Why Predict Microvascular Complications?
Clinical prediction of microvascular events is not as yet advocated by guidelines. This is largely due to a lack of evidence at present regarding evidence-based therapies to prevent onset of microvascular events. ADVANCE reported that intensive glucose and blood pressure control reduce the risk of nephropathy (25), and although data from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial and VADT (Veterans Affairs Diabetes Trial) were less positive, results were consistent with reduction or delay in microalbuminuria and macroalbuminuria (26,27). A recent meta-analysis concluded there was inconsistent evidence to promote intensive interventions to prevent microvascular disease (28). Future trials in this area would benefit from better identification of high-risk patients to enable more effective evaluation of interventions. From our reclassification model (using the >15% 5-year risk predicted risk cutoff after addition of cardiac biomarkers), 13.2% of noncase subjects would be in the highest risk category and 44.9% of case subjects. Our results are thus important, since prediction of microvascular events, in particular nephropathy, would be useful for future trials of new agents designed to prevent or slow progression of nephropathy, an area of intense interest and activity (29). Indeed, there is a raft of ongoing work in the field of proteomics to improve the prediction of kidney disease (30,31). While -omics based technology is not yet ready for use in routine biochemistry in terms of standardization, quality control, or technical pragmatism, our data illustrate that simple clinical biomarkers predict nephropathy very well and that other simple and far less costly blood-based tests already in routine use, such as cardiac biomarkers, offer incremental predictive benefit. While our data are hypothesis generating, hinting at the potential for cardiac biomarkers to enhance prediction of diabetic nephropathy, it should be recognized that cardiac biomarkers are predictive of macrovascular risk (4); therefore, such biomarkers have the potential to be routinely assessed for other purposes. Further studies are required to assess the full potential clinical implications of our findings for microvascular risk prediction.