In this prospective study, we found that patients who presented to the ED with chest pain due to acute coronary artery disease had a higher level of MA and IgM-uria than those with non-specific chest pain. Indeed, IgM-uria was associated with a higher risk of occurrence of subsequent major cardiovascular events. Furthermore, IgM-uria predicted poor long term cardiovascular outcome, independently of levels of MA, kidney function, diabetes and hypertension.
Under normal conditions the glomerular filtration barrier (GFB) allows just tiny amounts of albumin (molecular radius 35.5 Å) to pass to the primary urine, just one molecule out of 10,000 . More than 97% of the filtered molecules are normally subsequently reabsorbed by the proximal tubules [19, 20]. However, the GFB is not a static filter, but rather a highly dynamic sieve, which can directly increase its permeability in systemic inflammation , after trauma , during hyperglycemia , or following elevations of circulating ANP (atrial natriuretic peptide) levels , or angiotensin II levels . Our data strongly suggest that albumin and other large proteins, such as IgG (mol. radius 55 Å) and IgM (mol. radius 120 Å) are able to pass the GFB only through large size-selective defects, “large pores” (shunts). An increased number of such shunt-like pores will functionally form in all of the pathophysiological conditions listed above resulting in albuminuria, IgG-uria and IgM-uria, while, at least initially, urinary tubular markers will stay unchanged. Consequently, the increased urinary IgM concentrations seen in patients with CAD must be secondary to decreases in size-selectivity of the GFB. Such size-selective defects are likely to be caused by endothelial dysfunction (due to atherosclerosis), acute systemic inflammation and/or ischemic (or HF-induced) release of ANP [20, 24, 26]. This is further strengthened by the fact that elevations of hs-CRP, reflecting systemic inflammation associated with atherosclerosis , and troponin T, more reflecting cardiac muscle ischemia, were coupled to the presence of CAD [28, 29] and to MA and IgM-uria, in turn signaling a poor cardiovascular outcome [12, 13]. Unfortunately, it is likely that the method for assessing IgG urine concentration may not have been sensitive enough compared with the methods for MA and IgM-uria, since IgG-uria was not as strongly coupled to predictions of outcome as were MA and IgM-uria. Urine IgM analysis is a simple, non-invasive urine test that could be incorporated in the routine laboratory analysis, for risk stratification of patients with chest pain [5, 30]. Addition of urine IgM analysis to the workup of patients with coronary artery disease could help to identify patients at higher risk of recurrent cardiovascular events. This prompts early introduction of an intensive multifactorial preventive treatment strategy to improve the overall cardiovascular risk profile .
The study is limited by its observational nature. It was conducted in one centre and the participants were almost only of Scandinavian origin. However, our study has more than a few strengths. First, the patients were included prospectively and consecutively. Second, the study has a relatively long follow up time. Third, there was no loss of subjects during the follow up. Furthermore, urine IgM was measured during the first doctor contact in the ED.