For decades, we have known that lower heart rate (HR) is associated with reduced morbidity and mortality. But HR is not stable - it is inherently """"""""noisy,"""""""" oscillating around the mean. Beginning in the 1980s, the clinical and physiological significance of these oscillations, now known as Heart Rate Variability (HRV), has been recognized. HRV predicts adverse outcomes following myocardial infarction or diagnosis of heart failure, progression of atherosclerosis in CAD patients, and the development of CAD in healthy community samples. Thus, measurement """"""""noise"""""""" in HR is now recognized as a valuable index of cardiovascular health. Today, blood pressure (BP) is in a similar position as HR was 40 years ago. While the clinical significance of mean blood pressure (BP) has been accepted for decades, within-subject BP varies considerably across multiple time scales. Once dismissed as noise, BP variability (BPV) now also is thought to contain valuable information. Measured repeatedly over weeks or even years, the standard deviation (SD) of clinic-to-clinic BP predicted the development of hypertension and mortality after 12-14 years follow-up. On a 24-hour scale, the SD of BP measured every 30 min was associated with cardiovascular mortality after 8.5 years follow-up and with greater target organ damage. At a still shorter time scale, BP varies on a beat-to-beat basis. Consensus in the field is that the ultimate prognostic value of BPV may require analysis of these beat-to-beat BP oscillations. However, because measurement of these more rapid oscillations has been technically demanding, associations of beat-to-beat BPV with clinical or with psychosocial variables linked to health have not been established. Technological advances have made beat-to-beat BPV increasingly available and exploration of its relationship to cardiovascular health and contextual sociodemographic and psychosocial cardiovascular risk factors has the potential to yield important clinical and physiological insights. Measuring beat-to-beat BP along with RR intervals also allows for computation of baroreflex sensitivity (BRS), the relationship of reflexive changes in RR interval to changes in BP. While BPV may represent a tonic autonomic index, BRS is an index of autonomic reflexes that predicts adverse outcomes after MI and in heart failure. However, to our knowledge, community studies of BPV and BRS do not exist. We propose to analyze the beat-to-beat BP data already collected but not analyzed from participants at rest and in response to psychological and orthostatic challenge from the wave 2 of data collection in the Midlife in the US (MIDUS II) study.
Our aims i n this R21 are to examine relationships between resting and reactive BPV and BRS and psychosocial and biomarker data across the age spectrum and in an exploratory prospective analysis, to test whether greater BPV and lower BRS are associated with greater mortality.

Public Health Relevance

For decades, mean blood pressure has been recognized as clinically significant and has been the focus of pressure-lowering therapies but recent evidence has demonstrated that variations in blood pressure (BPV) across a multiple time scales predict adverse outcomes independent of mean pressure and some have suggested that BPV also should be the target of therapeutic interventions. We have collected but never analyzed continuous BP waveforms to generate estimates of beat-to-beat BPV during rest and in response to challenge in 1255 participants in the Midlife in the US (MIDUS) study, a nationally representative community sample. In this application, we propose conduct what we believe to be the first community study ever to examine beat-to-beat BPV, assessing relationships between resting and reactive BPV and psychosocial and biomarker data collected across the age spectrum in MIDUS and prospectively, testing whether greater BPV is associated with increased mortality.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-BBBP-T (03))
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Nielsen, Lisbeth
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Columbia University
Schools of Medicine
New York
United States
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