Untreated Essential Hypertension Research Articles

Pharmacogenomics and the Concept of Personalized Medicine for the Management of Hypertension

Pharmacogenomics and the Concept of Personalized Medicine for the Management of Hypertension

A STUDY OF 24HOUR CENTRAL BLOOD PRESSURE VARIABILITY WITH MEASURES OF MACRO- AND MICROVASCULAR FUNCTION IN A POPULATION OF UNTREATED HYPERTENSIVE AND NORMOTENSIVE INDIVIDUALS

Objective: Central blood pressure (cBP) has been more closely associated with target-organ damage compared with brachial BP, although a bidirectional interplay between central and peripheral arteries exists. Brachial short term BP variability (BPV) has been increasingly related to impaired macro- and microvascular function. However, scarce data exists regarding 24hour central BPV (cBPV) and its impact on organ damage. This study aimed to measure 24h cBPV in a population of untreated essential hypertensive (UHTs) and normotensive (NTs) individuals and evaluate its association with measures of macro- and microvascular function. Design and method: Newly-diagnosed UHTs and NTs were enrolled. 24hour cBP and 24h pulse wave velocity (PWV) were measured with the Mobil-O-Graph device. BPV including average real variability (ARV) of 24h central systolic BP (cSBP) and diastolic BP (cDBP) was calculated according to a standardized formula based on the ambulatory BP monitoring (ABPM) measurements. Urine albumin excretion (UAE) was measured in 24h samples. Results: We recruited 119 individuals including 79 UHTs and 40 NTs that didn’t differ in baseline characteristics. As expected, PWV was increased in UHTs compared to NTs [7.7 (1.5) vs 6.7 (1.2) m/s, p<0.001]. Similarly, in a subset of 60 individuals, UAE was increased [12.1 (9.7) vs 6.4 (4.5) mg/24h, p = 0.008]. UHTs presented higher ARV of 24h, daytime and nighttime cSBP/cDBP compared to NTs (p<0.05 for all comparisons). In total population, 24h PWV positively correlated with ARV of 24h cSBP (r = 0.353, p<0.001) and cDBP (r = 0.235, p = 0.010), ARV of daytime cSBP (r = 0.342, p<0.001) and cDBP (r = 0.235, p = 0.010), and nighttime cSBP (r = 0.297, p = 0.007). Furthermore, UAE correlated with ARV of nighttime cDBP (r = 0.372, p = 0.017). In multivariate analysis after adjusting for age, sex, and hypertension, ARV of 24h cSBP remained an independent predictor of PWV (beta = 0.109, p<0.001). Likewise, ARV of nighttime cDBP independently predicted UAE (beta = 0.480, p = 0.002). Conclusions: In a population of untreated hypertensives and normotensives, cARV indices are significantly and independently associated with measures of macro- and microvascular function including PWV and UAE, respectively. Further studies are warranted to ascertain the clinical value of cARV in terms of risk stratification and management.

DYSLIPIDEMIA AND HYPERGLYCEMIA IN HYPERTENSIVE PATIENTS ASSOCIATE WITH GNB3 (RS5443) AND NOS3 (RS2070744) GENES’ ALLELIC STATE

Objective: More than 700 million people worldwide live with untreated essential arterial hypertension (EAH). The objective of the study was to evaluate the risks of metabolic disorders in EAH patients depending on guanine nucleotide-binding protein-↓3 subunit (GNB3, rs5443) and endothelial nitric oxide synthase (NOS3, rs2070744) genes’ allelic state. Design and method: The cohort case-control study involved 100 EAH patients (moderate-very high cardiovascular risks, aged 45-65 years) and 48 practically healthy (control). Metabolic disorders were evaluated by glucose blood value and lipids panel: total cholesterol (TC), triglycerides (TG), Low-, and High- density lipoprotein cholesterol (LDL-C, HDL-C) levels. The atherogenic index (AI) was calculated by the equation: (TC-HDL-C)/HDL-C. GNB3 (rs5443) and NOS3 (rs2070744) genotyping perfrmed by TaqMan probes in CFX96 Real-Time PCR Detection System. Results: Hyperglycemia (>6.1 mmol/l), hypertriglyceridemia (TG>1.7 mmol/l) and decreased HDL-C (<1.2 mmol/l) were relatively more common in EAH patients than in the control group by 36.11% (⇙2 = 17.88; p<0.001), 23.61% (⇙2 = 6.43; p = 0.011) and 25.0% (⇙2 = 8.32; p = 0.004) respectively. Therefore, the fasting hyperglycemia increases the EAH risk in the examined population ninefold [OR95%CI:2.86-27.08; p<0.001], hypertriglyceridemia and decreased HDL-C elevates the risk almost 3 and 3.5 times as well [OR95%CI:1.23-5.56; p = 0.009 and OR95%CI:1.46-8.71; p = 0.003], respectively. The risk of metabolic disorders (dyslipidemia and hyperglycemia) in EAH patients does not depend on NOS3 gene polymorphism (rs2070744). Contrary, in T-allele patients of the GNB3 gene (rs5443) prevailed subjects with elevated LDL-C (>3.0 mmol/l) over those with CC-genotype by 13.89% (p = 0.05). Other parameters of lipid metabolism and hyperglycemia did not differ significantly between GNB3 (rs5443) genes allelic state. However, the mutational T-allele of the GNB3 gene (825C>T) increases the risk of hyperlipidemia 8.5 times [OR 95%CI:0.99-72.70; p = 0.05] due to atherogenic LDL-C, with the protective role of CC-genotype [OR = 0.12; OR 95%CI:0.01-1.0; p = 0.048]. Conclusions: Fasting hyperglycemia, hypertriglyceridemia and lowered HDL-C, enhance the arterial hypertension risk 3-9 times (p<0.01). The polymorphic site of GNB3 (rs5443) gene, but not NOS3 (rs2070744) gene associate with hyperlipidemia in hypertensive patients.

S-28-2: EFFECT OF ESAXERENONE ON NOCTURNAL BLOOD PRESSURE COMBINED WITH RENIN-ANGIOTENSIN SYSTEM INHIBITOR OR CALCIUM CHANNEL BLOCKER IN UNCONTROLLED HYPERTENSION

Objective: To evaluate the nighttime blood pressure(BP)-lowering effects of esaxerenone with different concomitant antihypertensive treatments, we conducted a post hoc analysis of a multicenter, open-label, long-term phase 3 study (NCT02722265) of esaxerenone, a highly selective mineralocorticoid receptor blocker, alone or in combination with a calcium channel blocker (CCB) or a renin-angiotensin system (RAS) inhibitor in patients with essential hypertension. Design and method: Patients had previously untreated essential hypertension, or had received only one RAS inhibitor or CCB as a baseline antihypertensive agent at the start of the study. All patients had a sitting systolic BP of 140 to < 180 mmHg and a sitting diastolic BP of 90 to < 110 mmHg, a 24-h ambulatory BP of ≧130/80 mmHg. In this post hoc analysis, patients were classified into 3 treatment groups; esaxerenone monotherapy, combination with a CCB and combination with RAS inhibitor and targeted on the patient without any additional antihypertensive treatment at Week 28. For these 3 groups, mean changes in 24-hour, early morning, daytime, and nighttime systolic BP in 24-h ambulatory BP, mean changes in N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, and changes in dipping pattern (extreme dippers, dippers, non-dippers, risers) were evaluated at 28 Week to include as many patients as possible available for analysis. Results: Of the total 368 patients in the study, 248 patients were included in this analysis and there were 153 in esaxerenone monotherapy, 48 in combination with a CCB and 48 in combination with a RAS inhibitor. Nighttime systolic BP statistically significantly decreased in all groups at Week 28 compared to baseline, with combination with a RAS inhibitor group showing the greatest change (-20.6 mmHg). Those changes were numerically greater than the daytime systolic blood pressure in all groups. The decrease in NT-proBNP from baseline to Week 28 was statistically significant in all group (p < 0.001, respectively) and the decrease in combination with RAS inhibitor was numerically greater than that of monotherapy. A statistically significant shift in dipping pattern and changes from riser/non-dipper to dipper/extreme dipper pattern were found at Week 28 in Monotherapy (p < 0.05) and the same trend of shifting was shown in combination with RAS inhibitor (p = 0.1615). The prevalence of riser/non-dipper pattern was decreased from 58.2% to 47.7% in monotherapy and from 54.2% to 39.6% in combination with RAS inhibitor. Conclusions: Esaxerenone would provide a useful treatment option for nocturnal hypertension, especially in combination with RAS inhibitor, in uncontrolled hypertension.

Relationship Between Atherogenic Index of Plasma and Serum Uric Acid in Patients With Untreated Essential Hypertension in China: A Cross-Sectional Study.

Several studies have reported that the atherogenic index of plasma (AIP) is associated with serum uric acid (SUA) in healthy middle-aged men, kidney transplant patients, and diabetic patients. We assessed the relationship between AIP and SUA in patients with untreated essential hypertension (EH) in China. In the cross-sectional study, we evaluated 5003 patients with untreated EH in China; 1490 were assigned to the hyperuricemia (HUA) group and 3513 to the normouricemia (non-HUA) group according to the diagnostic criteria of HUA (SUA level≥6mg/dL in females and ≥7mg/dL in males). A higher AIP level was found in the HUA group (P < .001), and AIP was positively and independently correlated with SUA after adjusting for statistically significant variables (β = .204, P < .001). Moreover, multivariate logistic regression analysis showed that the AIP was closely and independently related to HUA after adjusting for confounders (odds ratio [OR]: 11.980, 95% confidence interval [CI]: 3.186-45.047, P < .001). Our findings suggested that the AIP was positively and independently associated with SUA, and elevated AIP might be a significant risk factor for HUA in patients with untreated EH in China.

ASSOCIATIONS BETWEEN EPICARDIAL FAT AND LEFT VENTRICULAR GEOMETRY IN YOUNG NON-OBESE HYPERTENSIVES

Objective: Epicardial adipose tissue (EAT) has been considered as a marker of cardiovascular risk. Previously association between the EAT volume with the insulin resistance index, metabolic parameters and emodelling parameters of the left heart was observed in young obese people with abdominal obesity. Aim: to evaluate the relations between epicardial adipose tissue thickness (EAT) with metabolic parameters and left ventricular geometry in young non-obese individuals with hypertension comparing to normotensive subjects. Design and method: 30 young non-obese subjects with untreated essential hypertension (HTN) diagnosed by office blood pressure (BP) measurements by Korotkoff method and/or ambulatory BP monitoring (ESH, 2018) were included as study group (mean age - 23 ± 3 yrs, 100% were male, mean BMI 26 ± 6 kg/m2, office SBP/DBP 138 [130; 171] / 74 [64; 97] mm Hg). The control group consisted of 20 healthy volunteers without HTN (mean age - 33 ± 6 yrs, 100% were male, mean BMI 26 ± 4 kg/m2, office SBP/DBP 126 [124; 128] / 70 [65; 75] mm Hg). The thickness and area of the epicardial fat were measured by CT-scan images with parasternal short axis view at basal, mid-ventricular and apical levels and horizontal long axis view directly surrounding the main coronary arteries Results: EAT thickness was higher in AH group comparing to healthy volunteers (7,42 [5,22; 11,01] vs 7,17 [4,67; 9,67] mm, p &lt; 0.05) and EAT square was larger in study group comparing to control group (93,5 [60,3; 267.0] vs 88,7 [50,7; 126,6] mm2, p &lt; 0.05). Correlations between EAT square and LDL-cholesterol (r = 0.53, p &lt; 0,05), HDL-cholesterol (r = -0,51, p &lt; 0,05), interventricular septum thickness of the left ventricle (r = 0.47, p &lt; 0,05), left ventricular posterior wall thickness (r = 0.56, p &lt; 0,05), relative wall thickness (r = 0.45, p &lt; 0,05) were found in AH group. No significant correlations were found in the control group. Conclusions: The accumulation of EAT among patients with AH is larger than among people with normal blood pressure. Epicardial adipose tissue thickness as early marker of visceral obesity associated with left ventricular emodelling in young non-obese patients with essential hypertension.

Skin microvascular function, as assessed with laser speckle contrast imaging, is impaired in untreated essential and masked hypertension.

Skin microcirculation has been proposed as a model of generalized microvascular function. Laser speckle contrast imaging (LSCI) is a novel, noninvasive method to assess skin microvascular function (SMF). To date, SMF data in hypertension are conflicting, and no study with LSCI exists. In addition, the application of LSCI in masked hypertension is scarce. We assessed SMF with LSCI coupled with postocclusive reactive hyperemia (PORH) in patients with newly diagnosed untreated essential hypertension (UHT) and masked hypertension (MH) compared to healthy normotensive (NT) individuals. We enrolled consecutive UHT and MH patients and NT individuals matched for age, sex, body mass index, and smoking status. All participants underwent SMF assessment by LSCI coupled with PORH (PeriCam PSI system, Perimed, Sweden). Correlation analyses were performed between SMF and common cardiovascular risk factors and BP parameters. In total, 70 UHT patients, 20 MH patients and 40 NT individuals were enrolled. UHT and MH patients exhibited significantly impaired SMF compared to NT individuals (UHT patients: base-to-peak flux (p < 0.001)), PORH amplitude (p < 0.001); MH patients: base-to-peak flux (p = 0.013), PORH amplitude (p = 0.022). MH patients did not differ compared to UHT patients. SMF was negatively associated with office, ambulatory and central BP. SMF was negatively associated with blood lipids and smoking. Hypertensive status was the single most important predictor of SMF. UHT and MH patients exhibit impaired SMF compared to NT individuals. MH patients did not differ compared to UHT patients. SMF is negatively associated with BP and cardiovascular risk factors. LSCI could be implemented as a useful tool to investigate SMF in hypertension.

Angiotensin II triggers release of neutrophil extracellular traps, linking thromboinflammation with essential hypertension.

Innate immunity and chronic inflammation are involved in atherosclerosis and atherothrombosis, leading to target organ damage in essential hypertension (EH). However, the role of neutrophils in EH is still elusive. We investigated the association between angiotensin II (Ang II) and neutrophil extracellular traps (NETs) in pathogenesis of EH. Plasma samples, kidney biopsies, and surgical specimens of abdominal aortic aneurysms (AAAs) from patients with EH were used. Cell-based assays, NETs/human aortic endothelial cell cocultures, and in situ studies were performed. Increased plasma levels of NETs and tissue factor (TF) activity were detected in untreated, newly diagnosed patients with EH. Stimulation of control neutrophils with plasma from patients with untreated EH generated TF-enriched NETs promoting endothelial collagen production. Ang II induced NETosis in vitro via an ROS/peptidylarginine deiminase type 4 and autophagy-dependent pathway. Circulating NETs and thrombin generation levels were reduced substantially in patients with EH starting treatment with Ang II receptor blockers, whereas their plasma was unable to trigger procoagulant NETs. Moreover, TF-bearing NETotic neutrophils/remnants accumulated in sites of interstitial renal fibrosis and in the subendothelial layer of AAAs. These data reveal the important pathogenic role of an Ang II/ROS/NET/TF axis in EH, linking thromboinflammation with endothelial dysfunction and fibrosis.

RENAL FUNCTIONAL RESERVE IS RELATED TO THE NON-DIPPING PHENOTYPE AND TO THE EXERCISE HEART RATE RESPONSE IN PATIENTS WITH ESSENTIAL HYPERTESION AND A PRESERVED RENAL FUNCTION

Objective: Renal functional reserve (RFR) defined as the difference between stress and resting glomerular filtration rate (GFR) may constitute a diagnostic tool to identify patients at higher risk of developing acute kidney injury or chronic kidney disease. A blunted RFR has been demonstrated in early stages of hypertension and has been attributed to an impaired vascular reactivity due to an overactive sympathetic nervous system. The purpose of this study was to investigate whether RFR correlates with other phenotypes expressing an over-activity of the SNS in patients with essential hypertension and a preserved renal function. Design and method: Thirty-six patients with untreated essential hypertension and a GFR &gt;60 ml/min/1.73m2 were enrolled. The following parameters were measured: RFR, a 24 h ambulatory BP profile, a treadmill stress test and an echocardiographic examination. Urine and venous samples were obtained for the determination of clinical parameters and calculation of RFR after an acute oral protein load (1 g/kg). Results: Twenty-one patients had a RFR below 30 ml/min/1.73m2 and 15 had a RFR above this cut-off. A non-dipping pattern of 24 h BP was significantly more frequent in patients with low RFR (57.1% vs. 25.0%, p &lt; 0.05 for systolic BP and 52.3% vs 10.0%, p &lt; 0.02 for diastolic BP). Moreover, patients with lower RFR values showed a blunted heart rate response to exercise during treadmill test (r = 0.439, p &lt; 0.05). None of the echocardiographic parameters differed between the two groups of patients. Conclusions: In hypertensive patients with a preserved GFR, a reduced RFR is related to non-dipping BP phenotype as well as with an attenuated exercise HR response. An overactivity of the sympathetic nervous may be a common pathway. Since a loss of RFR may represent a risk factor for acute or chronic kidney injury, hypertensive patients with a blunted RFR might need a more careful renal follow-up.

A HIGH ALDOSTERONE TO RENIN RATIO MEDIATES MICROVASCULAR AND MACROVASCULAR DAMAGE IN NEWLY-DIAGNOSED, TREATMENT-NAÏVE ESSENTIAL HYPERTENSION

Objective: The role of aldosterone in hypertension was generally considered in the context of primary hyperaldosteronism, an uncommon condition (less than 2% in the hypertensive population). However, based on an increased ambulant aldosterone-to-renin ratio (ARR), a marker of inappropriate aldosterone activity, the prevalence of primary hyperaldosteronism in the hypertensive population may be as high as 10% to 15%. There is increasing evidence to suggest a BP-independent effect of aldosterone on left ventricular structure, increased collagen deposition with fibrosis, diastolic dysfunction and arterial stiffness. We hypothesized that aldosterone and renin will be associated with microvascular and macrovascular alterations in never treated essential hypertension. Design and method: We prospectively studied newly diagnosed, untreated essential hypertensive and normotensive subjects (n = 1482, 47% females, mean age 51 ± 0.77, SEM). Pulse wave velocity (PWV), augmentation index (AIx), aortic systolic BP and pulse pressure amplification were measured with applanation tonometry(SphygmoCor). Albumin-creatinine ratio, urine sodium and potassium concentrations were determined from spot urine samples. Laboratory tests included serum creatinine and clearance, plasma renin activity, serum aldosterone, and high-sensitivity C-reactive protein(hs-CRP). Aldosterone to renin ratio(ARR) was divided into tertiles. Results were analysed using JMP Pro(Version 13, SAS for Windows). The patients gave informed consent and the study had Institutional ethics committee permission. Results: The top ARR tertile was associated with the highest levels of brachial BP, aortic systolic BP, AIx, pulse pressure amplification and PWV(P &lt; 0.001 for all). Stepwise regression analysis showed that the positive association between PWV and increasing ARR tertiles remained significant after adjustment for BP, age and other potential confounders(R2 = 0.39, p &lt; 0.05). The top ARR tertile was also associated with high potassium and low sodium urinary excretion, high ACR, low creatinine clearance and high hs-CRP (All p &lt; 0.01). Conclusions: In untreated hypertensive subjects with mild to moderate hypertension, there are significant interactions between ARR and indices of microvascular and macrovascular damage. Our findings indicate that aldosterone and renin adversely modulate microvascular and macrovascular function very early in the evolution of hypertension. While aldosterone antagonism is recommended currently for treatment-resistant hypertension, our findings suggest that it should be initiated early in hypertension.

EARLY RENAL DAMAGE IN YOUNG HYPERTENSIVE SUBJECTS: LINK WITH OFFICE AND 24-HOUR AMBULATORY SYSTOLIC AND DIASTOLIC BLOOD PRESSURE

Objective: Hypertension (HTN) and target organ damage rate in young subjects is underestimated in clinical practice according to latest population studies and treatment strategy of HTN is not well defined due to minor and controversial data of clinical studies. As a part of cohort study of HTN detection and evaluation in young population we investigated renal function in untreated hypertensive subjects with primary diagnosed essential hypertension. Design and method: We performed office BP evaluation and ambulatory blood pressure monitoring with oscillometric cuff-based device in 102 young subjects with untreated essential hypertension defined with ESH criteria of HTN according to office and ambulatory blood pressure monitoring (age 26.2 ± 7.7 (M ± SD) years, 88.3% male, office SBP 134.7 ± 15.8 mm Hg, office DBP 73.2 ± 12.4 mm Hg). Serum creatinine and albumin/creatinine ratio in urine were measured. GFR was calculated with CKD-EPI. For comparison of variables in quartiles of blood pressure we used one-way ANOVA for parametric ones and Kruskal-Wallis test – for non-parametric variables. Results: We compared glomerular filtration rate (GFR) and albumin/creatinine ratio (ACR) in quartiles of office and 24 h systolic and diastolic blood pressure. Significant difference in GFR was registered in office SBP quartiles: GFR in 1st and 4th quartiles was 105,1 ± 21,7 vs 90,3 ± 14 ml/min/1,73m2, with F 4.035, P value 0,0097 while there was no any significant difference of ACR levels according to office BP levels. ACR was significantly different in quartiles of mean nighttime DBP: ACR median in 1st quartile – 4 [0,75; 5,0] vs 8 [3,0; 29,0] in last quartile, P value 0,0056 with no significant difference for daytime DBP and daytime and nighttime SBP. Significant correlation between mean nighttime DBP and ACR was observed: r 0,243, P value 0,023. R for office SBP and GFR was (-0,325) with P value 0,002. Conclusions: In young untreated hypertensive subjects elevation of office SBP is associated with GFR decline while ACR has association with nighttime DBP elevation.

Comment on a Recent Article Titled “Irisin Correlates Positively With BMD in a Cohort of Older Adult Patients and Downregulates the Senescent Marker p21 in Osteoblasts”

In a recent issue of JBMR, Colaianni and colleagues reported the relationship of circulating irisin levels, a myokine synthesized from skeletal muscle, with bone and muscle parameters in a sample of older adults.(1) They showed that FNDC5 expression, an irisin precursor, in muscle biopsies positively correlated with osteocalcin mRNA in bone biopsies, suggesting a connection between these tissues. Interestingly, the treatment with irisin decreased p21 mRNA expression, a senescence marker, in osteoblasts in vitro. These findings may be a guide for novel therapeutic approaches to delaying age-related muscle atrophy and bone loss. However, a few points are worth discussing. The authors may not have accounted for several factors that could influence their results, including chronic diseases and some selected drugs. The prevalence of chronic conditions increases after the age of 60 years, and many older people develop more than one chronic disease. A recent cross-sectional study of 740 participants showed an association of serum irisin with adiposity, glucose tolerance, and insulin resistance in middle-aged individuals.(2) In the same study, patients with diabetes mellitus (DM) had lower irisin levels than those without DM.(2) Correspondingly, serum irisin concentrations significantly decreased among patients with DM in a cohort of adults older than 60 years.(3) On the other hand, experimental studies showed that bolus intravenous administration of irisin decreased arterial blood pressure by reducing vascular endothelial dysfunction via upregulation of NO synthesis and activating the AMPK-Akt-eNOS pathway.(4, 5) Lower circulating irisin levels were found to be associated with high systolic and diastolic blood pressure in patients with preeclampsia.(6) Besides, cardiac muscles are an important source of irisin synthesis, and the change in heart function may alter the production of this protein.(7) Many older individuals are prescribed drugs to manage chronic diseases. Metformin therapy is the first-line agent in the treatment of DM in older individuals. In an interventional study of patients with polycystic ovary syndrome, 3 months of metformin treatment decreased serum irisin levels and improved insulin resistance.(8) Lowering blood pressure with amlodipine and valsartan increased the circulating levels of irisin in patients with untreated essential hypertension.(9) An animal study showed that statin treatment increased irisin levels in skeletal muscle.(10) I would like to ask the authors whether they provide some data on this population's comorbidities and medication for diabetes mellitus, hypertension, and hyperlipidemia. Inclusion of new data in statistical analysis could help make the results stronger. New findings could raise the importance of this research, which aimed to explore the role of irisin in bone and muscle senescence.

Retinal microvascular metrics in untreated essential hypertensives using optical coherence tomography angiography.

To quantify early changes of macular microvascular density, complexity, and peripapillary vessel caliber in hypertension using optical coherence tomography angiography (OCTA). Hypertension (137 eyes) and healthy eyes (79 eyes) as control were involved in this prospective observational study. Indices of the microcirculation included vessel density (VD), skeleton density (SD), vessel diameter index (VDI), fractal dimension (FD) and foveal avascular zone (FAZ) of superficial retinal layer (SRL) and deep retinal layer (DRL), and peripapillary vessel calibers. The correlation of these indices with mean arterial pressure (MAP) and ocular perfusion pressure (OPP) was analyzed. Mean VD of DRL, SD of SRL and DRL, and FD of SRL and DRL were significantly reduced in the macula of hypertensive eyes (all P < 0.01). Meanwhile, hypertensive eyes had margin results of narrower peripapillary arteriolar caliber (P = 0.04). No significant finding was demonstrated on VD of SRL, VDI and FAZ of SRL and DRL, peripapillary total vascular caliber, and peripapillary venal caliber (all P > 0.05). SD and VD of the DRL correlated negatively with MAP (both R = - 0.152, P = 0.03). OCTA algorithms may provide an additional inexpensive tool to aid in the preclinical assessment of hypertensive subject.

Renal Functional Reserve Is Related to the Nondipping Phenotype and to the Exercise Heart Rate Response in Patients with Essential Hypertension and Preserved Renal Function

Background: Renal functional reserve (RFR), defined as the difference between stress and resting glomerular filtration rate (GFR), may constitute a diagnostic tool to identify patients at higher risk of developing acute kidney injury or chronic kidney disease. Blunted RFR has been demonstrated in early stages of hypertension and has been attributed to impaired vascular reactivity due to an overactive sympathetic nervous system (SNS). Objective: The purpose of this study was to investigate whether RFR correlates with other phenotypes expressing overactivity of the SNS in patients with essential hypertension and preserved renal function. Methods: Thirty-six patients with untreated essential hypertension and a GFR >60 mL/min/1.73 m² were enrolled. The following parameters were measured: RFR, 24-h ambulatory blood pressure (BP) profile, a treadmill stress test, and an echocardiographic examination. Urine and venous samples were obtained at specific time points for the determination of clinical parameters, and both resting and stress GFR were calculated by using endogenous creatinine clearance for the measurement of RFR after an acute oral protein load (1 g/kg). Results: Twenty-one patients had a RFR <30 mL/min/1.73 m² and 15 had a RFR above this cutoff. A nondipping pattern of 24-h BP was significantly more frequent in patients with low RFR (57.1 vs. 25.0%, p < 0.05 for systolic BP and 52.3 vs. 10.0%, p < 0.02 for diastolic BP). Moreover, patients with lower RFR values showed a blunted heart rate (HR) response to exercise during treadmill test (r = 0.439, p < 0.05). None of the echocardiographic parameters differed between the two groups of patients. Conclusions: In hypertensive patients with preserved GFR, reduced RFR is related to nondipping BP phenotype as well as to attenuated exercise HR response. Overactivity of the SNS may be a common pathway. Since loss of RFR may represent a risk factor for acute or chronic kidney injury, hypertensive patients with blunted RFR might need a more careful renal follow-up.

Retinol-binding protein 4 is closely correlated to blood pressure level and E/A in untreated essential hypertension patients.

Hypertension, a common chronic disease, is a leading cause of death and other cardiovascular diseases. Recent studies show that an inflammatory factor named retinol binding protein 4 (RBP4) was increased with cardiovascular diseases. However, the relationship between RBP4 and hypertension in patients remains unclear. The study cohort was composed of patients with essential hypertension (EH) and healthy control (HC) subjects from the Second Affiliated Hospital of Nanjing Medical University [2017-2019]. The levels of RBP4 and echocardiography were compared in the current study. Statistical differences between two groups were analyzed using unpaired Student's t-tests and the correlation between the two variables adopts Pearson correlation analysis. SPSS 23.0 was used for all statistical analysis. Analysis of patient plasma samples revealed that RBP4 in EH group was greater than HC group (P<0.05). The area under the ROC curve was 0.717. Specificity and sensitivity were 80.4% and 60.8%, respectively. RBP4 had positive correlation with left ventricular systolic diameter (LVDs), interventricular septal thickness (IVS) and left ventricular posterior wall thickness (LVPW), negative correlation with left ventricular shortening fraction (FS) and ejection fraction (EF) (P<0.05), and no correlation with left ventricular end-diastolic diameter (LVDd) (P>0.05). RBP4 was closely related with E/A, evaluation method of left ventricular diastolic function, in patients with EH. RBP4 levels are closely correlated with blood pressure (BP) levels and might be involved in the regulation of left ventricular diastolic function in patients with EH.

P1688Behavior of indices of sympathetic activity in relation to sleep time duration in untreated hypertensives

Abstract Background Short sleep duration and poor sleep quality has been reported to be associated with increased cardiovascular risk and increased incidence of cardiovascular events. Purpose Whether and what extent the pathophysiology of this association includes sympathetic abnormalities has never been examined via microneurography. Methods In 28 untreated mild-to moderate essential hypertensives aged 66.4±3.1 (mean±SEM) without other cardiovascular or non-cardiovascular disease (including obstructive sleep apnea) recruited from the outpatient clinic and referred for short sleep duration, we directly assessed at patients home via actigraphy (actiwatch spectrum activity monitor, Phillips) time sleep duration and efficiency. Measurements, performed during a day preceding or following the 7 day actigraphy evaluation, included microneurographic recording of efferent postganglionic sympathetic nerve traffic (MSNA), venous plasma norepinephrine (HPLC), clinic, 24 hour and beat to beat blood pressure and heart rate values. Sleep diary and a sleep questionnaire were also administered. Results Nine patients slept less than 6 hours per night (LSD), while the remaining ones between 6 to 7 (MSD, n=8) or more than 7 hours (GSD,N=11). The 3 groups showed similar age and gender distribution and a body mass index amounting to 28.1±0.8, 28.6±0.5 and 27.3±0.5 kg/m2 (P=NS). For similar mean blood pressure values LSD showed MSNA values significantly greater than GSD (53.4±4.9 vs 40.1±3.8bs/100hb, P&lt;0.03), this being the case also for MSD (49.7±4.4, P&lt;0.05 vs GSD but not SLD). HR was significantly elevated only in LSD group when compared to GSD, while no significant difference was found in plasma NE between the 3 groups. Conclusions The present study provides the first microneurographic direct evidence that short sleep duration is linked to a marked sympathetic activation, which may participate at the high cardiovascular risk of these subjects. The sympathetic overdrive affects both the cardiac and peripheral district but is not reflected by NE, which thus does not represent in this condition a valuable adrenergic marker.

P3405Association between heart rate thresholds for cardiovascular risk defined by new ESC/ESH Guidelines and neuroadrenergic markers

Abstract Background The ESC/ESH Guidelines for hypertension issued in 2018 identify resting heart rate (HR) values greater than 80 beats/minute as predictors of cardiovascular risk, with the undocumented evidence that this detection might represent the occurrence of a sympathetic cardiovascular overdrive. Purpose In the present study we tested this hypothesis throughout the use of direct and indirect markers of sympathetic neural function. Methods In 167 untreated and uncomplicated mild-to moderate essential hypertensives recruited for different investigations and aged 51.8±3.2 years (mean±SEM) without other cardiovascular or non-cardiovascular disease, we measured clinic and ambulatory blood pressure (BP), HR (EKG), venous plasma norepinephrine (NE, HPLC assay) and efferent postganglionic muscle sympathetic nerve traffic (MSNA, microneurography). We then subdivided the study population in 2 groups according to HR values ≤ or &gt;80 beats/minute. Results Sixty-eight patients displayed resting HR &gt;80 beats/minute while the remaining 99 below this threshold value, the 2 groups showing superimposable age values and gender distribution. Body mass index, clinic and ambulatory BP were similar in the 2 groups this being the case also for LVMI and metabolic variables. In contrast MSNA values were significantly greater (P&lt;0.02) in the former than in the latter group both when expressed as bursts incidence over time (49.2±1.8 vs 39.5±1.4 bs/min) and when corrected for HR (60.7±3.0 vs 51.4±2.5 bs/100 hb). NE showed a tendency to be greater in the former group without achieving, however, statistical significance. In the whole population there was a significant direct relationship between MSNA and HR values (r=0.61, P&lt;0.01) Conclusions Thus hypertensive patients displaying HR &gt;80 beats/minute are characterized by a marked sympathetic overdrive, particularly when direct adrenergic markers are employed. This finding suggests that cardiac and peripheral sympathetic activation may participate at the increased cardiovascular risk detected in this group of patients.

Reversal of an unfavorable effect of hydrochlorothiazide compared to angiotensin converting enzyme inhibitor on serum uric acid and oxypurine levels by estrogen–progestin therapy in hypertensive postmenopausal women

Background: The aim was to assess the effect of estrogen–progestin therapy (EPT) on serum levels of uric acid (SUA) and its precursors xanthine (X) and hypoxanthine (HX), and on uric acid (UA) renal excretion in hypertensive postmenopausal women treated with an angiotensin-converting enzyme inhibitor (ACEI) or thiazide diuretic (HCTZ) (ClinicalTrials.gov identifier: NCT03921736, registered 19 April 2019).Methods: Postmenopausal women with untreated essential hypertension were recruited to the study. The control group consisted of 40 postmenopausal women with normal blood pressure. Hypertensive women were randomized to two groups: hydrochlorothiazide (n = 50) or perindopril (n = 50) and to a group receiving or not receiving EPT (EPT+/EPT−) due to vasomotor symptoms. The follow-up period was one year. Blood pressure measurements as well as blood tests for SUA and its precursors X and HX were performed at baseline and after 12 months.Results: In hypertensive women, baseline serum X and HX were significantly higher when compared to the group of normotensive women. Treatment with HCTZ led to a statistically significant increase in SUA in the subgroup of EPT- women. In this group concentrations of X and HX increased significantly after 12 months. UA/X significantly decreased after treatment with HCTZ. Lack of EPT resulted in a decrease of renal plasma flow in the HCTZ group. However, in the HCTZ and EPT + group, SUA decreased significantly when compared to baseline. None of these unfavorable effects was observed in the ACEI group regardless of EPT.Conclusions: 1) EPT prevents the development of hyperuricemia during antihypertensive treatment with thiazide diuretics. 2) Arterial hypertension and menopause cause impairment of UA excretion and increase the levels of SUA and its precursors X and HX. 3) EPT reduces the risk of hyperuricemia in postmenopausal women.

Relationship between platelet count and platelet width distribution and serum uric acid concentrations in patients with untreated essential hypertension.

Hematological parameters have emerged as independent determinants of high serum concentrations of uric acid (UA) and predictive factors in the evaluation of the total cardiovascular risk in patients with essential hypertensive. Here, we have investigated the possible relationships between hematological factors and serum uric acid levels in hypertensive patients recruited as part of Mashhad Stroke and Heart Atherosclerotic Disorders cohort study. Two-thousand three-hundred and thirty-four hypertensive individuals were recruited from this cohort and these were divided into two groups; those with either high or low serum UA concentrations. Demographic, biochemical, and hematological characteristics of population were evaluated in all the subjects. Logistic-regression analysis was performed to determine the association of hematological parameters with hypertension (HTN). Of the 2334 hypertensive subjects, 290 cases had low UA, and 2044 had high serum UA concentrations. Compared with the low UA group, the patients with high serum UA, had higher values for several hematological parameters, whilst platelet counts (PLT) were lower. Multiple linear regression analysis showed that PLT and serum high sensitivity-c reactive protein (hs-CRP) were correlated with serum UA level. Stepwise multiple logistic regression model confirmed that platelet distribution width (PDW) and gender were independent determinant of a high serum UA. PDW and PLT appear to be independently associated with serum UA level in patients with HTN. © 2018 BioFactors, 44(6):532-538, 2018.

Epicardial Fat Thickness is Associated with Abnormal Left Ventricle Geometry in Newly Diagnosed Hypertension.

Epicardial adipose tissue is an emerging cardio metabolic risk factor. Although an association between epicardial fat thickness (EFT) and left ventricle (LV) hypertrophy in hypertensive patients is known, the relationship between abnormal LV geometric patterns and EFT has yet to be investigated. The aim of the present study was to investigate the relationship between EFT and abnormal LV geometric patterns in hypertensive patients. Measurements were obtained from 343 patients with untreated essential hypertension (mean age 51.6 ± 5.5 years) and 52 healthy control subjects (mean age 51.8 ± 4.5 years). Four different geometric patterns (NG; normal geometry, CR; concentric remodeling, EH; eccentric hypertrophy, and CH; concentric hypertrophy) were determined according to LV mass index (LVMI) and relative wall thickness (RWt). EFT was measured using transthoracic echocardiography. High sensitive C-reactive protein (hs-CRP) and other biochemical markers were measured in all participants. The highest EFT and hs-CRP values were determined in the CH group (EFT = 8.9 ± 2.1 mm) compared with the controls (EFT = 5.7 ± 1.5 mm), followed by the NG (EFT = 5.9 ± 1.6 mm), CR (EFT = 5.9 ± 1.3 mm) and EH groups (EFT = 6.5 ± 1.6 mm) (all p < 0.05). In addition, the EFT values of the EH group were higher than the control, NG and CR groups (all p < 0.05). Multivariate linear regression analysis showed that EFT was independently associated with LV geometry (β = 0.161, p = 0.032), total cholesterol level (β = -0.129, p = 0.003), triglyceride level (β = 0.266, p < 0.001), hs-CRP level (β = 0.349, p < 0.001), and creatinine level (β = 0.108, p = 0.010). EFT is independently associated with abnormal LV geometry, LV hypertrophy, creatinine level, and low grade chronic inflammation.