Diagnostic and Prognostic Accuracy of Cardiorespiratory Fitness for Detecting Cardiovascular Risk and Mitochondrial Disorders: An Overview of Systematic Reviews with Meta-Analyses

Abstract Background Cardiorespiratory fitness (CRF) is a powerful predictor of current and future health across all age groups. Recognising CRF’s ability to screen health-related outcomes is essential for supporting its use in clinical practice. Objective The aim was to evaluate the health-related diagnostic and prognostic accuracy of CRF using an overview of systematic reviews. Methods Five bibliographic databases (MEDLINE, Embase, Scopus, CINAHL and SPORTDiscus) were searched from January 2002 to April 2025 to identify systematic reviews with meta-analyses that reported on the health-related diagnostic and prognostic accuracy of CRF. The results were presented using forest plots, with the certainty of evidence assessed by a modified Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Results Of the 10,796 papers identified, six systematic reviews with meta-analyses ( n = 31,171 observations) were included. Of these, five examined cardiovascular disease, events, or risk, and one examined mitochondrial disorders. CRF was measured objectively or estimated by exercise as maximum or peak oxygen consumption, ventilatory efficiency or fluctuation, or exercise performance or tolerance. All included reviews were graded as having low to critically low quality. CRF demonstrated high prognostic accuracy for predicting severe cardiovascular events in adults with heart failure, with moderate certainty (diagnostic odds ratio dOR 4.1–8.1; area under the curve of a summary receiver operating characteristic curve SROC AUC 0.73–0.77), and moderate-to-high diagnostic accuracy for detecting coronary artery disease in adults with type 2 diabetes or with suspected coronary artery disease with very low certainty (dOR 2.3–7.6; SROC AUC 0.66–0.79), mitochondrial disorders among adults with high certainty (dOR 18.1–26.6; SROC AUC 0.70–0.83), and cardiovascular disease risk among apparently healthy children and adolescents with low certainty (dOR 3.6–5.7; SROC AUC 0.64–0.71). Conclusions CRF detects cardiovascular disease and mitochondrial disorders and predicts cardiovascular events among adults with chronic conditions and detects cardiovascular risk among apparently healthy children; however, the certainty of evidence ranged from very low to high certainty due to methodological limitations. Further research is needed to generate high-quality diagnostic evidence for CRF across diverse health outcomes and age groups in the general population. Trial Registration PROSPERO CRD42022370149.