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      Increased Levels of Pregnancy-Associated Plasma Protein A Are Associated with Mortality in Hemodialysis Patients: Preliminary Results

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          Pregnancy-associated plasma protein A (PAPP-A) is a new prognostic indicator of acute coronary syndrome. This protein is elevated in hemodialysis (HD) patients and is closely related to inflammation and oxidative stress. The aim of our pilot study was to find out whether PAPP-A is related to mortality in HD patients. 40 HD patients in a stable clinical state (20 men and 20 women, mean age 69 ± 12 years) were enrolled in the study and followed up for 20 months. PAPP-A was assessed immunochemically (TRACE method) in serum samples (before the HD session) at the beginning of the observation period. During the follow-up, 22 patients died, 15 of them due to cardiovascular events. PAPP-A levels were significantly higher in the patients who died, compared to living HD patients: 26.8 (21.6–36.8) vs. 20 (14.9–26.6) mU/l, p = 0.034. PAPP-A could also be a new prognostic marker in hemodialysis patients, probably due to its close association with cardiovascular risk. More extensive studies are required to confirm this hypothesis.

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          Pregnancy-associated plasma protein A as a marker of acute coronary syndromes.

          Circulating markers indicating the instability of atherosclerotic plaques could have diagnostic value in unstable angina or acute myocardial infarction. We evaluated pregnancy-associated plasma protein A (PAPP-A), a potentially proatherosclerotic metalloproteinase, as a marker of acute coronary syndromes. We examined the level of expression of PAPP-A in eight culprit unstable coronary plaques and four stable plaques from eight patients who had died suddenly of cardiac causes. We also measured circulating levels of PAPP-A, C-reactive protein, and insulin-like growth factor I (IGF-I) in 17 patients with acute myocardial infarction, 20 with unstable angina, 19 with stable angina, and 13 controls without atherosclerosis. PAPP-A was abundantly expressed in plaque cells and extracellular matrix of ruptured and eroded unstable plaques, but not in stable plaques. Circulating PAPP-A levels were significantly higher in patients with unstable angina or acute myocardial infarction than in patients with stable angina and controls (P<0.001). A PAPP-A threshold value of 10 mlU per liter identified patients who had acute coronary syndromes with a sensitivity of 89.2 percent and a specificity of 81.3 percent. PAPP-A levels correlated with levels of C-reactive protein and free IGF-I, but not with markers of myocardial injury (troponin I and the MB isoform of creatine kinase). PAPP-A is present in unstable plaques, and circulating levels are elevated in acute coronary syndromes; these increased levels may reflect the instability of atherosclerotic plaques. PAPP-A is a new candidate marker of unstable angina and acute myocardial infarction.
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            Circulating pregnancy-associated plasma protein a predicts outcome in patients with acute coronary syndrome but no troponin I elevation.

            Risk stratification in troponin (cTn)-negative acute coronary syndrome (ACS) remains a clinical challenge. We investigated the predictive value of circulating pregnancy-associated plasma protein A (PAPP-A), a novel marker of atherosclerotic plaque activity, in these patients. Two hundred consecutive hospitalized ACS patients were included, of whom 136 (69 men and 67 women; mean+/-SD age, 66+/-16 years) remained cTnI-negative for up to 24 hours. PAPP-A was measured at admission, 6 to 12 hours, and 24 hours. During 6-month follow-up, 26 (19.1%) of the cTnI-negative patients reached a primary end point (cardiovascular death, myocardial infarction, or revascularization). At a cutoff level of 2.9 mIU/L, elevated PAPP-A was an independent predictor of adverse outcome (adjusted risk ratio [RR], 4.6; 95% confidence interval, 1.8 to 11.8; P=0.002). Another independent predictor was admission CRP >2.0 mg/L (RR, 2.6; P=0.03). Measurement of plasma PAPP-A, a zinc-binding matrix metalloproteinase, is a strong independent predictor of ischemic cardiac events and need of revascularization in patients who present with suspected myocardial infarction but remain troponin negative.

              Author and article information

              Blood Purif
              Blood Purification
              S. Karger AG
              May 2004
              09 July 2004
              : 22
              : 3
              : 298-300
              aInstitute of Medical Biochemistry, bInstitute of Clinical Chemistry and Laboratory Diagnostics, cDepartment of Medicine Strahov, and dDepartment of Nephrology, 1st Faculty of Medicine and General Faculty Hospital, Charles University, Prague, Czech Republic
              78701 Blood Purif 2004;22:298–300
              © 2004 S. Karger AG, Basel

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