bluuebunny/crossref_metadata_2025 huggingface dataset:
HOME BLOOD PRESSURE MONITORING WITH A DIGITAL BLOOD PRESSURE COACH - A PROSPECTIVE ANALYSIS OF USER DATAi
Authors: Beger Christian , Lenz Anna , Wagner Steffen , Filler Andreas , Sévin Claire-Michelle , Heppler Michelle , Volland Dirk , Limbourg Florian
Published: June 2022

Objective:

Home blood pressure monitoring (HBPM) is recommended by guidelines for the management of hypertension. The Manoa smart phone app is a certified digital coach that informs, guides and supports users in guideline-compliant HBPM, which involves completion of at least 6 days of home BP measurements. The app has been freely available in all relevant app stores since April 2020.

Design and method:

From 4/20 to 3/21 we prospectively analyzed self-reported BP levels and user data from users who self-identified as having the diagnosis of hypertension. The prospective study protocol was approved by the local ethics committee.

Results:

To evaluate the effects of a digital BP coach on BP levels we analyzed the change in app-documented BP levels between baseline and follow-up HBPM periods (8–16 weeks, n = 864). Average baseline systolic home BP was 131.5 mmHg for the total group, which decreased significantly to 128.06 mmHg at follow-up (p < 0.05), resulting increased BP control from 70% of hypertensive users at baseline to 81% at the follow-up HBPM period. In the subgroup of users with uncontrolled BP at baseline, and who also had recorded follow-up BP data (n = 384), baseline BP was 138.8.0mmHg, which decreased significantly to 132.69 (p < 0.001).

We analyzed the change in SBP according to baseline SBP. To this end, we first used non-linear fitting followed by steady linear fitting and linear regression analysis. There was a significant negative linear correlation (r = -0.56, p < 0.001) between SBP lowering and baseline BP down to level of SBP of 125 mm Hg. Below this value, baseline SBP was not associated with SBP decrease at follow up (r = -0.19, p = 0.16).

Conclusions:

Our data show that the use of a digital BP coach by users with self-reported hypertension is associated with a reduction in average BP and an improvement in hypertension control after two periods of structured HBPM.
EFFECTS OF MINERALOCORTICOID RECEPTOR ANTAGONISTS ON ALDOSTERONE TO RENIN RATIO IN PATIENTS WITH PRIMARY ALDOSTERONISM
Authors: Pecori Alessio , Buffolo Fabrizio , Burrello Jacopo , Mengozzi Giulio , Rumbolo Francesca , Avataneo Valeria , D’Avolio Antonio , Rabbia Franco , Bertello Chiara , Veglio Franco , Mulatero Paolo , Monticone Silvia
Published: June 2022

Objective:

Current guidelines recommend to withdraw interfering antihypertensive drugs before to perform a screening test for primary aldosteronism (PA). Recent studies suggested that diagnostic work-up of PA might be performed without withdrawing mineralocorticoid receptor antagonist (MRA) treatment in selected patients, especially when severe hypertension and hypokalemia are difficult to control.

We designed a prospective study to evaluate the effects of MRA treatment on aldosterone to renin ratio (ARR) in patients with PA.

Design and method:

We prospectively recruited 121 patients with confirmed PA and started on canrenone treatment. Eighteen patients were enrolled in a short-term treatment cohort to assess the effects of MRA on aldosterone to renin ratio (ARR) and potassium after 2 and 8 weeks of canrenone therapy. One hundred and two patients were recruited in the long-term treatment cohort to evaluate the effects of canrenone on ARR after 2 to 12 months of MRA therapy.

Results:

Plasma renin activity and potassium displayed a significant increase, and ARR showed a significant reduction compared with baseline in patients with PA after MRA initiation. These effects were observed both after a short- and a long-term treatment with canrenone, and were progressively more significant after longer periods of therapy and with greater doses of MRA. We demonstrated that canrenone assumption severely impacts on the rate of false-negative screening tests for PA, which raised from 16.7% to 72.5% after 2 weeks and 7–12 months of MRA treatment, respectively.

Conclusions:

ARR testing for PA screening should not be performed under MRA therapy.
TAKOTSUBO SYNDROME REVEALING PHEOCHROMOCYTOMA
Authors: Cordeanu Elena-Mihaela , Mirea Corina , Tousch Jonathan , Ohlmann Patrick , Vix Michel , Diaye Gora N. , Henriette Victor , Stephan Dominique
Published: June 2022

Objective:

We report the case of 57-year old woman with no previously known cardiovascular disease.

Design and method:

Her conventional cardiovascular risk factors were type 2 diabetes (HbA1c< 6.5%), hypertension and active smoking. She presented to the ER for thoracic pain, headache, sweating and tachycardia (150 bpm).

Results:

Blood analysis showed an elevation of cardiac biomarkers (Troponin 2035ng/l; BNP 541ng/l, Ddimers 19500ug/l), and acute renal impairment (creatinin 158umol/l) while EKG showed inferior NSTEMI. Echocardiography visualized typical takotsubo aspect with apical hypokinesia. Thoraco-abdominal CT-scan showed an important left adrenal tumor. Plasmatic and urinary metanephrine and normetanephrine were high. The patient benefited from adrenal surgery with an optimal result on blood pressure control.

Conclusions:

Although the association TTS-pheochromocytoma has already been described, it remains uncommon. Catecholamine excessive secretion mediates TTS cardiomyopathy having a negative impact essentially on apical segments increasing wall stress and pressure, but different ventricular segments may be concerned as individual adrenoreceptors distribution patterns vary. TTS diagnosis should legitimate pheochromocytoma screening when associated with labile hypertension.
COMPARISON BETWEEN DISTINCT INSULIN RESISTANCE INDICES IN MEASURING THE DEVELOPMENT OF HYPERTENSION: THE CHINA HEALTH AND NUTRITION SURVEY
Authors: Yuan Yue , Sun Wei , Kong Xiangqing
Published: June 2022

Objective:

The link between insulin resistance (IR), obesity and the development of hypertension is well known. This study aimed to identify the relationship between several surrogate IR indices based on lipid products and the development of hypertension.

Design and method:

A total of 4797 participants aged 18 years or older enrolled in the China Health and Nutrition Survey from 2009 to 2015 were included in final analysis. Logistic regression was used to analyze the association between different IR indices and the presence of hypertension.

Results:

There were 1972 (41.1%) hypertensive participants in 2015. With regard to the homeostasis model assessment of insulin resistance (HOMA-IR) based on insulin level, subjects in the highest quartile of HOMA-IR values were more likely to develop hypertension [OR = 1.45(1.18–1.78), P < 0.001] in the fully adjusted model. Subjects in the highest quartile of the triglyceride glucose index (TyG) combined with body mass index (BMI) and waist circumference (WC) had more than 3 times the risk of hypertension after full adjustment compared with individuals in the lowest quartile (both P < 0.001), and the trend continued when adjusted for the HOMA-IR. Compared with those in the lowest quartile of HOMA-IR values, men in the highest quartile had a higher risk of developing hypertension than women [2.05 (1.59–2.64) vs. 1.97 (1.54–2.51)] after the full adjustment, which is the opposite of the association between the six lipid-based products and incident hypertension by sex.

Conclusions:

The results from our large-scale study elucidate the superiority of the TyG-BMI and TyG-WC compared with the HOMA-IR in hypertension prediction, which may be related to lipid deposition. The sex-specific predictive value is distinct for different IR indicators.
MEASUREMENT OF PULSE WAVE VELOCITY IN HEMODIALYSIS PATIENTS
Authors: Khadhar Meriam , Kheder-Elfekih Renia , Jebali Hela , Ikram Mami , Lilia Ben Fatma , Wided Smaoui , Media Krid , Soumaya Beji , Karim Zouaghi
Published: June 2022

Objective:

Cardiovascular complications represent the leading cause of death in chronic kidney disease.

These patients combine classical and unconventional cardiovascular risk factors. Arterial stiffness, assessed by measuring the pulse wave velocity (PWV), is a reliable means of assessing cardiovascular risk. It has been rarely studied in hemodialysis patients.

The purpose of our study was to evaluate the level of arterial stiffness by measuring carotid-femoral pulse wave velocity in a population of chronic hemodialysis patients and to investigate factors contributing to arterial stiffness.

Design and method:

We conducted a cross-sectional, descriptive study concerning the carotid-femoral pulse wave in hemodialysis patients during two years.

Results:

Our population included 38 chronic hemodialysis patients. Mean duration of hemodialysis was 29.21 ± 24.56 months. The mean age was 49 ± 13 years (16–78 years). Twelve patients were hypertensive (31.6%). Mean arterial pressure was 95 ± 13.5 mmHg. Hemoglobin value was 9.20 ± 1.66 g / dl. PTH was 714 ± 573 ng / l.

PWV was 9.03 ± 2.73 m / s (5–16 m / s). Univariate analysis concluded that PWV acceleration was correlated with age, history of stroke, history of coronary artery disease, diabetes, HTA, elevated PTH and elevated CRP.

Conclusions:

A better understanding of factors influencing arterial stiffness, allows to intensify primary and secondary prevention in hemodialysis patients.
ADIPOSITY AND VASCULAR AGEING: WHICH PARAMETER BETTER CORRELATES?
Authors: Guareschi Alessandro , Vicenzi Marco , Calcagnino Margherita , Carugo Stefano , Scuteri Angelo
Published: June 2022

Objective:

The increase in stiffness of large arteries is one of the mechanisms that could play a role in the association between obesity and increased risk of cardiovascular (CV) events. Carotid-femoral pulse wave velocity (cfPWV) represents a validated measure of large arteries stiffness and a good proxy of arterial ageing. We aimed at evaluating which body composition parameters better correlated with cfPWV and whether this correlation differed between men and women.

Design and method:

cfPWV was measured in all subjects; body composition was evaluated by bioimpedance analysis and waist circumference (W). Furthermore, each subject was characterized by sex, age, height, weight, body mass index (BMI), brachial blood pressure (BP) and heart rate. A linear correlation was used to define the relationship between cfPWV and parameters. Univariate and multivariate analysis were performed in male and female subgroup separately to select the main determinants of arterial stiffness, considering the following parameters: age, mean BP (mBP), BMI, W, fat mass (FM) and skeletal muscle mass (SMM). We enrolled 69 subjects (37 men, 32 women) with average age 34.5 years (min 19-max 76).

Results:

cfPWV was significantly correlated with age (r = 0.65, p < .0001), and mBP (r = 0.38, p < .01). Among the body composition parameters, W, BMI and FM percentage were significantly correlated with cfPWV (respectively: r = 0.48, r = 0.42, r = 0.41; p < .0001). Multivariable regression analysis in men revealed that age and mBP were significant determinants of cfPWV (respectively: b = 0.042, p = 0.002; b = 0.051, p = 0.004). Conversely, multivariate analysis in women showed that age, FM and SMM are retained as main determinants of increased cfPWV (respectively: b = 0.079; p < 0.0001; b = 0.217, p = 0.012; b = 0.125, p = 0.011).

Conclusions:

Irrespectively of gender, age is the main determinant of arterial stiffness. Our results demonstrated that the relationship between adiposity and arterial stiffness is verified only in female subjects. This suggests that this relationship is influenced by complex and not fully known mechanisms. Moreover, technical factors (algorithm and indirect methods to assess body composition) contribute to uncertainty regarding which parameter exploring adiposity is more accurate in stratifying CV risk. The present study recalls attention on possible gender-specific determinants of arterial ageing.
LACK OF LIFESTYLE MODIFICATIONS IN GLOBAL HYPERTENSION MANAGEMENT
Authors: Vay-Demouy Juliette , Blacher Jacques , Olie Valérie
Published: June 2022

Objective:

The aim of this study is to analyze the role of lifestyle modifications in global arterial hypertension management in France.

Design and method:

This retrospective cross-sectional study is an analysis of the database of ESTEBAN study which was led by Santé Publique France from 2014 to 2016 on a representative sample of the French population. Our study focused on the aware hypertensive adults of the ESTEBAN final sample: 440 participants aged 18 to 74. The main criteria are the proportion of participants who received lifestyle advice(s) in their overall arterial hypertension management, with or without associated pharmacological treatment, and the proportion of recommendations of the three main lifestyle advices: physical activity practice, weight reduction and dietary modifications.

Results:

More than half (57%) of participants declared not to have received any lifestyle advice in the framework of their arterial hypertension management, including 39% who were not treated pharmacologically (Figure 1). Physical activity practice was recommended to 31.8% of sedentary participants and weight reduction to 26.8% of overweight participants. Less than a quarter (20.1%) received dietary recommendations (Figure 2), 69% of them for the limitation of salt intake and 10.7% for the limitation of alcohol intake.

Conclusions:

Lifestyle modifications remain too rarely recommended. Time of a medical visit is probably too short, although lifestyle advices should be discussed with the hypertensive patient at the time of diagnosis and throughout the follow-up, with the triple goal of a more efficient treatment, a better treatment persistence and finally a better blood pressure control.
GEOGRAPHICAL ANALYSIS OF HYPERTENSION IN CANADIAN POPULATION
Authors: Leroux Denis , Cloutier Lyne
Published: June 2022

Objective:

A quarter of population is affected by hypertension in Canada. Substantial improvement has been achieved in HTN control in Canada over the past twenty-five years. However, disparities associated with factors like sex, ethnicity, location and health care access remain. Reliable information about trends in hypertension is needed at regional scale for the development of health policies and programs. Health geography and geographic information systems can provide a better understanding of HTN and its risk factors by detecting clusters using spatial analysis and mapping rates of HTN. The objectives of the study were to identify health regions with significantly high or low HTN rate using geostatistics and compare evolution from 2005 to 2019. It also seeks out to identify their populations’ characteristics using conventional statistical analysis.

Design and method:

Canadian Community Health Survey (2005, 2015, 2019) data were used for the analysis. The 130,000 respondents are located according to health regions and data can be analyzed using a geographic information system. Using age and gender as criteria for subgroups creation, we applied spatial autocorrelation analysis and hot spot/cold analysis to identify geographically contiguous health regions with high or low HBP rates. We then extracted the records in CCHS database for all respondents living in these regions for further statistical analysis.

Results:

HTN is still a major problem in Canadian population, especially for people aged 65 years and older although 72.9% considered themselves in good, very good or excellent health in 2015. Increase in HTN rate in health regions is spread all over Canada, although some regions showed a decrease in HTN rate. Getis-ord analysis located a cold spot region in western Canada while a hot spot was located in Ontario, central Canada. Cluster of health regions with high HTN rates shows more diabetes and more obese people even though 38.4% declared being in good, very good or excellent health.

Conclusions:

Increase in hypertension rate in health regions is spread all over Canada, even tough some regions showed a decrease in HBP rate.

Canadians 65 years and older with HBP where more prone to obesity & diabetes.
PREVALENCE, PHENOTYPES AND CONTROL OF HYPERTENSION IN END-STAGE KIDNEY DISEASE PATIENTS UNDERGOING PERITONEAL DIALYSIS
Authors: Vareta Georgia , Georgianos Panagiotis , Vaios Vasilios , Sgouropoulou Vasiliki , Roumeliotis Stefanos , Georgoulidou Anastasia , Dounousi Evangelia , Eleftheriadis Theodoros , Papagianni Aikaterini , Balaskas Elias , Zebekakis Pantelis , Liakopoulos Vassilios
Published: June 2022

Objective:

Prior studies conduced in peritoneal dialysis (PD) patients in late 1990 s provided considerably variable estimates of the prevalence and control of hypertension. The present study aimed to investigate the current state of hypertension management in this high-risk population.

Design and method:

In 140 stable PD patients, we performed standardized automated office blood pressure (BP) measurements and 24-hour ambulatory BP monitoring (ABPM) using the Mobil-O-Graph device (IEM, Germany). Hypertension was defined as: (a) office BP equal or higher than 140/90 mmHg; (b) 24-hour BP equal or higher than 130/80 mmHg. Patients treated with at least 1 BP-lowering medications were also classified as hypertensives.

Results:

The prevalence of hypertension was 92.9% using office BP and 95% by ABPM. In all, 92.1% of patients were being treated with an average of 2.4 BP-lowering medications daily. Adequate BP control was achieved in 52.3% and 38.3% of hypertensives by office BP and ABPM, respectively. The agreement between these 2 techniques in the identification of patients with BP levels above the diagnostic thresholds of hypertension was moderate (k-statistic: 0.524). In all, 5% of patients were normotensives with both techniques, 31.4% had controlled hypertension, 5% had white-coat hypertension, 19.3% had masked hypertension and 39.3% had sustained hypertension. Isolated nocturnal hypertension was detected in 23.6% of patients, whereas no patient had isolated hypertension during daytime.

Conclusions:

Among PD patients, hypertension is highly prevalent and remains often inadequately controlled. The use of ABPM enables the better classification of the severity of hypertension and identification of isolated nocturnal hypertension, which is a rather common BP phenotype in the PD population.
ELECTROCARDIOGRAM CHANGES IN PREHYPERTENSIVE SUBJECTS – EPIDEMIOLOGY OF HYPERTENSION IN CROATIA-1 (EH UH-1) STUDY
Authors: Frkanec Stjepan , Katic Luka , Strbac Tea , Trobonjaca Adrian , Jelakovic Ana , Djapic Kresimir , Domislovic Viktor , Gellineo Lana , Rak Benedict , Tarnovski Lorka , Jelakovic Bojan
Published: June 2022

Objective:

The aim of this study was to analyze the characteristics and changes in the ECG findings of adults with prehypertension (PHT) in a random sample of the general population included in the EH-UH 1 project.

Design and method:

Epidemiology of hypertension in Croatia 1 (EH UH-1) study is nation-wide survey on prevalence, awareness, treatment and control of hypertension (HT) in Croatia. In 2001–2003 a random sample of 1267 subjects were enrolled. Mortality data were analyzed after average period of 17 years. In this sub-analysis we included 189 untreated subjects whom GPs did an ECG. Subjects were divided into 3 groups: optimal blood pressure (OBP) < 120/80 mmHg (N = 42), PHT 120–139/80–89 mmHg (N = 78) and untreated HT (UHT) > = 140/90 mmHg (N = 69).

Results:

Atrial fibrillation was found in 2%, 3% and 4% in OBP, PHT and UHT group, respectively (PHT vs OBP p < 0.05). QTc interval was prolonged in 2%, 13% and 65% in OBP, PHT and UHT group, respectively (PHT vs OBP p < 0.05; UHT vs PHT p < 0.01). Tpe interval was elevated in 12%, 14% and 17% in OBP, PHT and UHT group, respectively. Left ventricular hypertrophy (Cornell) was diagnosed in 5%, 9%, and 13% in OBP, PHT and UHT group, respectively (PHT vs OBP p < 0.05; PHT vs UHT p < 0.05).

Conclusions:

Gradual increases in ECG changes were observed across BP groups. Even in this small cohort, we observed significantly more pathological ECG findings in the PHT group than in subjects with OBP. ECG is of utmost importance in risk stratification of subjects with PHT and helpful, simple and cheap tool in making decision how to treat PHT patient. ECG should be recorded in all subjects with PHT.
A COMPARISON OF EUROPEAN AND AMERICAN GUIDELINES TO GAUGE THE PREVALENCE OF HYPERTENSION IN 16–19 YEAR OLD BLOOD DONORS
Authors: Eason Stephen , Sayers Merlyn
Published: June 2022

Objective:

Against the background of increasing risk for hypertension in adolescents, we decided to investigate blood donation as an opportunity to compare national guidelines for identification of individuals, between 16–19 years of age, meeting hypertension criteria.

Design and method:

16–19 year old volunteers donating blood between 2015 and 2020 were enrolled. They were asked to identify their ethnicity. Those declining were identified as “other’’. Blood pressure was measured using automated equipment (Welch Allyn, ProBP). We compared the European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines for hypertension (> = 140/90 mmHg) with the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for hypertension (> = 130/80 mmHg).

Results:

There were 71912 participants, 63.2% (45441) and 36.8% (26471) were female and male respectively.

Conclusions:

More males, by comparison with females, met hypertension guideline criteria in all ethnicities. The prevalence of hypertension was highest in African Americans. Depending on which international hypertension criteria are chosen, there are significant differences in the size of population of 16–19 year olds identified for attention. Determining a suitable threshold that will justify investigation their investigation and treatment will require long term clinical trials.
INCIDENT AORTIC ROOT DILATATION IN THE GENERAL POPULATION: FINDINGS FROM THE PAMELA STUDY
Authors: Dell’Oro Raffaella , Cuspidi Cesare , Facchetti Rita , Vanoli Jennifer , Quarti-Trevano Fosca , Mancia Giuseppe , Grassi Guido
Published: June 2022

Objective:

We sought to assess the long-term changes in aortic root (AR) diameter in a population-based sample, focusing on new onset AR dilatation, as well as on the demographic and clinical variables independently related to this dynamic process.

Design and method:

A total of 1,122 participants with measurable echocardiographic parameters at baseline and after a ten-year follow-up were included in the analysis. Sex-specific upper limits of normality for absolute AR diameter, AR diameter indexed to body surface area (BSA) and to height were derived from 712 healthy normotensive PAMELA participants.

Results:

Over the ten-year follow-up new AR dilatation occurred in 3.4% (AR/BSA),4.4% (AR/height) and 7.3% (absolute AR), respectively. No substantial relationship was observed between baseline office and ambulatory BP or their changes over time and incident AR/BSA and AR/height dilatation. Baseline AR diameter and left ventricular mass index (LVMI) emerged as important predictors of AR dilation, regardless of the diagnostic criteria used. This was also the case for the 10-year change in LVMI. The strength of association between non-hemodynamic variables and new onset AR dilatation was variable, depending on the definition of the aortic phenotype.

Conclusions:

The incidence of AR dilatation in a general middle-aged population is a relatively infrequent but not so rare event and scarcely influenced by both office and out-office BP. On the contrary, it is strongly related to LVMI (and its variations over time). From a clinical perspective, this underlines that LVH prevention and regression can reduce the risk of AR dilatation in the community.
HIGH BLOOD PRESSURE IN THE EMERGENCY DEPARTMENT. A TOOL FOR DETECTION OF HYPERTENSION? A FOLLOW-UP STUDY OF UNSELECTED PATIENTS ATTENDING AN EMERGENCY DEPARTMENT
Authors: Bentzel Sara , Ohman Ottilia , Abdulla Karzan , Manhem Karin , Mourtzinis Georgios
Published: June 2022

Objective:

Hypertension is the most preventable cause of morbidity and mortality, but many individuals are not diagnosed and lack treatment control. High blood pressure (BP) in the emergency department (ED) is commonly observed but mostly used for short-term evaluation. We aimed to study the usefulness of high BP in the ED as a screening tool for undiagnosed hypertension.

Design and method:

We used the electronic medical record system to identify all patients that had attended the ED at a university hospital from 2018–01–01 to 2018–03–31 and from 2018-07-01 to 2018-09-30 with an obtained BP > = 160/100 mm Hg measured in the ED. We excluded patients with previously diagnosed hypertension and patients on any BP-lowering medication. All patients identified where contacted two years after attending the ED, by mail with a letter of consent and a questionnaire with the following question: 1. Have you measured your BP after your visit to the ED? 2. Have you been diagnosed with hypertension? 3. If yes – what kind of BP-medication has been prescribed?

Results:

5424 patients attended the ED during the 6-months-period. 2625 patients were excluded due to a BP < 160/100 mm Hg, 1365 patients were excluded because of present BP-lowering medication, 523 patients were excluded because no BP was recorded, and 638 patients were deceased. A total of 271 patients were identified as suitable for the study and asked to participate. 167 individuals (62%) agreed to participate in the study and responded the questionnaire. Mean age of participants were 63,8 years and 50,2% were women. 135 patients (81%) had measured their BP after the ED-visit (question 1), and 48 (36%) of those had been diagnosed with hypertension (question 2). 96% of patients diagnosed with hypertension were on BP-lowering medication and 28% were on 2 or more different BP-lowering agents.

Conclusions:

To follow-up BP > = 160/100 mm Hg after an ED-visit can reveal undiagnosed hypertension in one third of the patients. Given the amount of undiagnosed hypertension, an ED-measured BP might provide an important tool with potential to detect and start treatment of hypertension.
RELATIONSHIP BETWEEN CADMIUM EXPOSURE, TRIGLYCERIDE-GLUCOSE INDEX AND CAROTID ARTERY ATHEROSCLEROSIS
Authors: Kim Kwanghyun , Kim Dae Jung , Ha Kyoung Hwa , Kim Hyeon Chang
Published: June 2022

Objective:

Cadmium exposure is suggested to be associated with cardiovascular and metabolic diseases. We investigated the association between cadmium and carotid artery atherosclerosis and the mediating effect of serum triglyceride and glucose level represented by triglyceride-glucose index (TyG index).

Design and method:

Among Cardiovascular and Metabolic disease Etiology Research Center (CMERC) Cohort participants, participants who received serum heavy metal screening tests were selected (N = 200). Patients with more than 3 standard deviation level of serum cadmium were excluded (N = 1). TyG index was calculated as formula: ln [{fasting blood glucose (mg/dL) × triglyceride (mg/dL)}/2]. Carotid artery ultrasonography was conducted to test carotid artery atherosclerosis. Carotid artery plaque was considered present if the thickness is greater by 50% or more than the surrounding intima-media thickness or if its size was 1.5 mm or more. We used linear regression to test the association between serum cadmium level and TyG index, and Poisson regression to test the association between serum cadmium level, TyG index and number of plaques. Mediation analyses was conducted to detect the mediating effect of TyG index.

Results:

Serum cadmium level was associated with TyG index (=0.155, p-value = 0.042). Both serum cadmium level(=0.753, p-value = 0.039) and TyG index(=1.049, p = 0.010) were associated with number of carotid artery plaques. Mediation analyses showed that TyG index significantly mediated the association between serum cadmium level and carotid artery plaque (direct effect: =0.733, p-value = 0.042; indirect effect: =0.165, p-value = 0.048).

Conclusions:

Cadmium exposure increases the risk of carotid artery atherosclerosis. The assocaition is mediated by disturbance in serum triglyceride and glucose level.
ADDITIVE DAMAGE IN THE CONTRACTILITY OF INTRAMURAL CORONARY ARTERIOLES IN A RAT MODEL OF ANDROPAUSAL HYPERTENSION
Authors: Várbíró Szabolcs , Jósvai Attila , Hetthéssy Judit , Mátrai Máté , Monori-Kiss Anna , Makk Jennifer , Vezér Márton , Székács Béla , Nádasy György , Török Marianna
Published: June 2022

Objective:

Hypertension accelerates vascular aging, and changes associated with vascular aging play a role in hypertension. Andropause also contributes to age – related vascular damage and increases cardiovascular risk. Our aim is to investigate the combined effect of hypertension and androgen deficiency on the contractility of intramural coronary resistance arteries.

Design and method:

Male Sprague-Dawley rats were distributed into 4 groups: control (Co, n = 10); orchidectomized (OCT, n = 13), angiotensin II infused (AII, n = 10) and AII infused plus orchidectomized (AII+OCT, n = 8). Early hypertension was established using osmotic minipumps containing angiotensin II (100 ng / min / kg), while testosterone deficiency achieved via orchidectomy. After 4 weeks, spontaneous, thromboxane- and bradykinin-induced tones of intramural coronary resistance arterioles were investigated by in vitro pressure microarteriography.

Results:

Inner radius was reduced in the AII+OCT group compared to all other groups. Spontaneous tone was significantly higher in AII and AII+OCT groups than in Co and OCT groups. U46619-induced vasoconstriction was significantly smaller in OCT and AII+OCT groups compared to Co and AII rats. Bradykinin-induced relaxation was also significantly reduced in orchidectomized rats (OCT and AII+OCT groups) to a greater extent than in Co and AII animals.

Conclusions:

Spontaneous vascular tone is increased in AII hypertension. As a result of orchidectomy, adaptation range of the blood vessels narrows both regarding vasoconstriction and vasodilation. Therefore, the reactivity of the coronary arterioles deteriorates due to testosterone deficiency. In case of parallel manifestation of hypertension and testosterone deficiency, these two effects add up, which may increase age-related cardiovascular risk significantly in men.
GONADOECTOMY REDUCED THE DEGREE OF DEVELOPMENT OF RENOVASCULAR HYPERTENSION IN FEMALE RATS CAUSED BY STOP OF HIGH-SALT DIET
Authors: Artemieva Marina , Biriukova Natalia , Kuropatkina Tatiana , Medvedeva Natalia
Published: June 2022

Objective:

Excessive dietary salt intake is associated with an increased risk for hypertension. However, more research on measurement, storage and kinetics of sodium on blood pressure and sex hormones is required for dietary salt restrictions.

The aim was to study the influence of gonadoectomy and stop of the high-salt diet on the development of renovascular hypertension (RVH) in female rats.

Design and method:

Was used the model of RVH 1 kidney 1 clip (1K1C) on female Wistar rats. All manipulations with animals were carried out according to the Council Directive 86/609/EEC principles. Gonadoectomized and normal rats of 8 weeks old (eight groups) were used. |There were two control groups: one with gonads © and one without (OvE). 4 groups out of remaining 6 groups of rats, had a high salt diet (4%). All rats from 6 groups the Goldblatt’s (1K1C) surgery was subjected. We had two groups with RVH with normal diet (0,25 % NaCl - RVH and OvE-RVH; two groups with high salt diet - RVH-HS and OvE-RVH-HS; and two groups with high salt diet, which was stop in two weeks after the Goldblatt’s (1K1C) surgery: RVH-ChHS and OvE-RVH-ChHS. In all animals the systemic blood pressure (mBP), diastolic (dBP), systolic (sBP) pressure, left ventricular pressure (LVP) and heart rate was directly measured. Left ventricular hypertrophy (LVH) was calculated as (LVweight)/(rat b.w.)*100%.

Results:

In all RVH groups, with and without gonads, the systemic arterial hypertension was developed. The most level of RVH was in RVH-ChHS rats: mBP - 145,7 ± 9,5 mmHg, dBP - 123,5 ± 10,4 mmHg, LVH - 0,214 ± 0,013 %. Ovariectomy leads to significant (p < 0,05) decrease in the degree of development of RVH. In OvE-RVH-ChHS was mBP 122,2 ± 6,3 mmHg, dBP 94,0 ± 6,0 mmHg and LVH 0,182 ± 0,009 %.

Conclusions:

Changing the diet from high salt to normal during the development of renovascular hypertension in female rats leads to an increase in the degree of disease. This effect was not observed in gonadoectomized female rats.
PATHOGENICITY AND LONG-TERM OUTCOMES OF LIDDLE SYNDROME CAUSED BY A NONSENSE MUTATION OF SCNN1G IN A CHINESE FAMILY
Authors: Zhang Di , Qu Yi , Lu Yi-Ting , Yang Kun-Qi , Fan Peng , Liu Ya-Xin , Gao Ling-Gen , Zhou Xian-Liang
Published: June 2022

Objective:

Liddle syndrome (LS) is a common monogenic hypertension with continuous activation of epithelial sodium channels (ENaCs) encoded by SCNN1A, SCNN1B, and SCNN1G. This study aimed to identify the pathogenicity of a nonsense mutation in SCNN1G in a Chinese family with LS and the outcomes of tailored treatment with amiloride.

Design and method:

Clinical data were collected from six family members and this mutation site was reported by our team at 2015. To explore the pathogenicity of candidate variants, we constructed mutant and wild-type models in vitro and measured amiloride-sensitive current in Chinese Hamster Ovary cells using patch clamp technique. Participants were followed up for 6 years to monitor their target organ damage after tailored treatment with amiloride.

Results:

Four family members presented with severe hypertension and hypokalemia, and two had stroke. This nonsense variant resulted in a termination codon at codon 572, truncating the Pro-Pro-Pro-X-Tyr motif. The mutant epithelial sodium channels displayed higher amiloride-sensitive currents than the wild-type channels (P < 0.05). Tailored treatment with amiloride achieved ideal blood pressure control in the patients, and no adverse events occurred during follow-up.

Conclusions:

We found the pathogenicity of a nonsense SCNN1G mutation (p.Glu571*) with enhanced amiloride-sensitive currents in a LS family. Tailored treatment with amiloride may be an effective strategy for the long-term control of blood pressure and the prevention of cardiovascular events in these patients.
ARE METABOLIC DISORDERS IN HYPERTENSIVE PATIENTS ASSOCIATED WITH GNB3 (RS5443) GENETIC POLYMORPHISMS?
Authors: Sydorchuk Andrii , Voronyuk Ksenia , Sydorchuk Larysa , Repchuk Yulia , Semianiv Marianna , Sydorchuk Ruslan
Published: June 2022

Objective:

Primary/essential hypertension (PH) is the most common cause of left ventricular hypertrophy (LVH) and is often associated with metabolic disorders. The aim of the study was to analyse dependence of metabolic parameters on the guanine nucleotide binding protein (G-protein) 3 subunit gene polymorphism (GN3, rs5443) in hypertensive patients.

Design and method:

A cross-sectional study involved 72 PH patients of high and very high cardiovascular risk (29.16% men and 70.84% women); the average age 59.87 ± 7.98 y. The control group included 48 healthy individuals (aged 49.13 ± 6.28 y) and sex distribution (62.5% women and 37.5% men). GN3 (C825T) polymorphism was investigated by Real Time PCR. LVH was assessed by EchoKG. Metabolic disorders were studied by lipids panel (Total cholesterol (TC), Triglycerides (TG), Low-, and High- density lipoprotein cholesterol (LDL-C, HDL-C) levels) and Glucose blood value. The atherogenic index (AI) was calculated by the formula: (TC – HDL-C)/ HDL-C.

Results:

In CC-genotype carriers of the GN3 gene metabolic parameters were as follows: TC 5.50 ± 0.79 mmol/L, TG 2.10 ± 0.8 mmol/L, HDL-C 1.22 ± 0.22 mmol/L, LDL-C 4.03 ± 0.76 mmol/L, AI 3.66 ± 0.84 U, Glucose 7.7 ± 2.34 mmol/L. In PH patients with TC-genotype the concentration of TC was 5.82 ± 1.15 mmol/L (pCC>0.05), TG 1.73 ± 0.55 mmol/L (pCC> 0.05), HDL-C 1.30 ± 0.21mmol/L (pCC> 0.05); LDL-C 4.39 ± 1.07 mmol/L (pCC> 0.05), AI 3.61 ± 0.95 (pCC> 0.05), Glucose 7.37 ± 2.34 mmol/L (pCC> 0.05). In TT-genotype carriers the concentration of TC was 6.6 ± 0.64 mmol/L (it was higher than in C-allelle carriers by 20.0% (pCC> 0.05) and 13.79% (pTC = 0.016) as much), TG – 2.6 ± 1.27 mmol/L, that was higher than in C-allelle patients by 23.81% (pCC> 0.05) and 52.94% (pTC = 0.038), respectively. The other parameters did not differed significantly between genotypes’ carriers and in mutation homozygous T-allele carriers were as follows: HDL-C 1.3 ± 0.05 mmol/L (pCC, TC> 0.05), LDL-C 4.7 ± 0.69 mmol/L (pCC, TC> 0.05), AI 4.0 ± 0.69 (pCC, TC> 0.05), Glucose 6.20 ± 1.2 mmol/L (pCC,TC> 0.05).

Conclusions:

Therefore, the metabolic disorders in hypertensive patients do not depend on the GN3 (rs5443) gene polymorphism.
SALT SENSITIVITY IS MODULATED BY LANOSTEROL SYNTHASE RS2254524 POLYMORPHISM
Authors: Faienza Sipontina , Citterio Lorena , Messaggio Elisabetta , Zagato Laura , Manunta Paolo
Published: June 2022

Objective:

The blood pressure (BP) response to different salt intake is associated with hypertension (HT). Elevated levels of the steroid hormone Endogenous Ouabain (EO) have been also associated with HT and salt sensitivity.

We characterized the missense variation rs2254524 (V642: CC variant; L642: AA variant) of the Lanosterol Synthase (LSS), a key enzyme in steroid biosynthesis, because AA patients on a low salt diet showed a greater reduction in BP compared to the LSS CC and only CC patients had an increase in plasma EO after the low salt protocol. Hence, we hypothesized that LSS could affect salt-sensitive HT by regulation of EO biosynthesis.

Design and method:

We generated a knock-in mouse model carrying the variation ubiquitously. Male mice were fed with Normal Salt (NSD; 0.5% NaCl), High Salt (HSD; 4% NaCl) or Low Salt Diet (LSD; 0.03 % Na) for 15 days.

BP was measured by the tail-cuff system, on 5 consequent days in conscious trained mice.

Results:

LSS AA mice were viable, healthy, and undistinguishable phenotypically from LSS CC.

The LSS mRNA and protein levels were reduced in the adrenal gland of LSS AA mice at 3 months.

At baseline, the LSS did not affect kidney function, while at 9 and 12 months the Systolic BP (SBP) in LSS CC mice showed a progressive increase with age; this increase was not observed in LSS AA mice.

At 3 months, we observed an increase in SBP in both genotypes upon HSD compared to those on an NSD, however only the AA mice showed a significant SBP reduction after an LSD (Fig.1).

The same response of BP upon HSD has also been observed in AA e CC mice at 12 months but only AA mice showed statistically significant cardiac hypertrophy (Fig. 2), a common feature of hypertensives.

Conclusions:

The new LSS mouse model resembles what was observed in hypertensive patients and provides a good model to prove our hypothesis. In the perspective of clinical practice, these findings allow the identification of patients whose SBP can seriously benefit from a low salt diet as a lifestyle modification.
PROTEOMIC PROFILE OF CYSTEINE OXIDATION IN VASCULAR SMOOTH MUSCLE CELLS IN HUMAN HYPERTENSION
Authors: Camargo Livia , Samji Sheon , Lilla Sergio , Zanivan Sara , Bulleid Neil , Hartley Richard , Delles Christian , Leiper James , Fuller Will , Montezano Augusto , Touyz Rhian
Published: June 2022

Objective:

Phenotypic switching of vascular smooth muscle cells (VSMCs) is a fundamental process in vascular dysfunction and remodeling associated with hypertension. Mechanisms underlying this process involve reactive oxygen species (ROS) and redox-dependent signaling pathways. However, the proteomic signature and effects of ROS on VSMC proteome in human hypertension are unknown. Using high fidelity proteomic analysis, we characterized the proteome of VSMC in human hypertension.

Design and method:

VSMC from resistance arteries from normotensive (NT) and hypertensive (HT) subjects were studied. Protein expression and cell migration were assessed by immunoblotting and wound healing assay respectively. VSMC proteins were labelled with isobaric tandem mass tags and identified by liquid chromatography tandem mass spectrometry. The oxidative proteome was assessed using stable isotope-labelled iodoacetamide to target cysteine thiols.

Results:

VSMCs from HT subjects exhibit reduced expression of alpha-SMA (0.05+0.01 vs NT:0.20 + 0.03, p < 0.05), increased expression of the proliferation marker, PCNA (0.162 + 0.3 vs NT:051 + 0.004, p < 0.05) and increased migration (54.68 + 2.86 vs NT:23.37 + 8.36, p < 0.05). The proteomic analysis identified 207 proteins upregulated in HT subjects (fold change> 1.5, p < 0.05). Gene ontology enrichment of upregulated proteins in HT showed that most proteins belong to extracellular space and plasma membrane compartments and were involved in biological processes such as extracellular matrix organization, immune response, proteolysis and cell proliferation. Extracellular matrix (ECM) proteins COL1A1, COL9A1, COL10A1, FBN1, FBLN1 were increased in cells from HT (fold change> 1.5, p < 0.05), suggesting a switch to a fibroblast-like phenotype in hypertension. Expression of proteins related to the interferon and IL-1beta pathways (IFIT1, IFIT2, IFIT3, MX1, MX2, ABCA1, ABCA2, IL1RAP, CD36, ICAM1) were also increased in cells from HT subjects (fold change> 1.5, p < 0.05). Considering the importance of oxidative stress in hypertension, we assessed the VSMC oxidative proteome. Results identified 130 significant cysteine-containing peptides, 88 showed increased oxidation in HT (fold change> 1.5, p < 0.05). Among the highly oxidized proteins in HT were ECM proteins, COL11A1, COL16A1, FBLN1 and FBLN2 (fold change> 1.5, p < 0.05).

Conclusions:

Our study provides new insights into the proteomic changes related to vascular phenotype in hypertension and highlights differentially oxidised candidate targets that may drive phenotypic switching associated with vascular injury and remodeling in hypertension.
ASSOCIATION OF NDUFC2 POLYMORPHIC VARIANTS WITH LEFT VENTRICULAR HYPERTROPHY IN HUMAN HYPERTENSION
Authors: Gallo Giovanna , Forte Maurizio , Tocci Giuliano , Cotugno Maria , Marchitti Simona , Stanzione Rosita , Bianchi Franca , Palmerio Silvia , Sciarretta Sebastiano , Volpe Massimo , Rubattu Speranza
Published: June 2022

Objective:

Previous experimental studies showed that a dysfunction of the NADH dehydrogenase (ubiquinone), the mitochondrial Complex I (CI), is associated with the development of left ventricular hypertrophy (LVH). A deficiency of Ndufc2 (a subunit of CI) impairs CI activity and causes severe mitochondrial dysfunction. The NDUFC2/rs11237379 polymorphic variant is associated with reduced gene expression and impaired mitochondrial function, contributing to increased susceptibility to vascular diseases.

We examined the association of NDUFC2/rs11237379 and another NDUFC2 polymorphic variant (rs641836) with the development of LVH in hypertensive patients.

Design and method:

Two-hundred-fourty-six hypertensive subjects (147 male, 59.7%) with a mean age of 59 ± 15 years were studied. Seventy-nine individuals (32%) presented LVH.

Results:

The association analysis for both SNPs showed that hypertensive patients carrying the TT genotype at the NDUFC2/rs11237379 had a significant increase of echocardiographically assessed septal thickness (p = 0.001), posterior wall thickness (p = 0.003), relative wall thickness (RWT) (p = 0.01), LV mass/ body surface area (BSA) (p = 0.012) and LV mass/height2.(p = 0.0033) compared to subjects carrying either CC or CT genotypes. To better dissect the genetic effect, a covariate ANOVA was performed for each cardiac variable, considering age, gender, body mass index (BMI), office blood pressure (BP), antihypertensive treatment with a combination of 2 or more drugs and the number of BP-lowering agents as covariates. The adjustment for covariates revealed significant differences for septal thickness (p = 0.07), posterior wall thickness (p = 0.008), RWT (p = 0.021), LV mass/BSA (p = 0.03). With regard to NDUFC2/rs641836, hypertensive subjects carrying the mutant A allele had a significant increase of septal thickness (p = 0.001), posterior wall thickness (p = 0.001), RWT (p = 0.005), LV mass (p = 0.001), LV mass/BSA(p = 0.001), LV mass/height2.7(p = 0.002) compared to wild-type homozygotes. After adjustment for covariates, the results were significant for septal thickness (p = 0.017), posterior wall thickness (p = 0.011), LV mass (p = 0.003), LV mass/BSA (p = 0.002) and LV mass/height2.7(p = 0.010).

Conclusions:

Our results demonstrate for the first time a significant association of NDUFC2 variants with LVH in hypertensives and highlight a novel role of CI dependent mitochondrial dysfunction on increased susceptibility to cardiac damage in human hypertension. This study paves the way of a new pathophysiological mechanism of LVH which may lead to new clinical strategies.
EFFICACY AND SAFETY OF SACUBITRIL/VALSARTAN (LCZ696) IN HYPERTENSION CONTROL AND ADVERSE CARDIOVASCULAR EVENT REDUCTION AMONG ASIANS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Cruz Patrick Vera , Ang Wisdom , Calatrava Jose
Published: June 2022

Objective:

To evaluate the benefits and harms of Sacubitril/Valsartan (LCZ696) for controlling hypertension and reducing the risk of adverse cardiovascular events (MACE) in Asians by synthesising data from randomised controlled trials.

Design and method:

This is a systematic review and meta-analysis. We searched PubMed, ScienceDirect, Cochrane databases, trial registries HERDINPlus, ClinicalTrials.gov, and forward and backward citations to identify applicable articles. All randomised controlled trials with data of Asian patients comparing the effect of Sacubitril/Valsartan (LCZ696) against an active control for cardiovascular mortality, heart failure hospitalisation, blood pressure control, and adverse events were included without language or date restrictions. We did separate fixed-effects meta-analysis for major adverse cardiovascular events (MACE), hypertension control, serious and non-serious adverse events. Evidences were synthesised as pooled hazards ratio(HR) for MACE, pooled odds ratio for blood pressure control, and safety outcomes. The quality of evidence was assessed with the Cochrane risk of bias tool.

Results:

Ten of 2249 articles were included involving 6,120 patients. With high certainty of evidence, pooled data showed that Asians with mild to moderate hypertension had better hypertension control with LCZ696 against olmesartan (OR 1.63; CI 1.38, 1.92; p < 0.00001; I2 = 7%) (Figure1). However, the risk for MACE was not significantly reduced for Asians with reduced ejection fraction (HR 0.89; CI 0.73, 1.08; p = 0.22; I2 = 0%) or acute myocardial infarction (HR 0.90; CI 0.65,1.24; p 0.50; I2 = 0%) given LCZ696 (Figure2). The overall safety of LCZ696 was comparable to conventional ACEi/ARB but subgroup analysis revealed greater pooled odds ratios for hypotension (OR 1.59; 95% CI 1.19, 2.13; p = 0.002; I2 0%) and dizziness (OR 3.54; 95% CI 1.61, 7.81; p = 0.002; I2 0%) with LCZ696 and reduced pooled odds for cough occurrence(OR 0.70; 95% CI0.56, 0.87; p = 0.002; I2 0%) (Figure 3&4).

Conclusions:

Among Asians, LCZ696 is strongly associated with better hypertension control against olmesartan. However, its efficacy in reducing MACE is not as robust. Finally, the overall safety profile of sacubitril/valsartan is comparable to conventional ACEi/ARBs but it is associated with hypotension and dizziness with a lower risk for cough.