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Carlos M Ferrario,1 JaNae Joyner,2 Chris Colby,3 Alex Exuzides,3 Michael Moore,2,6 Debra Simmons,2 William Bestermann Jr,4 Feride Frech-Tamas51Department of Surgery, Internal Medicine–Nephrology, Wake Forest University School of Medicine, Winston-Salem, NC, USA; 2Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA; 3ICON Late Phase and Outcomes Research, San Francisco, CA, USA; 4Vascular Medicine Center, Holston Medical Group, Kingsport, TN, USA; 5Department of Health Economics, Daiichi Sankyo, Inc, Parsippany, NJ, USA; 6Danville Regional Medical Center, Danville, VA, USAAbstract: The Global Vascular Risk Management (GVRM) Study is a 5-year prospective observational study of 87,863 patients (61% females) with hypertension and associated cardiovascular risk factors began January 1, 2010. Data are gathered electronically and cardiovascular risk is evaluated using the Consortium for Southeastern Hypertension Control™ (COSEHC™)-11 risk score. Here, we report the results obtained at the completion of 33 months since study initiation. De-identified electronic medical records of enrolled patients were used to compare clinical indicators, antihypertensive medication usage, and COSEHC™ risk scores across sex and diabetic status subgroups. The results from each subgroup, assessed at baseline and at regular follow-up periods, are reported since the project initiation. Inference testing was performed to look for statistically significant differences between goal attainments rates between sexes. At-goal rates for systolic blood pressure (SBP) were improved during the 33 months of the study, with females achieving higher goal rates when compared to males. On the other hand, at-goal control rates for total and low-density lipoprotein (LDL) cholesterol (chol) were better in males compared to females. Diabetic patients had lower at-goal rates for SBP and triglycerides but higher rates for LDL-chol. The LDL-chol at-goal rates were higher for males, while high-density lipoprotein (HDL)-chol rates were higher for females. Utilization of antihypertensive medications was similar during and after the baseline period for both men and women. Patients taking two or more antihypertensive medications had higher mean COSEHC™-11 scores compared to those on monotherapy. With treatment, hypertensive patients can reach SBP and cholesterol goals; however, population-wide improvement in treatment goal adherence continues to be a challenge for physicians. The COSEHC™ GVRM Study shows, however, that continuous monitoring and feedback to physicians of accurate longitudinal data is an effective tool in achieving better control rates of cardiovascular risk factors.Keywords: cardiovascular risk, coronary heart disease, dyslipidemia, electronic medical records, hypertension, metabolic syndrome

Pregnancy is a physiological condition characterized by a progressive increase of the different components of the renin-angiotensin system (RAS). The physiological consequences of the stimulated RAS in normal pregnancy are incompletely understood, and even less understood is the question of how this system may be altered and contribute to the hypertensive disorders of pregnancy. Findings from our group have provided novel insights into how the RAS may contribute to the physiological condition of pregnancy by showing that pregnancy increases the expression of both the vasodilator heptapeptide of the RAS, angiotensin-(1-7) [Ang-(1-7)], and of a newly cloned angiotensin converting enzyme (ACE) homolog, ACE2, that shows high catalytic efficiency for Ang II metabolism to Ang-(1-7). The discovery of ACE2 adds a new dimension to the complexity of the RAS by providing a new arm that may counter-regulate the activity of the vasoconstrictor component, while amplifying the vasodilator component. The studies reviewed in this article demonstrate that Ang-(1-7) increases in plasma and urine of normal pregnant women. In preeclamptic subjects we showed that plasma Ang-(1-7) was suppressed as compared to the levels found in normal pregnancy. In addition, kidney and urinary levels of Ang-(1-7) were increased in pregnant rats coinciding with the enhanced detection and expression of ACE2. These findings support the concept that in normal pregnancy enhanced ACE2 may counteract the elevation in tissue and circulating Ang II by increasing the rate of conversion to Ang-(1-7). These findings provide a basis for the physiological role of Ang-(1-7) and ACE2 during pregnancy.

We previously demonstrated that kidney and urine levels of angiotensin-(1-7) [ANG-(1-7)] were increased in pregnancy. To explore the role of ANG-(1-7) on fluid and electrolyte homeostasis during pregnancy, we evaluated the effect of the ANG-(1-7) antagonist D-alanine-[ANG-(1-7)] (A-779) on kidney function. Virgin and pregnant rats received infusion of vehicle or A-779 (48 [micro]g x [kg.sup.-1] x [h.sup.-1]) for 8 days by osmotic minipumps. Metabolic studies were done on treatment day 7-8. Virgin and pregnant rats at day 15 and 19 were killed, and blood and kidneys were collected. Kidneys were prepared for Western blot analysis for aquaporin-1 (AQP1) and aquaporin-2. In virgin female rats, A-779 increased urine volume and decreased urinary osmolality and AQPI with no change in water intake. In 19-day pregnant rats, A-779 significantly decreased water intake and urine volume and increased urinary osmolality and kidney AQPl expression. Only in late gestation did A-779 treatment decrease the difference between intake and output (balance). A-779 treatment increased plasma vasopressin in late gestation but did not change vasopressin in virgins. In virgin and pregnant animals, A-779 administration had no effect on blood pressure, plasma volume, blood volume, or urinary electrolytes. These results suggest that ANG-(1-7) produces antidiuresis associated with upregulation of AQP1 in virgin rats, whereas ANG-(1-7) produces diuresis in late gestation with downregulation of AQP1. ANG-(1-7) contributes to the enhanced water intake during pregnancy, allowing maintenance of the normal volume-expanded state despite diuresis produced in part by decreased AVP and AQPI. renin-angiotensin system; pregnancy; angiotensin-(1-7); D-alanine[angiotensin-(1-7)]; D-alanine; aquaporin; vasopressin

We recently demonstrated that renin-angiotensin system (RAS) overactivity during late gestation in rats is associated with increased kidney and urine levels of ANG-(1-7) and enhanced kidney immunostaining of ANG-(1-7) and angiotensin-converting enzyme 2 (ACE2). To understand the temporal-spatial changes in normal and hypertensive pregnancies, the renal distribution of ANG-(1-7) and ACE2 in association with kidney angiotensin peptides and ACE2 activity was examined in virgin, normal pregnant (NP; gestational days 5, 15, and 19) and reduced uterine perfusion pressure (RUPP at day 19) pregnant Sprague-Dawley rats. ANG-(1-7) and ACE2 immunocytochemical staining increased 1.8- and 1.9-fold and 1.7- and 1.8-fold, respectively, at days 15 and 19 of NP, compared with virgin rats. ANG-(1-7) and ANG II concentrations were increased in the kidney at 19 days of gestation. ACE2 activity measured using a fluorescent substrate was increased 1.9- and 1.9-fold in the cortex and 1.9- and 1.8-fold in the medulla at days 15 and 19 of NP. In the RUPP animals, ANG-(1-7) immunostaining and concentration were significantly decreased compared with 19-day NP rats. ACE2 activity was unchanged in the cortex and medulla of RUPP rats. In conclusion, during NP, the concurrent changes of ACE2 and ANG-(1-7) suggest that ACE2 plays an important role in regulating the renal levels of ANG-(1-7) at mid to late gestation. However, the decrease in renal ANG-(1-7) content in the absence of a concomitant decrease in ACE2 implicates the participation of other ANG-(1-7) forming or degrading enzymes during hypertensive pregnancy. renin-angiotensin system; pregnancy; reduced uterine perfusion pressure doi:10.1152/ajpregu.00387.2006

Plumb Beach, Brooklyn, New York in USA is an important horseshoe crab breeding and nursery ground that has experienced substantial anthropogenic influence, including pollution, erosion and subsequent restoration. Since little is known about the relationship between sediment microbial communities and juvenile horseshoe crab survival, next generation sequencing was used to characterize and compare the sediment microbiome of three distinct areas of Plumb Beach:- a tidal creek with abundant juveniles, East Beach with moderate number of juveniles, and West Beach- a highly disturbed area where juvenile crabs are rarely seen. The microbiome of juvenile crab intestinal content (both dissected gut content and fecal flush content) from the tidal creek site was also examined. The results showed that in our 2017 survey, the overall dominant sediment orders at all beach sites were Vibrionales (30%), Flavobacteriales (22%) and Alteromonadales (21%). Although alpha diversity was similar among the three beach sites, Bray-Curtis distances assessed by Permanova revealed significant differences in Beta diversity, with a unique microbial assemblage found in the tidal creek. Both crab gut and fecal flush samples did not sequence well, showing low species diversity and very high variability. This study is the first to use next generation sequencing to characterize Plumb Beach sediment microbes and the first attempt to examine the gut microbiome of juvenile horseshoe crabs. This information will contribute to understanding the relationships between sediment microbial assemblages and juvenile crab populations within this important urban habitat. [ABSTRACT FROM AUTHOR]