C Iacobaeus1, T Kahan2, G Jörneskog3, K Bremme4, E Andolf1, M Thorsell1. 1. Division of Obstetrics and Gynecology, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. 2. Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. 3. Division of Medicine, Microcirculation Laboratory, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. 4. Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Abstract
OBJECTIVE: To investigate the relationship between levels of circulating maternal pregnancy-associated plasma protein-A (PAPP-A) and first-trimester maternal vascular function. METHODS: This was a cross-sectional study of 53 healthy, non-smoking, nulliparous pregnant women in Stockholm, Sweden. PAPP-A levels and vascular function were assessed during gestational weeks 11-14. Forearm skin microcirculation was investigated by laser Doppler perfusion imaging during iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to assess endothelium-dependent and -independent microvascular vasodilatation, respectively. Microvascular endothelial function index was calculated as peak ACh/peak SNP. Endothelium-dependent and -independent vasodilatation in the brachial artery was evaluated, respectively, by postischemic hyperemia-induced flow-mediated vasodilatation (FMD) and by response to sublingual intake of glyceryl trinitrate (GTN). RESULTS: PAPP-A was correlated with skin microvascular endothelial function index (β = 1.008 (95% CI, 0.34-1.68), r2 = 0.17, P = 0.004). PAPP-A also correlated inversely with FMD (β = -0.052 (95% CI, -0.094 to -0.011), r2 = 0.13, P = 0.014) but did not relate to forearm endothelial function index (i.e. FMD/GTN). The results were retained in multivariate analyses including known confounding factors. CONCLUSIONS: First-trimester endothelium-dependent skin microvascular reactivity was positively related to PAPP-A levels. If confirmed, these novel findings suggest that first-trimester skin microvascular reactivity could be a useful early pregnancy marker of placental function.
OBJECTIVE: To investigate the relationship between levels of circulating maternal pregnancy-associated plasma protein-A (PAPP-A) and first-trimester maternal vascular function. METHODS: This was a cross-sectional study of 53 healthy, non-smoking, nulliparous pregnant women in Stockholm, Sweden. PAPP-A levels and vascular function were assessed during gestational weeks 11-14. Forearm skin microcirculation was investigated by laser Doppler perfusion imaging during iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to assess endothelium-dependent and -independent microvascular vasodilatation, respectively. Microvascular endothelial function index was calculated as peak ACh/peak SNP. Endothelium-dependent and -independent vasodilatation in the brachial artery was evaluated, respectively, by postischemic hyperemia-induced flow-mediated vasodilatation (FMD) and by response to sublingual intake of glyceryl trinitrate (GTN). RESULTS:PAPP-A was correlated with skin microvascular endothelial function index (β = 1.008 (95% CI, 0.34-1.68), r2 = 0.17, P = 0.004). PAPP-A also correlated inversely with FMD (β = -0.052 (95% CI, -0.094 to -0.011), r2 = 0.13, P = 0.014) but did not relate to forearm endothelial function index (i.e. FMD/GTN). The results were retained in multivariate analyses including known confounding factors. CONCLUSIONS: First-trimester endothelium-dependent skin microvascular reactivity was positively related to PAPP-A levels. If confirmed, these novel findings suggest that first-trimester skin microvascular reactivity could be a useful early pregnancy marker of placental function.