Sodium restriction in patients with chronic heart failure and reduced ejection fraction: A randomized controlled trial.

BACKGROUND: 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. METHODS: 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). RESULTS: 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 (p > 0.05 for both). Adverse safety events were not significantly different between the arms (p > 0.6 for all). In the per protocol analysis, patients who achieved a sodium intake < 2500 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 (p > 0.3 for all). CONCLUSIONS: 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 intake < 2500 mg/day appeared to have improvements in NT-proBNP and quality of life without any adverse safety signals. CLINICALTRIALS: gov Identifier: NCT03351283.

Changes in circulating concentrations of soluble fms-like tyrosine kinase-1 and placental growth factor measured by automated electrochemiluminescence immunoassays methods are predictors of preeclampsia.

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 (<34 weeks, P  ≤  0.003), and at 24-28 weeks in women who later developed preeclampsia (P  ≤  0.024). The risk for developing preeclampsia was higher among women with PlGF concentration values in the lowest quartile or with sFlt-1 levels and sFlt-1/PlGF ratio in the highest quartile of the control distribution. The odds ratios were higher and appeared earlier in women destined to develop early preeclampsia than in women who presented preeclampsia later. The sFlt-1/PlGF ratio was more tightly associated with risk of preterm or term preeclampsia than either angiogenic factor alone. CONCLUSION: Changes in circulating concentrations of PlGF, sFlt-1, and in the sFlt-1/PlGF ratio precede the onset of preeclampsia. The risk profile of circulating angiogenic factors for developing preeclampsia distinctly evolves depending on whether this condition is manifested at preterm or term.

Stimulating autoantibodies against the angiotensin II type 1 receptor are not associated with preeclampsia in Mexican-Mestizo women.

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.

Application of new homologous in vitro bioassays for human lactogens to assess the actual bioactivity of human prolactin isoforms in hyperprolactinaemic patients.

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.