Vitamin D, Subclinical Cardiovascular Disease, and Orthostatic Hypotension in Older Adults

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Each year, nearly one third of adults aged 65 years or older experiences a fall and the rate of falls in the US is rising. Older adults frequently do not recover from falls, resulting in permanent disability and premature death. Given the aging US population, identifying mechanisms by which falls occur and interventions to prevent falls are recognized public health priorities. This proposal focuses on an innovative hypothesis that undetected or subclinical cardiovascular disease (CVD), a condition highly prevalent in older adults, may contribute to falls in older adults. Our scientific premise is based on our recently published work in middle-aged adults, which demonstrated that subclinical CVD was strongly associated with orthostatic hypotension, a fall risk factor. Given the essential role of the cardiovascular system to support functions of both muscle and the central nervous system, we believe that CVD might promote falls in several ways beyond orthostasis, including muscle strength, gait speed, and balance, and that elevations in markers of subclinical CVD would be associated with a higher risk of falling. However, these pathways have not been tested in a population of older adults. This supplement proposal aims to (1) determine the contribution of subclinical CVD toward the pathogenesis of falls via orthostatic hypotension, and (2) determine the impact of vitamin D3 supplementation, an intervention for falls, on subclinical CVD. We will accomplish these aims by measuring subclinical CVD via two reliable and highly sensitive markers of cardiovascular injury and strain: high sensitivity cardiac troponin I (hs-cTnI) and N- terminal pro b-type natriuretic peptide (NT-proBNP) in stored specimens of the NIA-funded trial (STURDY). STURDY tests the effects of vitamin D3 supplementation on falls in high-risk adults, age 70 and older, and includes detailed assessments of muscle strength, gait speed, and balance along with comprehensive assessments of orthostatic hypotension, secondary to Dr. Juraschek's K23 ancillary proposal. Furthermore, STURDY's randomized design, which involves one of four vitamin D3 doses administered to adults with insufficient or deficient vitamin D, affords a tremendous opportunity to determine the direct effects of appropriately dosed vitamin D3 on subclinical CVD. This innovative proposal brings together (1) an expert team of STURDY investigators on orthostatic hypotension, supplements, and the measurement of CVD biomarkers (Drs. Juraschek, Appel, Christenson), (2) an ongoing industry partnership with Siemens which significantly reduces assay costs, (3) an incredibly unique and established NIA study population, and (4) a remarkable track record of productivity. This proposal has the potential to shift paradigms in how orthostatic hypotension is understood and establish subclinical CVD as a critical focus of subsequent fall prevention strategies. Furthermore, our proposal will provide definitive evidence as to whether one fall intervention, vitamin D3 supplementation, reduces subclinical CVD. Together these aims will inform future intervention studies focused on subclinical CVD to prevent orthostatic hypotension and prevent falls in older adults.