Microcirculation and Macrocirculation in Hypertension: A Dangerous Cross-Link?

Microcirculation and macrocirculation are tightly interconnected into a dangerous cross-link in hypertension. Small artery damage includes functional (vasoconstriction, impaired vasodilatation) and structural abnormalities (mostly inward eutrophic remodeling). These abnormalities are major determinants of the increase in total peripheral resistance and mean blood pressure (BP) in primary hypertension, which in the long term induces large artery stiffening. In turn, large artery stiffening increases central systolic and pulse pressures, which are further augmented by wave reflection in response to the structural alterations in small resistance arteries. Finally, transmission of high BP and flow pulsatility to small resistance arteries further induces functional and structural abnormalities, thus leading to increased total peripheral resistance and mean BP, thus perpetuating the vicious circle. Hyperpulsatility, in addition to higher mean BP, exaggerates cardiac, brain, and kidney damages and leads to cardiovascular, cerebral, and renal complications. The dangerous cross-link between micro and macrocirculation can be reversed into a virtuous one by ACE (angiotensin-converting enzyme) inhibitors, sartans, and calcium channel blockers. These three pharmacological classes are more potent than β-blockers and diuretics for reducing arterial stiffness and small artery remodeling. The same ranking was observed for their effectiveness at reducing left ventricular hypertrophy, preserving glomerular filtration rate, and preventing dementia, suggesting that they can act beyond brachial BP reduction, by breaking the micro/macrocirculation vicious circle.

The role of maternal echocardiography and uterine artery Doppler at 11-14 weeks in the prediction of pre-eclampsia in nulliparous women

Background: Pre-eclampsia (PE) complicates 2% of pregnancies and may have serious effects on mother and child, which makes it an important threat to public health in both developed and developing countries. Once high-risk women are identified, they can be targeted for more intense prenatal surveillance and preventative measures. Predicting PE in the first trimester requires the use of maternal echocardiography and the uterine artery pulsatility index (UAPI). Objective of the study was to see whether maternal echocardiography and uterine artery Doppler at 11-14 weeks can predict subsequent development of PE in nulliparous women.Methods: This prospective observational cohort study was carried out in outdoor patients of obstetrics and gynecology of Bangabandhu Sheikh Mujib Medical University (BSMMU), with collaboration with department of cardiology, National Institute of Nuclear Medicine and Allied Sciences (NINMAS), BSMMU, Dhaka, during 01 December 2013 to July 2015. A total of 135 healthy nulliparous women at 11-14 weeks of gestation were included in this study. Data was processed and analyzed by statistical package for the social sciences (SPSS) version 24.0.Results: Among 135 patients, two (1.5%) patients developed preeclampsia during 1st follow-up (20-28 weeks) and four (2.9%) patients developed preeclampsia during (29-36 weeks). Mean total peripheral resistance was found to be 1332.0±75.2 dynes/sec/cm5 in preeclampsia and 1157.0±139.2 dynes/sec/cm5 in non preeclamptic pregnancy. The difference between two groups was statistically significant. MAP and total peripheral resistance were statistically significant (p<0.05) between two groups.Conclusions: In first trimester of pregnancy UAPI is the best predictor for detection of PE.

Abstract MP19: Endogenous 5-hydroxytryptamine May Regulate Skeletal Muscle Vascular Resistance In Normal Healthy Rats

Infusing low doses of 5-hydroxytryptamine (5-HT) into normal rats causes chronic (weeks to months) hypotension and a fall in total peripheral resistance. These effects are mediated by activation of 5-HT 7 receptors. Therefore, we generated 5-HT 7 receptor knockout rats (5-HT 7 KO) to explore possible cardiovascular effects of 5-HT 7 receptors under normal and pathophysiological conditions. We previously reported that healthy 5-HT 7 KO rats have normal blood pressure and total peripheral resistance at rest. This suggested that 5-HT 7 receptors plays no role in cardiovascular regulation under normal conditions. But total peripheral resistance is determined by multiple vascular beds that differ in their sensitivity to 5-HT. Others have indicated that 5-HT 7 receptors in the skeletal muscle vasculature are particularly sensitive to the effects of 5-HT. Therefore, we hypothesized that 5-HT 7 KO rats would show both reduced responsiveness to exogenous 5-HT and increased resting skeletal muscle vascular resistance. Experiments were performed in isoflurane-anesthetized, male Sprague-Dawley (SD) (n=6), 5-HT 7 wild-type (5-HT 7 WT) (n=5) and 5-HT 7 KO (n=6) rats at 7-8 months of age. Arterial pressure was measured with an aortic catheter. Blood flow to the hindquarters (mostly skeletal muscle) was measured with transit-time, ultrasound flowmetry. After 10 minutes of baseline hemodynamic measurements were obtained, 5-HT was infused iv at a rate of 25 μg/kg/min for 15 minutes, followed by a 15-minute recovery period. As expected, 5-HT 7 KO rats did not show a significant fall in hindquarter vascular resistance (HQVR) during 5-HT infusion, while SD and 5-HT 7 WT did. More importantly, HQVR at baseline was significantly (p < 0.05) higher in 5-HT 7 KO rats (16.0 ± 2.0 mmHg/ml/min) than in 5-HT 7 WT rats (10.9 ± 0.06 mmHg/ml/min) or SD rats (7.0 ± 0.03 mmHg/ml/min). These results support our hypothesis that in healthy (albeit anesthetized) rats, 5-HT 7 receptors reduce skeletal muscle vascular resistance.

THE SYSTEMIC CIRCULATION IN MEN UNDER 60 YEARS OF OLD WITH MYOCARDIAL INFARCTION AND ACUTE KIDNEY INJURY

Relevance. Hemodynamics changes in myocardial infarction complicated by acute kidney injury are interpreted in different ways. Aim. To evaluate peripheral hemodynamics changes in men under 60 years old with myocardial infarction complicated by acute kidney injury to improve prevention and outcomes. Material and methods. The study included men 19-60 years old with type I myocardial infarction. The patients were divided into two age-comparable groups: I - study group, with acute kidney injury - 25 patients; II - control, without it - 486 patients. A comparative assessment of circulation indices changes in first 48 hours (1) and the end of third week disease (2), their dynamics, also acute kidney injury development risk analysis (ANOVA) were performed. Results. The study group differed from the control group in lower values of heart rate1 (66.3±12.2 and 75.8±18.8 (bpm), respectively; p=0.003) and higher - arterial pressure, systolic1 (155.6±24.0 and 139.5±28.9 (mm Hg); p=0.006), diastolic1 (98.0 ± 16.0 and 86.6 ± 18.9 (mm Hg); p = 0.002), mean1 (117.2±17.6 and 104.3±21.3 (mm Hg); p=0.001). In the study group compared in the control group, there was a greater decrease in blood pressure (mean: -18.3 and -8.3%, respectively) and total peripheral resistance (-33.5 and -26.3%) (p<0.0001). The risk markers of the acute kidney injury development were the mean arterial pressure1≥106.7, systolic1≥140.0, diastolic1≥90.0 (mm Hg) and heart rate1˂66 bpm. Conclusions. Men under 60 years old with acute kidney injury in myocardial infarction are characterized by arterial hypertension and bradycardia in the first hours of the disease, as well as more pronounced decline dynamics of blood pressure and total peripheral resistance at the end of its subacute period. The listed above values of the circulation parameters should be used in the high-risk groups for the acute kidney injury development formation, as well as prognostic modeling.

P–779 Vascular stiffness in children born after embryo transfer at 8–9 years of age

Study question Do 8–9-year-old singletons conceived after frozen (FET) or fresh embryo transfer (Fresh ET) have increased vascular stiffness compared to naturally conceived (NC) children? Summary answer FET and Fresh ET was not associated with increased vascular stiffness or altered cardiovascular autonomic reflexes as compared to NC children. What is known already Normally, vascular stiffness increases during childhood, and in adults with the metabolic syndrome increased vascular stiffness is associated with symptomatic cardiovascular disease. Children conceived after FET and Fresh ET are at risk of being large- and small-for-gestational-age, respectively. Epigenetic modulation during assisted reproductive technologies (ART) has been suggested to influence cardiovascular risk factors, and previous studies have shown that children conceived after ART are at increased risk of insulin resistance, endothelial dysfunction and increased arterial blood pressure. It is not known if ART procedures alter vascular stiffness of children. Study design, size, duration In a cohort study including 8–9 years old singletons conceived after FET, Fresh ET and NC (50 in each group), we used cardiac magnetic resonance imaging (CMR) and cardiovascular autonomic reflex testing (CART) to compare arterial stiffness. The study was powered to detect a difference between groups of aortic distensibility from 8.9 to 8.0, comparable to what is seen in a 5-year older cohort of children (beta 0.80, alpha 0.05). Inclusion period 18 months. Participants/materials, setting, methods Singletons were identified through the Danish IVF Registry and the Medical Birth Registry. NC children were matched by sex and birth year with FET children. Exclusion criteria were congenital heart disease, maternal preeclampsia, gestational diabetes or diabetes mellitus. Artery stiffness was assessed from blood pressure and aortic distensibility, pulse wave velocity (PWV), cardiac output and total peripheral resistance by CMR. CART was investigated non-invasively in 40 children. Measurements were performed blinded to the child group. Main results and the role of chance Maternal age at delivery was higher in the FET (42.5±5.5 years) and Fresh ET (40.5±6.1 years) compared to the NC group (38.2±5.7 years). In the ART groups, mothers were more likely to have a high educational level (FET 50% and Fresh ET 56.2%) compared to mothers in the NC group (30.6%) (both ANOVA-p&lt;0.05). As expected, children conceived after FET had a higher birth weight standard-deviation-score (0.4±1.1+) compared to Fresh ET (–0.1±1.0) and NC (–0.2±1.1). Among study groups, no significant differences were observed in systolic and diastolic blood pressure (FET 109±6/64±6 mmHg; Fresh ET 109±7/65±5 mmHg; NC 108±8/65±5 mmHg; ANOVA-p&gt;0.05). Heart rate was also similar in all study groups (FET 79±12 bpm; Fresh ET 79±9 bpm; NC 78±11 bpm; ANOVA-p&gt;0.05). No significant differences were observed between groups in total aortic PWV (FET 3.69±0.75 m/s; Fresh ET 3.49±0.31 m/s; NC 3.59±0.61 m/s; ANOVA-p&gt;0.05). Aorta ascendens distensibility was similar in study groups (FET 11.12±3.55 10–3mmHg–1; Fresh ET 11.77±2.97 10–3mmHg–1; NC 11.43±2.82 10–3mmHg–1, ANOVA-p&gt; 0.05). Furthermore, distensibility of aorta descendens and aorta abdominalis, PWV of arcus aorta and PWV from aorta descendens to abdominalis, cardiac output, total peripheral resistance and CART were similar in study groups. Outcome variables remained non-significant after adjustment for potential confounders. Limitations, reasons for caution The participation rate was higher in the ART groups (FET 40% and Fresh ET 32%) compared to NC (17%) and hence a selection bias is possible. Data from CART should be interpreted cautiously due to lower number of participating children in these tests. Wider implications of the findings: Our study did not find any associations between FET or Fresh ET compared to NC children and arterial stiffness. Nor, any associations to CART could be made. Further studies are needed in younger adults to better exclude important long-term effects of ART. Trial registration number NCT03719703

PERIPHERAL HEMODYNAMICS PECULIARITIES IN YOUNG AND MIDDLE-AGED MEN WITH A RECIDIVATING MYOCARDIAL INFARCTION

Relevance. Hemodynamics changes in recidivating myocardial infarction and early postinfarction angina are not well understood. In recent years, the frequency of these complications has been increasing. Aim. To evaluate peripheral hemodynamics changes in men under 60 years old with recurrent myocardial infarction and early postinfarction angina to improve prevention and outcomes. Material and methods. The study included men aged 19-60 years old with type I myocardial infarction. Patients are divided into two age-comparable groups: I - the study group, with recurrent myocardial infarction - 102 patients; II - control, without it - 541 patients. A comparative assessment of hemodynamics changes in first 48 hours (1) and the end of third week disease (2), also risk analysis of recurrent ischemia and poor outcome in selected groups were performed. Results. The study group was distinguished by a high level of total peripheral resistance1 (2055.5±965.2 (dyn×sec×cm-5)) from the control (2055.5± 965.2 (dyn×sec×cm-5); p=0.02). In both groups, a decrease in the values of all indicators was noted (p<0.05). A more pronounced decrease in total peripheral resistance was found in the study group, and in the parameters of blood pressure and heart rate - in the control group. The values of total peripheral resistance1 ≥1600 dyne×sec×cm-5 were the markers of the risk of ischemia recurrence. Predictors of poor outcome are blood pressure levels1 (systolic <97; diastolic <70; mean <93.3 (mm Hg)); total peripheral resistance1 <1746.2 dyne×sec×cm-5 and heart rate (˃92 per min). Conclusions. Patients with recurrent ischemia are characterized by higher levels of total peripheral resistance in the first hours of myocardial infarction. For both groups, a decrease in all studied indicators is determined. The above values of hemodynamic parameters should be used in the formation of groups with a high risk of early recurrence of ischemia and an unfavorable outcome, as well as for prognostic modeling of these complications.

Characterization of the Renin-Angiotensin-Aldosterone System in Young Healthy Black Adults: The African Prospective Study on the Early Detection and Identification of Hypertension and Cardiovascular Disease (African-PREDICT Study)

This study presents a detailed profile of the renin-angiotensin-aldosterone system (RAAS), electrolytes, volume loading, blood pressure (BP), and total peripheral resistance in healthy young Black and White adults. We also explored longitudinal associations between BP and RAAS. We included normotensive Black (N=543) and White (N=573) adults (20–30 years) and followed N=324 over ≈4.5 years. We measured clinic (central, brachial) and 24-hour BP, total peripheral resistance and left ventricular dimensions. We determined serum NT-proBNP (N-terminal prohormone B-type natriuretic peptide), RAAS, and 24-hour urinary and serum Na + and K + . RAAS components, left ventricular internal diameter (diastole), end diastolic volume and NT-proBNP were lower ( P <0.001) in Black than White adults, despite similar clinic SBP. However, central systolic BP and total peripheral resistance were higher in Black adults ( P <0.001). Plasma renin activity and angiotensin II were comparable between Black and White groups ( P >0.05) only in quartile 1 of Na + /K + values. In both groups, RAAS was lower in the higher quartiles of 24-hour Na + and NT-proBNP (all P -trend≤0.014). Over 4.5 years, all BPs increased in the Black ( P <0.001) but not White group. The increase in central systolic BP over time was associated with elevated serum aldosterone only in Black adults (β=0.18, P =0.038). We found that RAAS concentrations in healthy Black adults were half of those of White participants, which may not be explained by volume expansion. Yet, baseline aldosterone predicted BP elevation over time in Black adults. RAAS was similar in Black and White adults only at low Na + /K + scenarios, suggesting an essential role of potassium. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03292094.

MO096ROLE OF THE ENDOTHELIN SYSTEM IN THE INTERACTIONS OF THE VASOPRESSOR SYSTEMS IN VIVO IN MEN - IMPORTANCE OF GENETIC HOST FACTORS

Background and Aims Arterial hypertension is one of the most common diseases of the cardiovascular system worldwide and is still the cause of most deaths in Germany. Data on interactions of the endothelin-system with the renin-angiotensin- and the sympathoadrenergic system in the regulation of systemic hemodynamics in humans are lacking. In our present investigation we study the effects of Endothelin A-, Alpha1- and Angiotensin II-type-1-receptor antagonization on the systemic pressor effects of intravenous Endothelin-1-application in young, healthy men. In addition, we analyzed the effects of the genetic variations of the GNB3 C825T-polymorphism on hemodynamic changes. GNB3 825CT/TT-allele-carriers are considered to have a higher risk for multiple diseases with structural, vascular degeneration, such as arterial hypertension, diabetes mellitus and obesity. Method 21 healthy male volunteers were included in this double- blind, randomized, placebo-controlled cross-over study and were studied on four days. Endothelin-1 (ET-1) (0.5, 1, 2.5, 5 ng/kg/min for 20 min each) was given intravenous 2.0 hours after oral application of either placebo or Doxazosin, 3.5 hours after oral application of Candesartan (Candesartan 8 mg) or in the presence of a continuous infusion of the ET-A-selective antagonist BQ123 (60 μg/min). Blood pressure (BP) and heart rate (HR) were recorded and total peripheral resistance (TPR) was measured using impedance cardiography. ET-1-dose-response curves were analyzed with ANOVA. Data are presented as mean ± SD. Since we suspected an effect of the GNB3 C825T-polymorphism we divided the overall collective into 2 sub-collectives according to the GNB3 C825T-genotypes (n = 21, GNB3 825CC: n = 10, GNB3 825CT/TT: n = 11). Our analyses considered the overall collective and compared the sub-collectives intraday and interday. Results ET-1 increased systolic blood pressure (SBD) (p ≤ 0,01), diastolic blood pressure (DBD) and mean arterial pressure (MBP) as well as total peripheral resistance (TPR) (each p ≤ 0,001) with decreasing heart rate (HR5) (p ≤ 0,05). Elevation of blood pressure existed in both sub-collectives (GNB3 825CC: SBD & MBD: p ≤ 0,01, DBP & TPR: p ≤ 0,05, GNB3 825CT/TT: DBD, MBD & TPR: p ≤ 0,01, SBP p ≤ 0,05). Antagonization of ETA-receptors reversed the effect in the overall collective as well as in the sub-collectives. Both, Doxazosin, as well as Candesartan led to a decrease in blood pressure, however, dose-response relationship was influenced more by doxazosin (DBD: p ≤ 0,001, MBD: p ≤ 0,01) than by candesartan (all values: p &gt; 0,05). For both drugs, blood pressure and TPR remained elevated under maximum ET-1-application compared to baseline measurement. Blood pressure dependent heart rate changes were observed in the overall collective and in GNB3 825CC-allele-carriers under sole ET-1-therapy (p ≤ 0.05) (Fig. 1). Candesartan reversed the effect of ET-1 on the sub-collectives (p &gt; 0.05). GNB3 825CT/TT-allele-carriers showed no reduction in heart rate under ET-1-application, but with accompanying candesartan therapy (p ≤ 0.01) (Fig. 2). The genotype collectives thus behaved oppositely to the drugs in this respect. Conclusion In summary, ET-1 increased systolic, diastolic and mean arterial blood pressure as well as systemic vascular resistance. Doxazosin, Candesartan and BQ123 led to a decrease in blood pressure. Blood pressure and TPR remained elevated under maximum ET-1 application plus Candesartan or Doxazosin. The heart rate changes of the genotype-separated sub-collectives were opposite when ET-1 was administered compared to ET-1 and Candesartan.

Analysis of Relationships between Indicators of Body Component Composition and Cardiovascular System of Young Females with Different Types of Hemodynamics

Representatives of different body constitutions have characteristic features of anthropometric indicators, body composition, endocrine and immune systems, circulatory system. It is important to study the relationship between hemodynamic parameters and the constitutional features of a healthy person, which in turn are due to the diversity of body components. The purpose of the study was to identify correlations between body composition components and cardiovascular parameters in women aged 18-22 with different types of hemodynamics. Material and methods. The study involved 90 healthy female students aged 18 to 22 years (M±m = 19.3±1.3). The women studied at Ivan Franko National University of Lviv, majoring in secondary education (various subject specializations), did not have any acute or chronic diseases, and were assigned to the main medical group. The method of bioelectrical impedance analysis was used in the work. The following heart rate parameters were analyzed: heart rate, blood pressure, minute blood volume, stroke volume, cardiac index, stroke index, total peripheral resistance, peripheral resistivity. The type of central hemodynamics was determined according to the modified scheme of N. I. Arinchin. Correlation analysis was performed according to Pearson. The samples were compared using a Student's t-test, differences at p <0.05 were considered significant. Results and discussion. Eukinetic type of hemodynamics was found in 18.89% of women, hypokinetic in 81.11%. Indicators of the body composition of both groups did not differ (p >0.05). Women with eukinetic type of hemodynamics had higher stroke volume (10.63 ml, p <0.01), shock index (6.64 ml/ m2, p <0.01), minute blood volume 1.87 l/ min, p <0.001), heart rate (20 beats/ min, p <0.05). Women with hypokinetic hemodynamic type had higher (p <0.001) values of total and specific peripheral resistance (1.82 and 1.85 times, respectively). The value of muscle mass correlates with indicators of stroke volume (mean correlation – r = 0.565, p <0.05), minute blood volume (r = 0.524, p <0.05) and total peripheral resistance (r = -0.555, p <0.01). Conclusion. The shock index of women with a hypokinetic type of hemodynamics was weakly related to body mass index (r = -0.238, p <0.05), visceral fat content (r = -0.264, p <0.05), the content of m muscle mass (r = 0.372, p <0.01) and water content (r = 0.289; p <0.05). There were also correlations of the average strength between the heart index and muscle mass content (average correlation – r = 0.425, p <0.01), water content (weak correlation – r = 0.272, p <0.05)