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Mancia G.,Clinica Medica | Grassi G.,University of Milan Bicocca
Handbook of Clinical Neurology | Year: 2013

The sympathetic nervous system participates in the development and progression of the essential hypertensive state, as shown by increased circulating plasma levels of the adrenergic neurotransmitter norepinephrine, elevated norepinephrine spillover rate, and augmented sympathetic nerve traffic discharge detected in the high blood pressure state. In addition, the sympathetic overdrive participates in the development of the metabolic disarray as well as target organ damage frequently detected in this condition. The above mentioned sympathetic abnormalities explain why adrenergic overdrive represents an important therapeutic target in the treatment of hypertension. © 2013 Elsevier B.V.

Schmieder R.E.,Friedrich - Alexander - University, Erlangen - Nuremberg | Redon J.,University of Valencia | Grassi G.,Clinica Medica | Kjeldsen S.E.,University of Oslo | And 6 more authors.
Journal of Hypertension | Year: 2012

Experts from the European Society of Hypertension prepared this position paper in order to summarize current evidence, unmet needs and practical recommendations on the application of percutaneous transluminal ablation of renal nerves [renal denervation (RDN)] as a novel therapeutic strategy for the treatment of resistant hypertension. The sympathetic nervous activation to the kidney and the sensory afferent signals to the central nervous system represent the targets of RND. Clinical studies have documented that catheter-based RDN decreases both efferent sympathetic and afferent sensory nerve traffic leading to clinically meaningful systolic and diastolic blood pressure (BP) reductions in patients with resistant hypertension. This position statement intends to facilitate a better understanding of the effectiveness, safety, limitations and issues still to be addressed with RDN. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Grassi G.,Clinica Medica
Expert Opinion on Pharmacotherapy | Year: 2012

Current guidelines on antihypertensive treatment emphasize the importance of combination drug treatment for achieving a full blood pressure control. The TALENT Study, involving more than 400 high-risk hypertensive patients, aimed to evaluate the efficacy and safety profile of nifedipine gastrointestinal therapeutic system (GITS) 20 mg/telmisartan 80 mg combination, as compared to the single monotherapies. After 8 weeks, ambulatory blood pressure values were significantly more reduced by the combination treatment than by single monotherapies. These potentiated blood-pressure-lowering effects were mirrored by a higher trough-to-peak ratio and smoothness index. They were also accompanied by: i) significantly greater blood pressure (particularly systolic) control; ii) a greater ability of combination drug treatment to achieve a controlled blood pressure at a time earlier than that found in single monotherapies; and iii) a better side-effects profile. © 2012 Informa UK, Ltd.

Corrao G.,Unit of Biostatistics and Epidemiology | Corrao G.,University of Milan Bicocca | Nicotra F.,Unit of Biostatistics and Epidemiology | Parodi A.,Unit of Biostatistics and Epidemiology | And 6 more authors.
Hypertension | Year: 2011

Guidelines recommend a combination of 2 drugs to be used as first-step treatment strategy in high-risk hypertensive individuals to achieve timely blood pressure control and avoid early events. The evidence that this is associated with cardiovascular (CV) benefits compared with initial monotherapy is limited, however. The objective of this study was to assess whether, compared with antihypertensive monotherapy, a combination of antihypertensive drugs provides a greater CV protection in daily clinical practice. A population-based, nested case-control study was carried out by including the cohort of 209 650 patients from Lombardy (Italy) aged 40 to 79 years who were newly treated with antihypertensive drugs between 2000 and 2001. Cases were the 10 688 patients who experienced a hospitalization for CV disease from initial prescription until 2007. Three controls were randomly selected for each case. Logistic regression was used to model the CV risk associated with starting on and/or continuing with combination therapy. A Monte-Carlo sensitivity analysis was performed to account for unmeasured confounders. Patients starting on combination therapy had an 11% CV risk reduction with respect to those starting on monotherapy (95% CI: 5% to 16%). Compared with patients who maintained monotherapy also during follow-up, those who started on combination therapy and kept it along the entire period of observation had 26% reduction of CV risk (95% CI: 15% to 35%). In daily life practice, a combination of antihypertensive drugs is associated with a great reduction of CV risk. The indication for using combination of blood pressure drugs should be broadened. © 2011 American Heart Association, Inc.

Grassi G.,Clinica Medica | Seravalle G.,Istituto Auxologico Italiano | Quarti-Trevano F.,Clinica Medica
Experimental Physiology | Year: 2010

Data collected in experimental animals and in humans support the hypothesis that sympathetic neural mechanisms are involved in the development and progression of hypertension. Direct approaches to assess human adrenergic cardiovascular drive have shown that sympathetic activation occurs in hypertensive patients, the magnitude of which is proportional to the degree of elevation of the blood pressure. Evidence has also been obtained that sympathetic activation participates in the development of hypertension-related target organ damage, such as left ventricular diastolic dysfunction, left ventricular hypertrophy and arterial remodelling and hypertrophy. Despite the large amount of information collected on the main features of the hypertension-related neurogenic abnormality, the causes of the sympathetic activation remain undefined, although alterations in the reflex modulation of adrenergic drive and/or participation of metabolic factors are likely candidates. This paper will provide background information on the behaviour of the sympathetic nervous system in experimental hypertension, followed by a review of the main features, mechanisms and effects of the sympathetic overdrive in human hypertension. Finally, the new frontiers of research in the area of therapeutic intervention aimed at reducing the adrenergic overdrive will be highlighted. © 2010 The Physiological Society.

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