CRP Levels Tied to Statin Effects on Contrast Nephropathy in PRATO-ACS Analysis

Marlene Busko

December 16, 2014

PRATO, ITALY — In patients with non–ST-segment-elevation ACS (NSTE-ACS) who are about to undergo cardiac catheterization, early administration of high-dose rosuvastatin protects against contrast-induced acute kidney injury (AKI), especially in those with higher baseline levels of C-reactive protein (CRP), new research shows[1].

"In this series of NSTE-ACS patients, our study confirms previous clinical and experimental studies [showing that] high levels of systemic and/or local (renal) inflammation may contribute to the development of acute kidney injury after contrast medium exposure," Dr Anna Toso (Santo Stefano Hospital, Italy) told heartwire in an email.

Moreover, it "adds another piece of information—that is, that 'the higher the baseline CRP levels, the higher the [contrast-induced] AKI and adverse renal and cardiovascular event rates and the higher the benefits of on-admission rosuvastatin administration.' "

Measuring baseline CRP levels—and correlating this with other comorbidities, levels of other inflammatory markers, and the extent of myocardial damage—can identify the NSTE-ACS patients who have a higher risk of contrast-induced nephropathy, she noted.

The findings, based on data from the Protective Effect of Rosuvastatin and Antiplatelet Therapy on Contrast-Induced Nephropathy and Myocardial Damage in Patients With Acute Coronary Syndrome Undergoing Coronary Intervention (PRATO-ACS) study, were published online December 16, 2014 in JACC: Cardiovascular Interventions.

Looking at CRP Levels in PRATO-ACS

Previously in the PRATO-ACS randomized study, the researchers showed that statin-naive patients with NSTE-ACS who were about to undergo coronary angiography, in addition to receiving standard preventive measures (intravenous hydration, use of low- or iso-osmolar contrast media, and reduced dosages of contrast agents), early high-dose rosuvastatin reduced the risk of contrast-induce AKI and improved short- and mid-term clinical outcomes.

Other studies have suggested that systemic inflammation (evidenced by elevated CRP levels) could make the kidneys more vulnerable to local inflammation caused by iodinated contrast medium, which contributes to the development of contrast-induced acute kidney injury.

Thus, the researchers aimed to investigate how inflammation might explain the pathogenesis of AKI in the PRATO-ACS population.

PRATO-ACS had randomized 504 statin-naive patients scheduled for early invasive angiography to a statin group (40-mg rosuvastatin on admission followed by 20 mg/day) or a control group with no statins. The primary outcome was contrast-induced AKI, defined as an increase in serum creatinine of >0.5 mg/dL or >25% over the baseline value within 72 hours after the administration of contrast agent.

The study participants were stratified into tertiles according to their baseline CRP levels: <2.7 mg/L; 2.7 to <7.5 mg/L; and >7.5 mg/L.

Overall, 55 patients developed contrast-induced AKI: 17 of 252 patients (6.7%) in the statin group and 38 of 252 patients (15.1%) in the control group (odds ratio after adjustment for CRP 0.41, 95% CI 0.22–0.77; P=0.005).

Contrast-induced AKI increased with increasing tertiles of baseline CRP. Of the 55 patients who developed this complication, nine patients had the lowest CRP levels; 14 patients had intermediate CRP levels; and 32 patients had the highest levels (P=0.0001).

The beneficial effect of rosuvastatin was significant for patients in the highest CRP tertile (odds ratio 0.20, 95% CI 0.07–0.54; P=0.002).

Rosuvastatin treatment was followed by improved short-term outcomes at 30 days (acute renal failure requiring dialysis, persistent renal damage, all-cause mortality, MI, or stroke) and mid-term outcomes (death or MI at 6 months), especially in patients with high systemic inflammation at baseline.

Among patients who were in the highest baseline tertile of CRP, compared with control patients, those who received early rosuvastatin had a significantly lower rate of adverse events at 30 days (7.2% vs 17.4%, P=0.043); there was also a trend toward better outcomes at 6 months (6.02% vs 13.04%, P=0.12).

The group concludes: "Whether or not these benefits are due to the anti-inflammatory properties of rosuvastatin cannot be established on the basis of this study, but our findings represent a further reason in favor of early use of high-dose statin therapy and assessment of [CRP] in ACS patients."

The study was supported by the Centro Cardiopatici Toscani. The authors have reported that they have no relevant financial relationships.

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