Influence of age on the prognostic value of mid-regional pro-adrenomedullin in the general population

Objective Experimental studies have shown that adrenomedullin (ADM) has an important role in circulatory homeostasis. Mid-regional pro-ADM (MR-proADM) is a stable form of ADM. Observational studies found an important association with age, body mass index and kidney function. The aim of this study was to evaluate the prognostic performance of MR-proADM in the general population, controlling for these potential confounders. Methods 7903 subjects (mean age 49 +/- 13 years, 49% male) from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort with a median follow-up of 10.5 years were enrolled in a prospective cohort study. Results Mean baseline MR-proADM was 0.39 +/- 0.14 nmol/l. In cross-sectional analyses, age, blood pressure, C reactive protein, cystatin-C, N-terminal pro-brain type natriuretic peptide and urinary albumin excretion remained as independent determinants of MR-proADM. In prospective analyses, MR-proADM was associated with the primary endpoint (combined cardiovascular mortality and cardiovascular morbidity), with event rates ranging from 8% in the lowest quintile to 45% in the highest quintile (p for trend <0.001) independent of age, sex, components of the Framingham risk score and other cardiovascular markers. Overall Net Reclassification Improvement against the Framingham risk score was 2.2%, which was non-significant. However, significant modification of the effect of MR-proADM on outcome by age was observed. In subjects aged <= 70 years (N=7475), 8.8% were correctly reclassified in a higher risk category (p=0.017) and 3.4% in a lower risk category (p<0.001). In subjects aged >70 years (N=428) there was no improvement of reclassification (p=0.32). Conclusion This study gives a detailed overview of the distribution of ADM in a general population and provides evidence that it is a potent and interesting biomarker in predicting cardiovascular events. These results seem especially applicable to younger subjects.