Association of neutrophil/high-density lipoprotein cholesterol ratio with the cardiovascular-kidney-metabolic syndrome and its cardiovascular mortality

Abstract

Background: Cardiovascular-kidney-metabolic (CKM) syndrome is a novel multi-system disease defined by the American Heart Association (AHA). This study aims to investigate the associations between the neutrophil/high-density lipoprotein cholesterol ratio (NHR) and CKM syndrome and its association with cardiovascular disease (CVD) mortality.

Methods: The data for this study were derived from the National Health and Nutrition Examination Survey (NHANES) conducted from 2005 to 2018 and the National Death Index (NDI) database. Weighted multivariate logistic regression and Cox regression were the primary analytical methods. restricted cubic spline (RCS) and subgroup analyses were also carried out.

Results: A total of 13,165 participants were included in this study. The weighted mean of NHR was 3.14 ± 0.03. The prevalence rate of CKM syndrome was 17.36%. The results of the weighted logistic regression indicated that there was a positive association between NHR and CKM syndrome (OR_{per SD}: 1.25, 95% CI: 1.10-1.42, p < 0.001). Among the quartile groups of NHR, the prevalence rate of CKM syndrome showed an increase (p for trend <0.0001). Among individuals with CKM syndrome, the results of the weighted Cox regression demonstrated that NHR also significantly predicted CVD mortality (HR_{per SD}: 1.31, 95% CI: 1.14-1.50, p < 0.001). Among the quartile groups of NHR, the risk of CVD mortality also increased in a trend (p for trend = 0.01). Furthermore, RCS analysis showed a positive linear association between NHR and CKM syndrome (non-linear p = 0.075) and between NHR and CVD mortality (non-linear p = 0.300). The subgroup analysis suggested that the relationship between NHR and the outcomes was robust, and there was no significant interaction.

Conclusion: Our study demonstrates that NHR is not only associated with an increased prevalence of CKM syndrome but also serves as an effective predictor for CVD mortality in patients with CKM syndrome. This provides new insights into the clinical identification and prognostic evaluation of CKM syndrome.

Keywords: CVD mortality; NHANES; cardiovascular-kidney-metabolic syndrome; neutrophil/high-density lipoprotein cholesterol ratio; observational study.

Figure 1

Flow chart of participant recruitment. NHR, neutrophil/high-density lipoprotein cholesterol ratio; NHANES, National Health and Nutrition Examination Survey; CKM, cardiovascular-kidney-metabolic syndrome.

Figure 2

Dose-response relationship between NHR and CKM syndrome. The adjusted restricted cubic spline model was adjusted for age, sex, race, marital status, education, poverty-to-income ratio, drinking, smoking, total energy intake, weekly physical activity level, body mass index, diabetes, cancer, hypertension, liver diseases, thyroid diseases, arthritis, statins, and the levels of serum total cholesterol. NHR, neutrophil/high-density lipoprotein cholesterol ratio; CKM, cardiovascular-kidney-metabolic syndrome; OR, odds ratio; CI, confidence interval.

Figure 3

Dose-response relationship between NHR and CVD mortality among individuals with CKM syndrome. The adjusted restricted cubic spline model was adjusted for age, sex, race, marital status, education, poverty-to-income ratio, drinking, smoking, total energy intake, weekly physical activity level, body mass index, diabetes, cancer, hypertension, liver diseases, thyroid diseases, arthritis, statins, and the levels of serum total cholesterol. NHR, neutrophil/high-density lipoprotein cholesterol ratio; CKM, cardiovascular-kidney-metabolic syndrome; HR, hazard ratio; CI, confidence interval.

Figure 4

Subgroup analyses for the association between NHR and CKM syndrome. Models were adjusted for age, sex, race, marital status, education, poverty-to-income ratio, drinking, smoking, total energy intake, weekly physical activity level, body mass index, diabetes, cancer, hypertension, liver diseases, thyroid diseases, arthritis, statins, and the levels of serum total cholesterol. CKM, cardiovascular-kidney-metabolic syndrome; OR, odds ratio; NHR, neutrophil/high-density lipoprotein cholesterol ratio; PIR, poverty-to-income ratio; MET, metabolic equivalent; DM, diabetes mellitus; IFG, impaired fasting glycemia; IGT, impaired glucose tolerance; OR, odds ratio; CI, confidence interval.

Figure 5

Subgroup analyses for the association between NHR and the risk of CVD mortality among individuals with CKM syndrome. Models were adjusted for age, sex, race, marital status, education, poverty-to-income ratio, drinking, smoking, total energy intake, weekly physical activity level, body mass index, diabetes, cancer, hypertension, liver diseases, thyroid diseases, arthritis, statins, and the levels of serum total cholesterol. CKM, cardiovascular-kidney-metabolic syndrome; NHR, neutrophil/high-density lipoprotein cholesterol ratio; MET, metabolic equivalent; DM, diabetes mellitus; IFG, impaired fasting glycemia; IGT, impaired glucose tolerance; HR, hazard ratio; CI, confidence interval.