Physical health composite and risk of cancer mortality in the REasons for Geographic and Racial Differences in Stroke Study

Highlights

• Physical health composite is combined physical activity and rate-pressure product.

• Physical health composite is associated with 71% increased cancer mortality risk.

• Among both normal weight and obese participants, this risk was nearly 2-fold.

• Higher RPP is associated with 34% increased risk for cancer mortality.

• No physical activity is associated with 27% increased risk for cancer mortality.

Abstract

It is unclear how resting myocardial workload, as indexed by baseline measures of rate-pressure product (RPP) and physical activity (PA), is associated with the overall risk of cancer mortality. We performed prospective analyses among 28,810 men and women from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. We used a novel physical health (PH) composite index and categorized participants into one of four groups based on combinations from self-reported PA and RPP: 1) No PA and High RPP; 2) No PA and Low RPP; 3) Yes PA and High RPP; and 4) Yes PA and Low RPP. We examined the association between baseline PH composite and cancer mortality adjusted for potential confounders using Cox regression. A total of 1191 cancer deaths were observed over the 10-year observation period, with the majority being lung (26.87%) and gastrointestinal (21.49%) cancers. Even after controlling for sociodemographics, health behaviors, baseline comorbidity score, and medications, participants with No PA and High RPP had 71% greater risk of cancer mortality when compared to participants with PA and Low RPP (adjusted HR: 1.71, 95% CI: 1.42–2.06). These associations persisted after examining BMI, smoking, income, and gender as effect modifiers and all-cause mortality as a competing risk. Poorer physical health composite, including the novel RPP metric, was associated with a nearly 2-fold long-term risk of cancer mortality. The physical health composite has important public health implications as it provides a measure of risk beyond traditional measure of obesity and physical activity.

Introduction

Cancer is a leading cause of morbidity and death in United States (US) resulting in over 600,000 annual deaths (Siegel et al., 2019; Centers for Disease Control and Prevention, n.d). However, in recent decades, earlier detection and advances in targeted therapies have contributed to five-year cancer survival rates approaching 70% (Gloeckler Ries et al., 2003; Welch et al., 2000). Still, due in part to societal modernization, characterized by technological advancements including accessibility to calorie-rich diets and sedentary behaviors, there is a growing segment of the population living with cardiovascular chronic diseases (Akinyemiju et al., 2016; Moore et al., 2017; Ogden et al., 2014; Tsujimoto et al., 2016; Falkner and Cossrow, 2014). Furthermore, as more than one in three US adults live with obesity, obesity and excess body weight are responsible for nearly 9% of incident cancers and 6.5% of all cancer deaths (Gallagher and LeRoith, 2015; Islami et al., 2018a; Islami et al., 2018b; Sung et al., 2019; Flegal et al., 2015). Despite the known importance of physical activity it is estimated that 44.6% of Americans, and 40% of cancer survivors do not participate in leisure-time physical activity (Yang and Toriola, 2017; Weinsier et al., 2002; Hunter et al., 2015; Ussery et al., 2018). Nevertheless, adequate physical activity (i.e., 150 min·week⁻¹) represents a key modifiable lifestyle factor that may mitigate the risk of cancer mortality through multiple divergent and overlapping pathways.

Increased physical health and activity are inversely associated with all-cause mortality, cancer incidence, and cancer survival (Lahart et al., 2015; Garcia and Thomson, 2014; Ibrahim and Al-Homaidh, 2011; Meyerhardt et al., 2006; Meyerhardt et al., 2009; Moore et al., 2016; Arem et al., 2015). For example, in a large meta-analysis among more than one million US and European participants, those in the highest percentiles of leisure-time physical activity were at 27%, 13%, and 7% reduced risk of lung, colon, and breast cancers, respectively, even after accounting for body mass index (Moore et al., 2016). While insufficient physical activity has been linked with cardio-metabolic disease and overall mortality, it is unclear whether resting myocardial workload is associated with an elevated overall risk of cancer mortality. Though studies have examined the association between physical activity and cancer survival, researchers are often reliant on self-reported physical activity (Moore et al., 2016; Arem et al., 2015) and/or usage of accelerometers (Pedisic and Bauman, 2015) that may have limited objectivity. Thus, we propose using the product of resting heart rate and resting systolic blood pressure to quantify rate-pressure product (RPP), an objective non-invasive index of myocardial oxygen demand (Carter et al., 2016), as a predictor of cancer mortality. To our knowledge, this work will be the first to examine the association between baseline assessment of RPP and cancer mortality.

Few studies have focused on the association between baseline health, using cardiovascular health parameters like RPP, and physical activity with long-term risk of cancer mortality among a nationally representative cohort of community-dwelling participants. Given that health status is multi-dimensional, influenced by diet, physical activity, cardiovascular determinants, and psychological factors, we sought to incorporate self-reported physical activity in combination with objectively measured RPP. Therefore, we aimed to investigate whether a lower physical health composite at baseline, as evidenced by low self-reported PA and higher RPP, is associated with greater risk of cancer mortality.