Statin use and calcific uremic arteriolopathy: a matched case-control study.

BACKGROUND: Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is characterized by vascular calcification, thrombosis and intense inflammation. Prior research has shown that statins have anticalcification, antithrombotic and antiinflammatory properties; however, the association between statin use and CUA has not been investigated. METHODS: This matched case-control study included 62 adult maintenance hemodialysis (HD) patients with biopsy-confirmed CUA diagnosed between the years 2002 and 2011 (cases). All cases were hospitalized at the time of diagnosis. Controls (n = 124) were hospitalized maintenance HD patients without CUA (matched to cases by gender and timing of hospitalization). Univariate and multivariable logistic regression models were applied to compute odds ratio (OR) and 95% confidence intervals (CI) for CUA in statin users, and also to examine previously described associations. RESULTS: The mean age of cases was 58 years. Most were females (68%), and of white race (64%). Statin use was more common in controls than in cases (39 vs. 19%, p < 0.01). Statin use was associated with lower odds of CUA in unadjusted (OR 0.38, 95% CI 0.18-0.79) and adjusted (OR 0.20, 95% CI 0.05-0.88) analyses. Hypercalcemia (OR 2.25, 95% CI 1.14-4.43), hypoalbuminemia (OR 5.73, 95% CI 2.79-11.77), calcitriol use (OR 5.69, 95% CI 1.02-31.77) and warfarin use (OR 4.30, 95% CI 1.57-11.74) were positively associated with CUA in adjusted analyses whereas paricalcitol and doxercalciferol were not (OR 1.33, 95% CI 0.54-3.27). CONCLUSION: Statin use may be negatively associated with odds of CUA. Further large prospective studies with attention to potential confounders are needed to confirm these findings.

Levels of angiogenic factors in pregnancy and post-partum bleeding.

We have studied if serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placenta growth factor (PlGF) in pregnancy could predict excess post-partum bleeding. In 392 normotensive singleton pregnancies, concentrations of sFlt-1 and PlGF in the first, second, and third trimester were compared between women with and without excess post-partum bleeding, defined as blood loss volume of at least 500 mL. Mean concentrations of sFlt-1 were consistently higher in all three trimesters among women who had excess post-partum bleeding compared to women without this, but significantly higher only in the second trimester. For PlGF, there were no significant differences between the groups. High concentrations of the anti-angiogenic factor sFlt-1 in maternal circulation during pregnancy may be associated with an increased risk of excess post-partum bleeding.

Labor therapeutics and BMI as risk factors for postpartum preeclampsia: A case-control study.

OBJECTIVES: This study aims at identifying associations between therapeutics used during labor and the occurrence of postpartum preeclampsia (PPPE), a poorly understood entity. STUDY DESIGN AND MAIN OUTCOME MEASURES: This is a case-control study of women who received an ICD-9 code for PPPE (cases) during the years 2009-2011, compared to women with a normotensive term pregnancy, delivery and postpartum period until discharge (controls), matched on age (±1year) and delivery date (±3months). Cases were defined as women having a normotensive term pregnancy, delivery and initial postpartum period (48h post-delivery) but developing hypertension between 48h and 6weeks postpartum. Single variable and multiple variable models were used to determine significant risk factors. RESULTS: Forty-three women with PPPE were compared to 86 controls. Use of vasopressors and oxytocin did not differ between cases and controls, but rate of fluids administered during labor (OR=1.68 per 100cc/h; 95% CI: 1.09-2.59, p=0.02) and an elevated pre-pregnancy/first trimester BMI (OR=1.18 per kg/m2, 95% CI: 1.07-1.3, p=0.001) were identified as significant risk factors in multivariate analysis. CONCLUSIONS: We identified two potentially modifiable risk factors for PPPE; further studies are needed to better define the role of these two variables in the development of PPPE.

Two variants of the C-reactive protein gene are associated with risk of pre-eclampsia in an American Indian population.

BACKGROUND: The etiology of pre-eclampsia (PE) is unknown; but it is accepted that normal pregnancy represents a distinctive challenge to the maternal immune system. C-reactive protein is a prominent component of the innate immune system; and we previously reported an association between PE and the CRP polymorphism, rs1205. Our aim was to explore the effects of additional CRP variants. The IBC (Cardiochip) genotyping microarray focuses on candidate genes and pathways related to the pathophysiology of cardiovascular disease. METHODS: This study recruited 140 cases of PE and 270 matched controls, of which 95 cases met criteria as severe PE, from an American Indian community. IBC array genotypes from 10 suitable CRP SNPs were analyzed. A replication sample of 178 cases and 427 controls of European ancestry was also genotyped. RESULTS: A nominally significant difference (p value <0.05) was seen in the distribution of discordant matched pairs for rs3093068; and Bonferroni corrected differences (P<0.005) were seen for rs876538, rs2794521, and rs3091244. Univariate conditional logistic regression odds ratios (OR) were nominally significant for rs3093068 and rs876538 models only. Multivariate logistic models with adjustment for mother's age, nulliparity and BMI attenuated the effect (OR 1.58, P = 0.066, 95% CI 0.97-2.58) for rs876538 and (OR 2.59, P = 0.050, 95% CI 1.00-6.68) for rs3093068. An additive risk score of the above two risk genotypes shows a multivariate adjusted OR of 2.04 (P = 0.013, 95% CI 1.16-3.56). The replication sample also demonstrated significant association between PE and the rs876538 allele (OR = 1.55, P = 0.01, 95% CI 2.16-1.10). We also show putative functionality for the rs876538 and rs3093068 CRP variants. CONCLUSION: The CRP variants, rs876538 and rs3093068, previously associated with other cardiovascular disease phenotypes, show suggestive association with PE in this American Indian population, further supporting a possible role for CRP in PE.

Correction: Two Variants of the C-Reactive Protein Gene Are Associated with Risk of Pre-Eclampsia in an American Indian Population.

[This corrects the article on p. e71231 in vol. 8.].

[Preeclampsia: oxidative stress, inflammation and endothelial dysfunction]. / Pré-eclâmpsia: estresse oxidativo, inflamação e disfunção endotelial.

Preeclampsia is a systemic syndrome characterized by inflammatory and antiangiogenic states. The pathogenesis of preeclampsia involves deficient trophoblast invasion that is responsible for altered uterine blood flow and placental oxidative stress. The damaged placenta produces higher concentrations of sFlt-1, a soluble receptor for VEGF and PlGF that is released in the maternal circulation and is involved in endothelial dysfunction. Actually, all processes involved in inflammation, endothelial dysfunction and oxidative stress are strongly correlated and act in a synergistic way. Recent data have shown that an increase in serum concentrations of sFlt-1 initiates 5 to 6 weeks before the clinical manifestations of preeclampsia and these alterations correlate with a decrease in serum concentrations of PlGF. Therefore, both sFlt-1 and PlGF have been suggested to be useful for an early-diagnosis of preeclampsia. The knowledge about the role of antiangiogenic factors in the pathogenesis of preeclampsia has raised the possibility of a therapy involving these factors.In this article we revisited the pathogenesis of preeclampsia addressing its antiangiogenic and inflammatory states.In conclusion, we correlated these alterations with the higher risk for cardiovascular diseases presented by these women in future life.

Pré-eclâmpsia: estresse oxidativo, inflamação e disfunção endotelial / Preeclampsia: oxidative stress, inflammation and endothelial dysfunction

Pré-eclâmpsia é uma síndrome sistêmica caracterizada por intenso estado inflamatório e antiangiogênico. A fisiopatologia da pré-clâmpsia envolve alterações no processo de invasão trofoblástica, com consequente inadequado suprimento sanguíneo uterino e estresse oxidativo do tecido placentário. As alterações placentárias decorrentes desse processo levam à maior produção de sFlt-1, um receptor solúvel para as moléculas de VEGF e PlGF. O sFlt-1 impede com que VEGF e PlGF realizem suas funções na homeostase endotelial, culminando com disfunção dessas células. De uma maneira geral, os processos inflamatórios, de disfunção endotelial e estresse oxidativo estão interligados e agem de maneira sinérgica. Trabalhos recentes têm demonstrado que elevações nas concentrações séricas de sFlt-1 ocorrem 5 a 6 semanas antes das manifestações clínicas da pré-eclâmpsia. Concomitantemente, observa-se queda nas concentrações séricas de PlGF. Sendo assim, as dosagens séricas de sFlt-1 e PlGF têm sido sugeridas para o diagnóstico precoce de pré-eclâmpsia. Ademais, os conhecimentos adquiridos a respeito dos fatores antiangiogênicos proporcionam ainda a possibilidade de novas linhas de pesquisa sobre possíveis terapias para a pré-eclâmpsia. Neste artigo, foram revisados os aspectos inflamatórios e antiangiogênicos envolvidos na fisiopatologia da pré-eclâmpsia. Por fim, foram correlacionados esses aspectos com o risco elevado para doenças cardiovasculares apresentado por essas pacientes ao longo de suas vidas.

Preeclampsia is a systemic syndrome characterized by inflammatory and antiangiogenic states. The pathogenesis of preeclampsia involves deficient trophoblast invasion that is responsible for altered uterine blood flow and placental oxidative stress. The damaged placenta produces higher concentrations of sFlt-1, a soluble receptor for VEGF and PlGF that is released in the maternal circulation and is involved in endothelial dysfunction. Actually, all processes involved in inflammation, endothelial dysfunction and oxidative stress are strongly correlated and act in a synergistic way. Recent data have shown that an increase in serum concentrations of sFlt-1 initiates 5 to 6 weeks before the clinical manifestations of preeclampsia and these alterations correlate with a decrease in serum concentrations of PlGF. Therefore, both sFlt-1 and PlGF have been suggested to be useful for an early-diagnosis of preeclampsia. The knowledge about the role of antiangiogenic factors in the pathogenesis of preeclampsia has raised the possibility of a therapy involving these factors.In this article we revisited the pathogenesis of preeclampsia addressing its antiangiogenic and inflammatory states.In conclusion, we correlated these alterations with the higher risk for cardiovascular diseases presented by these women in future life.