Proteomic investigations into hypertension: what's new and how might it affect clinical practice?

Introduction: Hypertension is a multifactorial disease that has, thus far, proven to be a difficult target for pharmacological intervention. The application of proteomic strategies may help to identify new biomarkers for the early diagnosis and prompt treatment of hypertension, in order to control blood pressure and prevent organ damage. Areas covered: Advances in proteomics have led to the discovery of new biomarkers to help track the pathophysiological processes implicated in hypertension. These findings not only help to better understand the nature of the disease, but will also contribute to the clinical needs for a timely diagnosis and more precise treatment. In this review, we provide an overview of new biomarkers identified in hypertension through the application of proteomic techniques, and we also discuss the difficulties and challenges in identifying biomarkers in this clinical setting. We performed a literature search in PubMed with the key words 'hypertension' and 'proteomics', and focused specifically on the most recent literature on the utility of proteomics in hypertension research. Expert opinion: There have been several promising biomarkers of hypertension identified by proteomics, but too few have been introduced to the clinic. Thus, further investigations in larger cohorts are necessary to test the feasibility of this strategy for patients. Also, this emerging field would profit from more collaboration between clinicians and researchers.

Estimating the impact of obesity and metabolic phenotype on sickness absence. Results from the ICARIA study.

BACKGROUND AND AIMS: To assess the impact of obesity and being overweight on sickness absence (SA) as a function of healthy/unhealthy metabolic phenotype. METHODS AND RESULTS: A total of 173 120 healthy workers who underwent a routine check-up, consisting of a structured interview, anthropometric measurements and blood pressure and fasting blood analysis, were included as the study sample (67.1% males; 49.2% manual workers; mean age 40.6 ± 21.9 years). Workers were classified according to their body mass index (BMI) and metabolic phenotype. A metabolically unhealthy phenotype was defined as the presence of three or more of the following criteria: glycaemia ≥110 mg/dL or previously diagnosed type I/II diabetes or treatment for diabetes; triglycerides ≥150 mg/dL or lipid-lowering therapy; HDL <40/50 mg/dL M/F; blood pressure ≥130/85 mmHg or previously diagnosed hypertension or antihypertensive therapy; waist circumference >102/88 cm M/F. A one-year follow-up was conducted to evaluate the incidence of work-related and non-work-related SA (WRSA/NWRSA). The association of BMI with SA was tested using Poisson regression (standard error correction), segmenting on the basis of metabolic phenotype. The overall percentages of workers who were overweight, obese and/or had a metabolically unhealthy phenotype were 37.7%, 16.3% and 8.8%, respectively. BMI was associated with increased incidence of NWRSA in both phenotypes. It was also associated with WRSA in subjects with a BMI in the range of 35-39.99 kg/m2 and in metabolically healthy individuals. WRSA was lower in subjects with a BMI ≥40 kg/m2 and among metabolically unhealthy individuals. CONCLUSION: Obesity is associated with health problems that have a significant impact on SA.

Finerenone protects against progression of kidney and cardiovascular damage in a model of type 1 diabetes through modulation of proinflammatory and osteogenic factors.

The non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone (FIN) improves kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) in type 2 diabetes (T2D). We explored the effect of FIN in a novel model of type 1 diabetic Munich Wistar Frömter (MWF) rat (D) induced by injection of streptozotocin (15 mg/kg) and additional exposure to a high-fat/high-sucrose diet. Oral treatment with FIN (10 mg/kg/day in rat chow) in diabetic animals (D-FIN) was compared to a group of D rats receiving no treatment and a group of non-diabetic untreated MWF rats (C) (n = 7-10 animals per group). After 6 weeks, D and D-FIN exhibited significantly elevated blood glucose levels (271.7 ± 67.1 mg/dl and 266.3 ± 46.8 mg/dl) as compared to C (110.3 ± 4.4 mg/dl; p < 0.05). D showed a 10-fold increase of kidney damage markers Kim-1 and Ngal which was significantly suppressed in D-FIN. Blood pressure, pulse wave velocity (PWV) and arterial collagen deposition were lower in D-FIN, associated to an improvement in endothelial function due to a reduction in pro-contractile prostaglandins, as well as reactive oxygen species (ROS) and inflammatory cytokines (IL-1, IL-6, TNFα and TGFß) in perivascular and perirenal adipose tissue (PVAT and PRAT, respectively). In addition, FIN restored the imbalance observed in CKD between the procalcifying BMP-2 and the nephroprotective BMP-7 in plasma, kidney, PVAT, and PRAT. Our data show that treatment with FIN improves kidney and vascular damage in a new rat model of DKD with T1D associated with a reduction in inflammation, fibrosis and osteogenic factors independently from changes in glucose homeostasis.

[2022 Practice guidelines for the management of arterial hypertension of the Spanish Society of Hypertension]. / Guía práctica sobre el diagnóstico y tratamiento de la hipertensión arterial en España, 2022. Sociedad Española de Hipertensión - Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA).

Hypertension is the most important risk factor for global disease burden. Detection and management of hypertension are considered as key issues for individual and public health, as adequate control of blood pressure levels markedly reduces morbidity and mortality associated with hypertension. Aims of these practice guidelines for the management of arterial hypertension of the Spanish Society of Hypertension include offering simplified schemes for diagnosis and treatment for daily practice, and strategies for public health promotion. The Spanish Society of Hypertension assumes the 2018 European guidelines for management of arterial hypertension developed by the European Society of Cardiology and the European Society of Hypertension, although relevant aspects of the 2017 American College of Cardiology/American Heart Association guidelines and the 2020 International Society of Hypertension guidelines are also commented. Hypertension is defined as a persistent elevation in office systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg, and assessment of out-of-office blood pressure and global cardiovascular risk are considered of key importance for evaluation and management of hypertensive patients. The target for treated blood pressure should be < 130/80 for most patients. The treatment of hypertension involves lifestyle interventions and drug therapy. Most people with hypertension need more than one antihypertensive drug for adequate control, so initial therapy with two drugs, and single pill combinations are recommended for a wide majority of hypertensive patients.

A review of renal, cardiovascular and mortality endpoints in antihypertensive trials in diabetic patients.

Renal disease is highly prevalent in people with type 2 diabetes, and co-existence with hypertension increases the risk of cardiac events and mortality. Despite many large randomized trials, controversies remain regarding optimal antihypertensive therapy in diabetic patients, including whether some classes of antihypertensive drugs have specific renal protective properties, and the relationships between renal, cardiovascular and mortality endpoints. In this article, we review landmark antihypertensive drug trials from the last two decades in patient populations composed, or including substantial proportions, of patients with type 2 diabetes. Several points emerge. Firstly, treatment effects can vary widely among different renal, cardiovascular and mortality endpoints. Secondly, combinations of antihypertensive drugs vary in their ability to prevent major renal and cardiovascular events, even if they produce similar reductions in blood pressure. Thirdly, simply adding further antihypertensive drugs may not improve outcomes, even if it produces further reductions in blood pressure. In most trials, a reduction in microalbuminuria was associated with evidence of renal protection, but further evidence is needed relating changes in proteinuria with cardiovascular risk. The study that aligns best with the current reappraisal of ESH guidelines, with regard to blood pressure goals, use of an adequate combination and simultaneously protecting the kidney and the cardiovascular system, is the ADVANCE study.

[Awareness, treatment and control of blood pressure according to place of recruitment and sex in the May Measure Month 2018 survey in Spain]. / Conocimiento, tratamiento y control de la presión arterial según lugar de reclutamiento y sexo en la encuesta May Measure Month 2018 en España.

OBJECTIVE: To analyse the data, according to recruiting place and sex, of the survey May Measure Month in 2018 (MMM18) in Spain, promoted by the International Society of Hypertension. METHODS: Subjects more than 18 years old were studied. MMM18 protocol was performed. Volunteers were recruited through the Spanish Society of Community Pharmacy (SEFAC) and the Spanish Society of Hypertension (SEH-LELHA). General linear models of blood pressure (BP) were carried out in subjects with and without treatment, and adjusted by age, sex, tobacco use, obesity and recruitment site. RESULTS: 7 511 individuals (mean age 51.7 ± 19.6 years, 36.8% males) were screened. Systolic and diastolic BP was higher in males (129.0-16.7/119.6-18.2 mmHg) (78.3-11.1/74.8-10.7 mmHg) (p < 0.001). There was a linear relationship between systolic BP, age and sex, with higher values in males (11.2 mmHg in untreated and 4.5 mmHg in treated) (p < 0.001). Diastolic BP was inverted U-shaped, with highest level in males and between 50-55 years. The proportion of individuals with hypertension (pharmacies; public and clinical area) was 47.2% (54.2; 34.1 and 34.8%). Seventy-five percent were aware of their diagnosis (77.5; 61.5 and 69.2%), with 22% of them without pharmacological treatment (20.7; 26.0 and 27.9%). Sixty-four point five percent of those under antihypertensive treatment met targets (62.9; 65.6 and 69.1%) (p < 0.001). CONCLUSIONS: There is big room for improvement in MMM indicators in Spain. Nearly half of subjects are hypertensive. Of those aware of their condition, 1 in 5 did not follow pharmacological treatment and of those treated, 1 in 3 did not meet targets. BP levels were significantly higher in males. Our study suggests that gender differences described should be considered in the BP thresholds established.

2021 Spanish Society of Hypertension position statement about telemedicine.

The pandemic caused by coronavirus SARS-CoV-2 (COVID-19) has forced, in many cases, to replace face-to-face consultation with the telematic consultation, in order to reduce the risk of contagion associated with the presence of patients in health centres. This change may represent an opportunity for a different and more effective communication between professionals and patients, allowing better accessibility to medical care and more systematic and comprehensive approach to patients with hypertension and cardiovascular risk. However, organisational tools are needed to facilitate communication between patients and professionals, specifically with the exchange of clinical data by remote monitoring of variables associated with hypertension and cardiovascular risk (blood pressure, weight, height, blood tests…), and allow monitoring of adherence to treatments, lifestyles and risk factors. It would be desirable for this to be carried out by multidisciplinary teams, both from primary care, hospital and community pharmacy, with an adequate coordination of care. This document of the Spanish Society of Hypertension (SEH-LELHA) tries to give the keys to improve the quality of care of telematic consultations of patients with hypertension and cardiovascular risk, provide basic criteria of telematic or face to face attention and systematise their content. Likewise, the follow-up criteria are proposed by the different professionals.

Determinants of urinary albumin excretion within the normal range in patients with type 2 diabetes: the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study.

AIMS/HYPOTHESIS: In contrast to microalbuminuric type 2 diabetic patients, the factors correlated with urinary albumin excretion are less well known in normoalbuminuric patients. This may be important because even within the normoalbuminuric range, higher rates of albuminuria are known to be associated with higher renal and cardiovascular risk. METHODS: At the time of screening for the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) Study, the urinary albumin/creatinine ratio (UACR) was 0.44 mg/mmol in 4,449 type 2 diabetic patients. The independent correlates of UACR were analysed. RESULTS: Independent correlates of UACR during baseline were (in descending order): night-time systolic BP (r(s) = 0.19); HbA(1c) (r(s) = 0.18); mean 24 h systolic BP (r(s) = 0.16); fasting blood glucose (r(s) = 0.16); night-time diastolic BP (r(s) = 0.12); office systolic BP, sitting (r(s) = 0.11), standing (r(s) = 0.10); estimated GFR (r(s) = 0.10); heart rate, sitting (r(s) = 0.10); haemoglobin (r(s) = -0.10); triacylglycerol (r(s) = 0.09); and uric acid (r(s) = -0.08; all p

Management of hypertension in the very old: aggressive reduction of blood pressure is harmful in most patients.

Arterial hypertension is particularly prevalent in the elderly and treatment is required according to the literature. Treatment in subjects between 65 and 80 years of age resembles by characteristics and results that obtained in younger population. The treatment of arterial hypertension in the very elderly differs in a relevant percentage of them. It is quite similar in those with a good physical fitness with or without cardiovascular disease. A series of factors as the presence of real sustained hypertension, orthostatic hypotension, frailty and disability, and the boundary of safety recommended by international recent guidelines analysed here are relevant to characterize a clearly elevated risk of complications in the remaining very elderly patients.

[Position statement on ambulatory blood pressure monitoring (ABPM) by the Spanish Society of Hypertension (2019)]. / Documento de la Sociedad Española de Hipertensión-Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA) sobre monitorización ambulatoria de la presión arterial (MAPA) 2019.

Conventional blood pressure (BP) measurement in clinical practice is the most used procedure for the diagnosis and treatment of hypertension (HT), but is subject to considerable inaccuracies due to, on the one hand, the inherent variability of the BP itself and, on the other hand biases arising from the measurement technique and conditions, Some studies have demonstrated the prognosis superiority in the development of cardiovascular disease using ambulatory blood pressure monitoring (ABPM). It can also detect "white coat" hypertension, avoiding over-diagnosis and over-treatment in many cases, as well detecting of masked hypertension, avoiding under-detection and under-treatment. ABPM is recognised in the diagnosis and management of HT in most of international guidelines on hypertension. The present document, taking the recommendations of the European Society of Hypertension as a reference, aims to review the more recent evidence on ABPM, and to serve as guidelines for health professionals in their clinical practice and to encourage ABPM use in the diagnosis and follow-up of hypertensive subjects. Requirements, procedure, and clinical indications for using ABPM are provided. An analysis is also made of the main contributions of ABPM in the diagnosis of "white coat" and masked HT phenotypes, short term BP variability patterns, its use in high risk and resistant hypertension, as well as its the role in special population groups like children, pregnancy and elderly. Finally, some aspects about the current situation of the Spanish ABPM Registry and future perspectives in research and potential ABPM generalisation in clinical practice are also discussed.

Microvascular injury and the kidney in hypertension.

Renal macrocirculation participates in the development of arterial hypertension. The elevation in systemic blood pressure (BP) can damage the kidney starting in the microcirculation. Established arterial hypertension impinge upon the large arteries and stiffness develops. As a consequence central BP raises and BP pulsatility appear and contribute to further damage renal microcirculation by direct transmission of the elevated BP.

Obesity and hypertension in Latin America: Current perspectives.

In the countries of Central America, South America and the Caribbean, there has been a dramatic rise in obesity, the metabolic syndrome, hypertension and other cardiovascular risk factors in the last few decades. Epidemiological evidence highlights a consistent correlation between obesity and hypertension, and the presence of obesity predisposes an individual to a greater risk of hypertension although the mechanisms remain unclear. Obesity and hypertension are two key drivers of the cardio-renal disease continuum, and patients with uncontrolled cardiovascular risk in their mid-life will likely have an increased risk of clinical cardiovascular and renal outcomes in old age. This article summarizes the current status for the prevalence and consequences of obesity and hypertension in Latin America, with the aim of initiating a call to action to all stakeholders for greater implementation of primary prevention strategies, particularly in the young.

[Spanish Society of Hypertension position statement on the 2017 ACC/AHA hypertension guidelines]. / Documento de la Sociedad Española de Hipertensión-Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA) sobre las guías ACC/AHA 2017 de hipertensión arterial.

The American College of Cardiology (ACC) and the American Heart Association (AHA) have recently published their guidelines for the prevention, detection, evaluation, and management of hypertension in adults. The most controversial issue is the classification threshold at 130/80mmHg, which will allow a large number of patients to be diagnosed as hypertensive who were previously considered normotensive. Blood pressure (BP) is considered normal (<120mmHg systolic and <80mmHg diastolic), elevated (120-129 and <80mmHg), stage 1 (130-139 or 80-89mmHg), and stage 2 (≥140 or ≥90mmHg). Out-of-office BP measurements are recommended to confirm the diagnosis of hypertension and for titration of BP-lowering medication. In management, cardiovascular risk would be determinant since those with grade 1 hypertension and an estimated 10-year risk of atherosclerotic cardiovascular disease ≥10%, and those with cardiovascular disease, chronic kidney disease and/or diabetes will require pharmacological treatment, the rest being susceptible to non-pharmacological treatment up to the 140/90mmHg threshold. These recommendations would allow patients with level 1 hypertension and high atherosclerotic cardiovascular disease to benefit from pharmacological therapies and all patients could also benefit from improved non-pharmacological therapies. However, this approach should be cautious because inadequate BP measurement and/or lack of systematic atherosclerotic cardiovascular disease calculation could lead to overestimation in diagnosing hypertension and to overtreatment. Guidelines are recommendations, not impositions, and the management of hypertension should be individualized, based on clinical decisions, preferences of the patients, and an adequate balance between benefits and risks.

Cardiovascular risk profile and risk stratification of the hypertensive population attended by general practitioners and specialists in Spain. The CONTROLRISK study.

The CONTROLRISK study was designed to determine the cardiovascular risk profile of the hypertensive population attended at primary care and specialist setting in Spain and to investigate whether physicians stratify the risk correctly, according to the 2003 European guidelines. A total of 8920 patients were recruited from primary care (n=4485) and specialist outpatient clinic (n=4435). The age criteria was 62.6+/-11.1 years; 51.6% were women. No differences were observed in the severity of hypertension. More than 85% presented other cardiovascular risk factors, similarly in both groups. Target organ damage (TOD) and associated clinical conditions (ACC) were more frequent in specialist setting (57.6 vs 34.3% and 39 vs 28.7%, both P<0.0001). The most common risk factor was age. The most frequently reported TOD was left ventricular hypertrophy (42.3 and 22.1%; P<0.0001). Ischemic heart disease was the most common ACC (21.5 vs 13.1%; P<0.0001). The risk profile was significantly higher in specialist population (75.1 vs 60.3% of patients belonged to high- or very high-risk groups). Specialists and primary care physicians stratified only 54.6 and 48% of their patients correctly, respectively (P<0.05). Both, specialists and general practitioners (GPs) strongly underestimated the risk. Very high-risk patients were adequately assessed only in 44.9% of cases by specialists and in 25.3% by GPs (P<0.001). More than half of the hypertensive patients attended by GPs in Spain belong to the high- or very high-risk groups. GPs and specialists tend to underestimate the cardiovascular risk in daily clinical practice, mainly in very high-risk patients.

Hypertension in Latin America: Current perspectives on trends and characteristics.

The region of Latin America, which includes Central America, the Caribbean and South America, is one that is rapidly developing. Signified by socio-economic growth, transition and development over the last few decades, living standards in countries like Brazil and Mexico have improved dramatically, including improvements in education and health care. An important marker of socio-economic change has been the epidemiological shift in disease burden. Cardiovascular disease is now the leading cause of death in Latin America, and the drop in prevalence of infectious diseases has been accompanied by a rise in non-communicable diseases. Hypertension is the major risk factor driving the cardiovascular disease continuum. In this article we aim to discuss the epidemiological and management trends and patterns in hypertension that may be specific or more common to Latin-American populations - what we term 'Latin American characteristics' of hypertension - via a review of the recent literature. Recognizing that there may be a specific profile of hypertension for Latin-American patients may help to improve their treatment, with the ultimate goal to reduce their cardiovascular risk. We focus somewhat on the countries of Brazil, Mexico and Venezuela, the experience of which may reflect other Latin American countries that currently have less published data regarding epidemiology and management practices.

Efficacy and safety of valsartan, an angiotensin II receptor antagonist, in hypertension after renal transplantation: a randomized multicenter study.

BACKGROUND: The prevalence of posttransplant hypertension is high, and it appears to be a major risk factor for graft and patient survival. The aim of this study was to assess the efficacy and safety of valsartan, an angiotensin-receptor blocker (ARB), in the treatment of posttransplant hypertension. METHODS: A multinational, multicenter, prospective, randomized, double-blind, placebo-controlled study was performed on the treatment of hypertension (systolic blood pressure [BP] >/= 140 and/or diastolic BP >/= 90 mm Hg) in adult cyclosporin-treated renal transplant recipients randomized to receive either valsartan (80 mg once daily) or a matching placebo for 8 weeks. After the first 4 weeks, furosemide 20 mg twice daily was added on a open basis if systolic BP remained >/= 130 mm Hg and/or diastolic BP remained >/= 85 mm Hg. RESULTS: One hundred fifteen (valsartan = 57, placebo = 58) uncontrolled hypertensive patients despite monotherapy for hypertension, other than angiotensin-converting enzyme inhibitor or ARB, were randomized. In the valsartan group, significant decreases were seen in systolic BP (from 153 +/- 11 to 140.9 +/- 18.35 mm Hg at 4 weeks, and 136.5 +/- 15 mm Hg at 8 weeks) and diastolic BP (from 93 +/- 9 to 85.2 +/- 11.28 mm Hg at 4 weeks, and 83.8 +/- 9.2 mm Hg at 8 weeks). There was no significant change in the placebo group. In the valsartan group, a statistically but not clinically significant reduction was observed in the mean hemoglobin concentration (12.9 +/- 1.6 g/dL versus 13.8 +/- 1.6 g/dL at 4 weeks, P < .01; and 12.3 +/- 1.6 versus 13.8 +/- 1.7 at 8 weeks; P < .001) as well as a significant increase in serum potassium (4.4 +/- 0.5 mmol/L versus 4.1 +/- 0.4 mmol/L at 4 weeks, P < .01) vs placebo. CONCLUSIONS: Valsartan is effective in the treatment of posttransplant hypertension and is well tolerated.

[Benefits of spironolactone as the optimal treatment for drug resistant hypertension. Pathway-2 trial review]. / Utilidad de la espironolactona en el manejo farmacológico de la hipertensión arterial resistente. Comentarios sobre el estudio Pathway-2.

Pathway-2 is the first randomised, double-blind and crossover trial that compares spironolactone as a fourth drug with alfa-blocker, beta-blocker and placebo. This study shows that spironolactone is the drug with more possibilities of success for the management of patients with difficult-to-treat hypertension in patients with a combination of three drugs and poor control. The results validate the widespread treatment with mineralocorticoid receptor antagonists in resistant hypertension.

[Cardiovascular risk study in patients with renin-angiotensin system blockade by means of the proteone of circulating extracellular vesicles]. / Estudio del riesgo cardiovascular en pacientes con bloqueo del sistema renina-angiotensina a través del proteoma de las vesículas extracelulares circulantes.

INTRODUCTION: Extracellular vesicles (EVs) are released to the bloodstream by certain cell types due to transport, activation and cell death processes. Blood count of EVs from platelet and endothelial origin has been proved to be a cardiovascular risk biomarker. Thus, EVs proteome might reflect the underlying cellular processes in hypertensive patients with albuminuria. MATERIAL AND METHODS: Protein content of circulating EVs was analyzed by liquid chromatography coupled to mass spectrometry. EVs were isolated by an ultracentrifugation protocol optimized in order to avoid contamination by blood plasma proteins. Purity of the isolated fraction was verified by electronic and confocal microscopy, and by flow cytometry. RESULTS: We hereby show a method to isolate circulating EVs from hypertensive patients with/without albuminuria with high yield and purity. Besides, we provide a reference proteome of the EVs of these patients, composed of 2,463 proteins, and prove that the proteins carried by these vesicles are associated with crucial processes involved in the inherent cardiovascular risk. CONCLUSION: The proteome of circulating EVs is an interesting source of indicators in the evaluation of cardiovascular risk in hypertensive patients with renin-angiotensin system blockage.