Lipoprotein(a) plasma levels, bone mineral density and risk of hip fracture: a post hoc analysis of the Women's Health Initiative, USA

Bernhard Haring, Carolyn J Crandall, Laura Carbone, Simin Liu, Wenjun Li, Karen C Johnson, Jean Wactawski-Wende, Aladdin H Shadyab, Margery L Gass, Victor Kamensky, Jane A Cauley, Sylvia Wassertheil-Smoller, Bernhard Haring, Carolyn J Crandall, Laura Carbone, Simin Liu, Wenjun Li, Karen C Johnson, Jean Wactawski-Wende, Aladdin H Shadyab, Margery L Gass, Victor Kamensky, Jane A Cauley, Sylvia Wassertheil-Smoller

Abstract

Objectives: Elevated Lipoprotein(a) (Lp[a]) is a well-known risk factor for cardiovascular disease. However, its roles in bone metabolism and fracture risk are unclear. We therefore investigated whether plasma Lp(a) levels were associated with bone mineral density (BMD) and incident hip fractures in a large cohort of postmenopausal women.

Design: Post hoc analysis of data from the Women's Health Initiative (WHI), USA.

Setting: 40 clinical centres in the USA.

Participants: The current analytical cohort consisted of 9698 white, postmenopausal women enrolled in the WHI, a national prospective study investigating determinants of chronic diseases including heart disease, breast and colorectal cancers and osteoporotic fractures among postmenopausal women. Recruitment for WHI took place from 1 October 1993 to 31 December 1998.

Exposures: Plasma Lp(a) levels were measured at baseline.

Outcome measures: Incident hip fractures were ascertained annually and confirmed by medical records with follow-up through 29 August 2014. BMD at the femoral neck was measured by dual X-ray absorptiometry in a subset of participants at baseline.

Statistical analyses: Cox proportional hazards and logistic regression models were used to evaluate associations of quartiles of plasma Lp(a) levels with hip fracture events and hip BMD T-score, respectively.

Results: During a mean follow-up of 13.8 years, 454 incident cases of hip fracture were observed. In analyses adjusting for confounding variables including age, body mass index, history of hysterectomy, smoking, physical activity, diabetes mellitus, general health status, cardiovascular disease, use of menopausal hormone therapy, use of bisphosphonates, calcitonin or selective-oestrogen receptor modulators, baseline dietary and supplemental calcium and vitamin D intake and history of fracture, no significant association of plasma Lp(a) levels with low hip BMD T-score or hip fracture risk was detected.

Conclusions: These findings suggest that plasma Lp(a) levels are not related to hip BMD T-score or hip fracture events in postmenopausal women.

Trial registration number: NCT00000611; Post-results.

Keywords: bone mineral density; fractures; lipoprotein (a); postmenopausal women.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

References

    1. Frank S, Durovic S, Kostner GM. The assembly of lipoprotein Lp(a). Eur J Clin Invest 1996;26:109–14. 10.1046/j.1365-2362.1996.112255.x
    1. Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, et al. . Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA 2009;301:2331–9. 10.1001/jama.2009.801
    1. Nordestgaard BG, Langsted A. Lipoprotein (a) as a cause of cardiovascular disease: insights from epidemiology, genetics, and biology. J Lipid Res 2016;57:1953–75. 10.1194/jlr.R071233
    1. Boffa MB, Koschinsky ML. Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease? J Lipid Res 2016;57:745–57. 10.1194/jlr.R060582
    1. Anglés-Cano E, de la Peña Díaz A, Loyau S. Inhibition of fibrinolysis by lipoprotein(a). Ann N Y Acad Sci 2001;936:261–75. 10.1111/j.1749-6632.2001.tb03514.x
    1. O’Keefe RJ. Fibrinolysis as a target to enhance fracture healing. N Engl J Med 2015;373:1776–8. 10.1056/NEJMcibr1510090
    1. Kamstrup PR, Tybjærg-Hansen A, Nordestgaard BG. Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population. J Am Coll Cardiol 2014;63:470–7. 10.1016/j.jacc.2013.09.038
    1. Kronenberg F, Kuen E, Ritz E, et al. . Lipoprotein(a) serum concentrations and apolipoprotein(a) phenotypes in mild and moderate renal failure. J Am Soc Nephrol 2000;11:105–15.
    1. Orozco P. Atherogenic lipid profile and elevated lipoprotein (a) are associated with lower bone mineral density in early postmenopausal overweight women. Eur J Epidemiol 2004;19:1105–12. 10.1007/s10654-004-1706-8
    1. Pliatsika P, Antoniou A, Alexandrou A, et al. . Serum lipid levels and bone mineral density in Greek postmenopausal women. Gynecol Endocrinol 2012;28:655–60. 10.3109/09513590.2011.650766
    1. Design of the Women’s Health Initiative clinical trial and observational study. The Women’s Health Initiative Study Group. Control Clin Trials 1998;19:61–109.
    1. Vu Dac N, Mezdour H, Parra HJ, et al. . A selective bi-site immunoenzymatic procedure for human Lp[a] lipoprotein quantification using monoclonal antibodies against apo[a] and apoB. J Lipid Res 1989;30:1437–43.
    1. Myers GL, Cooper GR, Winn CL, et al. . The centers for disease control-national heart, lung and blood institute lipid standardization program. an approach to accurate and precise lipid measurements. Clin Lab Med 1989;9:105–36. 10.1016/S0272-2712(18)30645-0
    1. Chang PY, Gold EB, Cauley JA, et al. . Triglyceride levels and fracture risk in midlife women: Study of Women’s Health Across the Nation (SWAN). J Clin Endocrinol Metab 2016;101:3297–305. 10.1210/jc.2016-1366
    1. Yamauchi M, Yamaguchi T, Nawata K, et al. . Increased low-density lipoprotein cholesterol level is associated with non-vertebral fractures in postmenopausal women. Endocrine 2015;48:279–86. 10.1007/s12020-014-0292-0
    1. Cui LH, Shin MH, Chung EK, et al. . Association between bone mineral densities and serum lipid profiles of pre- and post-menopausal rural women in South Korea. Osteoporos Int 2005;16:1975–81. 10.1007/s00198-005-1977-2
    1. Ghadiri-Anari A, Mortezaii-Shoroki Z, Modarresi M, et al. . Association of lipid profile with bone mineral density in postmenopausal women in Yazd province. Int J Reprod Biomed 2016;14:597–602. 10.29252/ijrm.14.9.597
    1. Makovey J, Chen JS, Hayward C, et al. . Association between serum cholesterol and bone mineral density. Bone 2009;44:208–13. 10.1016/j.bone.2008.09.020
    1. Yamaguchi T, Sugimoto T, Yano S, et al. . Plasma lipids and osteoporosis in postmenopausal women. Endocr J 2002;49:211–7. 10.1507/endocrj.49.211
    1. Jeong IK, Cho SW, Kim SW, et al. . Lipid profiles and bone mineral density in pre- and postmenopausal women in Korea. Calcif Tissue Int 2010;87:507–12. 10.1007/s00223-010-9427-3
    1. Wang Z, Li Y, Zhou F, et al. . Effects of statins on bone mineral density and fracture risk: a PRISMA-compliant systematic review and meta-analysis. Medicine 2016;95:e3042 10.1097/MD.0000000000003042
    1. Anagnostis P, Galanis P, Chatzistergiou V, et al. . The effect of hormone replacement therapy and tibolone on lipoprotein (a) concentrations in postmenopausal women: a systematic review and meta-analysis. Maturitas 2017;99:27–36. 10.1016/j.maturitas.2017.02.009
    1. Suk Danik J, Rifai N, Buring JE, et al. . Lipoprotein(a), hormone replacement therapy, and risk of future cardiovascular events. J Am Coll Cardiol 2008;52:124–31. 10.1016/j.jacc.2008.04.009
    1. Erqou S, Thompson A, Di Angelantonio E, et al. . Apolipoprotein(a) isoforms and the risk of vascular disease: systematic review of 40 studies involving 58,000 participants. J Am Coll Cardiol 2010;55:2160–7. 10.1016/j.jacc.2009.10.080
    1. Saleheen D, Haycock PC, Zhao W, et al. . Apolipoprotein(a) isoform size, lipoprotein(a) concentration, and coronary artery disease: a mendelian randomisation analysis. Lancet Diabetes Endocrinol 2017;5:524–33. 10.1016/S2213-8587(17)30088-8

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel