TIMP-1 as a biomarker in obstructive sleep apnea: screening, monitoring, risk stratification, and a step towards precision medicine.

The diagnosis of obstructive sleep apnea (OSA) is a complex time- and resource-intensive diagnostic procedure. Since tissue inhibitors of matrix metalloproteinases (TIMP's) are involved in various pathophysiological processes and are correlated with a high cardiovascular risk, TIMP's appear to be a suitable candidate for an OSA-biomarker. In a prospective controlled diagnostic study, TIMP-1 serum levels of 273 OSA-patients and controls were analyzed for correlation with OSA severity, BMI, age, sex, cardio-/ cerebrovascular comorbidities. Furthermore, longitudinal medium- and long-term effects of CPAP-treatment (n=15) on TIMP-1-levels were investigated. TIMP-1 was clearly linked to OSA as well as to disease severity (mild, moderate, severe; each p<0.001) and was not influenced by age, gender, BMI, or cardio-/cerebrovascular comorbidities. ROC curve analysis revealed an AUC of 0.91 ± 0.017 SE (p<0.001), suggesting a TIMP-1 cut-off value of 75 ng/ml (sensitivity 0.78; specificity 0.91) being especially sensitive for patients with severe OSA (sensitivity 0.89; specificity 0.91). The likelihood ratio was 8.88, while the diagnostic odds ratio was 37.14. CPAP-treatment led to a significant decrease of TIMP-1 after 6-8 months (p=0.008). TIMP-1 seems to fulfill the preconditions for a circulating OSA-biomarker: disease-specific with a mandatory presence in affected patients, reversible on treatment, reflects disease severity and provides a cutoff value between the healthy state and disease. In the clinical routine, TIMP 1 may help to stratify the individual OSA-associated cardiovascular risk and to monitor the treatment response to CPAP-therapy as a further step towards providing a personalized therapy.