Diagnostic performance of AASI, NT-proBNP, and hs-cTnI for target-organ damage in older patients with hypertension: A systematic review

Abstract

Background: Hypertension-mediated target organ damage (TOD) is a major determinant of cardiovascular and renal outcomes in older adults. Circulating biomarkers reflecting cardiac stress and myocardial injury, including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI), may complement the ambulatory arterial stiffness index (AASI, calculated as 1 minus the regression slope of diastolic blood pressure on systolic blood pressure derived from 24-hour ambulatory blood pressure monitoring), a non-invasive marker of vascular stiffness. This systematic review evaluated the available evidence for AASI, NT-proBNP, and hs-cTnI in the assessment of TOD in older patients with hypertension and examined the evidence supporting their potential integration into a multimarker assessment strategy. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to July 2026 for studies evaluating AASI, NT-proBNP, or hs-cTnI in relation to hypertension-mediated TOD. Two reviewers independently performed study selection, data extraction, and quality assessment. Diagnostic measures, including sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and optimal cut-offs, were extracted when available. Because the included studies differed substantially in index markers, clinical outcomes, and analytical approaches, and because no study measured AASI, NT-proBNP, and hs-cTnI simultaneously, a pooled meta-analysis of the triple-marker combination was not possible; the available evidence was therefore synthesized narratively according to the diagnostic, prognostic, and risk-stratification information provided by each marker. Results: Six studies involving 19,295 participants were included. The evidence differed in nature among the three markers. NT-proBNP showed moderate diagnostic accuracy for established TOD, with reported AUCs of approximately 0.78–0.79 and a specificity of approximately 95% at sex-specific cut-offs. hs-cTnI incorporated in clinical risk scores showed moderate diagnostic or predictive accuracy for renal damage, with a reported AUC of 0.849 (95% CI 0.809–0.892), although this estimate was predictive of future rather than diagnostic of concurrent TOD. Thus, the overall AUC range of approximately 0.78–0.85 applies only to these two biomarkers; no AUC values were reported for AASI, which primarily provided prognostic evidence (cardiovascular hazard ratio 1.13 per 1-standard-deviation increase). No included study evaluated AASI, NT-proBNP, and hs-cTnI simultaneously; consequently, the pooled diagnostic performance of the triple-marker model could not be estimated. In place of quantitative pooling, we performed a narrative synthesis of single-marker evidence, comparing reported diagnostic, prognostic, and risk-stratification parameters and rating the certainty of the combined-model evidence down for indirectness. Conclusions: Current evidence supports NT-proBNP as a potentially useful biochemical marker with moderate diagnostic accuracy for identifying hypertension-mediated TOD; hs-cTnI-based risk scores showed moderate predictive accuracy, particularly for future renal damage; whereas AASI lacked direct AUC data and primarily provided prognostic risk-stratification evidence.