Pulse oximetry values from 33,080 participants in the Apple Heart & Movement Study

www.nature.com/npjdigitalmed ARTICLE OPEN Pulse oximetry values from 33,080 participants in the Apple Heart & Movement Study 1234567890():,; Ian Shapiro 1 , Jeff Stein1, Calum MacRae2,3 and Michael O’Reilly 1✉ Wearable devices that include pulse oximetry (SpO2) sensing afford the opportunity to capture oxygen saturation measurements from large cohorts under naturalistic conditions. We report here a cross-sectional analysis of 72 million SpO2 values collected from 33,080 individual participants in the Apple Heart and Movement Study, stratified by age, sex, body mass index (BMI), home altitude, and other demographic variables. Measurements aggregated by hour of day into 24-h SpO2 profiles exhibit similar circadian patterns for all demographic groups, being approximately sinusoidal with nadir near midnight local time, zenith near noon local time, and mean 0.8% lower saturation during overnight hours. Using SpO2 measurements averaged for each subject into mean nocturnal and daytime SpO2 values, we employ multivariate ordinary least squares regression to quantify population-level trends according to demographic factors. For the full cohort, regression coefficients obtained from models fit to daytime SpO2 are in close quantitative agreement with the corresponding values from published reference models for awake arterial oxygen saturation measured under controlled laboratory conditions. Regression models stratified by sex reveal significantly different age- and BMIdependent SpO2 trends for females compared with males, although constant terms and regression coefficients for altitude do not differ between sexes. Incorporating categorical variables encoding self-reported race/ethnicity into the full-cohort regression models identifies small but statistically significant differences in daytime SpO2 (largest coefficient corresponding to 0.13% lower SpO2, for Hispanic study participants compared to White participants), but no significant differences between groups for nocturnal SpO2. Additional stratified analysis comparing regression models fit independently to subjects in each race/ethnicity group is suggestive of small differences in age- and sex-dependent trends, but indicates no significant difference in constant terms between any race/ethnicity groups for either daytime or nocturnal SpO2. The large diverse study population and study design employing automated background SpO2 measurements spanning the full 24-h circadian cycle enables the establishment of healthy population reference trends outside of clinical settings. npj Digital Medicine (2023)6:134 ; https://doi.org/10.1038/s41746-023-00851-6 INTRODUCTION Arterial blood oxygen saturation (SaO2) is the fraction of hemoglobin containing bound oxygen relative to the total functional hemoglobin, and represents a key parameter indicative of cardiopulmonary function. Direct SaO2 measurement necessitates an invasive arterial blood draw and blood gas analysis. Pulse oximetry enables non-invasive measurement of blood oxygen saturation (SpO2) and provides a convenient estimate of SaO2 that does not require arterial blood removal. The SpO2 measurement relies upon quantifying changes in optical attenuation at two separate wavelengths (typically one red and one infrared), with signal content arising from pulsatile arterial blood modulation in response to individual heartbeats. Depending on design, pulse oximeters may operate in either transmissive mode, with the interrogating light propagating across a thin section of capillary rich tissue (commonly fingertip, earlobe, or toe), or in reflectance mode wherein the interrogating light scatters back in the direction of the optical illuminator. Reflectance SpO2 is employed by consumer smart watch devices such as the Apple Watch (selected models) as well as selected products from Fitbit, Garmin, Samsung, Withings, and other manufacturers. Oxygen saturation determined from SaO2 or SpO2 is often considered a ”fifth vital sign” due to its relative ease of capture and high clinical utility1,2. As a physiological metric, arterial oxygen saturation directly impacts systemic oxygen delivery in conjunction with cardiac output and hemoglobin concentration. Among healthy awake individuals, typical SpO2 values lie in the range of 95–99%. Low blood oxygen saturation can arise from impaired lung function (e.g., reduced diffusion capacity), ventilation-perfusion mismatch, cardiac shunt, low cardiac output, or low oxygen concentration in the inspired air (e.g., due to altitude). No single universal SpO2 threshold is applied in all medical use cases, but values less than 92% from individuals breathing room air at sea level generally prompt further investigation, with values remaining persistently below 90% indicating hypoxemia. Oxygen saturation is utilized to guide management of cardiopulmonary conditions such as chronic obstructive pulmonary disease (COPD), obesity hypoventilation syndrome (OHS), and obstructive sleep apnea (OSA). Cross-sectional studies involving single-setting SpO2 or SaO2 measurements from nominally healthy individuals at constant altitude have consistently reported negative correlation of blood oxygen saturation with both age and body mass3–7. Studies incorporating multiple altitudes or a range of barometric pressure consistently report a positive linear relationship between awake arterial oxygen saturation and barometric pressure, in agreement with expectations based on the alveolar gas equation3,8,9. Less consistently, some studies have also reported positive correlation between SpO2 and female sex5,10,11, although others have reported negative or insignificant SpO2 findings with respect to 1 Apple Inc., Cupertino, CA, USA. 2Cardiovascular Medicine Division, Brigham and Women’s Hospital, Boston, MA, USA. 3Harvard Medical School, Boston, MA, USA. ✉email: Published in partnership with Seoul National University Bundang Hospital I. Shapiro et al. 1234567890():,; 2 sex12. A similar mix of conclusions has been published with respect to tobacco smoking status, with some studies reporting lower SpO2 values for current smokers6 and others reporting no significant relationship5. In the context of clinical screening and risk estimation for chronic cardiopulmonary disease, single-point SpO2 measurements below 95% saturation have been reported as predictive of a variety of cardiopulmonary conditions and outcomes13–18. The Tromsø Study examined single-event SpO2 values and 10-year outcomes for cardiopulmonary disease, reporting significant elevated risk for values ≤92% and 93–95% saturation, compared with 96–100% saturation14. Daytime SpO2 has been reported as a significant independent predictor of hypertension13, as well as circulatory impairment in the form of impaired left ventricular filling15. Mean overnight SpO2 has also been reported as predictive of both absolute waking blood pressure and magnitude of morning blood pressure surge16. Studies examining overnight SpO2 in the context of atheroscle (...truncated)