et al⁷ studied by dual-energy x-ray absorptiometry the BMC of both legs in 18 men presenting with symptomatic arterial disease of the lower limbs. The mean BMC of the leg more severely affected by arterial disease was significantly lower than that of the leg less affected. They suggest that demineralization seems to be related to a direct local effect of atherosclerosis and not to associated general risk factors (eg, tobacco consumption, sedentary lifestyle, lower body-build index). It is tempting to suggest that systemic atherosclerosis is reflected in carotid atherosclerosis and is responsible for osteoporosis.

Broulik and Kapitola⁸ demonstrated that women with osteoporosis had higher cholesterol levels than control subjects and that BMD in cigarette smokers was significantly lower than in nonsmokers and was not associated with low body weight. Hypercholesterolemia and tobacco consumption are known risk factors for atherosclerosis,^{3 9} and the link between these risk factors and osteoporosis could well be arterial disease.

Sato et al¹⁰ showed that many hemiplegic stroke patients have hypovitaminosis D and osteopenia. A combination of sunlight deprivation due to immobilization (which is caused by cerebral arteriosclerosis) together with decreased dietary intake of vitamin D may be responsible for osteoporosis in subjects with severe carotid atherosclerosis. Our results suggest a relation between osteoporosis and atherosclerosis.

	Selected Abbreviations and Acronyms

 

BMC = bone mineral content BMD = bone mineral density

Received February 12, 1997; revision received May 28, 1997; accepted May 28, 1997.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 
1. Dent CE, Engelbrecht HE, Godfrey RC. Osteoporosis of lumbar vertebrae and calcification of abdominal aorta in women living in Durban. Br Med J. 1968;4:76-79.

2. Fujita T, Okamoto Y, Sakagami Y, Ota K, Ohata M. Bone changes and aortic calcification in aging inhabitants of mountain versus seacoast communities in the Kii Peninsula. J Am Geriatr Soc. 1984;32:124-128.[Medline] [Order article via Infotrieve]

3. Handa N, Matsumoto M, Maeda H, Hougaku H, Ogawa S, Fukunaga R, Yoneda S, Kimura K, Kamada T. Ultrasonic evaluation of early carotid atherosclerosis. Stroke. 1990;21:1567-1572.[Abstract/Free Full Text]

4. Moon J, Bandy B, Davison AJ. Hypothesis: etiology of atherosclerosis and osteoporosis: are imbalances in the calciferol endocrine system implicated? J Am Coll Nutr. 1992;11:567-583.[Abstract]

5. Nordin BE, Horsman A, Crilly RG, Marshall DH, Simpson M. Treatment of spinal osteoporosis in postmenopausal women. Br Med J. 1980;280:451-455.

6. Linden V. Vitamin D and myocardial infarction. Br Med J. 1974;3:647-650.

7. Laroche M, Pouilles JM, Ribot C, Bendayan P, Bernard J, Boccalon H, Mazieres B. Comparison of the bone mineral content of the lower limbs in men with ischaemic atherosclerotic disease. Clin Rheumatol. 1994;13:611-614.[Medline] [Order article via Infotrieve]

8. Broulik PD, Kapitola J. Interrelations between body weight, cigarette smoking and spine mineral density in osteoporotic Czech women. Endocr Regul. 1993;27:57-60.[Medline] [Order article via Infotrieve]

9. Uyama O, Matsui Y, Shimizu S, Michishita H, Sugita M. Risk factors for carotid atherosclerosis and platelet activation. Jpn Circ J. 1994;58:409-515.[Medline] [Order article via Infotrieve]

10. Sato Y, Maruoka H, Oizumi K, Kikuyama M. Vitamin D deficiency and osteopenia in the hemiplegic limbs of the stroke patients. Stroke. 1996;27:2183-2187.[Abstract/Free Full Text]

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