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Sodium restriction is recommended for patients with heart failure (HF) despite the lack of solid clinical evidence from randomized controlled trials. Whether or not sodium restrictions provide beneficial cardiac effects is not known.The present study is a randomized, double-blind, controlled trial of stable HF patients with ejection fraction ≤ 40%. Patients were allocated to sodium restriction (2 g of sodium/day) vs. control (3 g of sodium/day). The primary outcome was change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 20 weeks. Secondary outcomes included quality of life and adverse safety events (HF readmission, blood pressure or electrolyte abnormalities).Seventy patients were enrolled. Median baseline sodium consumption was 3268 (2225-4537) mg/day. Adherence to the intervention based on 24-hour urinary sodium was 32%. NT-proBNP and quality of life did not significantly change between groups (p0.05 for both). Adverse safety events were not significantly different between the arms (p0.6 for all). In the per protocol analysis, patients who achieved a sodium intake2500 mg/day at the intervention conclusion showed improvements in NT-proBNP levels (between-group difference: -55%, 95% confidence interval -27 to -73%; p = 0.002) and quality of life (between-group difference -11 ± 5 points; p = 0.04). Blood pressure decreased in patients with lower sodium intake (between-group difference -9 ± 5 mmHg; p = 0.05) without significant differences in symptomatic hypotension or other safety events (p0.3 for all).Adherence assessed by 24-hour natriuresis and by the nutritionist was poor. The group allocated to sodium restriction did not show improvement in NT-proBNP. However, patients who achieved a sodium intake2500 mg/day appeared to have improvements in NT-proBNP and quality of life without any adverse safety signals. ClinicalTrials.gov Identifier: NCT03351283.

OBJECTIVE Preeclampsia is characterized by an imbalance in angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). We herein assessed whether these factors measured by a newly developed automated electrochemiluminescence immunoassay are associated with risk to develop preeclampsia. METHODS We performed a nested case-control study within a cohort of 230 women with singleton pregnancies. The study included all 37 women who eventually developed preeclampsia and 29 normotensive controls. Serum samples were collected at 4-week intervals (from weeks 20th to 36th). sFlt-1 and PlGF were measured using a commercial automated immunoassay (Elecsys). RESULTS Women destined to develop preeclampsia had lower PlGF levels and higher sFlt-1 levels and sFlt-1/PlGF ratio than women with normal pregnancies. These changes became significant at 20 weeks in women destined to develop early preeclampsia (

Objective Recent studies have demonstrated that stimulating autoantibodies against the angiotensin II type 1 receptor (AT1R-AA) are frequently detected in the sera from women with preeclampsia, suggesting that they may play an important role in the pathogenesis of this disease. Nevertheless, the real clinical significance of AT1R-AA in preeclampsia is still controversial due to the paucity of appropriate large comparative studies that require cumbersome, time-consuming, and expensive bioassays to detect AT1R-AA. At present, the prevalence of AT1R-AA in large populations of preeclamptic women is unknown. In an attempt to clarify this issue, we assessed the presence and potential clinical significance of AT1R-AA in a large population of Mexican-Mestizo women with preeclampsia. Methods Using a cross-sectional design, we determined the presence of AT1R-AA in 525 pregnant women (99 healthy pregnant, 96 with mild preeclampsia, and 330 with severe preeclampsia) by a new bioassay that employs human embryonic kidney-293 cells stably expressing the recombinant rat AT1R and a 4x nuclear factor of activated T cells responsive luciferase construct as well as by the reference assay in Chinese hamster ovary (CHO) cells. Results We found that IgG obtained from sera of healthy pregnant women and patients with preeclampsia were unable to induce luciferase activity in both HEK-293 and Chinese hamster ovary cells expressing functional angiotensin II receptor type 1. Therefore, the frequency of patients with AT1R-AA was zero. Conclusion We concluded that in Mexican-Mestizo women agonistic AT1R-AA cannot be invoked as a factor involved in the pathogenesis of preeclampsia. Whether these findings can be attributed to genetic or environmental factors remains unknown.

Context: It has been proposed that preeclampsia may result from of an imbalance in angiogenic factors. Although prolactin (PRL) is mainly related to lactation, it is also involved in other biological functions, including angiogenesis. Objective: Our objective was to determine the relationship among preeclampsia, serum and urinary PRL (uPRL) levels, and excretion of antiangiogenic PRL fragments in urine. Study design: Using a cross-sectional design, uPRL and serum PRL levels, and the presence of PRL isoforms were determined in 546 pregnant women: 207 healthy pregnant, 124 with gestational hypertension, 48 with mild preeclampsia, and 167 with severe preeclampsia (sPE). Results: uPRL concentrations were significantly (P < 0.001) higher in preeclampsia (11.99 ng/mg creatinine) than in healthy pregnancy (0.20 ng/mg creatinine) and gestational hypertension (0.19 ng/mg creatinine), and were even higher in sPE compared with mild preeclampsia (21.20 vs. 2.77 ng/mg creatinine, respectively; P < 0.001). Antiangiogenic PRL fragments (14–16 kDa) were detected in 21.6% of urine samples from women with sPE but in none from other groups. Patients with hemolysis, elevated liver enzymes, low platelet count syndrome, and/or eclampsia, placental abruption, acute renal failure, and pulmonary edema exhibited highest uPRL concentrations (P ≤ 0.028) and frequency of antiangiogenic PRL fragments in urine (P ≤ 0.036). High-serum PRL levels were associated with sPE independently of gestational age, proteinuria, and prolactinuria (P = 0.032). Conclusions: Preeclampsia is characterized by increased uPRL excretion. uPRL concentrations and their isoforms appear to be suitable markers to assess the severity of preeclampsia and occurrence of adverse outcomes. PRL and and/or its isoforms might be involved in the pathophysiology of preeclampsia.

Background: The protein:creatinine ratio in random, untimed urine samples correlates with 24-h protein excretion in pregnant women with and without hypertension. Nevertheless, whether this ratio is appropriate as a screening test for proteinuria is still unclear, in part because of the paucity of large studies. Methods: We measured protein:creatinine ratios in random urine samples and protein contents of 24-h urine samples in a cross-sectional study of 927 hospitalized pregnant women at ≥20-weeks of gestational age and in a 2nd cohort of 161 pregnant women. In the 2nd group, urine specimens were obtained before and after completion of the 24-h collections, avoiding 1st-morning void specimens. Results: Protein excretion was ≥300 mg/24 h in 282 patients (30.4%). The urine protein:creatinine ratio and the 24-h protein excretion were significantly correlated (r = 0.98, P 24 h apart. Conclusions: Random urinary protein:creatinine ratio is a reliable indicator of significant proteinuria (>300 mg/day) in nonambulatory pregnant women, irrespective of sampling time during the daytime. The protein:creatinine ratio may be reasonably used as an alternative to the 24-h urine collection method.

Summary Background Prolactin (PRL) plays a central role in mammary gland development and lactation. Due to its molecular heterogeneity, measurement of PRL immunoreactivity does not necessarily reflect its intrinsic bioactivity. For many years the Nb2 rat lymphoma cell bioassay has been the only reference bioassay for human lactogens. This bioassay, however, does not always correlate with the clinical features found in some patients exhibiting normal or elevated immunoreactive serum PRL concentrations. Objectives (1) To determine the concentrations of bioactive PRL in serum samples from individuals with normoprolactinaemia or with different forms of hyperprolactinaemia using two recently described homologous in vitro bioassays (i.e. a transcriptional bioassay in HEK-293 cells and a proliferation assay in Ba/F3 cells); and (2) to compare these results with those generated by the classical Nb2 cell bioassay. Design Cross-sectional study. Setting An institutional biomedical research laboratory. Participants Ten patients with symptomatic hyperprolactinaemia due to prolactinoma, 11 patients with asymptomatic hyperprolactinaemia and macroprolactinaemia, and nine normal women. Main outcome measures Measurement of immunoreactive and bioactive concentrations of serum PRL. Results Samples from normal women and patients with tumoral hyperprolactinaemia due to prolactinoma exhibited similar within-group concentration values of bioactive and immunoreactive serum PRL when tested by the three bioassays and the immunoradiometric assay employed. By contrast, measurement of bioactive PRL in samples from patients with macroprolactinaemia revealed that macroprolactin was poorly active in the homologous receptor bioassays, while it was more active in the Nb2 bioassay. Conclusions The reduced bioactivity of PRL in patients with macroprolactinaemia may further explain the absence of clinical features of hyperprolactinaemia in these individuals. In addition, our findings indicate that species-specificity and sensitivity of the bioassays are determinant factors in the measurement of the intrinsic biological activity of circulating PRL.