Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disorder characterized by persistent inflammation, airway remodeling, and immune activation in the lung parenchyma. Globally, COPD accounts for over 3 million deaths annually, making it the third leading cause of mortality. It is estimated to affect more than 10% of the population, with a steadily increasing prevalence (1). COPD is frequently accompanied by comorbid conditions, including depression, osteoporosis, and cardiovascular diseases, which collectively reduce overall health and life quality of those who are impacted.

Investigation has revealed that cardiovascular comorbidities and COPD have a significant association as they share common risk factors, pathophysiological mechanisms, symptoms, and clinical manifestations (2). Life’s Crucial 9 (LC9), a cardiovascular health score recently introduced by the American Heart Association, builds upon Life’s Essential 8 (LE8) by incorporating mental health as an additional component. LC9 consists of nine key metrics: diet, physical activity, smoking cessation (nicotine exposure), sleep health, body mass index (BMI), blood lipids, blood glucose, blood pressure, and mental well-being. While LC9 has been linked to cardiovascular events, recent studies have also reported associations between LC9 and conditions such as overactive bladder (OAB) (3) and infertility among U.S. women (4). Given the high prevalence of cardiovascular co-morbidities in COPD and the multifactorial nature of COPD risk factors as well as the common physiopathological mechanisms of inflammation in cardiorespiratory diseases, whereas previous studies have only been limited to exploring the analysis of the association of LC9 with COPD and the potential mediating role of lean body mass (LBM) in the association of LC9 with COPD (5, 6), while neglecting the importance of inflammation. It is therefore crucial to explore the association of LC9 with COPD and the underlying mechanisms of its inflammation.

A new inflammatory biomarker based on the numbers of monocytes, neutrophils, and lymphocytes is the systemic inflammation response index (SIRI). Chronic airway inflammation is a hallmark of COPD, often accompanied by systemic inflammation, which has been associated with adverse outcomes such as recurrent acute exacerbations of COPD (AECOPD) (7). Emerging evidence suggests that SIRI is associated with all-cause and cardiovascular mortality in chronic kidney disease (CKD) patients (8), increased stroke prevalence in individuals with asthma (9), and higher mortality in adult asthma patients (10). A recent study also identified SIRI as an independent risk factor for COPD (11). This study postulates that SIRI mediates the relationship between LC9 and COPD, considering these findings. Utilizing data from the 2005–2018 NHANES cycles, this study aims to investigate the interrelationships among SIRI, LC9, and COPD.

We examined data from 25,721 people in the NHANES 2005–2018 cohort for our cross-sectional analysis, including 1,257 individuals with COPD and 24,464 without COPD. Compared to COPD patients, non-COPD patients exhibited higher LC9 scores and lower SIRI levels. The results demonstrated a negative relationship between the prevalence of COPD and LC9, whereas SIRI and COPD were positively correlated. Additionally, SIRI partially mediated the association between LC9 and COPD, according to mediation analysis.

Cardiovascular diseases (CVD) are common comorbidities in COPD, and the relationship between these two conditions is complex, contributing to the increased prevalence of both and affecting symptoms and prognosis. Studies have shown that the prevalence of CVD is increased in those with COPD (15), and COPD-related mortality is linked to cardiovascular comorbidities (16). Among COPD patients, deaths due to cardiovascular diseases are more common than those caused by respiratory failure (17, 18). COPD and CVD share many common risk factors, making the control of these risk factors critical in reducing the burden of both diseases. To reduce cardiovascular disease mortality, the American Heart Association has introduced psychological health factors (including traumatic stress, chronic stress, anxiety, and depression) into the Life’s Essential 8 (LE8) scoring system, creating the new cardiovascular health score, LC9. SIRI is a new composite indicator combining the counts of neutrophils, monocytes, and lymphocytes, three distinct kinds of white blood cells, reflecting systemic inflammation, which is a hallmark of COPD, characterized by chronic airway inflammation, often involving changes in neutrophil and lymphocyte counts. For instance, in patients with AECOPD, neutrophil levels in airway cells are significantly elevated, and although neutrophil and lymphocyte counts decrease during stable periods, they remain the predominant inflammatory cells in stable COPD patients.

Higher LE8 scores lower the risk of COPD in those over 40, according to prior research that found a negative linear association between LE8 scores and COPD risk (19). SIRI has been found to be a separate risk factor for COPD (11) and is associated with exacerbations in stable COPD, predicting deterioration in COPD patients. However, the psychological health component added to LE8 has not been incorporated into these studies. Prior research indicates that LC9 is associated with various conditions, such as all-cause cardiovascular mortality (20), overactive bladder (3), infertility (4), and severe abdominal aortic calcification (21). Previous research involving 10,461 participants demonstrated that better cardiovascular health, as assessed by LC9, was associated with improved pulmonary function (Shi et al.) (5). Similarly, Guo et al. reported in a study of 14,818 participants that LC9 was linked to a reduced risk of COPD, potentially through increased lean body mass (LBM) (6). However, the inflammatory mechanisms underlying the relationship between LC9 and COPD have not yet been investigated. To address this gap, the present study is the first to evaluate the association between LC9 and COPD in a large population-based sample of 25,721 participants, and to examine the potential mediating role of SIRI. These findings may inform early preventive strategies for COPD and contribute to reducing its economic and societal burden.

The pathogenesis of COPD remains unclear, though it is often defined as having an FEV1/FVC ratio less than 0.7. The main risk factor for COPD is smoking, which induces chronic airway inflammation and oxidative stress (22). Chronic inflammation over time leads to progressive declines in lung function (23), including reductions in FVC, FEV1, and FEV1/FVC (24). Pezzuto et al. confirmed the benefits of smoking cessation in COPD patients, enhancing all respiratory function metrics, such as obstructive parameters in the large and small airways (FEV1, FEF25/75), and symptoms (mMRC score) (25).

Research has shown a close relationship between body weight and COPD. Both general obesity and abdominal obesity are associated with reduced FEV1 and FVC (26). According to a large Chinese prospective study, abdominal obesity and low body mass index (BMI) raise the risk of COPD (27). Additionally, obese individuals are often insulin resistant, leading to increased blood glucose levels. Increases in fasting blood glucose by 1 mmol/L are associated with reductions in FVC, FEV1, FVC% %, and FEV1% by 25 mL, 13 mL, 0.71–1.03%, and 0.46–0.72%, respectively (28). Compared to non-diabetic individuals, diabetic patients experience increased oxidative stress and elevated production of reactive oxygen species (ROS), and previous studies have shown that COPD development is linked to an imbalance between oxidative stress and antioxidant defenses (29). Excessive ROS production in diabetic patients can cause oxidative damage to the airways, leading to alveolar structural damage, destruction of alveolar walls, emphysema, and eventually airway airflow limitation, resulting in COPD (30). Dyslipidemia, often observed in obese and hyperglycemic patients, is also linked to inflammation, oxidative stress, and lung function (31). Elevated serum triglycerides can exacerbate respiratory resistance, while increased cholesterol levels worsen central and overall respiratory resistance (32). Dyslipidemia leads to fatty acid infiltration into macrophages, activating cytotoxic T cells and sustaining inflammatory responses (33), indirectly contributing to the development of COPD.

A healthy diet can reduce the incidence of obesity, hyperglycemia, and hyperlipidemia, potentially decreasing the prevalence of COPD. Studies have shown that antioxidant-rich diets have beneficial effects on lung function (34), with total dietary antioxidant capacity positively correlated with FEV1 and FVC (35, 36). This may help slow the decline in lung function by reducing oxidative damage. Exercise capacity is considered a key indicator of the effectiveness of pulmonary rehabilitation in COPD patients, with the six-minute walk test widely recognized as a measure of exercise capacity. Increasing evidence suggests that exercise training, including aerobic activities and resistance training, can enhance exercise endurance, muscle strength, arm function, maximal oxygen uptake, heart rate, and quality of life in COPD patients (37). Exercise may prevent the increase in macrophage and neutrophil counts in COPD mice, reducing ROS-mediated oxidative stress (38). Sufficient sleep is often associated with positive mood, while mental health disorders, especially anxiety and depression, are common comorbidities in COPD. Psychological health issues are frequently associated with high-risk lifestyle choices (e.g., smoking, high-fat, high-sugar diets), indirectly contributing to COPD development. Therefore, this study, based on the LE8 model, incorporated psychological factors and found that, compared to COPD patients, non-COPD patients had higher average mental health scores.

This research has some advantages: (1) It is the first to investigate the potential relationship between systemic inflammation and the prevalence of LC9 and COPD in the American population, suggesting that LC9 has great prospects as a preventive method for COPD. (2) SIRI, as a novel inflammation index, can predict the occurrence of COPD and provide insights for future COPD-related biomarkers. (3) The large sample size enhances the robustness of our findings, making sure that the outcomes appropriately represent the demographics of the US population.

However, this study is not without limitations. We must consider the following: (1) The only data included in our analysis is from the NHANES 2005–2018 database, which mainly shows changes among Americans. As a result, our findings might not be as applicable to different people throughout the world. (2) The existence of unmeasured variables is still a possible cause of bias even after thorough corrections for confounding variables. (3) Because this study is cross-sectional, we are unable to prove a link between the prevalence of COPD and LC9. To further understand the connection between LC9 and COPD, more prospective research is required to supply more clinical data. (4) Due to the constraints of the NHANES database, we were unable to determine whether the blood samples used to calculate SIRI were collected during stable COPD or acute exacerbation. Given that systemic inflammatory markers can vary significantly depending on the clinical phase of the disease, this limitation may affect the interpretation of the observed associations. Future studies with longitudinal data and detailed clinical information are warranted to validate our findings.

In summary, we discovered a strong inverse connection between LC9 and COPD, which SIRI partially mediated. This discovery highlights the possible connection between cardiovascular health and COPD, providing fresh perspectives on COPD therapy and prevention. A comprehensive strategy that emphasizes managing inflammation and enhancing cardiovascular health may decrease the incidence of COPD.