Cardiorespiratory fitness (CRF) is a recognized health indicator that refers to the ability of the lungs, heart, and skeletal muscles to acquire and utilize oxygen during physical activity, typically quantified by maximal oxygen consumption (VO2 max) (1). However, in clinical practice, standardized exercise tests to assess CRF are challenging for individuals with limited mobility and require specialized equipment and personnel, leading to increased costs (2). As a result, Jackson et al. proposed a method for estimating non-exercise cardiorespiratory fitness (NEE-CRF), which has gradually become a widely accepted approach for evaluating CRF in recent years (3). The predictive equation for NEE-CRF incorporates gender, age, easily obtainable physical measurements, and self-reported variables (4). The American Heart Association has noted that NEE-CRF can serve as an alternative to standardized exercise tests for CRF when exercise-based predictions are not sufficiently accurate (5). Numerous studies have explored the association between NEE-CRF and various diseases. For instance, research by Robert A. and colleagues consistently found that higher NEE-CRF is negatively correlated with metabolic risk (6). Some researchers have highlighted a strong association between higher NEE-CRF and a lower incidence of type 2 diabetes (7). Furthermore, a study demonstrated that NEE-CRF can effectively predict mortality even in the absence of actual exercise testing (8). The ability of NEE-CRF to assess metabolic diseases and mortality underscores its significant research potential for further exploration of its relationship with hypertension and all-cause mortality.

Hypertension is a common chronic disease associated with the regulation of the endocrine system, microcirculation, and large arteries (9). Hypertension often contributes to the development of various cardiovascular diseases, stroke, and heart and kidney failure (10). Globally, it is the third leading cause of death, with approximately 12.5% of the global population (one in every eight individuals) affected (11). According to reports from the World Health Organization, approximately 40% of individuals aged 25 and older have hypertension (12). Despite the rising prevalence of hypertension, the rates of control and treatment remain inadequate, placing a significant economic burden on countries (13). All-cause mortality is defined as the total number of deaths from all causes in a given population over a specified period, typically expressed as deaths per 1,000 or 100,000 individuals per year (14). For example, in 2022, cardiovascular diseases caused 19.8 million deaths worldwide (15), while cancer mortality rates have also continued to rise (16). Therefore, using accurate and easily obtainable health parameters like NEE-CRF to monitor the incidence of hypertension and all-cause mortality is of great value.

Currently, studies that simultaneously examine the relationship between NEE-CRF and both hypertension and all-cause mortality are limited. Systematic analyses that combine multiple databases are still scarce, particularly those focusing on different countries and populations. To address this research gap, our study utilized two authoritative public databases—the China Health and Retirement Longitudinal Study (CHARLS) and the US National Health and Nutrition Examination Survey (NHANES)—to systematically analyze the relationship between NEE-CRF, hypertension, and all-cause mortality in both American and Chinese populations.

This study, using data from the Chinese CHARLS and American NHANES databases, found that higher levels of NEE-CRF are associated with a lower risk of hypertension and all-cause mortality. These findings carry significant clinical implications. First, in resource-limited clinical settings, healthcare professionals can easily and non-invasively estimate CRF through non-exercise assessment methods, enabling earlier implementation of disease prevention and rehabilitation measures (20). This approach not only streamlines clinical procedures but also facilitates the creation of personalized health management plans for patients (21). Second, for individuals at high risk of hypertension, NEE-CRF-based data can guide healthcare professionals in promptly adjusting lifestyle recommendations, thereby effectively reducing the risk of developing the condition (21). Furthermore, improving NEE-CRF levels can help lower mortality rates from various diseases and enhance patient prognosis (22). Through continuous health management and lifestyle interventions, patients can reduce the likelihood of disease recurrence, extend their life expectancy, and improve their quality of life (22).

Previous studies have explored the relationship between NEE-CRF and both hypertension and all-cause mortality. For instance, in a rural Chinese cohort study, Zhao et al. found that patients with more than a 2% increase in NEE-CRF had a 24% lower incidence of hypertension, while those with more than a 2% decrease in NEE-CRF had a 52% higher risk (23). A follow-up study of American Caucasians indicated that both a high NEE-CRF trajectory and a high average NEE-CRF were associated with a reduced risk of hypertension (21). Similarly, Liu et al.'s study involving 4,286 elderly Chinese individuals showed that those with higher NEE-CRF exhibited better arterial pressure performance, characterized by lower systolic and diastolic blood pressure over time (24). Another study involving 330,769 American retirees demonstrated that higher NEE-CRF was independently associated with a lower risk of mortality (22). Research from England found a consistent association between NEE-CRF and both all-cause and cardiovascular mortality, with a 12%–15% reduction in all-cause mortality for every 1.6–1.7 unit increase in NEE-CRF (20). Additionally, a study on an American population reported that for each 1-MET increase in NEE-CRF, cancer mortality risk decreased by 30% in men and 28% in women (25). Since the parameters used to assess NEE-CRF are often closely related to an individual's lifestyle (e.g., diet, weight), which also significantly influence hypertension, this further underscores the connection between the two (4, 26). Lee et al.'s research pointed out that higher NEE-CRF in middle-aged Europeans was associated with lower subclinical atherosclerosis and vascular stiffness (27), both of which are high-risk factors for the development of hypertension (28). Moreover, studies have shown that good cardiorespiratory fitness implies a stronger ability to adapt to daily activities and environmental changes, thereby reducing mortality risk due to various factors (29, 30). In summary, existing literature confirms that an increase in NEE-CRF can reduce the risk of hypertension and all-cause mortality, which aligns with our study findings.

The relationship between NEE-CRF and reduced all-cause mortality is complex and multifaceted, involving a variety of mechanisms. Some key mechanisms include: Firstly, improving NEE-CRF means the heart can pump blood more efficiently, providing adequate oxygen and nutrients to various parts of the body, thereby reducing the risk of heart disease (31). It also helps lower resting blood pressure, which reduces the incidence of cardiovascular events such as heart attacks and strokes (21). Additionally, enhanced NEE-CRF helps regulate autonomic nervous function, which normalizes the excessive activation of the sympathetic nervous system, thereby lowering the risk of fatal arrhythmias (32). Improved NEE-CRF also combats atherosclerosis and positively influences cardiovascular risk factors such as lipids, blood pressure, glucose, and obesity (33). This not only enhances metabolic health but also promotes lipid metabolism, reducing the risk of diabetes, obesity, and metabolic syndrome (34). Collectively, these benefits contribute to reduced all-cause mortality. Secondly, enhancing NEE-CRF can also improve mental and cognitive health (35). Research shows that higher levels of NEE-CRF are associated with greater gray matter volume in regions of interest related to Alzheimer's disease, reduced white matter hyperintensities, and better cognitive function and emotional states (36). These improvements not only lower the risk of developing Alzheimer's disease and depression but also protect brain structure, thereby promoting overall mental health (37). Improved mental health significantly benefits physical health, ultimately helping to reduce all-cause mortality (38). Regarding hypertension, a common chronic disease, its impact on all-cause mortality involves multiple complex physiological mechanisms and pathological processes, including: Firstly, hypertension can damage vascular endothelium and lead to arteriosclerosis. Over time, arterial walls thicken and lose elasticity, restricting blood flow and increasing the workload on the heart (39). Persistent hypertension may result in left ventricular hypertrophy, potentially progressing to heart failure, which significantly increases the risk of death (40). Additionally, hypertension is a major risk factor for coronary artery disease, leading to severe cardiac events such as angina and myocardial infarction, further raising all-cause mortality (41). Secondly, hypertension increases the risk of stroke (42). Vascular damage caused by hypertension can trigger systemic inflammatory responses, impairing endothelial function and increasing the risk of thrombosis (43). These clots can travel to the brain, causing infarction (44). Long-term hypertension also impacts small cerebral vessels, leading to narrowing, blockage, or bleeding, which increases the risk of stroke (42). Finally, long-term hypertension can cause hardening and narrowing of small renal arteries, affecting the kidneys' blood supply (45). Persistent ischemia and damage to renal tubules can lead to interstitial inflammation and fibrosis, ultimately damaging renal structure and function (46). This can result in serious consequences such as uremia, further increasing all-cause mortality (46).

Our subgroup analysis and interaction results indicate that, within the American population, increases in NEE-CRF are significantly more effective in reducing the risks of hypertension and all-cause mortality in non-diabetic and non-stroke populations compared to diabetic and stroke populations. Diabetic individuals face a higher risk of hypertension due to factors such as insulin resistance, inflammatory responses, and metabolic syndrome (47). Additionally, diabetes, being a metabolic disease, is often accompanied by high insulin levels and hyperglycemia, leading to endothelial dysfunction, which increases the likelihood of hypertension and all-cause mortality (48). For stroke patients, cardiovascular health is often severely compromised post-stroke (49). Many stroke patients may have had undiagnosed hypertension or other cardiovascular diseases prior to the event (50). For instance, chronic hypertension can result in lacunar ischemic strokes due to repeated brain injuries associated with perivascular edema, leading to hyaline deposits, fibrinoid necrosis, thickening of small artery walls, luminal narrowing, and eventually thrombosis and stroke (51). Consequently, the risk of hypertension is generally higher in stroke populations.

Our study has several strengths. Firstly, the two databases we used come from two of the world's largest countries—China and the United States—which exhibit significant differences in factors such as ethnicity and lifestyle. The consistency of findings between these two countries further strengthens our conclusions. Secondly, we not only simultaneously investigated the associations of NEE-CRF with hypertension and all-cause mortality but also employed a complex, multi-stage probability sampling method in analyzing the NHANES database, ensuring that the results are broadly representative of the entire U.S. population.

On the other hand, this study has some limitations. Firstly, the follow-up period of the CHARLS study is relatively short, limiting our ability to assess the long-term impact of NEE-CRF on hypertension and all-cause mortality. Secondly, key variables in this study were based on self-reported data, which may introduce recall bias and social desirability bias. Additionally, differences between the CHARLS and NHANES study samples, including racial, cultural, and lifestyle variations, may affect the applicability of the NEE-CRF equation across diverse populations. Additionally, while our statistical methods were robust, a more detailed standardization process for variables could further enhance the comparability between datasets. Lastly, while our statistical methods were robust, the standardization of variables across datasets could have been more explicitly detailed, which might impact cross-population comparisons.

Despite these limitations, our research demonstrates that NEE-CRF is associated with a lower risk of hypertension and reduced all-cause mortality in two different populations, highlighting its potential clinical significance.

These findings suggest potential clinical implications, showing a negative correlation between NEE-CRF and both hypertension and all-cause mortality. Based on these results, we recommend considering the regular assessment of NEE-CRF levels in future health monitoring and research. This approach could be valuable for hypertension prevention and may also contribute to improving overall health outcomes.