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Erschienen in: Calcified Tissue International 4/2006

01.10.2006

Carotid Plaque Echogenicity and Risk of Nonvertebral Fractures in Women: A Longitudinal Population-Based Study

verfasst von: L. Jørgensen, O. Joakimsen, E. B. Mathiesen, L. Ahmed, G. K. R. Berntsen, V. Fønnebø, R. Joakimsen, I. Njølstad, H. Schirmer, B. K. Jacobsen

Erschienen in: Calcified Tissue International | Ausgabe 4/2006

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Abstract

Atherosclerosis and osteoporosis appear to be related, but prospective studies on the relationship are sparse. In order to examine whether carotid artery plaques with different morphology predict nonvertebral fractures, we followed 2,733 women, aged 55–74 years (75% of the eligible population in Tromsø, Norway), for 6 years. At baseline, plaque morphology in terms of ultrasound echogenicity was categorized into three groups, ranging from low echogenicity (echolucent plaques with a high content of soft tissue) to strong echogenicity (echogenic plaques with a high content of dense fibrous tissue and calcified material). We found that the age-adjusted relative risk (RR) of fracture was significantly higher among women with echogenic plaques than among women without plaques: 1.7 (95% confidence interval [CI] 1.0-2.7). After adjustment for bone mineral density at baseline in addition to age, the RR was 1.6 (95% CI 1.0-2.6), and further adjustments for body mass index, body height, high-density lipoprotein cholesterol, smoking status, and muscle strength did not influence the association. Subjects with other plaque types were not at an increased risk compared to subjects without plaques: RR ≤ 1.1, after multiple adjustments. We conclude that in the general population elderly women with echogenic carotid plaques are at higher risk of nonvertebral fractures than women without plaques.
Literatur
1.
Zurück zum Zitat Banks LM, Lees B, MacSweeney JE, Stevenson JC (1994) Effect of degenerative spinal and aortic calcification on bone density measurements in post-menopausal women: links between osteoporosis and cardiovascular disease? Eur J Clin Invest 24:813–817PubMedCrossRef Banks LM, Lees B, MacSweeney JE, Stevenson JC (1994) Effect of degenerative spinal and aortic calcification on bone density measurements in post-menopausal women: links between osteoporosis and cardiovascular disease? Eur J Clin Invest 24:813–817PubMedCrossRef
2.
Zurück zum Zitat Barengolts EI, Berman M, Kukreja SC, Kouznetsova T, Lin C, Chomka EV (1998) Osteoporosis and coronary atherosclerosis in asymptomatic postmenopausal women. Calcif Tissue Int 62:209–213PubMedCrossRef Barengolts EI, Berman M, Kukreja SC, Kouznetsova T, Lin C, Chomka EV (1998) Osteoporosis and coronary atherosclerosis in asymptomatic postmenopausal women. Calcif Tissue Int 62:209–213PubMedCrossRef
3.
Zurück zum Zitat Boukhris R, Becker KL (1972) Calcification of the aorta and osteoporosis. A roentgenographic study. JAMA 219:1307–1311PubMedCrossRef Boukhris R, Becker KL (1972) Calcification of the aorta and osteoporosis. A roentgenographic study. JAMA 219:1307–1311PubMedCrossRef
4.
Zurück zum Zitat Hak AE, Pols HA, van Hemert AM, Hofman A, Witteman JC (2000) Progression of aortic calcification is associated with metacarpal bone loss during menopause: a population-based longitudinal study. Arterioscler Thromb Vasc Biol 20:1926–1931PubMed Hak AE, Pols HA, van Hemert AM, Hofman A, Witteman JC (2000) Progression of aortic calcification is associated with metacarpal bone loss during menopause: a population-based longitudinal study. Arterioscler Thromb Vasc Biol 20:1926–1931PubMed
5.
Zurück zum Zitat Jie KG, Bots ML, Vermeer C, Witteman JC, Grobbee DE (1996) Vitamin K status and bone mass in women with and without aortic atherosclerosis: a population-based study. Calcif Tissue Int 59:352–356PubMedCrossRef Jie KG, Bots ML, Vermeer C, Witteman JC, Grobbee DE (1996) Vitamin K status and bone mass in women with and without aortic atherosclerosis: a population-based study. Calcif Tissue Int 59:352–356PubMedCrossRef
6.
Zurück zum Zitat Jørgensen 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 160:549–556PubMedCrossRef Jørgensen 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 160:549–556PubMedCrossRef
7.
Zurück zum Zitat Kiel DP, Kauppila LI, Cupples LA, Hannan MT, O’Donnell CJ, Wilson PWF (2001) Bone loss and the progression of abdominal aortic calcification over a 25 year period: the Framingham Heart Study. Calcif Tissue Int 68:271–276PubMedCrossRef Kiel DP, Kauppila LI, Cupples LA, Hannan MT, O’Donnell CJ, Wilson PWF (2001) Bone loss and the progression of abdominal aortic calcification over a 25 year period: the Framingham Heart Study. Calcif Tissue Int 68:271–276PubMedCrossRef
8.
Zurück zum Zitat Schulz E, Arfai K, Liu X, Sayre J, Gilsanz V (2004) Aortic calcification and the risk of osteoporosis and fractures. J Clin Endocrinol Metab 89:4246–4253PubMedCrossRef Schulz E, Arfai K, Liu X, Sayre J, Gilsanz V (2004) Aortic calcification and the risk of osteoporosis and fractures. J Clin Endocrinol Metab 89:4246–4253PubMedCrossRef
9.
Zurück zum Zitat 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 57:14–26PubMed 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 57:14–26PubMed
10.
Zurück zum Zitat Tanko LB, Bagger YZ, Christiansen C (2003) Low bone mineral density in the hip as a marker of advanced atherosclerosis in elderly women. Calcif Tissue Int 73:15–20PubMedCrossRef Tanko LB, Bagger YZ, Christiansen C (2003) Low bone mineral density in the hip as a marker of advanced atherosclerosis in elderly women. Calcif Tissue Int 73:15–20PubMedCrossRef
11.
Zurück zum Zitat Uyama O, Yoshimoto Y, Yamamoto Y, Kawai A (1997) Bone changes and carotid atherosclerosis in postmenopausal women. Stroke 28:1730–1732PubMed Uyama O, Yoshimoto Y, Yamamoto Y, Kawai A (1997) Bone changes and carotid atherosclerosis in postmenopausal women. Stroke 28:1730–1732PubMed
12.
Zurück zum Zitat Aoyagi K, Ross PD, Orloff J, Davis JW, Katagiri H, Wasnich RD (2001) Low bone density is not associated with aortic calcification. Calcif Tissue Int 69:20–24PubMedCrossRef Aoyagi K, Ross PD, Orloff J, Davis JW, Katagiri H, Wasnich RD (2001) Low bone density is not associated with aortic calcification. Calcif Tissue Int 69:20–24PubMedCrossRef
13.
Zurück zum Zitat Frye MA, Melton LJ 3rd, Bryant SC, Fitzpatrick LA, Wahner HW, Schwartz RS, Riggs BL (1992) Osteoporosis and calcification of the aorta. Bone Miner 19:185–194PubMedCrossRef Frye MA, Melton LJ 3rd, Bryant SC, Fitzpatrick LA, Wahner HW, Schwartz RS, Riggs BL (1992) Osteoporosis and calcification of the aorta. Bone Miner 19:185–194PubMedCrossRef
14.
Zurück zum Zitat Reid IR, Evans MC, Ames R, Wattie DJ (1991) The influence of osteophytes and aortic calcification on spinal mineral density in postmenopausal women. J Clin Endocrinol Metab 72:1372–1374PubMedCrossRef Reid IR, Evans MC, Ames R, Wattie DJ (1991) The influence of osteophytes and aortic calcification on spinal mineral density in postmenopausal women. J Clin Endocrinol Metab 72:1372–1374PubMedCrossRef
15.
Zurück zum Zitat Vogt MT, San Valentin R, Forrest KY, Nevitt MC, Cauley JA (1997) Bone mineral density and aortic calcification: the Study of Osteoporotic Fractures. J Am Geriatr Soc 45:140–145PubMed Vogt MT, San Valentin R, Forrest KY, Nevitt MC, Cauley JA (1997) Bone mineral density and aortic calcification: the Study of Osteoporotic Fractures. J Am Geriatr Soc 45:140–145PubMed
16.
Zurück zum Zitat Hamerman D (2005) Osteoporosis and atherosclerosis: biological linkages and the emergence of dual-purpose therapies. QJM 98:467–484PubMedCrossRef Hamerman D (2005) Osteoporosis and atherosclerosis: biological linkages and the emergence of dual-purpose therapies. QJM 98:467–484PubMedCrossRef
17.
Zurück zum Zitat Wendelhag I, Wiklund O, Wikstrand J (1993) Atherosclerotic changes in the femoral and carotid arteries in familial hypercholesterolemia. Ultrasonographic assessment of intima-media thickness and plaque occurrence. Arterioscler Thromb 13:1404–1411PubMed Wendelhag I, Wiklund O, Wikstrand J (1993) Atherosclerotic changes in the femoral and carotid arteries in familial hypercholesterolemia. Ultrasonographic assessment of intima-media thickness and plaque occurrence. Arterioscler Thromb 13:1404–1411PubMed
18.
Zurück zum Zitat Wofford JL, Kahl FR, Howard GR, McKinney WM, Toole JF, Crouse JR III (1991) Relation of extent of extracranial carotid artery atherosclerosis as measured by B-mode ultrasound to the extent of coronary atherosclerosis. Arterioscler Thromb 11:1786–1794PubMed Wofford JL, Kahl FR, Howard GR, McKinney WM, Toole JF, Crouse JR III (1991) Relation of extent of extracranial carotid artery atherosclerosis as measured by B-mode ultrasound to the extent of coronary atherosclerosis. Arterioscler Thromb 11:1786–1794PubMed
19.
Zurück zum Zitat Grønholdt ML (1999) Ultrasound and lipoproteins as predictors of lipid-rich, rupture-prone plaques in the carotid artery. Arterioscler Thromb Vasc Biol 19:2–13PubMed Grønholdt ML (1999) Ultrasound and lipoproteins as predictors of lipid-rich, rupture-prone plaques in the carotid artery. Arterioscler Thromb Vasc Biol 19:2–13PubMed
20.
Zurück zum Zitat Burstein M, Scholnick HR, Morfin R (1970) Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions. J Lipid Res 11:583–595PubMed Burstein M, Scholnick HR, Morfin R (1970) Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions. J Lipid Res 11:583–595PubMed
21.
Zurück zum Zitat Jacobsen BK, Nielsen H (2000) High education is associated with low fat and high fibre, beta-carotene and vitamin C. Computation of nutrient intake based on a short food frequency questionnaire in 17,265 men and women in the Tromsø Study. Nor J Epidemiol 10:57–62 Jacobsen BK, Nielsen H (2000) High education is associated with low fat and high fibre, beta-carotene and vitamin C. Computation of nutrient intake based on a short food frequency questionnaire in 17,265 men and women in the Tromsø Study. Nor J Epidemiol 10:57–62
22.
Zurück zum Zitat Berntsen GK, Tollan A, Magnus JH, Søgaard AJ, Ringberg T, Fønnebø V (1999) The Tromsø Study: artifacts in forearm bone densitometry prevalence and effect. Osteoporos Int 10:425–432PubMedCrossRef Berntsen GK, Tollan A, Magnus JH, Søgaard AJ, Ringberg T, Fønnebø V (1999) The Tromsø Study: artifacts in forearm bone densitometry prevalence and effect. Osteoporos Int 10:425–432PubMedCrossRef
23.
Zurück zum Zitat Berntsen GK, Fønnebø V, Tollan A, Søgaard AJ, Joakimsen RM, Magnus JH (2000) The Tromsø Study: determinants of precision in bone densitometry. J Clin Epidemiol 53:1104–1112CrossRef Berntsen GK, Fønnebø V, Tollan A, Søgaard AJ, Joakimsen RM, Magnus JH (2000) The Tromsø Study: determinants of precision in bone densitometry. J Clin Epidemiol 53:1104–1112CrossRef
24.
Zurück zum Zitat Emaus N, Berntsen GK, Joakimsen R, Fønnebø V (2006) Longitudinal changes in forearm bone mineral density in women and men aged 45–84 years: the Tromsø Study, a population-based study. Am J Epidemiol 163:441–449PubMedCrossRef Emaus N, Berntsen GK, Joakimsen R, Fønnebø V (2006) Longitudinal changes in forearm bone mineral density in women and men aged 45–84 years: the Tromsø Study, a population-based study. Am J Epidemiol 163:441–449PubMedCrossRef
25.
Zurück zum Zitat Joakimsen O, Bønaa KH, Stensland-Bugge E (1997) Reproducibility of ultrasound assessment of carotid plaque occurrence, thickness, and morphology. The Tromsø Study. Stroke 28:2201–2207 Joakimsen O, Bønaa KH, Stensland-Bugge E (1997) Reproducibility of ultrasound assessment of carotid plaque occurrence, thickness, and morphology. The Tromsø Study. Stroke 28:2201–2207
26.
Zurück zum Zitat Joakimsen RM, Fønnebø V, Søgaard AJ, Tollan A, Størmer J, Magnus JH (2001) The Tromsø Study: registration of fractures, how good are self-reports, a computerized radiographic register and a discharge register? Osteoporos Int 12:1001–1005PubMedCrossRef Joakimsen RM, Fønnebø V, Søgaard AJ, Tollan A, Størmer J, Magnus JH (2001) The Tromsø Study: registration of fractures, how good are self-reports, a computerized radiographic register and a discharge register? Osteoporos Int 12:1001–1005PubMedCrossRef
27.
28.
Zurück zum Zitat Johnston SC, O’Meara ES, Manolio TA, Lefkowitz D, O’Leary DH, Goldstein S, Carlson MC, Fried LP, Longstreth WT Jr (2004) Cognitive impairment and decline are associated with carotid artery disease in patients without clinically evident cerebrovascular disease. Ann Intern Med 140:237–247PubMed Johnston SC, O’Meara ES, Manolio TA, Lefkowitz D, O’Leary DH, Goldstein S, Carlson MC, Fried LP, Longstreth WT Jr (2004) Cognitive impairment and decline are associated with carotid artery disease in patients without clinically evident cerebrovascular disease. Ann Intern Med 140:237–247PubMed
29.
Zurück zum Zitat Mathiesen EB, Waterloo K, Joakimsen O, Bakke SJ, Jacobsen EA, Bønaa KH (2004) Reduced neuropsychological test performance in asymptomatic carotid stenosis: the Tromsø Study. Neurology 62:695–701PubMed Mathiesen EB, Waterloo K, Joakimsen O, Bakke SJ, Jacobsen EA, Bønaa KH (2004) Reduced neuropsychological test performance in asymptomatic carotid stenosis: the Tromsø Study. Neurology 62:695–701PubMed
30.
Zurück zum Zitat Parhami F, Garfinkel A, Demer LL (2000) Role of lipids in osteoporosis. Arterioscler Thromb Vasc Biol 20:2346–2348PubMed Parhami F, Garfinkel A, Demer LL (2000) Role of lipids in osteoporosis. Arterioscler Thromb Vasc Biol 20:2346–2348PubMed
31.
Zurück zum Zitat Yamaguchi T, Sugimoto T, Yano S, Yamauchi M, Sowa H, Chen Q, Chihara K (2002) Plasma lipids and osteoporosis in postmenopausal women. Endocr J 49:211–217PubMedCrossRef Yamaguchi T, Sugimoto T, Yano S, Yamauchi M, Sowa H, Chen Q, Chihara K (2002) Plasma lipids and osteoporosis in postmenopausal women. Endocr J 49:211–217PubMedCrossRef
33.
Zurück zum Zitat Browner WS, Lui LY, Cummings SR (2001) Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women. J Clin Endocrinol Metab 86:631–637PubMedCrossRef Browner WS, Lui LY, Cummings SR (2001) Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women. J Clin Endocrinol Metab 86:631–637PubMedCrossRef
34.
Zurück zum Zitat Jono S, Ikari Y, Shioi A, Mori K, Miki T, Hara K, Nishizawa Y (2002) Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation 106:1192–1194PubMedCrossRef Jono S, Ikari Y, Shioi A, Mori K, Miki T, Hara K, Nishizawa Y (2002) Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation 106:1192–1194PubMedCrossRef
35.
Zurück zum Zitat Kiechl S, Schett G, Wenning G, Redlich K, Oberhollenzer M, Mayr A, Santer P, Smolen J, Poewe W, Willeit J (2004) Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation 109:2175–2180PubMedCrossRef Kiechl S, Schett G, Wenning G, Redlich K, Oberhollenzer M, Mayr A, Santer P, Smolen J, Poewe W, Willeit J (2004) Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation 109:2175–2180PubMedCrossRef
36.
Zurück zum Zitat Rhee EJ, Lee WY, Kim SY, Kim BJ, Sung KC, Kim BS, Kang JH, Oh KW, Oh ES, Baek KH, Kang MI, Woo HY, Park HS, Kim SW, Lee MH, Park JR (2005) Relationship of serum osteoprotegerin levels with coronary artery disease severity, left ventricular hypertrophy and C-reactive protein. Clin Sci (Lond) 108:237–243CrossRef Rhee EJ, Lee WY, Kim SY, Kim BJ, Sung KC, Kim BS, Kang JH, Oh KW, Oh ES, Baek KH, Kang MI, Woo HY, Park HS, Kim SW, Lee MH, Park JR (2005) Relationship of serum osteoprotegerin levels with coronary artery disease severity, left ventricular hypertrophy and C-reactive protein. Clin Sci (Lond) 108:237–243CrossRef
37.
Zurück zum Zitat Schoppet M, Sattler AM, Schaefer JR, Herzum M, Maisch B, Hofbauer LC (2003) Increased osteoprotegerin serum levels in men with coronary artery disease. J Clin Endocrinol Metab 88:1024–1028PubMedCrossRef Schoppet M, Sattler AM, Schaefer JR, Herzum M, Maisch B, Hofbauer LC (2003) Increased osteoprotegerin serum levels in men with coronary artery disease. J Clin Endocrinol Metab 88:1024–1028PubMedCrossRef
38.
Zurück zum Zitat Ueland T, Yndestad A, Oie E, Florholmen G, Halvorsen B, Froland SS, Simonsen S, Christensen G, Gullestad L, Aukrust P (2005) Dysregulated osteoprotegerin/RANK ligand/RANK axis in clinical and experimental heart failure. Circulation 111:2461–2468PubMedCrossRef Ueland T, Yndestad A, Oie E, Florholmen G, Halvorsen B, Froland SS, Simonsen S, Christensen G, Gullestad L, Aukrust P (2005) Dysregulated osteoprotegerin/RANK ligand/RANK axis in clinical and experimental heart failure. Circulation 111:2461–2468PubMedCrossRef
39.
Zurück zum Zitat van Meurs JB, Dhonukshe-Rutten RA, Pluijm SM, van der Klift M, de Jonge R, Lindemans J, de Groot LC, Hofman A, Witteman JC, van Leeuwen JP, Breteler MM, Lips P, Pols HA, Uitterlinden AG (2004) Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med 350:2033–2041PubMedCrossRef van Meurs JB, Dhonukshe-Rutten RA, Pluijm SM, van der Klift M, de Jonge R, Lindemans J, de Groot LC, Hofman A, Witteman JC, van Leeuwen JP, Breteler MM, Lips P, Pols HA, Uitterlinden AG (2004) Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med 350:2033–2041PubMedCrossRef
40.
Zurück zum Zitat McLean RR, Jacques PF, Selhub J, Tucker KL, Samelson EJ, Broe KE, Hannan MT, Cupples LA, Kiel DP (2004) Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med 350:2042–2049PubMedCrossRef McLean RR, Jacques PF, Selhub J, Tucker KL, Samelson EJ, Broe KE, Hannan MT, Cupples LA, Kiel DP (2004) Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med 350:2042–2049PubMedCrossRef
41.
Zurück zum Zitat Kanis J, Oden A, Johnell O (2001) Acute and long-term increase in fracture risk after hospitalization for stroke. Stroke 32:702–706PubMed Kanis J, Oden A, Johnell O (2001) Acute and long-term increase in fracture risk after hospitalization for stroke. Stroke 32:702–706PubMed
42.
Zurück zum Zitat Ramnemark A, Nyberg L, Borssén B, Olsson T, Gustafson Y (1998) Fractures after stroke. Osteoporos Int 8:92–95PubMedCrossRef Ramnemark A, Nyberg L, Borssén B, Olsson T, Gustafson Y (1998) Fractures after stroke. Osteoporos Int 8:92–95PubMedCrossRef
43.
Zurück zum Zitat Hatano S (1976) Experience from a multicentre stroke register: a preliminary report. Bull World Health Organ 54:541–553PubMed Hatano S (1976) Experience from a multicentre stroke register: a preliminary report. Bull World Health Organ 54:541–553PubMed
44.
Zurück zum Zitat Engstad T, Bønaa KH, Viitanen M (2000) Validity of self-reported stroke: the Tromsø Study. Stroke 31:1602–1607PubMed Engstad T, Bønaa KH, Viitanen M (2000) Validity of self-reported stroke: the Tromsø Study. Stroke 31:1602–1607PubMed
45.
Zurück zum Zitat Sanders KM, Pasco JA, Ugoni AM, Nicholson GC, Seeman E, Martin TJ, Skoric B, Panahi S, Kotowicz MA (1998) The exclusion of high trauma fractures may underestimate the prevalence of bone fragility fractures in the community: the Geelong Osteoporosis Study. J Bone Miner Res 13:1337–1342PubMedCrossRef Sanders KM, Pasco JA, Ugoni AM, Nicholson GC, Seeman E, Martin TJ, Skoric B, Panahi S, Kotowicz MA (1998) The exclusion of high trauma fractures may underestimate the prevalence of bone fragility fractures in the community: the Geelong Osteoporosis Study. J Bone Miner Res 13:1337–1342PubMedCrossRef
46.
Zurück zum Zitat Marshall D, Johnell O, Wedel H (1996) Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 312:1254–1259PubMed Marshall D, Johnell O, Wedel H (1996) Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 312:1254–1259PubMed
Metadaten
Titel
Carotid Plaque Echogenicity and Risk of Nonvertebral Fractures in Women: A Longitudinal Population-Based Study
verfasst von
L. Jørgensen
O. Joakimsen
E. B. Mathiesen
L. Ahmed
G. K. R. Berntsen
V. Fønnebø
R. Joakimsen
I. Njølstad
H. Schirmer
B. K. Jacobsen
Publikationsdatum
01.10.2006
Erschienen in
Calcified Tissue International / Ausgabe 4/2006
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-006-0071-x

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