Pregnancy-associated plasma protein-A is a stronger predictor for adverse cardiovascular outcomes after acute coronary syndrome in type-2 diabetes mellitus

Abstract

BackgroundThe risk prediction of pregnancy-associated plasma protein-A (PAPP-A) for future cardiovascular (CV) events post acute coronary syndrome (ACS) in patients with type-2 diabetes mellitus (T2DM) was investigated in comparison to other risk factors.MethodsPAPP-A was measured at hospital admission in 320 consecutive ACS patients (136 with T2DM and 184 without). All patients were followed for 2 years for occurrence of CV death, non-fatal MI or stroke. Effect of PAPP-A on the CV event risk was estimated using Cox regression models. Receiver operating characteristics (ROC) curves were generated to demonstrate the sensitivity and specificity of PAPP-A in predicting CV events.ResultsACS patients with T2DM had higher PAPP-A (19.29 ± 16.36 vs. 13.29 ± 13.90 ng/ml, p < 0.001) and higher rate of CV events 2 years post ACS (27.2 vs. 13.6%, p = 0.002) than those without. Higher levels of PAPP-A were significantly associated with increased risk of CV events during 2-year follow-up [HR = 2.97 for 1 SD increase in log10(PAPP-A), 95% CI 2.11–4.18, p < 0.001] in T2DM and (HR = 3.16, 95% CI 2.27–4.39, p < 0.001) in non-T2DM. Among patients with T2DM, PAPP-A showed a larger area under the curve (AUC 0.79) that was significantly more predictive than hsCRP (AUC 0.64), eGFR (AUC 0.66) and LVEF < 50% (AUC 0.52); predictive ability did not improve significantly by including those factors into the model.ConclusionsPatients with T2DM had higher levels of PAPP-A and increased risk of CV events. Elevated PAPP-A compared to other risk factors was a stronger predictor for future CV events 2 years post ACS in patients with T2DM. Trial registration ISRCTN10805074. Registered on 20 January 2017, retrospectively registered.

Prognostic value of the Stanniocalcin-2/PAPP-A/IGFBP-4 axis in ST-segment elevation myocardial infarction

“…Collectively, the Stanniocalcin-2/PAPP-A/IGFBP-4 axis regulates local IGF bioavailability and signaling with potential biological implications in cardiovascular disease [ 8 ]. Despite recent studies showing that PAPP-A and IGFBP-4 are potentially important biomarkers for the prediction of adverse outcomes in patients with acute coronary syndrome [ 11 , 12 ], the evidence is scarce in contemporary-treated STEMI patients promptly reperfused, and to date, there are no reports on the prognostic value of Stanniocalcin-2 in this population.

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Pregnancy-Associated Plasma Protein A Induces Inflammatory Cytokine Expression by Activating IGF-I/PI3K/Akt Pathways

“…Previous studies from our group and other investigators have indicated that PAPP-A might be a marker for ACS and could predict clinical outcomes [3, 8, 11, 22, 23]. A meta-analysis has also demonstrated that an elevated PAPP-A level was positively associated with cardiovascular events, and this positive association was not affected by follow-up duration, coronary artery disease type, and different measurements of PAPP-A [24].…”

“…Increased PAPP-A activity can increase lipid accumulation and impair cholesterol efflux from macrophages via negative regulation of ABCA-1, ABCG-1, and SR-B1 associated with activated macrophages and smooth muscle cells [27, 28]. In our previous study, we found that PAPP-A was a stronger predictor of the increased risk for future cardiovascular events in patients with ACS [8]. Additionally, PAPP-A expression and production can be induced by CRP through the NF- κ B-dependent pathway in human peripheral blood mononuclear cells, and this mechanism may play a critical role in increasing serum PAPPA levels during ACS [29].…”

“…It has been demonstrated that PAPP-A induced a prothrombotic phenotype in endothelial cells since it promoted the expression of functionally active tissue factor (TF) in these cells [7]. Furthermore, previous studies from our group and other investigators have found that an increase in PAPP-A plasma levels in patients with stable coronary disease or ACS was associated with a higher risk of developing future acute cardiovascular events [8–11]. Notably, several animal model studies have shown the involvement of PAPP-A in atherosclerotic lesion development [12–15].…”

Evaluation of pregnancy-associated plasma protein-A and some inflammation markers for atherosclerosis in psoriasis patients

“…It is reported that metabolic and cardiovascular diseases are more common in psoriasis patients [21]. Li et al found that both levels of hs-CRP and PAPP-A were significantly higher in patients with type 2 diabetes [22]. O'Donoghue [23].…”