The aggregate index of systemic inflammation (AISI) and the risk of all-cause, cardiovascular, and cardio-cerebrovascular mortality in congestive heart failure patients: results from NHANES 1999-2018

Abstract

Congestive heart failure (CHF) is a prevalent cardiovascular disease, with increasing incidence and mortality rates associated with aging populations and rising rates of chronic diseases. Systemic inflammatory response is recognized to play a pivotal role in the pathogenesis of CHF, and the aggregate index of systemic inflammation (AISI) has garnered widespread attention as a comprehensive indicator reflecting inflammatory status in recent years. However, there is currently a lack of large-scale epidemiological studies investigating the relationship between AISI and all-cause, cardiovascular, and cardio-cerebrovascular mortality risks among CHF patients. This study aims to utilize data from the NHANES database spanning 1999 to 2018 to analyze the association between AISI and prognosis in CHF patients, aiming to provide new evidence to support research into the pathophysiology and clinical management of CHF. This study enrolled 1624 patients aged ≥ 18 years with congestive heart failure (CHF) from the National Health and Nutrition Examination Survey spanning 1999 to 2018. Patients were stratified into four groups based on the aggregate index of systemic inflammation (AISI). Survival differences among the groups were compared using log-rank tests and Kaplan-Meier curves. Additionally, multivariable Cox regression and restricted cubic spline analyses were employed to explore the relationship between AISI and all-cause, cardiovascular, and cardio-cerebrovascular mortality. Overall, during a mean follow-up of 76.4 ± 56.6 months among patients with congestive heart failure, a total of 828 participants (51.042%) died. Among these, 314 (19.389%) deaths were attributed to cardiovascular diseases, and 344 (21.226%) were related to cardio-cerebrovascular mortality. Kaplan-Meier analysis revealed significant differences in all-cause, cardiovascular, and cardio-cerebrovascular mortality among AISI quartiles (log-rank test: all P < 0.001). Multivariable adjusted models demonstrated that participants in the highest AISI quartile had increased risks of all-cause mortality (hazard ratio [HR] = 1.599, 95% confidence interval [CI] 1.595-1.602), cardiovascular mortality (HR = 1.070, 95% CI 1.066-1.074), and cardio-cerebrovascular mortality (HR = 1.173, 95% CI 1.168-1.177) compared to those in the lowest quartile. Additionally, restricted cubic spline analysis indicated a nonlinear association between AISI and all-cause mortality (P = 0.0064), with an inflection point at AISI 8.66. On the left flank of the inflection point, each twofold increase in AISI was associated with a 19.6% higher risk of all-cause mortality (HR = 1.196, 95% CI 0.930-1.538), while on the right flank, there was a 126.2% increase (HR = 2.262, 95% CI 1.506-3.395). Furthermore, each twofold change in AISI was nonlinearly associated with a 60.2% higher risk of cardiovascular mortality (HR = 1.602, 95% CI 1.075-2.388) and a 56.6% higher risk of cardio-cerebrovascular mortality (HR = 1.566, 95% CI 1.072-2.286). E-value analysis suggested robustness to unmeasured confounding. In the population of patients with congestive heart failure aged 18 years and older in the United States, irrespective of established risk factors, AISI was significantly associated with all-cause, cardiovascular, and cardio-cerebrovascular mortality. Further research is needed to validate this.

Keywords: All-cause mortality; Cardio-cerebrovascular mortality; Cardiovascular mortality; NHANES; The aggregate index of systemic inflammation AISI.

Fig. 1

Flow chart of the participants.

Fig. 2

Kaplan–Meier curves for all-cause (A), cardiovascular mortality (B) and cardio-cerebrovascular mortality(C) according to AISI quartiles. AISI: Aggregate index of systemic inflammation (AISI: neutrophils (NEU) * platelets (PLT) * monocytes (MONO)/lymphocytes (LYM)).

Fig. 2

Kaplan–Meier curves for all-cause (A), cardiovascular mortality (B) and cardio-cerebrovascular mortality(C) according to AISI quartiles. AISI: Aggregate index of systemic inflammation (AISI: neutrophils (NEU) * platelets (PLT) * monocytes (MONO)/lymphocytes (LYM)).

Fig. 3

Restricted cubic spline curves of relations between AISI with all-cause (A), cardiovascular mortality (B) and cardio-cerebrovascular mortality (C). Analysis was adjusted for gender, age, race, education level, marital status, body mass index, white blood cell, lymphocyte, monocyte, segmented neutrophils, hemoglobin, platelet, cholesterol, triglycerides, uric acid, creatinine, smokers, coronary heart disease, angina pectoris, stroke, hypertension, high cholesterol level, diabetes mellitus. The solid and dashed lines symbolize the hazard ratios and corresponding 95% confidence intervals, respectively.

Fig. 3

Restricted cubic spline curves of relations between AISI with all-cause (A), cardiovascular mortality (B) and cardio-cerebrovascular mortality (C). Analysis was adjusted for gender, age, race, education level, marital status, body mass index, white blood cell, lymphocyte, monocyte, segmented neutrophils, hemoglobin, platelet, cholesterol, triglycerides, uric acid, creatinine, smokers, coronary heart disease, angina pectoris, stroke, hypertension, high cholesterol level, diabetes mellitus. The solid and dashed lines symbolize the hazard ratios and corresponding 95% confidence intervals, respectively.

Fig. 4

Restricted cubic spline curves of relations between AISI and mortality in different sex groups. (A) all-cause mortality; (B) cardiovascular mortality; (C) cardio-cerebrovascular mortality. Analysis was adjusted for gender, age, race, education level, marital status, body mass index, white blood cell, lymphocyte, monocyte, segmented neutrophils, hemoglobin, platelet, cholesterol, triglycerides, uric acid, creatinine, smokers, coronary heart disease, angina pectoris, stroke, hypertension, high cholesterol level, diabetes mellitus.

Fig. 4

Restricted cubic spline curves of relations between AISI and mortality in different sex groups. (A) all-cause mortality; (B) cardiovascular mortality; (C) cardio-cerebrovascular mortality. Analysis was adjusted for gender, age, race, education level, marital status, body mass index, white blood cell, lymphocyte, monocyte, segmented neutrophils, hemoglobin, platelet, cholesterol, triglycerides, uric acid, creatinine, smokers, coronary heart disease, angina pectoris, stroke, hypertension, high cholesterol level, diabetes mellitus.