Context: Normal pregnancy is associated with sodium and water retention, which results in plasma volume expansion prior to placental implantation. The explanation offered for these events is that pregnancy ‘resets’ both volume and osmoreceptors. Evidence Acquisition: The mechanisms for such an enigmatic ‘resetting’ in pregnancy have not previously been explained. However, recent human pregnancy studies have demonstrated that the earliest hemodynamic change in pregnancy is primary systemic arterial vasodilation. This arterial underfilling is associated with a secondary increase in cardiac output and activation of the neurohumoral axis, including stimulation of the renin-angiotensin-aldosterone, sympathetic, and non-osmotic vasopressin systems. Resistance to the pressor effects of angiotensin and sympathetic stimulation in pregnancy is compatible with an increase in endothelial nitric oxide synthase activity. Results: In contrast to the sodium and water retention which occur secondary to the primary arterial vasodilation in cirrhosis, glomerular filtration and renal blood flow are significantly increased in normal pregnancy. A possible explanation for this difference in arterial vasodilation states is that relaxin, an arterial vasodilator which increases during pregnancy, has a potent effect on both systemic and renal circulation. Endothelial damage in pregnancy is pivotal in the pathogenesis of preeclampsia in pregnancy. Conclusions: Against a background of the primary arterial vasodilation hypothesis, it is obvious that reversal of the systemic vasodilatation in pregnancy, without subsequent activation of the renin-angiotensin-aldosterone system (78), will evoke a reversal of all the links in the chain of events in normal pregnancy adaptation, thus, it may cause preeclampsia. Namely, a decrease of renal vasodilation will decrease glomerular filtration rate. Keywords: Pregnancy; Arterial; Osmolar Concentration; Relaxin; Nitric Oxide; Pre-Eclampsia, Endothelium

Extracellular circulating microRNAs (miRNAs) are currently a focus of interest as non-invasive biomarkers of cardiovascular pathologies, including coronary artery disease (CAD) and acute coronary syndromes (ACS): myocardial infarction with and without ST-segment elevation (STEMI and NSTEMI) and unstable angina (UA). However, the current data for some miRNAs are controversial and inconsistent, probably due to pre-analytical and methodological variances in different studies. In this work, we fulfilled the basic pre-analytical requirements provided for circulating miRNA studies for application to stable CAD and ACS research. We used quantitative PCR to determine the relative plasma levels of eight circulating miRNAs that are potentially associated with atherosclerosis. In a cohort of 136 adult clinic CAD patients and outpatient controls, we found that the plasma levels of miR-21-5p and miR-146a-5p were significantly elevated in ACS patients, and the level of miR-17-5p was decreased in ACS and stable CAD patients compared to both healthy controls and hypertensive patients without CAD. Within the ACS patient group, no differences were found in the plasma levels of these miRNAs between patients with positive and negative troponin, nor were any differences found between STEMI and NSTEMI. Our results indicate that increased plasma levels of miR-146a-5p and miR-21-5p can be considered general ACS circulating biomarkers and that lowered miR-17-5p can be considered a general biomarker of CAD.

Background—Hyponatremia at hospital admission is a well-known risk factor of morbidity and mortality in patients with heart failure (HF). However, there are few data about hyponatremia developing during hospitalization in patients with HF. The present study compares hospital-acquired hyponatremia (HAH) with community-acquired hyponatremia (CAH) in HF patients with respect to outcome. Methods and Results—A total of 5347 consecutive hospitalized patients with a diagnosis of HF were analyzed. CAH was defined as a serum sodium value of ≤135 mEq/L at the time of hospital admission. HAH was defined as development of a serum sodium level of ≤135 mEq/L during hospitalization in the setting of a serum sodium value >135 mEq/L on admission. In-hospital mortality, length of stay, worsening kidney function, and discharge to short-/long-term care facilities were analyzed. CAH and HAH were identified in 1039 patients (19.4%) and in 1302 patients (24.4%) of the 5347 patients admitted, respectively. Both types of hyponatremia were associated with increased mortality, length of stay, rate of discharge to short-/long-term care facilities, and worsening kidney function. In-hospital mortality did not differ between CAH and HAH, but differences in demographics and comorbidities were present. Conclusions—The present results identified HAH as a risk factor for increased mortality in HF as has been previously described for CAH. HAH was associated with increased length of stay, discharge to short-/long-term care facilities, and development of cardio-renal failure. Thus, hyponatremia in hospitalized patients with a diagnosis of HF, either on admission or during hospitalization, is a prognostic marker for poor outcomes.