Hypertension is a critical health problem affecting >1 billion people worldwide and has been recognized as a risk factor for cardiovascular disease (CVD), cancer, diabetes, and all-cause mortality. (Del Pozo Cruz et al., 2022a; Petrie et al., 2018; Sionakidis et al., 2021; Wang et al., 2022) With the aging of the population and the increasing lifestyle risk factors, the prevalence of hypertension and its adverse effects on incidence of cancer, CVD and diabetes are aggravating, causing a considerable social and financial burden. (Del Pozo Cruz et al., 2022a; Petrie et al., 2018; Sionakidis et al., 2021; Wang et al., 2022) Therefore, in addition to positively preventing hypertension, it is also necessary to find cost-effective strategies to reduce risks of major chronic diseases in individuals with hypertension. There is adequate evidence that regular physical activity is beneficial in treating of hypertension (Unger et al., 2020) and thus may reduce risks of CVD, cancer and diabetes mellitus type 2 (T2DM) in individuals with hypertension.

It is well recognized that walking is a part of physical activity and can benefit physical and mental health conditions. (Boone-Heinonen et al., 2009; Carl J Caspersen, 2008; Ukawa et al., 2014; Williams, 2014) At the same time, walking is the most common and acceptable form of physical activity for most middle-aged and older adults. Although total volume of walking is frequently studied (Boone-Heinonen et al., 2009; Carl J Caspersen, 2008; Ukawa et al., 2014; Williams, 2014), for example by distance or time, habitual walking pace has also been investigated as a surrogate marker of physical activity for its positive impacts on long-term physical health. Several studies have shown that average or brisk walking pace is associated with decreased risks of CVD, T2DM and cancer (overall, prostate, and endometrial cancers). (Boonpor et al., 2023; Du et al., 2014; Imran et al., 2019; Quan et al., 2020; Richman et al., 2011; Stamatakis et al., 2018; Veronese et al., 2018; Welsh et al., 2020) However, another study based on the UK Biobank suggests that brisk walking pace is not linked to many types of cancer risk, except for an increased risk of prostate cancer. (Celis-Morales et al., 2019) Furthermore, the current studies primarily apply to the general population, but for individuals with hypertension who were known to be at high risks for CVD, T2DM and cancer, there is insufficient evidence on whether walking pace can affect risks of these diseases.

Although current research has explored the association between walking pace and a variety of major chronic diseases (Boonpor et al., 2023; Du et al., 2014; Imran et al., 2019; Quan et al., 2020; Richman et al., 2011; Stamatakis et al., 2018; Veronese et al., 2018; Welsh et al., 2020), the mechanisms still need to be fully elucidated, especially evidences from the population-based studies. Low-grade inflammation, usually chronic, is characterized by elevated levels of inflammatory biomarkers such as C-reactive protein (CRP), white blood cells (WBC) and neutrophil to lymphocyte ratio (NLR), but without any observable clinical symptoms. (Bonaccio et al., 2016; Peng et al., 2023) There is evidence that physical activity is related to reducing low-grade inflammation (Hamer and Steptoe, 2008; Pedersen, 2006), considered a common contributing factor to cancer, CVD and T2DM. (Barbe-Tuana et al., 2020; Furman et al., 2019) Meanwhile, as a simple and easy type of exercise, studies have documented that walking pace is negatively associated with low-grade inflammation markers, including WBC, CPR, and NLR. (Dupont et al., 2021; Guo et al., 2021; Renner et al., 2022) Thereafter, more research is needed to explore the potential role of low-grade inflammation in the association between walking pace and risks of cancer, CVD and T2DM.

In this study, we evaluated the association between walking pace and risks of major chronic diseases including cancer, CVD and T2DM in individuals with hypertension based on a prospective study with large sample size in UK Biobank. Ulteriorly, we explored the extent to which the lower risk of cancer, CVD and T2DM associated with walking pace may be mediated by low-grade inflammation. This will benefit individuals with hypertension to prevent adverse outcomes and provide clues for the exploration of underlying mechanisms in the future.