They investigators state that they have found that women with osteopenia (low bone density) are at an increased risk of stroke. Each standard deviation decrease in bone density at the calcaneus (0.10 g/cm2) was associated with a 1.31-fold increase in incident stroke (95% confidence interval: 1.03 - 1.65), and a 1.7-fold increase (95% CI: 1.1 - 2.7) in fatal stroke, adjusted for age and follow-up time, a result that has now also been seen in two separate cohort studies. There have also been several new advances in cellular biology establishing links between calcium-regulating hormones, the vascular system, and thrombosis. They propose a nested case-cohort study within the Study of Osteoporotic Fractures (SOF) to look for biologic explanations for this association; for example, perhaps elevated levels of parathyroid hormone, are associated with stroke. Participants in SOF (n=9704 women ages 65 years and older) have been followed since 1986-88. Bone density was measured using photon absorptiometric techniques. Serum samples were obtained from these women at baseline, and frozen at -190 degrees Celsius since then. Women with an incident ischemic non-cardiogenic stroke during follow-up (n = 300) will be compared with controls (n = 300). Cases of stroke will be identified by review of annual questionnaires, Medicare and health maintenance organization data tapes, and death certificates, and will be validated by blinded review of medical records using preset criteria. """"""""Controls"""""""" will be randomly selected from the cohort. They will measure several factors in serum (including parathyroid hormone, endogenous estrogens, calcitriol, insulin-like growth factor (IGF)-1, homocysteine, osteocalcin, calcium, phosphate, creatinine and albumin) that may be related to stroke. With 300 cases and 300 controls, the study will have 90% power (at two-sided alpha = 0.05) to detect whether one of these factors is associated with stroke at a relative hazard of 1.26 per standard deviation or more. Should they identify new predictor(s) of stroke, they will compare levels in black women participating in SOF (n = 130) with those in the controls, and will attempt to determine whether there are racial differences in these predictor(s). The investigators point out that many of these potential new risk factors for stroke are amenable to relatively simple treatments. For example, high levels of parathyroid hormone in the elderly can be treated with calcium supplementation. Thus, they state that determining a biologic explanation for the osteopenia-stroke association may suggest new ways to prevent tow of the most common disease of elderly women.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS036016-03
Application #
2735707
Study Section
Special Emphasis Panel (ZRG4-EDC-1 (04))
Program Officer
Marler, John R
Project Start
1996-09-30
Project End
2000-09-30
Budget Start
1998-07-01
Budget End
2000-09-30
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Northern California Institute Research & Education
Department
Type
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94121
Rodondi, N; Taylor, B C; Bauer, D C et al. (2007) Association between aortic calcification and total and cardiovascular mortality in older women. J Intern Med 261:238-44
Brophy, Victoria H; Ro, Sunhee K; Rhees, Brian K et al. (2006) Association of phosphodiesterase 4D polymorphisms with ischemic stroke in a US population stratified by hypertension status. Stroke 37:1385-90
Rutledge, Thomas; Matthews, Karen; Lui, Li-Yung et al. (2003) Social networks and marital status predict mortality in older women: prospective evidence from the Study of Osteoporotic Fractures (SOF). Psychosom Med 65:688-94
Tice, Jeffrey A; Browner, Warren; Tracy, Russell P et al. (2003) The relation of C-reactive protein levels to total and cardiovascular mortality in older U.S. women. Am J Med 114:199-205
Browner, W S; Lui, L Y; Cummings, S R (2001) Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women. J Clin Endocrinol Metab 86:631-7
Johnston, S C; Messina, L M; Browner, W S et al. (2001) C-reactive protein levels and viable Chlamydia pneumoniae in carotid artery atherosclerosis. Stroke 32:2748-52
Johnston, S C; Gress, D R; Browner, W S et al. (2000) Short-term prognosis after emergency department diagnosis of TIA. JAMA 284:2901-6