Evidence on the use of alternative substances and therapies in hypertension / Evidencias sobre el uso de sustancias y terapias alternativas en hipertensión

Objective: Review of some of the best-known biological and non-biological complementary/alternative therapies/medicines (CAM) and their relationship with blood pressure (BP) and hypertension (HT). Search strategy: Narrative review assessing a recent series of systematic reviews, meta-analyses, and clinical trials published in recent years, focusing on the effects of CAM on BP and HT. Selection of studies: We searched EMBASE, MEDLINE, Cochrane Library and Google Scholar, obtaining a total of 4336 articles, finally limiting the search to 181 after applying filters. Synthesis of results: Some studies on biological therapies show some usefulness in BP reduction with an adequate benefit–risk balance, although there is a scarcity of high-quality trials that support these results. Some mind-body therapies have shown hypothetical benefit; in contrast, others lack robust evidence. Conclusions: Although some therapies present a reasonable risk–benefit ratio, they should in no case replace pharmacological treatment when indicated.(AU)

Objetivo: Revisar algunas de las más conocidas terapias/medicinas biológicas y no biológicas complementarias/alternativas (MCA), y su relación con la presión arterial (PA) e hipertensión arterial (HTA). Estrategia de búsqueda: Revisión narrativa en la que se valoraron una serie reciente de revisiones sistemáticas, metaanálisis y ensayos clínicos publicados en los últimos años, centrada en los efectos de la MCA sobre la PA y HTA. Selección de estudios: Se realizaron búsquedas en EMBASE, MEDLINE, Cochrane Library y Google Scholar, obteniéndose un total de 4.336 artículos, limitándose finalmente a 181 tras aplicar filtros. Síntesis de resultados: Algunos trabajos sobre terapias biológicas parecen demostrar cierta utilidad en reducción de la PA con adecuado balance beneficio/riesgo, aunque existe escasez de ensayos de alta calidad que avalen estos resultados. Algunas terapias cuerpo/mente han mostrado un hipotético beneficio; en cambio, otras carecen de evidencia robusta. Conclusiones: Aunque algunas terapias presentan una relación riesgo/beneficio razonable, no deberían sustituir en ningún caso al tratamiento farmacológico cuando este esté indicado.(AU)

Evidence on the use of alternative substances and therapies in hypertension.

OBJECTIVE: Review of some of the best-known biological and non-biological complementary/alternative therapies/medicines (CAM) and their relationship with blood pressure (BP) and hypertension (HT). SEARCH STRATEGY: Narrative review assessing a recent series of systematic reviews, meta-analyses, and clinical trials published in recent years, focusing on the effects of CAM on BP and HT. SELECTION OF STUDIES: We searched EMBASE, MEDLINE, Cochrane Library and Google Scholar, obtaining a total of 4336 articles, finally limiting the search to 181 after applying filters. SYNTHESIS OF RESULTS: Some studies on biological therapies show some usefulness in BP reduction with an adequate benefit-risk balance, although there is a scarcity of high-quality trials that support these results. Some mind-body therapies have shown hypothetical benefit; in contrast, others lack robust evidence. CONCLUSIONS: Although some therapies present a reasonable risk-benefit ratio, they should in no case replace pharmacological treatment when indicated.

Association of blood manganese concentrations with 24-h based brachial and central blood pressure, and pulse-wave velocity.

Potential environmental determinants of BP and hypertension in older adults are far less known than their lifestyle risk factors. Manganese (Mn) is an essential element for life that may induce changes in blood pressure (BP), but the direction of the association is unclear. We aimed to examine the association of blood manganese (bMn) with 24-h-based brachial, central BP (cBP), and pulse-wave velocity (PWV). With this purpose, we analyzed data from 1009 community-living adults aged >65 years without BP medication. bMn was measured using inductively-coupled plasma-mass spectrometry and 24-h BP with validated devices. The association of bMn (median: 6.77 µg/L; IQR: 5.59-8.27) with daytime brachial and central systolic (SBP) and with diastolic BP (DBP) was non-linear, with BP increases up to around the median of Mn and then stabilization or slight rightward decrease. Mean BP differences (95% confidence interval) comparing Mn Q2 to Q5 (vs Q1 quintile) for brachial daytime SBP were 2.56 (0.22; 4.90), 3.59 (1.22; 5.96), 3.14 (0.77; 5.51) and 1.72 (-0.68; 4.11) mmHg, respectively; and 2.22 (0.70, 3.73), 2.55 (1.01, 4.08), 2.45 (0.91; 3.98), and 1.68 (0.13; 3.24), respectively, for DBP. Daytime central-pressures showed a similar dose-response relationship with bMn as daytime brachial-pressures. The association with nighttime BP was linearly positive for brachial BPs, and only increasing for Q5 for cBP. Regarding PWV, a tendency to significant linear increase along bMn levels was observed (p-trend = 0.042). The present findings extend the scarce evidence on the association between Mn and brachial BP to 2 other vascular parameters, suggesting Mn levels as a candidate risk factor for increasing levels of both brachial and cBPs in older adults, yet further research is needed with larger cohort studies in adults at all age ranges.

[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.

Hypertension: The most common chronic health problem in Spain. A call to action

Hypertension (HYP) is the first cause of death and disability worldwide. In Spain, one in 3 adults was hypertensive in 2010 (62% in those >65 years in 2017). Despite improvement in HYP management over time, only half of treated hypertensive patients are adequately controlled, which translates in 30,000 annual cardiovascular deaths attributable to HYP. Among modifiable determinants of lack of blood pressure (BP) control in Spain are: (a) the white-coat phenomenon (accounting for 20–50% of apparent lack of control) due to not using ambulatory BP monitoring (ABPM, use ≈20%) or self-measurement of home BP (HBPM, use ≈60%) for confirming HYP diagnosis; (b) insufficient patientś adherence to BP-lowering lifestyles (e.g., only 40% of hypertensive patients have a sodium intake <2.4g/day, or follow a weight reduction advice), and (c) use of drug monotherapy (≈50% currently), usually insufficient to achieve an optimal control. It is necessary to implement strategies to monitor the evolution of the proportion of subjects with HYP with reasonable national update, to promote population's knowledge of their BP figures and of other cardiovascular risk factors, to improve the degree of HYP control and vascular risk in Spain.(AU)

La hipertensión arterial (HTA) sigue constituyendo la primera causa de mortalidad y discapacidad en el mundo. En España, el 33% de los adultos eran hipertensos en 2010 (62% en >65 años en 2017). Y, aunque ha habido mejora en su manejo, solo uno de cada 2 hipertensos adultos tratados está adecuadamente controlado; ello se traduce en unas 30.000 muertes cardiovasculares anuales atribuibles a la hipertensión. Entre los determinantes modificables de la falta de control de la presión arterial (PA) en España destacan: (a) el fenómeno de bata blanca (un 20-50% de los casos de aparente falta de control), en parte por la escasa utilización de monitorización ambulatoria de la PA (MAPA -uso, ≈20%) e incluso de automedida de la PA en el hogar (AMPA -uso, ≈60%) para confirmar el diagnóstico de HTA; (b) la insuficiente adherencia del paciente a estilos de vida reductores de la PA (p. ej., solo el 40% de los hipertensos siguen el consejo de ingesta no elevada de sodio, o el de reducir su excesivo peso); y c) el uso insuficiente de terapia farmacológica combinada (≈50% actualmente) para lograr un control óptimo. Es necesario implementar estrategias para monitorizar la evolución de la proporción de sujetos con HTA con una razonable y decorosa actualización en el contexto internacional, fomentar el conocimiento de la población de sus cifras de PA y de otros factores de riesgo cardiovascular, y mejorar el grado de control de la HTA y el riesgo cardiovascular en España.(AU)

Hypertension: The most common chronic health problem in Spain. A call to action.

Hypertension (HYP) is the first cause of death and disability worldwide. In Spain, one in 3 adults was hypertensive in 2010 (62% in those >65 years in 2017). Despite improvement in HYP management over time, only half of treated hypertensive patients are adequately controlled, which translates in 30,000 annual cardiovascular deaths attributable to HYP. Among modifiable determinants of lack of blood pressure (BP) control in Spain are: (a) the white-coat phenomenon (accounting for 20-50% of apparent lack of control) due to not using ambulatory BP monitoring (ABPM, use ≈20%) or self-measurement of home BP (HBPM, use ≈60%) for confirming HYP diagnosis; (b) insufficient patients adherence to BP-lowering lifestyles (e.g., only 40% of hypertensive patients have a sodium intake <2.4g/day, or follow a weight reduction advice), and (c) use of drug monotherapy (≈50% currently), usually insufficient to achieve an optimal control. It is necessary to implement strategies to monitor the evolution of the proportion of subjects with HYP with reasonable national update, to promote population's knowledge of their BP figures and of other cardiovascular risk factors, to improve the degree of HYP control and vascular risk in Spain.

Selenium and impaired physical function in US and Spanish older adults.

BACKGROUND: Selenium (Se) is a trace element with a narrow safety margin. OBJECTIVES: To evaluate the cross-sectional and longitudinal dose-response association between Se exposure and measures of impaired physical function and disability in older adults. DESIGN: NHANES 2011-2014 cross-sectional (US, n = 1733, age ≥60 years) and Seniors-ENRICA-2 2017-2019 cross-sectional and longitudinal (Spain, n = 2548 and 1741, respectively, age ≥65 years) data were analyzed. Whole blood and serum Se levels were measured using inductively coupled plasma-mass spectrometry. Lower-extremity performance was assessed with the Short Physical Performance Battery, and muscle weakness with a dynamometer. Incident mobility and agility limitations, and disability in instrumental activities of daily living (IADL) were ascertained with standardized questionnaires. Analyses were adjusted for relevant confounders, including physical activity. Results across studies were pooled using random-effects meta-analysis. RESULTS: Meta-analyzed odds ratios (95% confidence interval) per log2 increase in whole blood Se were 0.54 (0.32; 0.76) for weakness, 0.59 (0.34; 0.83) for impaired lower-extremity performance, 0.48 (0.31; 0.68) for mobility limitations, 0.71 (0.45; 0.97) for agility limitations, and 0.34 (0.12; 0.56) for disability in at least one IADL. Analyses for serum Se in NHANES showed similar results. Findings suggest the inverse association with grip strength is progressive below 140 µg/L (p-value for non-linear trend in the Seniors-ENRICA-2 study = 0.13), and above 140 µg/L (p-value for non-linear trend in NHANES = 0.11). In the Seniors-ENRICA-2 cohort, with a 2.2 year follow-up period, a doubling in baseline Se levels were associated with a lower incidence of weakness [odds ratio (95% confidence interval): 0.45 (0.22; 0.91)], impaired lower-extremity performance [0.63 (0.32; 1.23)], mobility [0.43 (0.21; 0.91)] and agility [0.38 (0.18; 0.78)] limitations. DISCUSSION: In US and Spanish older adults, Se concentrations were inversely associated with physical function limitations. Further studies are needed to elucidate underlying mechanisms.

[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.

[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.

Patterns of alcohol consumption and risk of falls in older adults: a prospective cohort study.

Falls are a major health problem in older adults, but their relationship with alcohol consumption in this population remains unclear. In a cohort with 2170 older adults followed up for 3.3 years, both moderate drinking and the Mediterranean drinking pattern were associated with a lower risk of falls and injurious falls. INTRODUCTION: This study aims to examine the association between certain patterns of alcohol consumption, including the Mediterranean drinking pattern (MDP), and the risk of falls in older adults. METHODS: A prospective cohort with 2170 community-dwelling individuals aged ≥60 years was recruited in Spain in 2008-2010 and followed up through 2012. At baseline, participants reported alcohol consumption and, at the end of follow-up, their falls during the previous year. The MDP was defined as moderate alcohol consumption (threshold between moderate and heavy intake was 40 g/day for men and 24 g/day for women) with preference for wine and drinking only with meals. Analyses were conducted with negative binomial or logistic regression, as appropriate, and adjusted for the main confounders. RESULTS: Compared with never drinkers, the number of falls was lower in moderate drinkers (incidence rate ratio (95% confidence interval), 0.79 (0.63-0.99)) and drinkers with MDP (0.73 (0.56-0.96)). Also, moderate drinkers and those with MDP showed a lower risk of ≥2 falls (odds ratio (95% confidence interval), 0.58 (0.38-0.88) and 0.56 (0.34-0.93), respectively) and of falls requiring medical care (0.67 (0.46-0.96) and 0.61 (0.39-0.96), respectively). CONCLUSION: Both moderate drinking and the MDP were associated with a lower risk of falls and injurious falls in older adults. However, sound advice on alcohol consumption should balance risks and benefits.

[Use of ambulatory blood pressure monitoring]. / Utilización de la monitorización ambulatoria de la presión arterial.

Hypertension (HT) is the most important risk factor in the development of cardiovascular disease. Classically diagnosis and management have been based on conventional office blood pressure (BP) but it has as main limitation that only offers information of a particular time and presents multiple biases dependent on inherent variability of blood pressure and measurement technique itself. Ambulatory blood pressure monitoring (ABPM) consists of performing multiple measurement of blood pressure, performed automatically, outside the medical setting, during the normal activities of the individual and in a 24-hour period. Multiple studies have demonstrated the prognosis superiority in the development of cardiovascular disease of ABPM, it allows detection of white coat HT as well, avoiding overdiagnosis and overtreatment and the detection of patients with masked H T, who contrarily are at risk of underdetection and undertreatment. Also it provides nighttime BP and circadian variability that provides additional prognostic value. © 2017 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

[Epidemiology of hypertension]. / Epidemiología de la hipertensión arterial.

Hypertension (HT) is the first cause of death and disability worldwide. One in 3 adults in Spain is hypertensive (66% in those > 60 years). Despite improvement in hypertension management over time, only half of treated hypertensive patients are adequately controlled. This translates in 40,000 annual cardiovascular deaths attributable to H T. Among modifable determinants of lack of blood pressure (BP) control in Spain are: a) the white coat phenomenon (accounting for 20-50% of false lack of control) due to not using ambulatory BP monitoring (current use, 20%) or self-BP measurement (use, 60%) for confirming HT diagnosis; b) insufficient patients adherence to BP reducing lifestyles (e.g., only 40% of hypertensive patients have a sodium intake < 2.4 g/day, or follow a weight reduction advice), and c) use of drug monotherapy (≈50%), usually insufficient to achieve adequate control. © 2017 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

[Ambulatory blood pressure monitoring for hypertension diagnosis?] / ¿Monitorización ambulatoria de la presión arterial en el diagnóstico de la hipertensión arterial?

The early and accurate diagnosis of hypertension is essential given its importance in the development of cardiovascular disease. The boundaries between normal blood pressure (BP) and hypertension are arbitrary and based on the benefits of treating exceeding those of not treating. Conventional BP measurement at the clinic only offers information of a particular time and presents multiple biases dependent on inherent variability of BP and measurement technique itself. Multiple studies have demonstrated the prognosis superiority in the development of cardiovascular disease of ambulatory blood pressure monitoring (ABPM), allows detection of white coat hypertension, avoiding overdiagnosis and overtreatment, and the detection of patients with masked hypertension who are at risk of underdetection and undertreatment. ABPM also assess nightime BP and circadian variability, providing additional prognostic value. ABPM is recognized in the diagnosis of hypertension in 2011 British NICE Guidelines, very argued at the 2013 European Society of Hypertension guidelines, and recommended in the US Preventive Services Task Force in 2015, 2016 Canadian Guidelines and the 2016 Spanish Program of Preventive Activities and Health Promotion (PAPPS). Its generalization is likely to be only a matter of time.

Walking speed and high blood pressure mortality risk in a Spanish elderly population.

This study analyzed the relationship between blood pressure and all-cause mortality according to objectively measured walking speed in a Mediterranean population-based sample of older persons. We used data from the longitudinal 'Peñagrande' Cohort Study, initiated in 2008 in a sex- and age-stratified random sample of 1250 people aged ⩾65 years living in Madrid (Spain). A total of 814 individuals participated in the first study wave. The average of two standardized blood pressure readings was used. Walking speed was measured over a 3-m walk and classified as faster (⩾0.8 m s(-1)) or slower. A total of 314 individuals were slower walkers, 475 were faster walkers and 25 did not complete the walk test. Cox proportional hazards models stratified by walking speed were used to assess the association between blood pressure and all-cause death. Non-linear relationship between BP and mortality was explored by a restricted cubic spline analysis. There were 171 deaths from study entry through 31 March 2013. Systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mmHg were associated with higher mortality than blood pressure values above 140 and 90 mm Hg, respectively, but this association reached statistical significance only for systolic blood pressure and only in the slower walkers. In conclusion, systolic blood pressure levels <140 mm Hg were found associated with higher risk of total mortality among slower walkers in an old Spaniard population cohort.

Atherogenic dyslipidemia: prevalence and management in lipid clinics. / Dislipemia aterogénica: prevalencia y control en las unidades de lípidos.

BACKGROUND AND OBJECTIVE: Atherogenic dyslipidemia, which is characterized by increased triglyceride levels and reduced HDL cholesterol levels, is underestimated and undertreated in clinical practice. We assessed its prevalence and the achievement of therapeutic objectives for HDL cholesterol and triglyceride levels in patients treated at lipid and vascular risk units in Spain. PATIENTS AND METHOD: This was an observational, longitudinal, retrospective, multicenter study performed in 14 autonomous Spanish communities that consecutively included 1828 patients aged ≥18 years who were referred for dyslipidemia and vascular risk to 43 lipid clinics accredited by the Spanish Society of Arteriosclerosis. We collected information from the medical records corresponding to 2 visits conducted during 2010 and 2011-12, respectively. RESULTS: Of the 1649 patients who had a lipid profile in the first visit (90.2%), 295 (17.9%) had atherogenic dyslipidemia. The factors associated with atherogenic dyslipidemia were excess weight/obesity, not taking hypolipidemic drugs (statins and/or fibrates), diabetes, myocardial infarction and previous heart failure. Of the 273 (92.5%) patients with atherogenic dyslipidemia that had a lipid profile in the last visit, 44 (16.1%) achieved the therapeutic objectives for HDL cholesterol and triglyceride levels. The predictors of therapeutic success were normal weight and normoglycemia. CONCLUSION: One of every 6 patients treated in lipid and vascular risk units had atherogenic dyslipidemia. The degree to which the therapeutic goals for HDL cholesterol and triglyceride levels were achieved in these patients was very low.

Heart rate and heart rate variability in resistant versus controlled hypertension and in true versus white-coat resistance.

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.