An Integrated Platelet Index Derived From PCA Is Associated With Long-Term Atherothrombotic Risk in Acute Coronary Syndrome

BackgroundPlatelet morphological indices, such as mean platelet volume and distribution width, reflect platelet turnover and thrombo-inflammatory activity relevant to acute coronary syndrome (ACS), but their individual prognostic value remains inconsistent. This study aimed to derive an Integrated Platelet Index (IPI) using principal component analysis (PCA) to capture a multidimensional platelet morphological phenotype influenced by cardiometabolic and inflammatory stress and to examine its association with long-term major adverse cardiovascular and cerebrovascular events (MACCE) in ACS. MethodsThis prospective observational study included 1,467 ACS patients from the Beijing Hospital Atherosclerosis Study. Five routinely measured platelet indices--platelet count, mean platelet volume, platelet distribution width, plateletcrit, and platelet large-cell ratio--were integrated via PCA to construct the IPI. The primary endpoint was MACCE. Cox models, restricted cubic splines, Kaplan-Meier curves, and prespecified subgroup analyses assessed the prognostic relevance of the IPI and its consistency across metabolic and clinical strata. ResultsOver a median follow-up of 55.0 months, 141 patients (9.6%) experienced MACCE. Lower IPI values were associated with higher risk. Each unit increase in IPI was independently associated with a 27% lower MACCE risk after full adjustment (HR 0.73; 95% CI: 0.59-0.90). A significant L-shaped nonlinear relationship was observed, with steep risk reduction at lower IPI values. Event-free survival increased progressively across IPI tertiles. Associations remained consistent across cardiometabolic subgroups, with no significant interactions. ConclusionsThe PCA-derived IPI represents an integrated platelet morphological phenotype associated with long-term atherothrombotic risk in ACS. Its nonlinear behavior and robust performance across metabolic backgrounds support its potential as an accessible, phenotype-based marker for refining secondary prevention risk stratification. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/25342328v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@7a6e84org.highwire.dtl.DTLVardef@1eda7a3org.highwire.dtl.DTLVardef@198df1forg.highwire.dtl.DTLVardef@160722b_HPS_FORMAT_FIGEXP M_FIG C_FIG What Are the Clinical Implications?Platelet morphology and turnover are influenced by cardiometabolic and inflammatory stress, yet routine platelet indices are rarely incorporated into ACS risk assessment because each parameter reflects only a single dimension of platelet biology. By integrating five commonly available platelet indices into a single PCA-derived morphological phenotype, the Integrated Platelet Index (IPI) provides a multidimensional representation of platelet alterations relevant to atherothrombotic risk. In this study, lower IPI values consistently identified patients at higher long-term risk of MACCE, and the L-shaped nonlinear association suggests that relatively small reductions in this phenotype may reflect disproportionately adverse platelet remodeling. Because the IPI relies solely on automated complete blood count parameters, it is low-cost, universally available, and feasible for implementation in secondary prevention pathways, including in resource-limited settings. Clinically, the IPI may improve risk stratification in ACS by capturing thrombo-inflammatory and metabolic influences not detected by traditional predictors. Its stability across cardiometabolic subgroups supports broad applicability. Future studies should determine whether serial IPI monitoring can identify patients with persistent thrombotic risk and whether incorporating the IPI into validated ACS risk models enhances individualized management. HighlightsO_LIWe derived an Integrated Platelet Index (IPI) representing a PCA-based morphological phenotype from five routine platelet indices. C_LIO_LILower IPI values identified patients with heightened long-term atherothrombotic risk after acute coronary syndrome. C_LIO_LIThe IPI captures multidimensional platelet alterations shaped by thrombo-inflammatory and cardiometabolic stress. C_LIO_LIThe association between IPI and adverse outcomes remained consistent across major cardiometabolic subgroups. C_LIO_LIThe IPI provides an accessible, low-cost phenotype with potential utility for risk stratification in secondary prevention. C_LI