Pregnancy-associated plasma protein A predicts adverse vascular events in patients with coronary heart disease: a systematic review and meta-analysis

Introduction: Prospective studies about the association between elevated circulating pregnancy-associated plasma protein A (PAPP-A) and adverse vascular events in patients with coronary heart diseases (CHD) are inconsistent. We performed a meta-analysis to clarify this issue. Material and methods: We identified prospective studies by searching MEDLINE. The vascular outcomes included all-cause mortality, combination of all-cause mortality and non-fatal myocardial infarction (MI), and combined cardiovascular events. Prospective studies providing multivariable adjusted relative risks (RRs) and their 95% confidence intervals (CIs) of pre-mentioned outcomes were included. A random-effects model was used to calculate the pooled RRs. Subgroup and sensitivity analyses were used to explore the potential sources of heterogeneity or modifiable factors. Results: Fourteen studies with a total of 12 830 participants were included. Elevated PAPP-A level was associated with all-cause mortality (pooled RR 1.74, 95% CI: 1.45 to 2.09, p < 0.001), combined all-cause mortality and non-fatal MI (RR 1.59, 95% CI: 1.37 to 1.85, p < 0.001) and combined cardiovascular events (RR 1.50, 95% CI: 1.22 to 1.85, p < 0.001). There was no significant heterogeneity. Subgroup and sensitivity analyses showed that the positive association was not affected by follow-up term, CHD type, different assay methods of PAPP-A, or studies with less than 5 adjusted variables. Conclusions: Elevated serum PAPP-A level is associated with adverse vascular outcomes in patients with CHD.