Plasma Levels of the Cardiotonic Steroid Marinobufagenin in Ischemic Stroke Survivors and Treated Hypertensives: A Pilot Study

Abstract

Background: Numerous studies have demonstrated a strong relationship between circulating levels of marinobufagenin (MBG) and salt-sensitivity. Since salt-sensitive hypertensives have increased plasma levels of MBG and are known to be at a higher risk of having cardiovascular events, stroke and increased mortality, we evaluated the possibility of an association between MBG and ischemic stroke. In this pilot study, we determined plasma MBG levels in patients after surviving an ischemic stroke compared to similar age and gender groups of treated hypertensives and normotensive controls. Methods: We measured plasma MBG levels in a total of 40 participants subdivided into three groups: After an ischemic stroke STR (n = 13), participants with a diagnosis of hypertension receiving blood pressure medication HT (n = 14) and normotensive control subjects CTL (n = 13). We used inferential statistics (parametric or non-parametric) and ordered logistic regression models (unadjusted and adjusted) and all statistical analyses were performed using Stata 14. Results: We did not include a subject from the CTL group because of a diagnosis of glucose-6-phosphate dehydrogenase deficiency and an extreme plasma MBG value of 2,246 pmol/L. Participants’ mean age was 60.4 ± 11.5 years; 56% were male. There was no significant difference between study groups (p > 0.05) for gender, age, and body mass index. HbA1c levels were significantly higher in the STR as compared to the CTL p < 0.05). In the STR group MBG levels were below the normal range (< 200 pmol/L) in three (23%), eight (61%) were in the normal range (200–400 pmol/L), while two (16%) had increased MBG values (> 400 pmol/L). Also, among the STR, the plasma MBG levels did not differ between those receiving and not receiving thrombolytic therapy (p > 0.05). From the 14 HT participants, six (43%) had MBG plasma levels within the normal range, and eight (57%) had high concentrations (> 400 pmol/L). Four (29%) of the treated hypertensives had extreme MBG levels (> 1,000 pmol/L) and normal values of blood pressure. Conclusion: There was no significant elevation of plasma MBG in survivors 24 h or more after an ischemic stroke. The extreme values of plasma MBG in 29% of the treated hypertensives suggests the presence of salt-sensitivity and a possible side effect of a specific combination of medications. Both of these findings contribute new knowledge to the design of studies to define if there is an MBG molecular mechanism underlying the complex associations among salt-sensitivity, hypertension, and ischemic stroke.