Reference ranges for third-trimester maternal cardiovascular function parameters measured in normotensive pregnant women using a non-invasive cardiac output monitor: A study based on data from the prospective PEACH cohort study.

OBJECTIVE: We defined reference ranges for maternal cardiac output, systemic vascular resistance, and stroke volume measured in the third trimester of pregnancy using the Ultrasound Cardiac Output Monitor 1A. DESIGN: Based on data from the prospective PEACH (PreEclampsia, Angiogenesis, Cardiac dysfunction and Hypertension) cohort study. SETTING: Rigshospitalet and Hvidovre Hospital, Denmark. SAMPLE: Normotensive pregnant women aged 18-45 years with singleton pregnancies, enrolled in the PEACH study in 2016-2018. METHODS: We modelled cardiac output, systemic vascular resistance and stroke volume as a function of gestational age using multilevel linear models with fractional polynomials. MAIN OUTCOME MEASURES: Unconditional and conditional reference ranges for cardiovascular parameters measured in gestational weeks 28-40. RESULTS: Our study cohort included 405 healthy pregnant women who contributed 1210 cardiovascular function measurements for analysis. Maximum cardiac output and stroke volume values were measured in gestational weeks 30-32 and decreased over the third trimester, whereas systemic vascular resistance increased during the same period. We created reference ranges for eight combinations of maternal height, age and parity. We also created a simple calculator to allow for implementation of the reference ranges in clinical practice. CONCLUSIONS: Our reference ranges allow the use of a bedside ultrasound device to non-invasively assess cardiac function in pregnancy and identify women at risk of complications. The unconditional ranges allow clinicians to evaluate isolated measurements and identify women needing follow-up. The conditional ranges incorporate information from previous measurements and improve monitoring over time.

Renal Expression and Localization of the Receptor for (Pro)renin and Its Ligands in Rodent Models of Diabetes, Metabolic Syndrome, and Age-Dependent Focal and Segmental Glomerulosclerosis.

The (pro)renin receptor ((P)RR), a versatile protein found in various organs, including the kidney, is implicated in cardiometabolic conditions like diabetes, hypertension, and dyslipidemia, potentially contributing to organ damage. Importantly, changes in (pro)renin/(P)RR system localization during renal injury, a critical information base, remain unexplored. This study investigates the expression and topographic localization of the full length (FL)-(P)RR, its ligands (renin and prorenin), and its target cyclooxygenase-2 and found that they are upregulated in three distinct animal models of renal injury. The protein expression of these targets, initially confined to specific tubular renal cell types in control animals, increases in renal injury models, extending to glomerular cells. (P)RR gene expression correlates with protein changes in a genetic model of focal and segmental glomerulosclerosis. However, in diabetic and high-fat-fed mice, (P)RR mRNA levels contradict FL-(P)RR immunoreactivity. Research on diabetic mice kidneys and human podocytes exposed to diabetic glucose levels suggests that this inconsistency may result from disrupted intracellular (P)RR processing, likely due to increased Munc18-1 interacting protein 3. It follows that changes in FL-(P)RR cellular content mechanisms are specific to renal disease etiology, emphasizing the need for consideration in future studies exploring this receptor's involvement in renal damage of different origins.

Influence of a Decrease in Blood Viscosity on Arterial Pressure in Normotensive and Spontaneously Hypertensive Rats.

We investigated the effect of a decrease in blood viscosity on the mean BP during isovolumic hemodilution and vasodilating activity of the endothelium in normotensive Wistar rats and spontaneously hypertensive rats (SHR). Blood viscosity was reduced by isovolumic hemodilution (replacement of 10% of circulating blood with an equal volume of plasma). Hemodilution caused the same reduction in blood viscosity by 16% in both groups of rats. In Wistar rats, a decrease in blood viscosity did not significantly change in the mean BP; no significant correlations between blood viscosity and mean BP were observed before and after hemodilution. In SHR, a decrease in blood viscosity led to a significant decrease in the mean BP by 18%. Correlations were found between the mean BP and blood viscosity in SHR before (r=0.63; p=0.028) and after (r=0.71; p=0.009) isovolumic hemodilution. In SHR, a decrease in the index of vasodilating activity of the endothelium due to a decrease in the vasodilatory response to intravenous administration of the endothelium-dependent vasodilator acetylcholine was revealed. In SHR, BP passively follows the change, in this case, the decrease in blood viscosity, which attests to impaired BP regulation in response to changes in shear stress on the vascular endothelium caused by the development of endothelial dysfunction in hypertensive animals.

Normotensive placental extracellular vesicles provide long-term protection against hypertension and cardiovascular disease.

BACKGROUND: Women with normotensive pregnancy are at a reduced risk of developing cardiovascular disease postpartum compared with those who experience hypertensive conditions during pregnancy. However, the underlying mechanisms remain poorly understood. During normotensive pregnancy, vast numbers of placental extracellular vesicles are released into the maternal circulation, which protect endothelial cells from activation and alter maternal vascular tone. We hypothesized that placental extracellular vesicles play a mechanistic role in lowering the risk of cardiovascular disease following normotensive pregnancy. OBJECTIVE: This study aimed to investigate the long-term effects of placental extracellular vesicles derived from normotensive term placentae on the cardiovascular system and explore the mechanisms underlying their biological effects. STUDY DESIGN: Spontaneously hypertensive rats were injected with placental extracellular vesicles from normotensive term pregnancies (2 mg/kg each time, n=8) or vehicle control (n=9) at 3 months of age. Blood pressure and cardiac function were regularly monitored from 3 months to 15 months of age. The response of mesenteric resistance arteries to vasoactive substances was investigated to evaluate vascular function. Cardiac remodeling, small artery remodeling, and renal function were investigated to comprehensively assess the impact of placental extracellular vesicles on cardiovascular and renal health. RESULTS: Compared with vehicle-treated control animals, rats treated with normotensive placental extracellular vesicles exhibited a significantly lower increase in blood pressure and improved cardiac function. Furthermore, the vasodilator response to the endothelium-dependent agonist acetylcholine was significantly enhanced in the normotensive placental extracellular vesicle-treated spontaneously hypertensive rats compared with the control. Moreover, treatment with placental extracellular vesicles reduced wall thickening of small renal vessels and attenuated renal fibrosis. CONCLUSION: Placental extracellular vesicles from normotensive term pregnancies have long-lasting protective effects reducing hypertension and mitigating cardiovascular damage in vivo.

A study of post exercise hypotension in normotensive offspring of hypertensives after acute exercise.

Background & objectives: Post exercise hypotension (PEH) is a well-known entity in hypertensive and borderline hypertensive patients. Since the results are inconsistent in normotensives and there is a genetic predisposition of the individuals to hypertension, we hypothesized that PEH is expected to occur in those normotensives who are offspring of hypertensive parents. In this study, we therefore aimed to compare the magnitude of PEH after an acute bout of moderate intensity continuous exercise (MICE) in the offspring of hypertensives vs. offspring of normotensives. Methods: Sixty normotensive participants of both genders (male and female in equal proportion), aged 18-40 yr, were divided into two groups based on their family history of hypertension. The cases (Group 1, n=30) consisted of the normotensives who were offspring of hypertensive parents while the normotensives who were offspring of normotensive parents were taken as the controls (Group 2, n=30). The hypertensive patients were excluded from the study. The individuals underwent a control session (sitting at rest for 5-10 min), followed by a single acute bout of MICE based on the target heart rate (60-70% of maximum heart rate) on a treadmill at the same time of the day (in the morning). The pre- and post-exercise measurements (after 10 min post exercise) of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) were taken in all the participants using mercury sphygmomanometer in sitting position on the left arm. The intergroup and intragroup net effects of exercise on BP were compared with P<0.05 considered significant. Results: The mean SBP was reduced by 5 mmHg than the baseline in the offspring of hypertensives (cases) as compared to the controls after exercise (P=0.01). The fall in mean DBP and MAP was insignificant across both the groups, but the magnitude of PEH measured as delta changes (BP before and after exercise) in SBP (~5 mmHg) and MAP (~4 mmHg) were significantly higher for the cases as compared to the controls (P=0.01). Interpretation & conclusions: PEH occurs in higher magnitude in normotensives who are genetically predisposed to hypertension, such as offspring of hypertensive parents, and may find regular exercise-induced PEH as an important primary preventive tool to prevent or delay the development of hypertension.

Successful treatment of nephrotic syndrome due to pregnancy-related crescentic IgA nephropathy: a case report.

BACKGROUND: Crescentic immunoglobulin A (IgA) nephropathy, defined as > 50% of the glomeruli with crescents, often has a poor renal prognosis. Because of the high prevalence of pre-eclampsia in the second trimester of pregnancy, we often fail to investigate the new onset of glomerulonephritis and the aggravation of subclinical nephropathies. We report a case of nephrotic syndrome suggestive of crescentic IgA nephropathy possibly triggered by pregnancy. CASE PRESENTATION: A 33-year-old multipara was referred for persistent proteinuria, hematuria, and hypoalbuminemia two months postpartum. The patient was diagnosed with proteinuria for the first time at 36 weeks of gestation. The patient was normotensive during pregnancy. Renal biopsy revealed crescentic IgA nephropathy, with cellular crescents in 80% of the glomeruli and no global sclerosis. After treatment with pulse steroids followed by high-dose oral glucocorticoids and tonsillectomy, a gradual improvement was seen in proteinuria, hematuria, and hypoalbuminemia. CONCLUSION: Although the precise mechanism remains unclear, pregnancy possibly triggered the new onset of crescentic IgA nephropathy or the aggravation of subclinical IgA nephropathy.

Health-related quality of life among postpartum women with preeclampsia, southern Ethiopia: a prospective cohort study.

BACKGROUND: Preeclampsia affects the health of the mother and the fetus during pregnancy and childbirth. To date, little is known about the impact of preeclampsia on postpartum health-related to quality of life (HRQoL) in the Sidama region of southern Ethiopia. This study aimed to measure the HRQoL and its contributing factors among postpartum women with preeclampsia in the Sidama region. METHODS: A prospective cohort study was conducted by enrolling pregnant women at ≥20 weeks of gestation up until the 37th week of gestation. We then followed them until 12 weeks after delivery. A locally validated, World Health Organization Quality-of-Life-BREF (WHOQOL-BREF) tool was used to assess participants' HRQoL at two time points; the 6th and 12th weeks postpartum. Assessment of HRQoL of participants was based on total scores on the WHOQoL-BREF. Higher scores on the WHOQoL-BREF reflected a higher HRQoL. Multiple linear regression analyses were performed to evaluate the contributing factors to HRQoL. The level of significance was determined at a p-value of < 0.05. RESULTS: The HRQoL of postpartum women with preeclampsia significantly improved over time from 6 (151 ± 17) to 12 weeks (167 ± 18), p < 0.001). However, the overall HRQoL scores were lower (156 ± 16, p < 0.001) among women with preeclampsia compared to normotensive women (181 ± 21). An experience of early neonatal death was found to have a significant negative effect on the HRQoL of women with preeclampsia [ß = - 2.1, 95% CI: - 3.43- - 0.85] compared to normotensive women who did not have early neonatal death. At 6 weeks of the postpartum period, the physical domain was found to have a significantly higher contribution to the lower HRQoL [ß = 1.04, 95% CI: 0.88-1.12] compared to normotensive women, while other factors were constant. CONCLUSIONS: The HRQoL of women with preeclampsia improved over time from 6 to 12 weeks in the postpartum period. Lower HRQoL was observed among postpartum women with preeclampsia, especially among those who experienced preterm birth or early neonatal death. The effects of preeclampsia on the HRQoL of postpartum women should be considered in redesigning postnatal care intervention services.

Relationship between lipid parameters and vascular mechanical characteristics among a normotensive population without diabetes mellitus residing at the Qinghai-Tibet plateau: a cross-sectional study.

BACKGROUND: There is limited evidence regarding the relationship between lipid parameters and vascular mechanical characteristics in the normotensive population without diabetes mellitus. The aim of this study was to identify an association between lipid parameters and changes in vascular mechanical characteristics between men and women, and in women before and after menopause. METHODS: Six hundred-seventy patients who underwent vascular functional testing and who fulfilled the inclusion and exclusion criteria were enrolled in our cross-sectional study. All participants were from the Qinghai-Tibet Plateau (Luhuo County, Ganzi Tibetan Autonomous Prefecture, Sichuan Province, China; mean altitude: 3860 m). Trained clinical physicians assessed brachial-ankle pulse wave velocity (Ba-PWV) and augmentation index adjusted to a 75-beats-per-minute heart rate (AIx@75). To investigate the relationship between lipid parameters and vascular mechanical characteristics in different sexes and menstrual stages, partial correlation analysis and multiple linear regression were used. RESULTS: The 670 participants comprised 445 women (103 post-menopausal). Mean Ba-PWV and AIx@75 were 1315.56 ± 243.41 cm/s and 25.07% ± 15.84%, respectively. Men had greater Ba-PWV values compared with women (1341.61 ± 244.28 vs 1302.39 ± 242.17 cm/s, respectively; P < 0.05), while AIx@75 values were higher in women compared with men (27.83% ± 15.85% vs 19.64% ± 14.40%, respectively; p < 0.001). In the partial correlation analysis adjusted for age, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (HDL-C) were associated with Ba-PWV in both men and women (p < 0.05); however, the magnitude was larger in men. Statistical significance was not seen for AIx@75 among both men and women. Multiple linear regression analysis revealed that TC (ß = 0.165, p = 0.024) and non-HDL-C (ß = 0.151, p = 0.042) remained independent predictors of change in Ba-PWV in men after adjusting for age, mean arterial pressure, waist circumference, hemoglobin, platelet count, fasting blood glucose, estimated glomerular filtration rate, and uric acid. After adjusting for traditional cardiovascular risk factors, pre-menopausal women had a similar association to that of men between LDL-C (ß = 0.126, p = 0.030), non-HDL-C (ß = 0.144, p = 0.013), TC/HDL-C (ß = 0.162, p = 0.005), LDL-C/HDL-C (ß = 0.142, p = 0.013) and Ba-PWV; however, post-menopausal women had no association between the lipid parameters and vascular function. CONCLUSIONS: Overall, TC and non-HDL-C were independent associated factors for vascular compliance alterations evaluated through Ba-PWV in normotensive men. In pre-menopausal women, LDL-C, non-HDL-C, TC/HDL-C and LDL-C/HDL-C were independent associated factors for vascular compliance alterations. After controlling for traditional risk factors, lipid profiles were not associated with these metrics for AIx@75, which can measure the amplification of reflex flow, because of the high number of confounding factors that do not genuinely reflect changes in vascular characteristics. Lipid factors did not appear to be linked to vascular function in post-menopausal women.

Prehospital Lactate is Associated with the Need for Blood in Trauma.

Background: Traumatic hemorrhage is the leading cause of preventable death, and its effects are often evident within the first 24 hours of hospital admission. We investigated the relationship between prehospital lactate measurement and administration of hospital blood products and life-saving interventions (LSIs) within 24 hours of hospital admission.Methods: We included trauma patients with recorded prehospital venous lactate transported by a single critical care transport service to a Level I trauma center between 2012 and 2019. We abstracted vital signs, mission type, anatomic location of injury, prehospital administration of crystalloid and blood products, and hospital LSIs started within 24 hours of admission. We used logistic regression to determine the association of prehospital lactate and in-hospital administration of blood products in groups with or without hypotensive patients. We investigated the effect of prehospital lactate concentration on secondary outcomes such as LSIs and mortality.Results: We included 2,170 patients transported from the scene or emergency department (ED), of whom 1,821 (84%) were normotensive. The median concentration of prehospital lactate was 2.10 mmol/L for the main population (IQR = 1.40-3.30) and 2.00 mmol/L for the normotensive subgroup (IQR = 1.30-2.90). A higher prehospital lactate concentration was associated with higher odds of needing early hospital blood products in the whole study population (OR = 1.12, (95% CI 1.06-1.20), p < 0.01) and in the normotensive subgroup (OR = 1.13, (95% CI 1.03-1.22), p = 0.01). These positive associations were also observed with the secondary outcome of hospital LSIs, and higher prehospital lactate was also associated with higher odds of mortality (OR = 1.32, (95% CI 1.20-1.45), p < 0.01).Conclusions: Higher concentrations of prehospital lactate were associated with the need for in-hospital blood transfusion within 24 hours of admission. The relationship between lactate and blood transfusion persisted among normotensive patients. Further work is needed to incorporate prehospital lactate into decision support tools for prehospital blood administration.

Utility of ambulatory blood pressure monitoring in detection of masked hypertension and risk of hypertension mediated organ damage in normotensive patients with type 2 diabetes mellitus.

PURPOSE: In patients with diabetes, unrecognised hypertension is a serious problem risk factor for the development and progression of chronic complications. The study aimed to determine the prevalence of masked hypertension in normotensive diabetic patients, the factors affecting it, and its association with diabetes complications using ambulatory blood pressure monitoring (ABPM). MATERIALS AND METHODS: A cross-sectional observational study was conducted on 150 normotensive diabetic patients. Patients were subjected to an interview and clinical examination to record demographic data, epidemiological data, and significant past history. ABPM was performed for each patient. Urine samples, echocardiogram, and ophthalmologic fundoscopy were done to check for diabetes-related complications. RESULTS: The mean age of all participants was 56.7 ± 7.8 years. A total of 93 patients (62%) were males. 99 (66%) patients had masked hypertension. A total of 85 (56.7%) were non-dippers, 49 (32.7%) were dippers, 1 (0.7%) was extreme dipper and 15 (10%) were reverse dippers. Non-dipping and reverse dipping were associated with concentric left ventricular hypertrophy LVH (p < .001). Masked hypertension was associated with concentric LVH (p = .001) and nephropathy (p =.008) whereas, nocturnal hypertension was associated with concentric LVH (p = .001) and nephropathy (p =.003). CONCLUSIONS: A single office blood pressure (BP) reading cannot rule out hypertension in patients with diabetes. Regardless of hypertension, clinicians should have all patients, especially patients with diabetes, undergo ABPM at least once. Masked hypertension, changes in nocturnal dipping and other phenomena that raise the risk of diabetes complications but cannot be measured by office BP can be measured by ABPM, and thus ABPM can provide a good prognostic benefit.

High prevalence of vitamin D deficiency among normotensive and hypertensive pregnant women in Ghana.

BACKGROUND: Hypovitaminosis D in pregnancy is associated with adverse health outcomes in mothers, newborns and infants. This study assessed the levels of 25-hydroxyvitamin D [25(OH)D] in normotensive pregnancies and in preeclampsia, evaluated the association between vitamin D deficiency and preeclampsia risk; and determined the foeto-maternal outcome in preeclamptic women with vitamin D deficiency. METHODS: This case-control study was conducted among pregnant women who visited the Comboni Hospital, in Ghana from January 2017 to May 2018 for antenatal care. A total of 180 pregnant women comprising 88 preeclamptic women (PE) and 92 healthy normotensive pregnant women (NP) were recruited. Socio-demographic, clinical and obstetric data were obtained using validated questionnaires. Blood pressure and anthropometrics were measured, and blood samples were collected for the estimation of 25- hydroxyvitamin D [25(OH)D] using enzyme-linked immunosorbent assay technique. Lipids (total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol) were also estimated. RESULTS: A total of 81.7% of the study participants had vitamin D deficiency. Of these, 88.6% of the women with PE had vitamin D deficiency compared to 75.0% in the NP. Vitamin D levels were significantly reduced in the PE women compared to the normotensive pregnant women (p = 0.001). A higher proportion of the preeclamptic women who were vitamin D deficient had preterm delivery (p < 0:0001) and delivered low birth weight infants (p < 0:0001), and infants with IUGR (p < 0:0001) compared to the control group (p < 0:0001). Pregnant women with PE presented with significant dyslipidemia, evidenced by significantly elevated TC (p = 0.008), LDL (p < 0.0001), triglycerides (p = 0.017) and a significantly reduced HDL (p = 0.001) as compared to NP. In the preeclamptic women, serum 25(OH) D showed an inverse, but not significant association with TC (ß = - 0.043, p = 0.722, TG (ß = - 0.144, p = 0.210) and LDL (ß = - 0.076, p = 0.524) and a positive, but not significant association with HDL (ß = 0.171, p = 0.156). CONCLUSION: The prevalence of vitamin D deficiency is high in both normotensive pregnancies and pregnancies complicated by preeclampsia but amplified in preeclampsia. Higher proportion of pregnant women with hypovitaminosis D had preterm babies and delivered low birth weight neonates. Additional studies are needed to explore the potential benefits and optimal dosing of vitamin D use in pregnancy, especially in sub-Saharan Africa.

Is salt intake reduction a universal intervention for both normotensive and hypertensive people: a case from Iran STEPS survey 2016.

PURPOSE: There is a direct association between salt intake and blood pressure (BP), one of the main risk factors for CVDs. However, yet there has been a debate that how strong is this association in people with and without hypertension. This study was conducted to evaluate the magnitude of the association between salt intake and BP in hypertensive and normotensive population among a nationally representative population. METHODS: The study was conducted on a nationally representative sample of 18,635 Iranian adults aged 25 years and older who participated in the STEPS survey 2016 and provided urine sample. Salt intake was estimated through spot urine sample and Tanaka equation. Multiple linear regression model in survey data analysis was used to assess the independent effect of salt intake on BP. RESULTS: After adjusting for covariates, there was a significant association between salt intake and SBP in hypertensive (p < 0.001) and normotensive people (p < 0.001). In hypertensive people, with 1 g of increase in salt intake, the SBP and DBP increased 0.37 mmHg and 0.07 mmHg, respectively. Whereas in normotensive people, with 1 g of increase in salt intake, the SBP and DBP increased 0.26 mmHg and 0.05 mmHg, respectively. Moreover, there was a significant trend toward an increase of SBP across salt intake quartiles in both hypertensive (p < 0.001) and normotensive people (p = 0.002), though the slope was steeper in hypertensive than in normotensive people. CONCLUSIONS: The present study demonstrated that salt intake significantly increased SBP in both hypertensive and normotensive people, though the magnitude of this increase was greater in hypertensive people as compared with normotensive people.

The relationship between diurnal blood pressure abnormalities and target organ damage in normotensive subjects. Which is more important? Increased blood pressure levels or circadian blood pressure abnormalities.

Objective: Circadian blood pressure (CBP) abnormalities are well-known risk factors for many diseases such as cardiovascular, cerebrovascular, and chronic kidney disease. The object of this study was to evaluate the relationship between abnormalities in CBP rhythm and target organ damage (TOD) in normotensive non-dipper (non-DP) subjects.Methods: The 24-h ambulatory BP monitoring (ABPM) and echocardiography were performed and urinary albumin excretion (UAE) was measured in 127 normotensive dipper (DP) (42 males, 85 females) and 337 (89 males, 248 females) normotensive non-DP subjects.Results: When we compared DP and non-DP subjects; Pulse wave velocity (PWV) (7.12 ± 1.72 vs 7.57 ± 1.87 m/s, p = 0.02), the percentile of corrected PWV (cPWV) (7.1 vs. 20.2, p= 0.001) and the percentile of corrected augmentation index (cAIx) (23.5 vs. 33.9, p = 0.03), left ventricle mass index (LVMI) (78.00 ± 23.27 vs. 95.59 ± 18.29 g/m2, p = 0.01), relative wall thickness (RWT)(0.36 ± 0.13 vs 0.46 ± 0.09, p = 0.01), percentile of proteinuria (8.6 vs 29.2%, p = 0.00) were higher in non-DP group. In the correlation analyses, the PWV, LVMI, RWT were negatively correlated with the rate of systolic fall in nighttime (%)(-0.15, p = 0.01 vs. -0.23, p = 0.02 vs. -0.27, p = 0.00). It was observed that cPWV, cAIx, and UAE were independently associated with age and non-DP status (NDS), in logistic regression analysis.Conclusions: Our results suggested that normotensive persons with CBP abnormalities had TOD. In light of the data of this article, non-dipper status is detected in the early period and if the provision of diurnal blood pressure rhythm may reduce the incidence of future adverse events in nondipper normotensive subjects.

Arterial Hypertension and Plasma Glucose Modulate the Vasoactive Effects of Nitroso-Sulfide Coupled Signaling in Human Intrarenal Arteries.

We have investigated the vasoactive effects of the coupled nitro-sulfide signaling pathway in lobar arteries (LAs) isolated from the nephrectomized kidneys of cancer patients: normotensive patients (NT) and patients with arterial hypertension (AH). LAs of patients with AH revealed endothelial dysfunction, which was associated with an increased response to the exogenous NO donor, nitrosoglutathione (GSNO). The interaction of GSNO with the H2S donor triggered a specific vasoactive response. Unlike in normotensive patients, in patients with AH, the starting and returning of the vasorelaxation induced by the end-products of the H2S-GSNO interaction (S/GSNO) was significantly faster, however, without the potentiation of the maximum. Moreover, increasing glycemia shortened the time required to reach 50% of the maximum vasorelaxant response induced by S/GSNO products so modulating their final effect. Moreover, we found out that, unlike K+ channel activation, cGMP pathway and HNO as probable mediator could be involved in mechanisms of S/GSNO action. For the first time, we demonstrated the expression of genes coding H2S-producing enzymes in perivascular adipose tissue and we showed the localization of these enzymes in LAs of normotensive patients and in patients with AH. Our study confirmed that the heterogeneity of specific nitroso-sulfide vasoactive signaling exists depending on the occurrence of hypertension associated with increased plasma glucose level. Endogenous H2S and the end-products of the H2S-GSNO interaction could represent prospective pharmacological targets to modulate the vasoactive properties of human intrarenal arteries.

CA125 levels in pregnancy: A case-control study amongst pregnant women in Aminu Kano teaching hospital, North-West Nigeria.

BACKGROUND: Induction of inflammatory response within the placenta in patients with pre-eclampsia triggers the expression of CA125, thus making CA125 a potential marker reflecting the severity of preeclampsia. OBJECTIVE: The study was aimed to assess and compare CA125 levels in pre-eclamptics and normotensives. SUBJECTS AND METHODS: A case-control design was used to study 83 each of the selected pre-eclamptics and normotensives women using a systematic sampling technique. Data were collected using interviewer-administered questionnaire; blood and urine samples were also collected and analysed in the laboratory. Data were summarised using frequencies, percentages, mean ± standard deviation (SD) or median, and range as appropriate. Inferential statistical measures were used to determine the relationship between the outcome and independent variables with a P value set to be statistically significant at ≤0.05. RESULTS: The ages of the pre-eclamptics and normotensives women were found to have a mean ± SD of 29.46 ± 6.92 and 29.70 ± 6.90 years, respectively. More than half 58 (69.9%) of the cases had proteinuria of 3+ (300 mg/dL). Significant difference was statistically (P < 0.01) found in mean serum CA125 levels between women with mild and severe pre-eclampsia with CA125 being more likely to be higher (>50 IU/mL) in severe pre-eclampsia than in mild pre-eclampsia. CONCLUSION: The study has shown that serum CA125 is elevated in pre-eclamptic pregnancies compared to normotensive pregnancies and the possibility of CA125 being a biomarker of severity and hence may provide information to make an informed choice in early-onset pre-eclampsia to consider conservative management and thus improve perinatal outcome.

Classifications of scleroderma renal crisis and reconsideration of its pathophysiology.

Categorization of scleroderma renal crisis (SRC) as hypertensive or normotensive can potentially overlook the underlying pathophysiology that might be unique in each patient, as they often exhibit a mixture of distinct pathological characteristics of narrowly defined SRC (nd-SRC) and systemic sclerosis associated thrombocytic micro-angiopathy (SSc-TMA). In this review, we provide evidence suggesting that better categorization of patients presenting with certain clinical features of both nd-SRC and TMA will improve treatment approaches. Based on our clinical experience and literature review, distinguishing between nd-SRC and SSc-TMA is important because the association of SSc-TMA with prior steroid administration and poor prognosis was stronger than that of nd-SRC. Although the two pathological entities cannot be easily distinguished based on blood pressure, we suggest that the detailed clinical course is helpful. Typically, nd-SRC exhibits prominently elevated blood pressure and worsening of renal function initially, followed by mild thrombocytopenia. Conversely, SSc-TMA presents first with severe thrombocytopenia, followed by elevated blood pressure and renal function deterioration. The degree of involvement in each pathological condition should be considered for determination of appropriate therapeutic interventions and prognostic prediction.

Dysglycemia and increased left ventricle mass in normotensive patients admitted with a first myocardial infarction: prognostic implications of dysglycemia during 14 years of follow-up.

BACKGROUND: Left ventricle mass (LVM) can be influenced by various conditions including hypertension and/or inherent cardiomyopathies. Dysglycemia is also thought to exert an anabolic effect on heart tissue by hyperinsulinemia and thereby promoting increased LVM. The primary aim of this study was to assess the influence of dysglycemia on LVM evaluated by an oral glucose tolerance test (OGTT) in patients admitted with a first myocardial infarction (MI) without hypertension. The secondary aim was to assess the impact of dysglycemia on major adverse cardiovascular events (MACE) and all-cause mortality during long-term follow-up. METHODS: Patients admitted with a first MI without known history of hypertension were included. All patients without previously known type 2 diabetes mellitus (T2DM) had a standardized 2-hour OGTT performed and were categorized as: normal glucose tolerance (NGT), impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) and newly detected T2DM (new T2DM). LVM was measured by echocardiography using Devereaux formula and indexed by body surface area. Multivariate linear regression analysis was used to assess the impact of confounders (dysglycemia by OGTT, known T2DM, age, sex and type of MI) on LVM. Cox proportional hazard model was used to assess the impact of dysglycemia on all-cause mortality and a composite endpoint of MACE (all-cause mortality, MI, revascularisation due to stable angina, coronary artery bypass graft, ischemic stroke or hemorrhagic stroke). RESULTS: Two-hundred-and-five patients were included and followed up to 14 years. In multivariate regression analysis, LVM was only significantly increased in patients categorized as new T2DM (ß = 25.3; 95% CI [7.5-43.0]) and known T2DM (ß = 37.3; 95% CI [10.0-64.5]) compared to patients with NGT. Patients with new T2DM showed higher rates of MACE and all-cause mortality compared to patients with IFG/IGT and NGT; however no significantly increased hazard ratio was detected. CONCLUSIONS: Dysglycemia is associated with increasing LVM in normotensive patients with a first acute myocardial infarction and the strongest association was observed in patients with new T2DM and patients with known T2DM. Dysglycemia in normotensive patients with a first MI is not an independent predictor of neither MACE nor all-cause mortality during long-term follow-up compared to normotensive patients without dysglycemia.

Altered expression of vascular endothelial growth factor, vascular endothelial growth factor receptor-1, vascular endothelial growth factor receptor-2, and Soluble Fms-like Tyrosine Kinase-1 in peripheral blood mononuclear cells from normal and preeclamptic pregnancies.

Preeclampsia (PE) is the leading cause of maternal and fetal morbidity and mortality. It complicates around 2%-10% pregnancies worldwide due to imbalance between proangiogenic and anti-angiogenic factors, leading to incomplete placentation, ischemia, and endothelial dysfunction. The study was aimed to analyze the mRNA expression of vascular endothelial growth factor (VEGF) and its receptors, i.e., VEGF receptor-1 (VEGFR-1), VEGF receptor-2 (VEGFR-2), and soluble Fms-like tyrosine kinase-1 (sFlt-1) from maternal peripheral blood mononuclear cells (PBMCs) of PE patients. This was a cross-sectional comparative study comprising 18 normotensive and 18 PE patients; the patients were further divided as early-onset preeclampsia (EOP) and late-onset preeclampsia (LOP). The expression level of VEGF, its receptors (VEGFR-1 and VEGFR-2), and sFlt-1 was investigated using real-time polymerase chain reaction. There was a significant change in the mRNA expression with a decrease in VEGF, VEGFR-1, and VEGFR-2 and an increase in sFlt-1 in PBMCs of PE and normal pregnancies (P < 0.001). sFlt-1 mRNA expression was increased by 2.95-fold in the PE group with an inverse correlation with expression of VEGFR-2 (Spearman's rho = 0.68). Based on these findings, we conclude that PE is associated with decrease in the mRNA expression of VEGF, VEGFR-1, and VEGFR-2 as compared to an increase in sFlt-1 in PBMCs.

The influence of angiotensin I-converting enzyme (ACE) I/D gene polymorphism on cardiovascular and muscular adaptations following 8 weeks of isometric handgrip training (IHG) in untrained normotensive males.

We examined the association between the angiotensin I-converting enzyme (ACE) I/D gene polymorphism and isometric handgrip (IHG) training on cardiovascular and muscular responses among normotensive males. Thirty (II = 10, ID = 10, and DD = 10) normotensive untrained males underwent IHG training at 30% of their maximal voluntary contraction 3 days per week for 8 weeks. Cardiovascular and muscular variables were measured before IHG, after a session of IHG and after 8 weeks of IHG. No significant interaction effect was found between ACE I/D genotype and IHG training session on all dependent variables (all p > 0.05). There was a significant main effect of IHG training session on systolic blood pressure (SBP) (p = 0.002), mean arterial pressure (MAP) (p = 0.015) and handgrip strength (HGS) (p = 0.001) scores, while no difference in diastolic blood pressure (DBP), pulse pressure, or heart rate scores was found. A greater improvement in cardiovascular parameters following 8 weeks of IHG training was observed in participants with the D allele than the I allele (SBP reduction: ID+DD genotype group (-5.53 ± 6.2 mmHg) vs. II genotype group (-1.52 ± 5.3 mmHg)); MAP reduction: ID + DD genotype group (-2.80 ± 4.5 mmHg) vs. II genotype group (-1.45 ± 3.5 mmHg). Eight weeks of IHG training improved cardiovascular and muscular performances of normotensive men. Reduction in SBP and MAP scores in D allele carriers compared to I allele carriers indicates that the ACE I/D polymorphism may have an influence on IHG training adaptation in a normotensive population.

The influence of uric acid level on erythrocyte morphology in normotensive patients.

OBJECTIVE: Introduction: Hyperuricemia is an independent risk factor for high-normal blood pressure (BP) both in men and women. The effect of uric acid (UA) on erythrocyte morphology in normotensive patients needs further study. The aim - to evaluate the impact of serum UA level on erythrocyte morphology in normotensive patients. PATIENTS AND METHODS: Materials and methods: Patients were divided into two group according to the UA level: the first group - 38 patients with UA level < 400 mcmol/L; the second group - 42 patients with UA level ≥ 400 mcmol/L. Studies on erythrocyte morphology were conducted using cytological analysis and scanning electron microscopy. RESULTS: Results: Patients of the 1st group had poikilocytosis level of 4,6%, while type I echinocytes were 3,2%, type II echinocytes - 1,1%, stomatocytes - 1,3%. In the 2nd group, poikilocytosis exceeding 5% was observed in 12 patients with mean values of altered shapes of 12,8±1,2%. In the 2nd group, type I echinocytes was 6,2% (9,4±0,9%) more, type II echinocytes - 1,3% (2,4±0,5%) more, stomatocytes - 0,3% (1,0±0,2%) more. In the study correlation between UA and poikilocytosis was found: in the 1st group - r = +0,21 and in the second group - r = +0,42. In the 1st group, correlation between UA and BP was moderate for SBP - r = +0,34 and weak for DBP - r = +0,29; in the 2nd group: SBP - r = +0,49 and r = +0,35 for DBP. CONCLUSION: Conclusions: Direct correlation between uric acid level and poikilocytosis level becomes more intensive when uric acid level exceeds ≥ 400 mcmol/L.