[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.

[Tools to improve efficiency in the clinical management of hypertensive patients]. / Herramienta para mejorar la eficiencia en el manejo clínico de pacientes hipertensos.

OBJECTIVE: To create a tool to evaluate the efficiency of the clinical management of hypertensive patients in Primary Care. MATERIAL AND METHODS: A web-based questionnaire was designed for Primary Care centres to self-evaluate the management of hypertension in five specific areas: information systems, diagnostic and analytical tests, organisational aspects, use of resources, and continuous training programmes for patients and healthcare professionals. A committee of experts previously defined these questions and their ideal responses or "control", based on the scientific literature or, if there were no published references, by consensus of the committee. A descriptive analysis was performed on the data, and an adherence score was created that ranged from 0 (no adherence) to 1 (total adherence). RESULTS: A total of 35 Primary Care centres entered their data into the website for the clinical management of hypertensive patients. The highest adherence to the ideal algorithm was observed in the area "Diagnostic and analytical tests" (0.69±0.10), and the lowest in "Continuous training programmes for patients and professionals" (0.42±0.21). CONCLUSIONS: The efficiency of clinical management in hypertensive patients can be analysed using the website tool created for this purpose. Its use allows an internal audit to detect the areas that need improvement, and also serves to make comparative evaluations in the different areas of management over time.

Influence of target organ lesion detection (assessment of microalbuminuria and echocardiogram) in cardiovascular risk stratification and treatment of untreated hypertensive patients.

European guidelines indicate the importance of the evaluation of global cardiovascular risk (CVR) to determine the management of the hypertensive patients (EH). However, in primary care, the diagnostic work-up (PCD) only includes the metabolic risk factors. The aim of this study was to assess the importance of microalbuminuria (MA) and echocardiogram (ECHO) in the process of risk stratification, and the number of patients to be treated with drugs at diagnosis. In total, 155 nontreated EH were included in the study. Blood pressure, a lipid profile and plasma glucose (LG) were determined after an overnight fast. MA was evaluated with dipstick MICRALTEST, and in those patients with two positive results, it was measured again in two 24-h urine samples and was considered positive (MA+) if the average was >30 mg/24 h. Left ventricular mass index was calculated and values>125 g/m2 were considered as LV hypertrophy (LVH+). When the patients were stratified according to PCD, 22 had to be treated with drugs. When MA, ECHO and both tests used together were added to the risk evaluation, the number of patients to be treated were 42, 51 and 64, respectively (P<0.001 vs PCD). It is mainly in patients who have moderate cardiovascular risk that risk changes, whereas risk hardly changes in those having low and very high risk. In conclusion, in EH with moderate risk, measurement of MA, due to its easy availability and low cost, seems to be a cost effective screening test to avoid the underestimation of the CVR.

Renin-angiotensin system gene polymorphisms: relationship with blood pressure and microalbuminuria in telmisartan-treated hypertensive patients.

This study analyzed the relationship between four renin-angiotensin system (RAS) gene polymorphisms and the response to blood pressure lowering and development of microalbuminuria in 206 patients with essential hypertension treated once daily for 12 months with telmisartan 80 mg. Seated cuff blood pressure and urinary albumin excretion (UAE) were measured throughout the study. Patients were screened for the presence of the A-6G variant of the angiotensinogen gene, angiotensin-converting enzyme insertion/deletion polymorphism, and the A1166C and C573T polymorphisms of the angiotensin II type 1 receptor gene. No significant association was found between the presence of any gene polymorphism and the reduction of blood or UAE following telmisartan treatment. The results indicate that these RAS gene polymorphisms do not affect the antihypertensive activity and renoprotection in mild-to-moderate hypertensive patients treated with telmisartan.

Impairment of renal vasodilation with l-arginine is related to more severe disease in untreated hypertensive patients.

Data remain insufficient to place the decreased response to L-arginine in hypertensive patients within a consistent pathophysiological sequence. The aim of the present study in patients with essential hypertension was to assess the relationships between the response to L-arginine and a set of relevant clinical and laboratory parameters. In this prospective, interventional study, we administered L-arginine to untreated hypertensive individuals and healthy control subjects and measured the clearance of inulin and of para-aminohippurate and a set of biochemical and clinical variables. L-Arginine infusion revealed major differences between control subjects and 1 subgroup (group B) of hypertensive individuals. Group B hypertensives (n=18) had no increase in inulin clearance and no decrease in renal vascular resistance with L-arginine; however, in another subset of hypertensive patients (group A, n=27), the insulin clearance increased and renal vascular resistance decreased similar to the control group (group C, n=11). The ambulatory blood pressure monitoring in group B showed both an increased mean diastolic pressure and a "nondipper" pattern in the nocturnal regulation of arterial pressure. These findings in group B were accompanied by significant alterations in optic fundus and left ventricle hypertrophy and increased microalbuminuria (all, P<0.05). Furthermore, group B individuals had significantly lower values of HDL cholesterol and a higher baseline atherogenic index, plasma insulin level, and glucose/insulin index. We disclose a previously undescribed relationship between end organ repercussion and decreased renal hemodynamic response to L-arginine. Our results may help to understand the mechanisms that lead to target organ damage in hypertension.

Doxazosin added to single-drug therapy in hypertensive patients with benign prostatic hypertrophy.

The purpose of this study was to evaluate the efficacy and safety of the addition of doxazosin in the treatment of hypertensive patients who are being treated on another antihypertensive drug. The open-labeled, noncomparative, multicenter study was carried out in 2363 male hypertensive outpatients > 40 years of age, under reasonable control with single antihypertensive drug treatment (diastolic blood pressure < 95 mm Hg), and diagnosed with benign prostatic hypertrophy. Doxazosin was started at a dose of 1 mg/day, which was increased at 2-week intervals to 2 mg/day and 4 mg/day. The study lasted 14 weeks. Blood pressure and heart rate were measured at each of the visits. At baseline and after 14 weeks of treatment, prostatism symptoms were quantified with the International Prostate Symptom Score and quality of life was determined with the American Urology Association Committee Guidelines. Adverse effects were recorded. At the fourth visit, when the patients were taking 4 mg of doxazosin, the blood pressure reduction was 10.7 +/- 3/7.1 +/- 7.1 mm Hg. The decrease in diastolic blood pressure was significantly more marked in patients treated with beta blockers than in patients on calcium antagonists or angiotensin-converting enzyme inhibitors. For systolic blood pressure, decreases were larger in patients treated with diuretics than with calcium antagonists or angiotensin-converting enzyme inhibitors. Prostatism symptoms decreased from 15 +/- 5.8 points to 7.9 +/- 4.3 points (p is less than 0.001) and quality of life improved. Tolerability was good, with only a 4.4% cumulative incidence of adverse effects related to doxazosin. The patients who experienced adverse effects were older and their final blood pressures were lower. The results of this open-label study suggest that the addition of doxazosin to another antihypertensive drug in hypertensive patients with benign prostatic hypertrophy is well tolerated and leads to a reduction in prostatic symptoms. The additional beneficial effects on blood pressure suggest that the use of doxazosin may provide a rational approach to this category of patients.(c)2001 Le Jacq Communications, Inc.

Hyperkalemia in patients infected with the human immunodeficiency virus: involvement of a systemic mechanism.

BACKGROUND: The appearance of hyperkalemia has been described in human immunodeficiency virus (HIV)-positive patients treated with drugs with amiloride-like properties. Recent in vitro data suggest that individuals infected with HIV have alterations in transcellular K+ transport. METHODS: With the objective of examining the presence of alterations in transmembrane K+ equilibrium in HIV-positive patients, we designed a prospective, interventional study involving 10 HIV-positive individuals and 10 healthy controls, all with normal renal function. An infusion of L-arginine (6%, intravenously, in four 30-min periods at 50, 100, 200, and 300 ml/hr) was administered, and plasma and urine electrolytes, creatinine, pH and osmolality, total and fractional sodium and potassium excretion, transtubular potassium gradient, plasma insulin, renin, aldosterone, and cortisol were measured. RESULTS: A primary disturbance consisting of a significant rise in plasma [K+] induced by L-arginine was detected in only the HIV patients but not in the controls (P < 0.001 between groups). A K+ redistribution origin of the hyperkalemia was supported by its rapid development (within 60 min) and the lack of significant differences between HIV-positive individuals and controls in the amount of K+ excreted in the urine. The fact that the HIV-positive individuals had an inhibited aldosterone response to the increase in plasma K+ suggested a putative mechanism for the deranged K+ response. CONCLUSIONS: These results reveal that HIV-infected individuals have a significant abnormality in systemic K+ equilibrium. This abnormality, which leads to the development of hyperkalemia after the L-arginine challenge, may be related, in part, to a failure in the aldosterone response to hyperkalemia. These results provide a new basis for understanding the pathogenesis of hyperkalemia in HIV individuals, and demonstrate that the risk of HIV-associated hyperkalemia exists even in the absence of amiloride-mimicking drugs or overt hyporeninemic hypoaldosteronism.

Induction of microalbuminuria by l-arginine infusion in healthy individuals: an insight into the mechanisms of proteinuria.

Despite evidence from individuals with diabetes mellitus or reduced renal mass, the actual relationship between protein- or amino acid-induced changes in renal function and urinary albumin excretion (UAE) is largely unknown in subjects without renal disease. In humans, infusions of l-arginine have been used recently in vascular and renal pathophysiological studies. The present study was undertaken to analyze the mechanisms involved in a particular effect; namely, the behavior of UAE during amino acid loading. A prospective interventional protocol was performed on 10 healthy adults by means of an intravenous infusion of l-arginine. The main results show that l-arginine induced a significant increase in UAE from 13.1 +/- 3.8 before to 53.3 +/- 11.1 microgram/min after the infusion (P < 0.005). This increment was simultaneous to an increase in glomerular filtration rate (GFR) and renal plasma flow (RPF). Furthermore, l-arginine markedly increased the urinary excretion of beta2-microglobulin. UAE correlated significantly with GFR (r = 0. 738; P = 0.014) and RPF (r = 0.942; P < 0.0001), but not with urinary beta2-microglobulin (r = 0.05; P = not significant). Furthermore, marked differences (P = 0.001) were found between the percentage of increase in UAE (306.8% +/- 163.2%) with respect to either albumin filtered load (FLAlb; 57.9% +/- 16.3%) and beta2-microglobulin excretion (1,088.5% +/- 424.6%). No changes were found in vehicle-infused individuals. In conclusion, the present study shows, in controlled conditions, that l-arginine infusion induces a relevant increase in UAE in healthy individuals that significantly exceeds that expected from the increase in GFR alone. The intense and simultaneous increment in beta2-microglobulin excretion strongly suggests that the effect of l-arginine on UAE is, in a relevant part, mediated through a blockade in the tubular protein reabsorption pathways. However, the profound differences observed in the changes induced by l-arginine on UAE and beta2-microglobulin excretion and the differences in the correlation of UAE and beta2-microglobulin with respect to GFR suggest that substantial diversity exists in the mechanisms by which l-arginine affects the renal management of albumin and beta2-microglobulin. These findings are relevant for understanding the renal response to l-arginine and protein/amino acid loads.

Characterization of angiotensin-(1-7) in the urine of normal and essential hypertensive subjects.

A total of 31 healthy volunteers [39 +/- 7 (SD) years] and 18 untreated essential hypertensive subjects [43 +/- 9 years] collected urine for 24 h after a physical examination and laboratory tests. Radioimmunoassay measurements of angiotensin-(1-7) [Ang-(1-7)] in urine and plasma were done as described previously. Sitting systolic and diastolic blood pressures (+/- SD) averaged 118 +/- 11/74 +/- 7 mm Hg and 146 +/- 16/96 +/- 8 mm Hg in normal and essential hypertensive subjects, respectively (P < .001), whereas 24 h urinary volume was not different in normal and essential hypertensive subjects (P > .05). The concentration of Ang-(1-7) in the urine of normal subjects averaged 62.6 +/- 22.6 pmol/L corresponding to a urinary excretion rate of 98.9 +/- 44.7 pmol/24 h. Concurrent measurements of plasma Ang-(1-7) showed that the content of Ang-(1-7) in urine was 2.5-fold higher than that measured in the plasma. In contrast, untreated essential hypertensive subjects had lower concentrations and 24 h urinary excretion rates of Ang-(1-7) averaging 39.4 +/- 18.0 pmol/L and 60.2 +/- 14.6 pmol/24 h, respectively, (P < .001). Differences in the excretory rate of Ang-(1-7) between normal volunteers and essential hypertensive subjects were not modified by normalization of the data by urinary creatinine excretion rates. Urinary concentrations of Ang-(1-7) correlated inversely with systolic, diastolic and mean arterial pressures (r = -0.48, P < .001). Both urinary Ang-(1-7) [odds ratio of 0.92 (95% CI: 0.88-0.97)] and age were independent predictors of systolic blood pressure. These studies demonstrated the presence of Ang-(1-7) in urine and the existence of reduced levels of the heptapeptide in individuals with untreated essential hypertension. The relatively higher concentrations of Ang-(1-7) in urine compared to plasma agrees with data that showed that Ang-(1-7) may contribute to the regulation of blood pressure. The inverse association between Ang-(1-7) and arterial pressure provides a potential marker for the characterization of forms of essential hypertension associated with reduced production or activity of vasodilator hormones.

Trough to peak ratio of once-daily lisinopril and twice-daily captopril in patients with essential hypertension.

The objective of this study was to assess the antihypertensive effect and the trough to peak (T:P) ratio of lisinopril and captopril, in patients with essential hypertension. After 2 weeks of placebo, 69 of 115 eligible patients had office diastolic blood pressure (DBP) between 90 and 114 mm Hg and daytime average DBP above 85 mm Hg during a 25-h ambulatory BP monitoring (ABPM) and were randomised to receive lisinopril (20 mg once daily) or captopril (50 mg twice daily) for 4 weeks. Office and ambulatory BP were then repeated. Indices of 24-h BP and T:P ratios were calculated and compared. Both drugs significantly reduced both office and ambulatory BP. The final BP obtained with lisinopril was less than with captopril. On office measurement, 75% of the patients treated with lisinopril and 44% on captopril were controlled (P < 0.001), but responses by ABPM were not significantly different. T:P ratios calculated in all patients were 0.75 and 0.66 for lisinopril and captopril respectively, but in patients who responded to each drug the corresponding ratios were 0.78 and 0.73. In conclusion both 20 mg once-daily lisinopril and 50 mg captopril twice-daily achieve a favourable T:P ratio in patients with essential hypertension.

Effects of captopril related to increased levels of prostacyclin and angiotensin-(1-7) in essential hypertension.

OBJECTIVE: To evaluate the contribution of angiotensin-(1-7) [Ang-(1-7)] and prostaglandins to the acute and long-term antihypertensive actions of captopril in mild-to-moderate essential hypertensive patients. DESIGN AND METHODS: Blood pressure, cardiac rate and the plasma concentrations of angiotensin I (Ang I), angiotensin II (Ang II), Ang-(1-7), prostaglandin E2 and 6-keto prostaglandin F1 alpha (the breakdown product of prostacyclin) were determined in the peripheral venous blood of 24 essential hypertensive subjects before and 3 h after administration of 50 mg captopril. Eleven of 24 patients completed a 6-month treatment period with captopril monotherapy (50 mg twice a day). The hemodynamic and hormonal response produced by a last 50 mg dose of captopril was determined once again in the 11 subjects who maintained blood pressure control with captopril monotherapy for 6 months. RESULTS: The fall in blood pressure produced 3 h after drug intake was comparable for the first and the last 50 mg captopril dose. Although the first response to captopril increased plasma levels of Ang I only, the response to the last dose of the drug (6 months after) caused significantly higher levels of Ang I and Ang-(1-7). Neither acute nor chronic therapy with captopril had a significant effect on plasma concentrations of Ang II. Although plasma levels of prostaglandin E2 and 6-keto prostaglandin F1 alpha were not modified by a first exposure to captopril, the concentrations of 6-keto prostaglandin F1 alpha but not prostaglandin E2 rose significantly in subjects treated with the inhibitor for 6 months. A negative correlation was also demonstrated between diastolic blood pressure and plasma Ang-(1-7) levels in the 11 essential hypertensive subjects in whom blood pressure was controlled with captopril monotherapy. CONCLUSIONS: Inhibition of angiotensin converting enzyme with captopril had a significant effect on blood pressure that was not directly accounted for by a suppression of plasma Ang II levels. Continuous therapy with captopril unmasked a contribution of Ang-(1-7) and prostacyclin to the antihypertensive actions of this drug.

[Effect of suppression of apnea on arterial pressure and plasma catecholamines in normotensive patients with sleep apnea]. / Efecto de la supresión de las apneas sobre la presión arterial y catecolaminas plasmáticas en normotensos con apnea del sueño.

BACKGROUND: The association of high blood pressure (HBP) and the sleep apnea syndrome (SPS) and the beneficial effect of SAS treatment on HBP are well known. The direct effect of the continuous nocturnal administration of positive air pressure (CPAP) on blood pressure is not, however, well known. The aim of this study was to evaluate the blood pressure (BP), plasma catecholamines (PC) and urinary derivatives of catecholamines (UDC) in 17 normotensive subjects (4 females; age 49 +/- 11 years) with SAS, prior to and after correction of apnea with CPAP. METHODS: Twenty-four hour outpatient registry of blood pressure (OPRBP) and after nocturnal polysomnography were performed both basal and during CPAP administration for two nights. Urine was collected over these 24 hour period for measurement of UDC. At 7 hours a blood sample was collected for measurement of PC. RESULTS: SAS was corrected by CPAP in all the patients with a reduction in mean BP (24 h: 87 +/- 6 vs 84 +/- 6 mmHg, p < 0.05, diurnal, 90 +/- 6 vs 87 +/- 6 mmHg, p < 0.05, nocturnal, 84 +/- 6 vs 82 +/- 7 mmHg, NS) and the percentage of diastolic BP > 90 mmHg (24 h: 10 +/- 7 mmHg vs 6.5 +/- 6 mmHg, p < 0.01, diurnal, 15 +/- 10 vs 10 +/- 10 mmHg, p < 0.05, nocturnal 5.2 vs 5 vs 3 +/- 4 mmHg, p < 0.05). The plasma catecholamines tended to reduce, although not significantly, without changes of urinary metabolites. CONCLUSIONS: There is a significant decrease in blood pressure with the administration of continuous positive air pressure even in normotensive patients. An early correction of sleep apnea syndrome may reduce the high prevalence of hypertension associated with this syndrome.