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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 TGFβ) 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., Competing Interests: Declaration of Competing Interest P. Kolkhof is a full-time employee of BAYER AG; R. Kreutz has received support of research and personal honoraria from BAYER AG, Berlin-Chemie Menarini, Daiichi Sankyo, Ferrer, Merck, Sanofi, and Servier; M. S. Fernández-Alfonso has received support of research by BAYER AG as principal investigator., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

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., (Copyright © 2022 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

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., (Copyright © 2021 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

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., (Copyright © 2020 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

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.

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., (Copyright © 2019 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

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.

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/m 2 and in metabolically healthy individuals. WRSA was lower in subjects with a BMI ≥40 kg/m 2 and among metabolically unhealthy individuals., Conclusion: Obesity is associated with health problems that have a significant impact on SA., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2018 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

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., (Copyright © 2018 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

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., (Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

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., (Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

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., (Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

Arterial stiffness as assessed by carotid-femoral pulse wave velocity (cfPWV) is a marker of preclinical organ damage and a predictor of cardiovascular outcomes, independently of blood pressure (BP). However, limited evidence exists on the association between long-term variation (Δ) on aortic BP (aoBP) and ΔcfPWV. We aimed to evaluate the relationship of ΔBP with ΔcfPWV over time, as assessed by office and 24-h ambulatory peripheral BP, and aoBP. AoBP and cfPWV were evaluated in 209 hypertensive patients with either diabetes or metabolic syndrome by applanation tonometry (Sphygmocor) at baseline(b) and at 12 months of follow-up(fu). Peripheral BP was also determined by using validated oscillometric devices (office(o)-BP) and on an outpatient basis by using a validated (Spacelabs-90207) device (24-h ambulatory BP). ΔcfPWV over time was calculated as follows: ΔcfPWV=[(cfPWVfu-cfPWVb)/cfPWVb] × 100. ΔBP over time resulted from the same formula applied to BP values obtained with the three different measurement techniques. Correlations (Spearman 'Rho') between ΔBP and ΔcfPWV were calculated. Mean age was 62 years, 39% were female and 80% had type 2 diabetes. Baseline office brachial BP (mm Hg) was 143±20/82±12. Follow-up (12 months later) office brachial BP (mm Hg) was 136±20/79±12. ΔcfPWV correlated with ΔoSBP (Rho=0.212; P=0.002), Δ24-h SBP (Rho=0.254; P<0.001), Δdaytime SBP (Rho=0.232; P=0.001), Δnighttime SBP (Rho=0.320; P<0.001) and ΔaoSBP (Rho=0.320; P<0.001). A multiple linear regression analysis included the following independent variables: ΔoSBP, Δ24-h SBP, Δdaytime SBP, Δnighttime SBP and ΔaoSBP. ΔcfPWV was independently associated with Δ24-h SBP (β-coefficient=0.195; P=0.012) and ΔaoSBP (β-coefficient= 0.185; P=0.018). We conclude that changes in both 24-h SBP and aoSBP more accurately reflect changes in arterial stiffness than do office BP measurements.

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., (Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.)

Hypertension is the most common cardiovascular disease and remains the most prevalent risk factor for cardiovascular diseases and a major cause of death worldwide. Despite the large number of antihypertensive drugs available, in the majority of patients blood pressure still remains not optimally controlled and persists at high risk of cardiovascular complications. The limitations of current therapies have stimulated the research and development of new classes of antihypertensive agents, with different mechanisms of action, that provide a better blood pressure control, greater protection against organ damage, better tolerability and more effective prevention of cardiovascular diseases. However, essential hypertension is a multifactorial and multigenic disorder, which means that various mechanisms contribute to a greater or lesser extent to increase BP. Recent advances in the understanding of the multiple and complex cellular signalling pathways that modulate vascular smooth muscle cell contraction and growth involved in the regulation of vascular tone and in hypertension-induced end-organ damage have provided valuable insight in identifying new therapeutic targets. This article reviews new antihypertensive drugs under development, focusing on their mechanisms of action and possible advantages compared with traditional drugs.

Sympathetic nervous system has an important role in resistant hypertension. Heart rate (HR) is a marker of sympathetic activity, but its association with resistant hypertension has not been assessed. We aimed to evaluate differences in HR values and variability between resistant and controlled patients and between true and white-coat resistant hypertensives (RHs). We compared office and ambulatory HR, nocturnal dip and s.d. in 14,627 RHs versus 11,951 controlled patients (on ⩽ 3 drugs) and in 8730 true (24 h blood pressure (BP) ⩾ 130 and/or 80 mm Hg) versus 4825 white-coat (24-h BP < 130/80 mm Hg) RHs. After adjusting for age, gender, body mass index, diabetes status and beta blocker use, HR values and variability were significantly elevated in resistant versus controlled patients and in true versus white-coat RHs. In logistic regression models, after adjustment for confounders, office HR (odds ratio for each increase in tertile: 1.337; 95% confidence interval: 1.287-1.388; P < 0.001), nocturnal dip (0.958; 0.918-0.999; P = 0.035) and night time s.d. (1.115; 1.057-1.177; P = 0.013) were all significantly associated with the presence of resistant hypertension. Moreover, night time HR (1.160; 1.065-1.265; P < 0.001), nocturnal dip (0.876; 0.830-0.925; P < 0.001) and 24-h s.d. (1.148; 1.092-1.207; P < 0.001) were all significantly associated with true resistant hypertension. In conclusion, both increased HR and variability are associated with resistant hypertension and with true resistance. These suggest the involvement of the sympathetic nervous system in the development of resistance to antihypertensive treatment.

It is well known that 24-h ambulatory blood pressure monitoring (ABPM) provides a more accurate picture of a patient's blood pressure (BP) compared with clinic BP measurement. Twenty-four-hour ABPM better predicts hypertension-related risks such as end-organ damage including left ventricular hypertrophy, cardiovascular (CV) events and mortality. Threshold BP values for hypertension based on 24-h ABPM results have been established, including daytime and night-time averages. Nevertheless, the relationship between 24-h ABPM and clinic BP measurement in patients on antihypertensive therapy, and in particular how each may change in response to antihypertensive therapy, is less clear. This review will provide an overview of current knowledge on the relation between clinic BP and ambulatory BP reductions in clinical trials on antihypertensive therapies. Reduction in CV risk and its correlation with the magnitude of reduction in both clinic and ambulatory BP are explored. The most striking result is that reduction in clinic BP and ambulatory BP do not correspond in a 1:1 fashion, that is, smaller changes in 24-h ABPM correspond to significantly larger changes in clinic BP.

Objectives: In this article, the results of clinical and experimental studies that examine the association of hyperuricemia and gout with hypertension and kidney disease are presented and discussed., Methods: Key papers for inclusion were identified by a PubMed search, and articles were selected according to their relevance for the topic, according to the authors' judgment., Results and Conclusions: Increasing evidence supports a causal role for Uric acid (UA) in hypertension. Further larger studies are needed to confirm the possible beneficial role of UA lowering drugs and/or xantine-oxidase (XO) inhibitors. Overall, clinical evidence suggests a relationship of UA level with incident chronic kidney disease (CKD). In addition, the results of clinical trials using urate lowering therapy provide some promising evidence that lowering UA levels may retard the progression of CKD. Reviewed data indicate the need for large, well designed studies in these patients to evaluate XO inhibitors or uricosuric drugs in cardio-renal diseases and further elucidate the role of UA in the development and progression of CKD.

Introduction: International guidelines emphasize the importance of blood pressure (BP) control to reduce cardiovascular risk. Telmisartan, an angiotensin II receptor blocker, provides large BP reductions and also prevents cardiovascular events in patients at high risk. The thiazide diuretic, hydrochlorothiazide (HCTZ), has a complementary mode of action, and combination with telmisartan is an established and rational treatment option for patients uncontrolled on monotherapy. A single-pill combination (SPC) of telmisartan 80 mg with high-strength HCTZ 25 mg (T80/H25) is widely available., Area Covered: Clinical data on T80/H25 SPC for the management of hypertension was identified via MEDLINE searches. T80/H25 SPC provides greater BP reductions and higher goal achievement rates in patients who cannot achieve BP goal with T80/HCTZ 12.5 mg SPC, and also as initial therapy compared with T80 monotherapy. T80/H25 also reduced BP significantly more than valsartan 160 mg/H25 combination, and demonstrated favorable tolerability in clinical trials., Expert Opinion: Patients with hypertension often do not achieve BP goal, even when treated, leaving them at increased cardiovascular risk. In part this is due to poor adherence, which can be exacerbated by treatment side effects. High BP goal achievement with SPC T80/H25, with maintained tolerability, provides a treatment option for increasing BP control.

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.

To investigate the association of office and ambulatory 24-h pulse pressure (PP) with clinical characteristics and cardiovascular risk factors in normoalbuminuric type 2 diabetic patients enrolled to the Randomised Olmesartan and Diabetes Microalbuminuria Prevention study, 4449 patients (2054 male and 2395 female; mean age 57.7±8.7 years) with type 2 diabetes, normoalbuminuria and at least one additional cardiovascular risk factor were included into the analysis. After adjustment by age, there were significant correlations between office PP and presence of hypertension (r=0.24; P<0.001), presence of cardiac and vascular disorders (r=0.17; P<0.001), metabolic syndrome (r=0.10; P<0.001), duration of diabetes (r=0.09; P<0.001), fasting blood glucose (r=0.08; P<0.001), albumin/creatinine ratio (r=0.07; P<0.001), insulin treatment, glycosylated haemoglobin (HbA1c), male gender and current smoking. In the subgroup of 1234 patients with ambulatory blood pressure measurement performed, ambulatory PP adjusted for office PP correlated with fasting blood glucose (r=0.16; P<0.001), metabolic syndrome (r=0.14; P<0.001), albumin/creatinine ratio (r=0.11; P<0.001) and indices of glycemic control (HbA1c: r=0.11; P<0.001). In this group of normoalbuminuric type 2 diabetic patients, office and ambulatory PP were associated with duration of diabetes, indices of glycemic control and cardiovascular risk factors. There was relationship between office and ambulatory PP and albuminuria even within normal albuminuria range.

Self-monitoring of blood pressure by patients at home (home blood pressure monitoring (HBPM)) is being increasingly used in many countries and is well accepted by hypertensive patients. Current hypertension guidelines have endorsed the use of HBPM in clinical practice as a useful adjunct to conventional office measurements. Recently, a detailed consensus document on HBPM was published by the European Society of Hypertension Working Group on Blood Pressure Monitoring. However, in daily practice, briefer documents summarizing the essential recommendations are needed. It is also accepted that the successful implementation of clinical guidelines in routine patient care is dependent on their acceptance by involvement of practising physicians. The present document, which provides concise and updated guidelines on the use of HBPM for practising physicians, was therefore prepared by including the comments and feedback of general practitioners.

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

Pharmacological treatment of hypertension represents a cost-effective way for preventing cardiovascular and renal complications. To benefit maximally from antihypertensive treatment blood pressure (BP) should be brought to below 140/90 mmHg in every hypertensive patient, and even lower (< 130/80 mmHg) if diabetes or renal disease co-exists. Most of the time such targets cannot be reached using monotherapies. This is especially true in patients who exhibit a high cardiovascular risk. The co-administration of two agents acting by different mechanisms considerably increases BP control. Such preparations are not only efficacious, but also well tolerated, and some fixed low-dose combinations have a tolerability profile similar to placebo. This is for instance the case for the preparation containing the angiotensin-converting enzyme inhibitor perindopril (2 mg) and the diuretic indapamide (0.625 mg), a fixed low-dose combination that has recently been shown in controlled interventional trials to be more effective than monotherapies in reducing albuminuria, regressing cardiac hypertrophy and improving macrovascular stiffness. Fixed-dose combinations are becoming more and more popular and are even proposed by current hypertension guidelines as a first-line option to treat hypertensive patients.

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.

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.

The following is a brief statement of the 2003 European Society of Hypertension (ESH)-European Society of Cardiology (ESC) guidelines for the management of arterial hypertension. The continuous relationship between the level of blood pressure and cardiovascular risk makes the definition of hypertension arbitrary. Since risk factors cluster in hypertensive individuals, risk stratification should be made and decision about the management should not be based on blood pressure alone, but also according to the presence or absence of other risk factors, target organ damage, diabetes, and cardiovascular or renal damage, as well as on other aspects of the patient's personal, medical and social situation. Blood pressure values measured in the doctor's office or the clinic should commonly be used as reference. Ambulatory blood pressure monitoring may have clinical value, when considerable variability of office blood pressure is found over the same or different visits, high office blood pressure is measured in subjects otherwise at low global cardiovascular risk, there is marked discrepancy between blood pressure values measured in the office and at home, resistance to drug treatment is suspected, or research is involved. Secondary hypertension should always be investigated. The primary goal of treatment of patient with high blood pressure is to achieve the maximum reduction in long-term total risk of cardiovascular morbidity and mortality. This requires treatment of all the reversible factors identified, including smoking, dislipidemia, or diabetes, and the appropriate management of associated clinical conditions, as well as treatment of the raised blood pressure per se. On the basis of current evidence from trials, it can be recommended that blood pressure, both systolic and diastolic, be intensively lowered at least below 140/90 mmHg and to definitely lower values, if tolerated, in all hypertensive patients, and below 130/80 mmHg in diabetics. Lifestyle measures should be instituted whenever appropriate in all patients, including subjects with high normal blood pressure and patients who require drug treatment. The purpose is to lower blood pressure and to control other risk factors and clinical conditions present. In most, if not all, hypertensive patients, therapy should be started gradually, and target blood pressure achieved progressively through several weeks. To reach target blood pressure, it is likely that a large proportion of patients will require combination therapy with more than one agent. The main benefits of antihypertensive therapy are due to lowering of blood pressure per se. There is also evidence that specific drug classes may differ in some effect or in special groups of patients. The choice of drugs will be influenced by many factors, including previous experience of the patient with antihypertensive agents, cost of drugs, risk profile, presence or absence of target organ damage, clinical cardiovascular or renal disease or diabetes, patient's preference.

Aim: The aim of this study was to determine the correlation of changes in left ventricular mass, with changes in office blood pressure (BP) and in 24-h ambulatory (ABP), with the trough-to-peak (T/P) ratio and with the smoothness index (SI), as induced by antihypertensive treatment with lercanidipine., Methods: This was done through an observational, prospective, open, non-comparative, single centre, pilot study in patients naïve to antihypertensive therapy. All patients were treated with lercanidipine 10-20 mg/day plus hydrochlorothiazide 12.5-25 mg/day if treated BP exceeded an arbitrarily defined safety level (>160/100 mmHg) after 1 month on monotherapy. ABP monitoring was repeated after 1 month and after 6 months. Two-dimensional mode echocardiography was performed twice, at the beginning and end of the study. Seventeen patients were included in the final analysis (aged 45.8 +/- 10.7 years, 35% women)., Results: Treatment-induced changes in left ventricular mass index (LVMI) were not found to correlate neither with changes in office BP, with changes in ABP values, nor with T/P. However, a significant correlation was found between LVMI changes and SI at 6 months (r=0.50, P=0.039)., Conclusion: The results of this study suggest that the SI has a higher predictive value, compared to other BP-derived parameters, for treatment-induced LVMI changes, in hypertensive patients treated with lercanidipine.

Effective treatment of hypertension is essential to reduce the risk of renal and cardiovascular (CV) morbidity. The risks associated with hypertension are modulated by the presence of other factors. This has prompted the quest for agents that have benefits beyond blood pressure (BP) lowering. The angiotensin II receptor blocker (ARB) class of antihypertensive agents represents an important addition to the therapeutic options for elevated BP. Their ability to control BP is equivalent to existing therapies and there is a considerable and mounting evidence-base for their ability to reduce hypertension-associated target organ damage and comorbidities. Studies show that ARBs have clinical benefits across the spectrum of disease severity. In particular, recent large studies have demonstrated that these benefits extend to patients with conditions predisposing to CV events, such as diabetes, left ventricular hypertrophy and microalbuminuria, and where risk factors coexist. Data from these studies suggest that the CV protective effects of ARBs are at least, in part, independent from the BP lowering action. In addition, ARBs are extremely well tolerated, and strong evidence suggests that compliance with therapy--a key factor in achieving adequate BP control--with ARBs is higher than with other antihypertensive agents. Furthermore, flexible dosing and good tolerability profile mean that, where necessary, ARBs can be combined with other classes of antihypertensive agents to achieve adequate BP control and reduce the risk of hypertension-associated morbidity.

Renal function is closely associated with cardiovascular risk, to the extent that even minor renal abnormalities, which are present in 10% of the general population, carry a greatly elevated risk of cardiovascular disease, target-organ damage and death. Reducing blood pressure by 20 mmHg or more in patients with severe hypertension (>160/100 mmHg) and advanced renal disease is sufficient to ensure a considerable reduction in proteinuria. In patients with less severe disease, however, blockade of the renin-angiotensin-aldosterone system (RAAS) is necessary to restore normal renal function. Clinical studies have shown that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), which both overcome the activity of angiotensin II, provide renoprotection in diabetics and non-diabetic populations. Which class of drugs is more effective remains a subject of debate, but the evidence favours ARBs for providing more effective renoprotection in patients at risk of diabetic nephropathy. The ARBs preserve renal haemodynamics and reduce progression to end-stage renal disease by around 25% in patients with overt nephropathy and prevent progression to overt disease by up to 70% in patients with mild renal impairment. The combination of ARBs and ACE inhibitors is even more protective, halving the number of patients with progression of renal impairment compared with either monotherapy. Long-term clinical studies now under way will help to establish the relative efficacies of the ARBs and ACE inhibitors and provide greater insight into the benefits of combination therapy.

Recently published guidelines recognize the relevance of the development of chronic kidney disease in the stratification of risk of the hypertensive patient. Adequate assessment of renal function, including estimation of glomerular filtration rate, is mandatory in order to ensure an adequate evaluation of global cardiovascular risk in the hypertensive patient. The presence of subtle elevations of serum creatinine concentrations is a potent predictor of a poor cardiovascular prognosis. Clustering of associated risk factors seems to justify the elevated cardiovascular risk observed in patients with essential hypertension and mild renal function derangement. Chronic kidney disease is associated with a significant increase in cardiovascular risk attributable to the simultaneous existence of other risk factors related to the metabolic syndrome. The inhibition of the effects of angiotensin II is necessary to ensure the best degree of renal protection. It has demonstrated to improve the long-term renal outcome of patients with nephrosclerosis and to reduce the appearance of cardiovascular complications in high risk patients The high prevalence of chronic kidney disease in the general and in the hypertensive populations forces the recognition of its relevance and the need for an integrative therapeutic approach to protect simultaneously renal and cardiovascular systems.

The capacity of microalbuminuria to predict an increased cardiovascular and renal risk is well established in diabetic patients, as well as in essential hypertensive patients and in general population. Detection of microalbuminuria could then be relevant to select specific therapeutic strategies for reducing or preventing cardiovascular events in patients with essential hypertension. Microalbuminuria is detectable in almost 40% of the population with established hypertension, particularly in those patients not controlled satisfactorily with medical therapy. Albuminuria may represent a marker of renal damage and cardiovascular risk in essential hypertension. Microalbuminuria seems to represent a simple and reproducible method to better define cardiovascular risk profile in the hypertensive patient and to stratify the prognosis in relation to renal and cardiovascular risk. ACE-inhibitors and more recently angiotensin II receptor antagonists seem to exhibit a more market capacity to reduce microalbuminuria in patients with essential hypertension or diabetes mellitus. Determination of this parameter in daily clinical practice could facilitate the stratification of risk as well as the choice of therapy in essential hypertensive patients.

Recently published guidelines recognize the relevance of the finding of chronic kidney disease (CKD) in the stratification of risk of the hypertensive patient. Determination of the presence of microalbuminuria and estimation of glomerular filtration rate are mandatory in order to ensure an adequate evaluation of global cardiovascular (CV) risk in the hypertensive patient. Indices of altered renal function (e.g. microalbuminuria, increased serum creatinine concentrations, decrease in estimated creatinine clearance or overt proteinuria) are independent predictors of CV morbidity and mortality. Clustering of associated risk factors seems to justify the elevated CV morbidity and mortality observed in patients with essential hypertension and mild alterations of renal function. The increased prevalence of CKD in the general and in the hypertensive populations forces the recognition of its relevance and the need for an integrative therapeutic approach to fully protect simultaneously renal and CV systems.

Hypertension rarely occurs in isolation, and many hypertensives have additional risk factors for cardiovascular disease in addition to elevated blood pressure. Each patient's cardiovascular disease risk profile should be determined individually, and the treatment approach tailored to each case. Cardiovascular disease risk factors and high blood pressure are closely linked, suggesting that the ideal treatment should not only lower blood pressure, but also effectively lower overall risk. This is likely to require more than one drug, and one of the most effective and safe combinations is that of an angiotensin receptor blocker with a diuretic. The completion of one of the most important trials undertaken to explore risk factors and anti-hypertensive treatment, the Valsartan long-term evaluation trial (VALUE), will certainly enhance understanding for the role of combination treatment in high-risk patients, as well as contribute to the design of rational treatments for blood pressure control.

Type 2 diabetes is increasing globally and is a major cause of conditions such as cardiovascular disease, retinopathy and nephropathy. The Diabetes Control and Complications Trial and the UK Prospective Diabetes Study demonstrated that the progression of renal disease could be slowed by tight glycaemic control and treating any associated hypertension with angiotensin-converting enzyme inhibition. Recent clinical trials have supported the use of angiotensin II receptor antagonists in the treatment of diabetic nephropathy, resulting in the approval of new therapeutic indications in the United States and Europe. The objective of this review is to demonstrate how results from the Program for Irbesartan Mortality and morbidity Evaluation studies apply to clinical practice, and to show how the benefits of irbesartan therapy can be realised at any stage of renal disease in patients with diabetes.

Blockade of the renin-angiotensin system with angiotensin converting enzyme inhibitors or with angiotensin receptor antagonists confers patients with arterial hypertension (AH) and associated risk factors, target organ lesion or cardiovascular disease with greater protection in morbidity and mortality terms. The objective of the present study was to evaluate the effect of irbesartan, an angiotensin II receptor antagonist, on the absolute cardiovascular risk in a cohort of hypertensive patients with moderate, high, or very high cardiovascular risk. This was a multicenter, prospective, observational, cohort study with 1974 patients (63 11 years; 47% males) with newly diagnosed essential AH or AH non-controlled with anti-hypertensive monotherapy, and moderate to very high cardiovascular risk. Irbesartan therapy at a dosage of 150300 mg was instituted as monotherapy or associated with hydrochlorothiazide, 12.5 mg. The clinical follow-up was 6 months. The evaluated parameters included the absolute cardiovascular risk, measured either quantitatively (Framingham algorithm) or qualitatively (low, moderate, high, and very high risk groups following the WHO/International Hypertension Society guidelines). Irbesartan therapy led to a significant (p = 0.0001) decrease in SBP (from 170.9 18.4 to 138.5 16.5 mmHg) and DBP (from 96.6 11 to 82 9 mmHg). The quantitative absolute cardiovascular risk decreased by 29.8% (from 12.14 8 to 8.65 6.2; p < 0.0001). The percentage of patients with very high cardiovascular risk decreased from 1.52% to 0.51% and that for patients with high cardiovascular risk from 92.77% to 88.32%. The latter patients changed to the moderate risk group. As a result, this moderate risk group increased from 5.71% to 11.17%. The adverse reaction rate was very low as only 2.2% of patients had some adverse reaction. In conclusion, irbesartan as monotherapy or associated with hydrochlorothiazide has been shown to be effective in reducing the absolute cardiovascular risk, which is obtained by a substantial decrease in arterial pressure and a good safety profile on the biochemical parameters. Tolerability was excellent, with a very low rate of adverse reactions.

The presence of an altered renal function in essential hypertension, advanced heart failure (HF) and after a myocardial infarction (MI) is associated with higher cardiovascular morbidity and mortality. Indices of altered renal function (e.g., microalbuminuria, increased serum creatinine concentrations, decrease in estimated creatinine clearance or overt proteinuria) are independent predictors of cardiovascular morbidity and mortality in any of the three clinical situations. These parameters should then be routinely evaluated in clinical practice. These facts have several therapeutic implications. First, although there is no evidence-based information on the level of blood pressure that confers optimal renal protection, levels substantially lower than past recommendations are advisable. Second, hypertensive kidney damage should be prevented by early treatment of hypertensive patients, particularly those with microalbuminuria. Finally, to avoid further aggravation of high cardiovascular risk, antihypertensive agents devoid of unwanted metabolic side effects should be used for the treatment of hypertensive vascular damage. In HF, the combination of an angiotensin-converting enzyme (ACE) inhibitor and a beta-blocker seem to be the most renoprotective. Renal outcome is also improved by ACE inhibition after an MI. Finally, renal and cardiovascular outcome seem to run in parallel in all these situations.