Elevated Atherogenic Index of Plasma Levels Predict Higher Death Risk in Cardiovascular-Kidney-Metabolic Syndrome: Study

CKM syndrome is a newly developed clinical syndrome which recognizes the intertwined pathophysiology of metabolic disease, chronic kidney disease (CKD), and cardiovascular disease (CVD). As cardiovascular death remains the leading cause of death in the globe, it is necessary to identify early predictive indicators in patients with CKM. The AIP, as measured by the log ratio of triglycerides to high-density lipoprotein cholesterol (log10[TG/HDL-C]), has proven to be a sensitive marker of atherosclerosis and cardiovascular disease risk. Yet until recently, proof linking AIP directly to mortality in CKM patients was sparse.

This large scale observational study used 15,703 CKM syndrome cases diagnosed from the National Health and Nutrition Examination Survey (NHANES) data, conducted between 2005 and 2018. AIP was estimated for all participants and mortality was ascertained through linkage to the National Death Index (NDI), with follow-up through December 31, 2019.

Researchers used Kaplan-Meier survival curves, Cox proportional hazards models, restricted cubic spline (RCS) models, and subgroup analyses to examine the correlation of AIP levels with mortality outcomes. Participants were divided into tertiles according to their AIP values to be compared.

Key Findings

• A median follow-up duration of 7.67 years saw 1,570 deaths in the participants out of which 344 cardiovascular deaths were reported specifically.

• All-cause mortality: Participants in the uppermost AIP tertile had a 19% increased risk of all-cause death than those in the lowermost tertile (Hazard Ratio [HR] = 1.19; 95% Confidence Interval [CI]: 1.08–1.31; P < 0.001).

• Cardiovascular mortality: Risk of cardiovascular death was 38% higher in the highest AIP tertile (HR = 1.38; 95% CI: 1.22–1.57; P < 0.001).

• A positive linear dose-response association existed between both types of mortality and AIP levels when AIP was treated as a continuous variable.

• Kaplan-Meier curves illustrated considerably better survival outcomes among participants in the lowest tertile of AIP.

• Subgroup analyses revealed that the associations between higher AIP and higher mortality were sustained in all but most clinical and demographic variables, with the exception of gender, suggesting potential sex differences in risk associated with AIP.

This NHANES-derived study presents strong evidence that high AIP levels are independently and strongly linked to higher all-cause and cardiovascular mortality in patients with CKM syndrome. These findings highlight AIP's utility as a simple, cost-effective, and non-invasive biomarker for mortality risk estimation. Routine clinical application of AIP could have a considerable advantage in managing and predicting patients with cardiometabolic and renal comorbidities.

Reference:

Zheng Q, Cao Z, Teng J, Lu Q, Huang P, Zhou J. Association between atherogenic index of plasma with all-cause and cardiovascular mortality in individuals with Cardiovascular-Kidney-Metabolic syndrome. Cardiovasc Diabetol. 2025 Apr 26;24(1):183. doi: 10.1186/s12933-025-02742-4. PMID: 40287685; PMCID: PMC12034140.