Associations of the atherogenic index of plasma and its modified indices with the incidence and progression of cardiovascular-liver-metabolic multimorbidity: a prospective cohort study from UK Biobank

BACKGROUND: The atherogenic index of plasma (AIP) and its modified indices integrate atherogenic dyslipidaemia with overall or central adiposity and have been associated with cardiovascular-liver-metabolic (CLM) diseases. However, their associations with cardiovascular-liver-metabolic multimorbidity (CLMM) remain unclear. This study examined the relationships of AIP and its modified indices with the incidence and progression of CLMM and further explored whether selected biomarkers explained part of these associations. METHODS: A total of 370,258 participants without baseline CLM diseases were included in this prospective cohort analysis. AIP and its seven modified indices were evaluated: AIP, AIP-BMI, AIP-WC, AIP-WHtR, AIP-ABSI, AIP-WWI, AIP-BRI, and AIP-VAI. Multivariable Cox models were applied to evaluate associations between these indices and both the incidence and progression of CLMM. Exploratory mediation analyses were further conducted to estimate the contributions of inflammatory, hepatic, and renal biomarkers. Predictive ability was evaluated using C-index, net reclassification improvement, and integrated discrimination improvement. RESULTS: During the median 16.0-year follow-up, 8646 participants developed CLMM, and each of the eight indices was associated with a higher risk of incident CLMM, with fully adjusted hazard ratios per standard deviation (SD) increase ranging from 1.18 for AIP-VAI to 1.68 for AIP and AIP-BMI. Consistent associations were also observed for CLMM progression, particularly for AIP-BMI, AIP-WC, and AIP-WHtR. Per 1-SD increase in each index, the risks of transition from a healthy state to the first CLM disease increased by 38%, 36%, and 37%, the risks of progression from the first disease to CLMM increased by 28%, 26%, and 27%, and the risks of progression from CLMM to triple diseases increased by 20%, 17%, and 18%, respectively. Exploratory mediation analyses indicated that biomarkers of systemic inflammation and impaired liver and kidney function jointly accounted for 28.28 to 45.45% of the observed associations. All indices improved predictive performance, with AIP-BRI and AIP-BMI showing the highest overall performance, followed by AIP-WC and AIP-WHtR. CONCLUSIONS: Higher AIP and its modified indices were independently associated with increased risks of both incident CLMM and its progression. These indices may help improve CLMM risk stratification and early identification of individuals at elevated risk.