Any Degree of Albuminuria Signals Increased Cardiovascular Risk

November 26, 2007 — Albuminuria, even in low levels within the "normal" range, is an independent predictor of cardiovascular and all-cause mortality, a new analysis of the Prevention of Events with an ACE inhibitor (PEACE) trial shows.
The study, published online November 19, 2007 in Circulation and scheduled for its December 4, 2007 issue, was conducted by a group led by Dr Scott Solomon (Brigham and Women's Hospital, Boston, MA).
Solomon commented to heartwire: "We found that virtually any degree of albuminuria, even albumin below the level we call microalbuminuria, placed a patient at significantly higher risk of cardiovascular events. A number of other studies have been suggestive of this — HOPE [Heart Outcomes Prevention Evaluation] in higher-risk vascular disease patients and LIFE [Losartan Intervention for End Point Reduction] in hypertension patients — but ours was a particularly low-risk population, so we've extended the findings to this low-risk group with stable CHD [coronary heart disease]. We should stop thinking about cut-off values for microalbuminuria. If albumin is detectable in the urine, the patient is at increased risk."
A new window to the health of the vasculature
Solomon explained that as such low levels of albumin cannot be detected with a dipstick test, they used a spot assay that measures the urinary albumin-to-creatinine ratio (ACR), which gives a more accurate measure of albumin status, as it takes into account the fact that the concentration of albumin in urine varies, depending on the amount of water consumed. "This is still a very easy, noninvasive, and cheap test. All you need is a urine sample. We do many far more invasive and expensive tests than this to risk-stratify patients. This test gives us a new window to the health of the vasculature that we should take advantage of," he added.
Noting that a previous analysis of the PEACE population had shown that a reduced glomerular filtration rate (GFR) was also associated with increased cardiovascular risk, Solomon said: "We have now shown that both measures of kidney function are markers of increased risk. If either one is compromised, then risk is increased, and if both are affected, then risk is very much increased. These two studies are telling us that we cardiologists need to pay more attention to kidney function in our patients and to understand that these are not patients who will ever come to dialysis or even necessarily see a nephrologist, but they do have mild kidney disease that puts them at increased risk for a cardiovascular event."
He pointed out that whether or not patients with minor renal dysfunction should be treated differently is open to debate but added: "There is a fair amount of evidence that inhibitors of the renin angiotensin system and ACE [angiotensin-converting enzyme] inhibitors in particular are of benefit to CHD patients with reduced renal function. So I would say that if you are undecided about whether to give an ACE inhibitor or not, this test could help you make that decision."
A measure of treatment efficacy
In the paper, the authors also note that microalbuminuria may represent an early marker of diffuse vascular endothelial dysfunction, and clinicians should consider serial quantification of ACR as a marker of risk, because its reduction may be a metric of treatment efficacy.
The main PEACE trial evaluated the effects of trandolapril vs placebo in 8290 patients with stable coronary artery disease and normal left ventricular ejection fraction. In the current analysis, the urinary ACR was assessed in a core laboratory in 2977 patients at baseline and in 1339 patients at follow-up (mean 34 months). The majority of patients (73%) had a baseline ACR within the normal range (<17 µg/mg for men and <25 µg/mg for women).
Results showed that independent of the estimated GFR and other baseline covariates, a higher ACR, even within the normal range, was associated with increased risks for all-cause mortality (p<0.001) and cardiovascular death (p=0.01). An increase in ACR over time was also associated with increased risk of cardiovascular death.
While the effect of trandolapril therapy on outcomes was not modified significantly by the level of albuminuria, trandolapril therapy was associated with a significantly lower mean follow-up ACR (12.5 vs 14.6 µg/mg, p=0.0002). Solomon suggested that the power of this analysis may have been insufficient to show an effect of trandolapril on outcomes. "We did see an effect of the drug on albuminuria and a definite relationship between degree of albuminuria and outcomes, but we probably had too few patients to show an actual relationship between trandolapril and outcomes," he commented to heartwire.
Source
Solomon S D, Lin J, Solomon C G et al. Influence of albuminuria on cardiovascular risk in patients with stable coronary artery disease. Circulation. 2007. Published online before print. November 19. DOI: 10.1161/CIRCULATIONAHA.107.723270