Association of inflammatory score with all-cause and cardiovascular mortality in patients with metabolic syndrome: NHANES longitudinal cohort study

Abstract

Background: Inflammatory scores are known to reflect the systemic inflammatory burden. Despite this, the association between the inflammatory score and the risk of all-cause and cardiovascular mortality in patients with metabolic syndrome (MetS) remains poorly understood. To address this gap in the literature, this study investigated this potential association between these two factors.

Methods: A total of 3401 patients with MetS from the National Health and Nutrition Examination Survey (1999-2010) were enrolled. Survival status and cause of death were obtained by linking data from the National Death Index (NDI). The inflammatory score was calculated based on the sum of the Z-scores for white blood cell (WBC) count and C-reactive protein (CRP) at baseline. The patients were divided into inflammatory score quartiles. Cox proportional hazards regression was used to determine the association between inflammatory score and mortality. Restricted cubic splines (RCS) were used to explore the dose-response relationship between inflammatory score and mortality. Stratified analyses and interaction tests were conducted according to sex, age, body mass index (BMI), alcohol consumption, smoking status, hypertension, diabetes, and stroke status.

Results: After a mean follow-up of 145.9 months, 1039 all-cause deaths and 295 cardiovascular deaths were recorded. The results of multivariate Cox regression analysis showed that compared to the lowest quartile (Q1), patients in the highest quartile (Q4) had a 1.74-fold increased risk of all-cause mortality (Model 3: HR = 1.74, 95%CI 1.30-2.32, P < 0.001) and a 1.87-fold increased risk of cardiovascular mortality (Model 3: HR = 1.87, 95%CI 1.12-3.13, P = 0.020). There was a 'J'-shaped nonlinear relationship between the inflammatory score and all-cause mortality (P for nonlinearity = 0.001), and a marginally significant 'J'-shaped relationship with cardiovascular mortality (P for nonlinearity = 0.057). The threshold points of the inflammatory score for adverse outcomes were - 0.643 and - 0.621, respectively.

Conclusion: The inflammatory score is independently associated with increased all-cause and cardiovascular mortality in patients with MetS, and risk stratification of these patients using inflammatory scores may provide specific therapeutic strategies to improve their prognosis.

Keywords: NHANES; cardiovascular mortality; inflammation; inflammatory score; metabolic syndrome.

Figure 1

Flow chart of the sample selection from NHANES 1999–2010.

Figure 2

Kaplan–Meier curves of the survival rate and the number (%) of at-risk MetS patients with different levels of inflammatory score. (A) all-cause mortality; (B) cardiovascular mortality.

Figure 3

Dose-response relationship between inflammatory score and all-cause and cardiovascular mortality in patients with metabolic syndrome. Dose-response relationship between inflammatory score and all-cause mortality in patients with metabolic syndrome: (A) crude and (B) adjusted models. Dose-response relationship between inflammatory score and cardiovascular mortality in patients with metabolic syndrome: (C) crude and (D) adjusted models. The red numbers in the figure represent the inflammatory score corresponding to the threshold points. Adjusted for sex, age, race, PIR, educational levels, BMI, smoking status, alcohol status, hypertension, DM, cancers, stroke, LDL-C. The solid and shaded areas represent estimates and their corresponding 95% CIs, respectively (cardiovascular: cardiovascular disease; PIR, poverty income ratio; BMI, body mass index; DM, diabetes mellitus; LDL-C, low-density lipoprotein cholesterol).

Figure 4

Dose-response relationship between inflammatory score and all-cause and cardiovascular mortality in metabolic syndrome patients within sex subgroups and age subgroups Dose-response relationship between inflammatory score and all-cause (A) and cardiovascular mortality (B) in metabolic syndrome patients within sex subgroups. Dose-response between inflammatory score and all-cause (C) and cardiovascular mortality (D) in metabolic syndrome patients within age subgroups. Adjusted for sex, age, race, PIR, educational levels, BMI, smoking status, alcohol status, hypertension, DM, cancers, stroke, LDL-C. The solid and shaded areas represent estimates and their corresponding 95% CIs, respectively (cardiovascular: cardiovascular disease; PIR, poverty income ratio; BMI, body mass index; DM, diabetes mellitus; LDL-C, low-density lipoprotein cholesterol).