AS661 - Objective physical activity and cardiovascular health (OPACH) 2

Investigator Names and Contact Information

Andrea LaCroix (alacroix@ucsd.edu)

Michael LaMonte

Introduction/Intent

Specific Aims

America’s “silver tsunami” will result in the nearly doubling of older Americans from 49 million today to 95 million by 2060 owing in part to declines in cardiovascular disease (CVD) mortality over the past half century. However, declines in CHD mortality among Americans aged 65-84 have been faster in older men than women from 1979-2011.¹ While prevalence of myocardial infarction (MI) remains higher among men than women across the adult age spectrum, rates of incident or recurrent MI and fatal CHD are higher among women aged 85 and older (120/1000) than men (85/1000).² Moreover, older women bear a disproportionate burden of disability and co-morbidity partly related to CVD. Yet, CVD prevention in older women is vastly understudied.

The national Physical Activity Guidelines for Americans, first published in 2008 and revised in 2018, are based on compelling evidence that regular physical activity (PA) and limiting sedentary behaviors (SB) is associated with lower risks of CVD as well as mobility disability and premature mortality.^{3, 4} The evidence base underlying these guidelines is largely based on self-reported PA and SB. It is now well documented that device-measures (e.g., accelerometer) characterize daily PA and SB patterns more accurately than questionnaires especially in measuring PA intensity and SB patterns in older adults.⁵ With NHLBI R01 HL105065 to Dr. LaCroix, our team successfully completed one of the largest prospective studies to date on objectively measured PA and SB in relation to incident CVD in older women, with paradigm shifting published results on the clear health benefits of below guideline recommended light intensity PA at older ages. The Objective Physical Activity and Cardiovascular Health (OPACH) Study, embedded within the Women’s Health Initiative (WHI), distributed triaxial, hip worn devices to 7,048 women, aged 63-99 years, in 2012-2014. We also conducted a laboratory calibration study -- the first of its kind specifically in older adults – to determine accelerometer cutpoints for absolute intensity relevant to the usual daily PA habits of older women.⁶ Our primary results, show a statistically significant, dose responsive, 20% reduction in CHD and a 10% reduction in CVD,⁷ and a 24% reduction in all-cause mortality⁸ for every additional hour spent in light PA (1.6-2.9 METS) in older women; and a 12% increased risk of CVD for every additional hour spent sedentary.⁹

Conventionally, absolute intensity has been used when assigning intensity values to both self-reported and device-based PA measures. This approach makes two critical assumptions: (1) resting metabolic rate, and (2) the energy cost of a given aerobic activity are constant and invariant across the adult age range. Evidence suggests that neither assumption holds true. Resting metabolic rate and maximal aerobic capacity decline with aging, whereas the energy cost of aerobic activity increases with age.¹⁰ Therefore, the relative intensity to complete a defined activity is higher in older adults compared to their younger peers. The magnitude and dose-response pattern of associations for relative PA intensity with CVD is unknown. Thus, the 2018 PA Guidelines Evidence Report urged researchers to: “Conduct prospective cohort studies of PA and physical function in older adults that include objective measures (e.g., heart rate monitors) of relative intensity of PA.” ⁴

In this competitive renewal of OPACH,¹¹ we propose to obtain a second accelerometer measurement of PA and SB with contemporaneous measurement of heart rate using a non-invasive cardiac monitor patch (Cardea SOLO). We also will ask OPACH 2 women complete a validated^{12, 13} 2 ½ minute, usual pace, self-administered walk test at home while wearing the accelerometer and SOLO patch, for assessment of peak exercise capacity (VO_2max). Together, these measurements will allow us to evaluate the relative intensity (i.e., percentage of VO_2max and heart rate max) of PA measured objectively by accelerometer in relation to incident CVD and indicators of CV health. We propose the following Aims:

Aim 1: Determine associations of accelerometer-measured relative PA intensity with incidence of CVD outcomes (CHD, heart failure, stroke) and mortality over 10-12 years of follow-up, and compare the magnitude of associations to absolute PA intensity.

Aim 2: Determine at a second accelerometer wear (2021-2022) cross-sectional associations of relative and absolute PA intensity, and SB with indicators of CV health including traditional risk factors (lipids, glycemia, inflammation, blood pressure, adiposity), novel biomarkers of CVD pathology (cardiac troponin, natriuretic peptide, galactin-3), heart rate variability (from Cardea Solo patch monitor), and objective physical functioning.

Aim 3: Determine the association of changes in accelerometer-measured PA (absolute and relative intensity) and SB over ≈10 years with changes in traditional cardiovascular risk factors, novel biomarkers, and physical functioning during the same interval, and with incidence of clinical CVD events and mortality up to 2027.

The long-term objective of this study is to further characterize the type, amount, and intensity of PA needed to maintain CV health in older adults, and to transform and refine guidelines by conveying accurate and realistic PA goals for older Americans.