Untreated Hypertensive Subjects Research Articles

Auto-Immune Cardiac Degeneration as a Complication of Essential Hypertension

Essential hypertension is persistent high blood pressure in the systemic arteries with no identifiable secondary cause. The study was designed to assess auto-immune cardiac degeneration in essential hypertensive patients in Ekiti State. The study included 40 subjects with no history of hypertension (control), 40 hypertensive subjects undergoing treatment and 40 hypertensive subjects without treatment. Body Mass Index (BMI) was calculated, systolic and diastolic blood pressure (SBP and DBP) readings were taken using digital sphygmomanometer, Aspartate Aminotransferase (AST) was measured using spectrophotometer, Cardiac Troponin (CTnI) and Anti-mitochondrial antibody M7 (AMA-M7) were estimated using ELISA. Results obtained were expressed as mean ± SD and statistical analysis was done using SPSS. Values were statistically significant at p<0.05. The results obtained showed that BMI and DBP of treated hypertensive patient was insignificant when compared with control subjects (p>0.05), whereas SBP, AST, AMA-M7 and CTnI were significantly higher (p<0.05) in treated hypertensive patients compared with the control subjects. Similarly, BMI, SBP, DBP, AMA-M7, AST and CTnI of untreated hypertensive patient were significantly higher (p<0.05) compared with non-hypertensive subjects (control). Furthermore, BMI, SBP, DBP, AMA-M7, AST and CTnI were significantly lower (p<0.05) in treated hypertensive patient compared with untreated hypertensive subjects. In conclusion, AMA-M7 is more sensitive marker in detecting auto-immune cardiac degeneration faster than the routine serum AST and Cardiac Troponin I in indicating the functional state of the heart. Therefore, early detection of auto-immune cardiac degeneration in hypertension subjects is important as there is a link between autoimmunity and hypertension.

Nephrin a biomarker of early glomerular injury in newly diagnosed untreated hypertensive subjects

Introduction and Aim: Hypertension and proteinuria is known to cause renal and cardiovascular disease and mortality in patients irrespective of diabetes. It is beneficial to identify proteinuria and probable glomerular injury early to take preventive measures from cardiovascular event. In our study, we aimed to evaluate whether a biomarker such as nephrin can detect early glomerular injury in treatment naïve hypertensive subjects. Materials and Methods: Forty newly diagnosed, treatment naïve hypertensive subjects were recruited for the study along with 40 normotensive controls after obtaining informed consent and procuring approval from. Institutional Ethics Committee. The hypertensive group was classified as diabetic and non-diabetic hypertensives and compared with apparently healthy controls (normotensive). Urine sample was analyzed for microalbumin, creatinine and nephrin. Blood sample was analyzed for glycated hemoglobin, urea, creatinine, sodium, and potassium. Statistical analysis was performed using ANOVA to compare the groups for various parameters. Odds ratio was calculated. Results: Hypertensives were sub-grouped based on amount of microalbumin excreted. Urine nephrin excretion was significantly higher in hypertensive subjects than normotensive subjects (nephrin cut-off: 0.09 mg/g of creatinine). Urine nephrin (mg/g) was found to be elevated (median 0.15; interquartile range, 0.12 and 0.17) in hypertensives with normoalbuminuria and it was significantly higher than normotensive subjects (median 0.07; interquartile range, 0.04 and 0.09). Conclusion: Urine nephrin may be used as a biomarker of early glomerular injury in hypertensive subjects even before microalbuminuria is detected.

Influence of Hypersensitive C-Reactive Protein on the Effect of Continuous Antihypertensive Pharmacological Therapy.

Systemic chronic inflammation, represented by hypersensitive C-reactive protein (hsCRP), is an essential contributing factor to hypertension. However, the influence of hsCRP levels on the effect of antihypertensive pharmacological therapy remains unknown. We evaluated hsCRP levels in 3756 newly diagnosed, untreated hypertensive subjects. Participants were grouped by tertiles of hsCRP and were randomly treated with nitrendipine + captopril, nitrendipine + spironolactone hydrochlorothiazide + captopril, and hydrochlorothiazide + spironolactone. Blood pressure (BP) was recorded every 2 weeks. A multivariate mixed linear model was used to evaluate the impact of baseline hsCRP levels on the continuous antihypertensive effect. After 3, 6, 9, and 12 months of continuous antihypertensive treatment, no significant difference was observed in BP decline among the different hsCRP groups. We identified interactions between baseline hsCRP levels and follow-up time. After adjusting for conventional risk factors and the interactions between hsCRP and follow-up time, there was no significant association between baseline hsCRP level and antihypertensive effects at 0-6 months of follow-up. However, from 6 to 12 months, subjects with higher baseline hsCRP levels exhibited a more marked BP-lowering effect ( P < 0.001 at 9 months, P = 0.002 at 12 months). Overall, there exist interaction effects between baseline hsCRP levels and follow-up time. Individuals with higher baseline hsCRP levels may exhibit a better response to antihypertensive therapy.

BLOOD PRESSURE CONTROL IS BETTER IN PRIMARY CARE THAN IN THE GENERAL POPULATION: A CROSS-SECTIONAL STUDY IN A MULTI-PROFESSIONAL RURAL HEALTH CENTER (DOMFRONT, NORMANDY, FRANCE)

Objective: In 2015, more than 11 million patients treated for arterial hypertension in France. According to several studies in the general population, about 50% of hypertensive subjects are treated and about 20% are treated and controlled. There are very few data in general medicine. Our work have studied how these data may have differed in general medicine. Design and method: A cross-sectional observational study was carried out in a rural health center (Domfront, Normandy, France) on subjects aged 18 to 65 in 2018. A subject was considered to be hypertensive if his blood pressure (taken in the office in routine care) was greater than 140/90 or if it was treated with antihypertensive drugs. Results: Of 1,925 subjects, there were 54.3% women, aged 54.6 ± 7.1 years. The mean blood pressure was 127 ± 13/76 ± 8 mmHg, 60.6% (682/1127) were overweight and 5.0% (96/1925) were diabetic. 646 (33.6%) were hypertensive and 410 hypertensive (63.5%) were treated. 39.0% (252/646) were treated and controlled. Conclusions: In general medicine, blood pressure control seems to be better than in the general population, whereas the general practitioner is often the first contact with the healthcare system. Poor blood pressure control in the population can be explained by the lack of general medicine consultations for untreated hypertensive subjects.

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.

MAY MEASUREMENT MONTH 2019. AN ANALYSIS OF BLOOD PRESSURE SCREENING RESULTS IN CRETE, GREECE

Abstract Objective: Worldwide, there is a high level of ignorance about elevated blood pressure (BP), which contributes to the large percentage of underdiagnosed and untreated hypertensive subjects. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and acting as a stimulus to improving screening programs. Design and method: An opportunistic cross-sectional survey of volunteers aged = &gt; 18 years was carried out in May 2019. Each adult individual underwent evaluation by 3 sitting BP measurements, a dedicated questionnaire regarding awareness of hypertension (HT) and control of it and other cardiovascular risk factors. Screenings sites in hospitals, shopping centres, workplaces, community centres, GP practices, and pharmacies were set up across the island of Crete as part of this initiative. HT was defined as SBP &gt; 140mmHg and/or DBP &gt; 90mmHg (average of 2nd and 3rd BP measurement) or previous HT diagnosis. BP control was defined as SBP/DBP &lt; 140/90 mmHg in treated hypertensives. Results: During this survey, a total of 1612 participants [729 (45.2%) men] were screened for high BP and associated risk factors. Their median age was 57 (range: 18–93) years. The prevalence of HT was 49.9% (57.9% in men and 43.4% in women; p &lt; 0.001). Only 584 out of 805 hypertensives (72.5%) were treated. Among those on anti-hypertensive medication 70.0% were controlled. Among hypertensive subjects, 13.7% did not have any other cardiovascular risk factor, 41.2% had dyslipidaemia, 25.8% were diabetics, 23.6% were smokers and 58.8% were obese. Conclusions: This study reveals that arterial hypertension prevalence continue to rise, with poor blood pressure control. There is an urgent need to conduct further national level screening campaigns to identify individuals with raised BP. This will ensure early detection and management of BP thereby reducing complications associated with it.

Haplotype of receptor for advanced glycation end products is associated with arterial stiffness in essential hypertension

Abstract Background What causes us to age has been extensively explored. The receptor for AGEs (RAGE) expression is up-regulated in atherosclerotic plaques and its activation leads to oxidative stress, cytokine and adhesion molecule formation, activation of nuclear factor-κB and cell apoptosis. We hypothesized that genetic variation in the RAGE receptor may be associated with arterial stiffness. Methods 309 untreated hypertensive subjects were tested for genotypes of –374T&amp;gt;A and –429T&amp;gt;C polymorphisms with polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Arterial stiffness was measured as pulse wave velocity (PWV), augmentation index (AIx) and central aortic blood pressure (BP). Data was analysed using JMP Version 13 (SAS for Windows). Results Both polymorphisms were in Hardy-Weinberg equilibrium. The –374A A allele carriers had significantly lower aortic systolic BP (143±2 vs. 154±1, p&amp;lt;0.001) while –429C allele carriers had lower aortic systolic BP (151±1 vs. 157±2, p&amp;lt;0.01) compared with T carriers. –429C allele carriers had lower PWV compared to 429TT individuals (8.86±1 vs. 10.70±2.5). –374A allele carriers had lower PWV compared to 374TT individuals (9.7±1.43 vs. 10.65±2.6). Subjects with the AC haplotype had the lowest and those with the TT haplotype the highest PWV and aortic BP than any of the other haplotypes containing one or more of the at-risk alleles. Conclusions The combined effect of the two genotypes was additive with AA homozygotes of –374T&amp;gt;A and C allele carriers of –429T&amp;gt;C and the haplotype AC, associated with lowest aortic BP and arterial stiffness. PWV &amp; RAGE haplotypes Funding Acknowledgement Type of funding source: None

Effect Of Α-Linolenic Acid On Vascular Function And Metabolic Risk Markers During The Fasting And Postprandial Phase: A Randomized Placebo-Controlled Trial In Untreated (Pre)Hypertensive Subjects

Background and Aims: Only a limited number of studies have examined the vascular and postprandial effects of α-linolenic acid (ALA, C18:3n-3). Therefore, we performed a well-controlled study focussing specifically on the effects of ALA on vascular function and metabolic risk markers during the fasting and postprandial phase in untreated (pre)hypertensive subjects.

Evaluation of Cardiorespiratory Function During Cardiopulmonary Exercise Testing in Untreated Hypertensive and Healthy Subjects.

Objective: This study aimed to compare differences in cardiorespiratory function between untreated hypertensive subjects (UHS) and healthy subjects (HS) during cardiopulmonary exercise testing (CPET). Additionally, it also aimed to explore the potential mechanisms of different exercise responses in cardiorespiratory function before, during and after CPET.Methods: Thirty subjects (15 UHS and 15 HS) were enrolled. Photoplethysmography (PPG), respiratory signal, and ECG were simultaneously collected while subjects were performing CPET. Fiducial points (a, b, c, d, e) were extracted from the second derivative of the PPG (SDPPG), and the ratios b/a, c/a, d/a, e/a, and (b-c-d-e)/a (named Aging Index, AGI) were calculated as markers of systolic and diastolic function. Additionally, respiratory rate was calculated and analyzed.Results:Before CPET, there were no significant differences in b/a, d/a, and AGI between two groups. However, after CPET, b/a (−0.9 ± 0.19 vs. −1.06 ± 0.19, p-value = 0.03) and AGI (−0.49 ± 0.75 vs. −1.15 ± 0.59, p-value = 0.011) of the UHS group were significantly higher than those of the HS. The d/a (−0.32 ± 0.24 vs. −0.14 ± 0.17, p-value = 0.024), and c/a (−0.33 ± 0.26 vs. −0.07 ± 0.19, p-value = 0.004) were significantly lower in UHS than those in HS. In contrast, before CPET, e/a (0.22 ± 0.11 vs. 0.32 ± 0.09, p-value = 0.007) in UHS was significantly lower than that in HS, while after CPET there was no significant difference between the two groups in this variable. In addition, during CPET, AGI (p-value = 0.003), and respiratory rate (p-value = 0.000) in UHS were significantly higher in comparison with before CPET.Conclusions: Different exercise responses showed the differences of cardiorespiratory function between UHS and HS. These differences not only can highlight the CV risk of UHS, but also can predict the appearance of arterial stiffness in UHS. Additionally, during CPET, significant differences in AGI, autonomic nervous function and respiratory activity assessed by respiratory rate were found between the two groups in comparison with before CPET.

Prognostic Value of Aortic Pulse Wave Velocity as Index of Arterial Stiffness in the General Population

Background: During a person’s lifetime, as part of the aging process or as a consequence of hypertension, atherosclerosis, or other pathological processes, the aorta stiffens. Accordingly, the forward pulse wave travels faster, and the arterial waves reflected from the periphery reach the heart early during systole, which leads to higher systolic but lower diastolic blood pressure, an augmentation of the cardiac workload, and a decrease of the coronary perfusion pressure. The aortic pulse wave velocity (APWV) reflects central arterial stiffness. Some studies addressed the prognostic significance of APWV above and beyond other cardiovascular risk factors. Furthermore, pulse pressure, an indirect measure of increased arterial stiffness, predicts a poor prognosis in treated and untreated hypertensive subjects. Methods: The study was conducted on a sex- and age-stratified random sample of 167 rural and suburban population of Haryana state aged 40 to 70 years. Results: Cox regression analysis was used to investigate the prognostic value of APWV, pulse pressure (PP) and other covariates. We adjusted for sex, age, body mass index. MAP measured in the office (conventional PP) and APWV by Periscope TM. With these adjustments, APWV maintained its prognostic significance in relation to each end point (P 0.19). In sensitivity analyses, APWV still predicted all cardiovascular events after standardization to a heart rate of 60 beats per minute, after adjustment for MAP. Conclusions: In a general population of Haryana, APWV predicted a composite of cardiovascular outcomes above and beyond traditional cardiovascular risk factors.

Molecular and genetic aspects of guanylyl cyclase natriuretic peptide receptor-A in regulation of blood pressure and renal function.

Natriuretic peptides (NPs) exert diverse effects on several biological and physiological systems, such as kidney function, neural and endocrine signaling, energy metabolism, and cardiovascular function, playing pivotal roles in the regulation of blood pressure (BP) and cardiac and vascular homeostasis. NPs are collectively known as anti-hypertensive hormones and their main functions are directed toward eliciting natriuretic/diuretic, vasorelaxant, anti-proliferative, anti-inflammatory, and anti-hypertrophic effects, thereby, regulating the fluid volume, BP, and renal and cardiovascular conditions. Interactions of NPs with their cognate receptors display a central role in all aspects of cellular, biochemical, and molecular mechanisms that govern physiology and pathophysiology of BP and cardiovascular events. Among the NPs atrial and brain natriuretic peptides (ANP and BNP) activate guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) and initiate intracellular signaling. The genetic disruption of Npr1 (encoding GC-A/NPRA) in mice exhibits high BP and hypertensive heart disease that is seen in untreated hypertensive subjects, including high BP and heart failure. There has been a surge of interest in the NPs and their receptors and a wealth of information have emerged in the last four decades, including molecular structure, signaling mechanisms, altered phenotypic characterization of transgenic and gene-targeted animal models, and genetic analyses in humans. The major goal of the present review is to emphasize and summarize the critical findings and recent discoveries regarding the molecular and genetic regulation of NPs, physiological metabolic functions, and the signaling of receptor GC-A/NPRA with emphasis on the BP regulation and renal and cardiovascular disorders.

THE INFLUENCE OF GENDER ON LEFT VENTRICULAR MECHANICS IN HYPERTENSIVE PATIENTS

Objective: The aim of this study was to evaluate the influence of gender on left ventricular (LV) mechanics in hypertensive individuals. Design and method: This cross-sectional study included 198 untreated hypertensive subjects and 107 normotensive controls who underwent 24-hour ambulatory blood pressure monitoring and comprehensive two-dimensional echocardiographic examination including strain assessment. Results: There was no difference in 24-h blood pressure between hypertensive men and women. LV mass index was significantly higher men than in women in hypertensive and normotensive group. Hypertensive men and women had significantly lower 2D LV global longitudinal, circumferential and radial strains than their normotensive counterparts. LV global longitudinal strain was lower in hypertensive men than in women (−20.2 ± 2.3 vs. −18.8 ± 2.0, p < 0.01). LV global circumferential strain was also worse in hypertensive men than in men (−21.4 ± 2.9 vs. −19.5 ± 2.5, p < 0.01). The difference in LV radial strain was not discovered between hypertensive women and men. Assessment of layer-specific LV strain showed that endocardial and mid-myocardial longitudinal and circumferential strains were significantly lower in hypertensive population and especially in hypertensive men comparing with hypertensive women. Furthermore, LV twist was significantly higher in hypertensive women than in hypertensive men (20.6 ± 6.8 degree vs. 21.6 ± 7.3 degree, p = 0.02). Female gender and arterial hypertension, as well as their interaction, were associated with LV hypertrophy, reduced LV global longitudinal strain and increased LV twist. Conclusions: LV longitudinal and circumferential strains were significantly reduced in hypertensive patients. Endo- and mid-myocardial LV layers were particularly influenced by arterial hypertension. However, hypertensive women suffered more significant changes in LV longitudinal strain and LV twist than hypertensive men.

Danhong Injection Protects Against Hypertension-Induced Renal Injury Via Down-Regulation of Myoglobin Expression in Spontaneously Hypertensive Rats

Background/Aims: High blood pressure is a major risk factor for chronic kidney disease. Currently, single-target anti-hypertensive drugs are not designed for high blood pressure-related organ damages. Danhong injection (DHI), made from the aqueous extracts of Radix Salviae miltiorrhizae and Flos Carthamus tinctorius, has various pharmacological effects, including BP lowering in SHR, mediated by the reduction of vascular remodeling and the up-regulation of Kallikrein-kinin system published recently by our team, yet if it renders renal protection remains unknown. The current study demonstrated a protective role of DHI in renal injury caused by hypertension and identified its molecular targets in the kidney of spontaneously hypertensive rats (SHR). Methods: Adult SHR and age/gender-matched normotensive Wistar-Kyoto (WKY) rats were treated with DHI, Losartan, or saline for 4 weeks. Serum levels of Creatinine (CRE), Micro-albumin (mAlb), Beta2-microglobulin (β2-MG), and Uric acid (UA) were detected using ELISA kits. Renal pathology was examined by hematoxylin and Eosin (H&E) stains. Microarray analysis was performed on kidney tissues, and gene expression changes were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses. Results: Renal histopathological scores showed that SHR exhibited serious kidney injury compared to normotensive WKY rats. The intervention with DHI potently suppressed the renal injury biomarker (KIM-1) and kidney lesions compared to the untreated hypertensive subjects. Microarray analysis revealed that among the 124 genes that were differentially expressed by DHI treatment in SHR kidney, down-regulation of renal myoglobin (Mb) gene was the most prominent and was subsequently confirmed by qRT-PCR and Western blot analysis. Conclusion: Hypertension-induced renal injury in SHR may be alleviated by DHI in part by local suppression of Kidney injury molecule-1 and down-regulation of Myoglobin. However, if this effect is independent of the known anti-hypertensive action of DHI in blood vessel remains to be determined.

Hemodynamic Determinants of the Short-Term Blood Pressure Variability: Differential Roles of Arterial Stiffness and Wave Reflection.

A high 24-hour ambulatory diastolic (DBP) but not systolic (SBP) blood pressure variability (BPV) is significantly predictive of long-term cardiovascular mortality in untreated hypertensive subjects, independent of office or 24-hour SBP. The present study was aimed to investigate hemodynamic factors that are independently associated with systolic and diastolic BPV from the 24-hour ambulatory blood pressure monitoring (ABPM). A cohort of 624 normotensive and 633 untreated hypertensive participants with baseline ABPM was drawn from a community-based survey. BPV was assessed by the read-to-read average real variability of the 24-hour SBP and DBP (ARVs and ARVd, respectively). Hemodynamic variables including total peripheral resistance (TPR), carotid-femoral pulse wave velocity (cf-PWV), and amplitudes of the decomposed forward (Pf) and backward (Pb) carotid pressure waves were analyzed. In multivariable analyses, hemodynamic variables independently associated with 24-hour SBP were 24-hour heart rate (HR), TPR, cf-PWV, Pf, and Pb (model r2 = 0.535). Hemodynamic factors independently associated with ARV were 24-hour HR, Pf, and Pb for ARVs, and 24-hour HR, cf-PWV, Pf, and Pb for ARVd (model R2 = 0.345 and 0.220, respectively). Addition of 24-hour SBP to the ARV models only slightly improved variance explained by the models (R2 = 0.383 and 0.224, respectively). Pb accounted for >50% of total variance of ARVs and ARVd, whereas cf-PWV was a minor determinant of ARVd (<5% of total variance). ARVd was associated with fewer hemodynamic variables than to 24-hour SBP. Among those hemodynamic variables wave reflection but not arterial stiffness had the dominant independent association with ARV.

LBOS 01-02 CLUSTERING OF SILENT HYPOTENSIVE EPISODES IN THE MORNING/LATE-MORNING HOURS IN SUBJECTS TREATED FOR HYPERTENSION

Objective: We have previously noted morning/late-morning hypotension (M/LM) in some hypertensive subjects. Here we intended to establish its prevalence in relation to daytime blood pressure (BP) in general. Design and Method: Daytime hypotension was defined as systolic BP<110mmHg or ≥25% lower than the mean 3 first awake recordings provided that it was also < 85% of the mean 24 h systolic-BP. We evaluated 781 ABPM (Spacelabs 90207/902017A) recordings from 179 subjects with normal BP and 602 hypertensive subjects. Results: Daytime hypotension (mean systolic pressure [SP] during hypotension 101+/−1 mmHg) was more common in subjects receiving antihypertensive drugs than in untreated hypertensive subjects [158/336 (43%) vs. 76/266 (29%); p < 0.05]. In treated hypertensive subjects hypotensive episodes tended to cluster in the M/LM hours [08:00–12:00]: in nearly 50% (76/158) of treated patients with daytime [06:00–23:00] hypotension, hypotensive episodes were detected in the M/LM, as compared to 19/79 (24%;) in untreated hypertensive subjects (p < 0.05). Clustering analysis revealed that M/LM hypotension was more prevalent, compared to other daytime hours in treated, but not in untreated hypertensive subjects (OR- 1.69 and 0.87, respectively; p < 0.0005). Among treated hypertensive subjects, M/LM clustering was seen in the uncontrolled subjects (p < 0.0005) but not in controlled patients. However, daytime SP was higher in treated subjects free of daytime hypotension compared to those with falls in BP (136 ± 14 vs. 130 ± 14; t-test, p < 0.0001). SP during M/LM falls was lower in controlled than in uncontrolled hypertensive subjects (93+/−7 vs. 103+/−12mmHg; p < 0. 0001). Age (68 ± 1.7 vs. 64 ± 1; p < 0.0001) was higher among treated subjects with M/LM falls compared with treated subjects without M/LM falls. Conclusions: Daytime hypotensive episodes are common and tend to cluster in the M/LM hours in treated older hypertensive subjects, particularly in the setting of uncontrolled hypertension. Age, dosing time and circadian decline in hormones affecting blood pressure may play a role in this phenomenon.

Morning blood pressure surge and markers of cardiovascular alterations in untreated middle-aged hypertensive subjects

The purpose of the study was to evaluate the degree of morning blood pressure surge (MBPS) and its relationship with markers of cardiovascular alterations in untreated middle-aged hypertensives. We studied 241 patients (mean age, 36.6 ± 10.7 years). Subjects with higher sleep-through MBPS (st-MBPS) were older (P = .003), had higher carotid intima-media thickness (cIMT) (P = .05) and lower E/A ratio (P = .01) than those with lower MBPS. Subjects with higher prewakening MBPS (pw-MBPS) had significantly higher deceleration time (P = .01) compared with those with lower pw-MBPS. St-MBPS correlated significantly with age, cIMT values, 24-hour systolic and diastolic BP, and systolic BP night-time fall. The significant correlations between pw-MBPS and cIMT values, deceleration time, 24-hour diastolic BP and systolic BP night-time fall were observed. A relationship between MBPS and cardiovascular alterations was observed both in dippers and nondippers, although in non-dippers, it was less pronounced. The results may imply a possible link between MBPS and markers of cardiovascular alterations in untreated hypertensive subjects.

Effect of sodium intake on renin level: Analysis of general population and meta-analysis of randomized controlled trials

BackgroundWe evaluated the association between sodium intake and plasma renin levels in the cross sectional study and meta-analysis of randomized controlled trials, whether there is a persistent elevation of plasma renin by longer-term sodium intake restriction. MethodsPlasma renin activity (PRA) and 24-h urine sodium (24HUNa) excretion were measured from individuals randomly selected from a community. Simple and multiple linear regression analyses adjusted for age, 24-h systolic blood pressure, 24-h average heart rate, fasting blood glucose and gender were performed. For meta-analysis, 74 studies published from 1975 to mid-2014 were identified in a systematic literature search using EMBASE, CINAHL, and MEDLINE. Random effects meta-analyses and a meta-regression analysis were performed. ResultsAmong the 496 participants recruited, 210 normotensive and 87 untreated hypertensive subjects were included in the analysis. There was no significant association between PRA and 24HUNa in the total population, or hypertensive and normotensive individuals. In the meta-analysis, the standard mean difference (SMD) of renin level by sodium intake reduction was 1.26 (95% CI: 1.08 to 1.44, Z=12.80, P<0.001, I2=87%). In the meta-regression analysis, an increase in a day of intervention was associated with a fall in SMD by −0.04 (95% CI: −0.05 to −0.02, Z=−5.27, P<0.001, I2=86%), indicating that longer duration of reduced sodium intake would lead to lesser SMD of renin level. ConclusionsThe present population based cross-sectional study and meta-analysis suggests that prolonged reduction in sodium intake is very unlikely associated with elevation of plasma renin levels.

Effects of the Antihypertensive Fixed-Dose Combinations on an Early Marker of Hypertensive Cardiac Damage in Subjects at Low Cardiovascular Risk.

In hypertensive subjects (HTs), isolated left ventricular diastolic dysfunction (LVDD) is an early marker of cardiac damage and is associated with poor prognosis. However, few intervention trials investigated the effects of antihypertensive therapy on isolated LVDD regression. This study investigates the blood pressure (BP)-lowering efficacy and the effect on LVDD of antihypertensive drugs administered as fixed-dose combinations in untreated HTs with isolated LVDD. A total of 168 HTs (23% of them having impaired fasting glucose (IFG)) aged 48±4.2 years were randomized to receive open-label once-daily oral treatment of beta-blocker + diuretic, angiotensin-converting enzyme inhibitor (ACEI) + diuretic, angiotensin II receptor blocker (ARB) + diuretic, ARB + calcium channel blocker (CCB), or ACEI + CCB. Clinic and 24-hour ambulatory BP values were measured before randomization and at the follow-up. Regression of LVDD was defined as normalization of both the E/A (ratio of early-to-late ventricular filling wave velocity) and E/E' (mitral velocity to early diastolic velocity of the mitral annulus) ratios. Comparisons were made between categorical variables using the χ(2) test and between continuous variables by gender using analysis of variance for repeated measures. BP reduction did not differ between groups. LVDD regression was significantly more prevalent in the ARB + CCB or ACEI + CCB groups than with other combinations; in HTs with IFG, it was most prevalent (46%) with ACEI + CCB. Independently of BP reduction, the fixed-dose combinations ARB + CCB and ACEI + CCB led to regression of isolated LVDD. In those with an IFG, ACEI + CCB was most effective.

Circadian changes in blood pressure in the brachial artery and the aorta assessed by simultaneous monitoringin untreated hypertension

Objective . To study and compare the daily changes of parameters of central pulse wave (PW) with the traditional indicators of 24‑hour ambulatory blood pressure monitoring (ABPM) on the brachial artery (BA) depending on daily profile in different age groups. Design and methods . Successful ABPM of brachial and central BP (&gt; 85 % valid readings) was performed by oscillometric BPLab VASOTENS system (“Petr Telegin”, Nizhniy Novgorod, Russia) in 84 untreated hypertensive subjects (mean age 55,8 ± 9,6 years, male 36,9 %, clinical BP 152,6 ± 9,2 / 94,8 ± 8,2 mm Hg). The device allows to derive aortic BP and augmentation index (AIx) from brachial PW. Gender differences of central BP and AIx were evaluated in different age groups: &lt; 55 (14 men, 23 women), 55–60 (7 men, 16 women), 61–70 years (10 men, 14 women). Differences were considered significant at p &lt; 0,05. Results. Nighttime central BP was disproportionately higher than daytime values, proven by a smaller difference between BP in BA and the aorta at night compared to daytime parameters. AIx@75 was higher at night than during day. The differences between systolic BP (SBP) and BP in BA and the aorta was 10,4 ± 2,2 and 11,4 ± 1,0 mmHg in daytime and lower at night — 8,1 ± 2,0 and 9,0 ± 1,8 mmHg. The number of non-dippers and night-pickers according to aortic SBP values was greater than according to SBP assessed in BA. Men had slightly higher levels of brachial and aortic SBP than women. More profound nocturnal decline of brachial and aortic SBP was found in in women than in men. Despite comparable heart rate, AIx@75 was higher in women at all time periods, however, nocturnal increase in AIx@75 was significantly more evident in men. Conclusions. Central BP was disproportionately higher at nighttime than during the day, proven by a smaller difference between BP in BA and the aorta at night than during the day. AIx and its diurnal variation are characterized by gender-associated differences across all age group and are dependent on SBP daily profile. This finding should be considered when interpreting the results 24‑hour monitoring of central BP and requires further investigation of its prognostic value.