Current Hypertension Reviews - Volume 7, Issue 2, 2011

Despite the large amount of information collected over the past years, several aspects related to the link between blood pressure and metabolic abnormalities remain unclear. This is particularly the case for the pathophysiology of the blood pressure/metabolic relationships and, more specifically, for the hypothesis that abnormalities in sympathetic cardiovascular function may represent the driving force responsible on one side for the blood pressure elevation and on the other for the hypertension-related metabolic disarray. First, direct and indirect evidence suggest that high blood pressure states are characterized by an adrenergic overactivity. Overdrive is present in the hypertensive state of the young, middle-age and elderly patients, in which it parallels the clinical severity of the hypertensive state. On the other hand, the obese state displays signs of adrenergic activation, such as increased resting heart rate values and elevated plasma norepinephrine values. An augmented sympathetic neural discharge to skeletal muscle as well as an increased spillover rate of norepinephrine from sympathetic nerve endings has been shown. As Dr Guido Grassi et al., mentioned in this issue, the mechanisms responsible for the hyperadrenergic drive described in hypertension, obesity, diabetes and in the other metabolic disease which may include both metabolic, humoral and reflex factors, such as the insulin resistance condition, the hyperleptinemic state, the activation of the renin-angiotensin system and the chemoreflex stimulation are parasympathetic impairment and sympathetic drive over expression. In the PAMELA study by Bombelli et al., blood glucose and serum cholesterol levels progressively increase while HDL-C progressively decreases with increasing clinic blood pressure category or home and 24-hour blood pressure quartile. The percentage of subjects with impaired fasting glucose or diabetes mellitus also progressively increases from the lowest to the highest category of clinic blood pressure and quartile of home or 24-hour blood pressure. By a multivariate analysis systolic and diastolic clinic, home and 24-hour blood pressure all appeared among factors independently associated to blood glucose and serum cholesterol level in the PAMELA population. Dr Patricio Lopez Jaramillo et al., in its paper reflects also that cardiac autonomic function is altered in subjects with one or more metabolic abnormalities, but without insulin resistance. Thus, they proposed that an over autonomic function may precede insulin resistance in the initiation of the Metabolic Sindrome. Furthermore, Nitric oxide seems to be also involved in the relationship between authonomic nervous system and endothelial dysfunction. Neuronal Nitric Oxide contributes to the regulation of renal function and NO performs an important role in kidney protection in opposing the effects of chronic renal renin-angiotensin system over activation, which contributes to renal hypertension and injury. Furthermore, the vascular and cardio protective functions of NO extend beyond the endothelium to involve neuronal NO and its role as a neuromodulator of the autonomic nervous system, maintaining vagal tone and suppressing sympathetic nervous system over activity through both central and peripheral nervous system signaling.....

Cardiometabolic diseases, such as hypertension, obesity, diabetes and metabolic syndrome, are characterized by well known abnormalities in the hemodynamic profile. Only in recent years, however, evidence has been collected that cardiometabolic diseases are also characterized by neuroadrenergic alterations, the most important being the sympathetic overactivity. The neuroadrenergic abnormality 1) occurs early in the clinical course of the hypertensive and metabolic diseases, 2) follows the blood pressure elevation and 3) is paralleled by marked metabolic abnormalities, such as hyperinsulinemia, hyperleptinemia and insulin resistance. These neuroametabolic changes can be favourably affected both by non pharmacological and pharmacological interventions.

The paper will review the contribution of the PAMELA Research Project to the epidemiology, pathophysiology and treatment of hypertension and hypertension-related cardiometabolic disease. This will be firstly done by examining the results of the PAMELA studies planned and performed in the past 20 years aimed at defining normality values for home and ambulatory blood pressure values as well as at determining precise figures for blood pressure control, taking into account different blood pressure measurements. It will also be done by taking into account different “weight” of clinic, home and ambulatory blood pressure values in determining end-organ damage and in assessing the capability of the different pressures to reflect the regression of target organ damage induced by antihypertensive drug treatment. The review will finally address three further issues of major clinical relevance, i.e. the definition and clinical implication of “white-coat” and “masked” hypertension, the prognostic significance over the long-term period of alterations in home and ambulatory blood pressures as compared to the clinic ones and finally the close relationships between blood pressure and metabolic alterations, including metabolic syndrome.

In the last decade there has been an accelerated growth in the prevalence of metabolic syndrome (MS), especially in Latin American countries, which has led an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (DM2). Recently has been raised the relationship between the autonomic nervous system (ANS), endothelial dysfunction (ED) and the appearance of MS. In the present article we review the evidence that support the proposal that abdominal obesity (AO) produce adypokines that result in insulin resistance and low degree inflammation, which increase the activity of ANS, causing vasoconstriction, hypertension, decreased peripheral glucose uptake, and decreased secretion of insulin, leading to hyperglycemia and increased lipolysis and hypertriglyceridemia. All these factors cause ED, explaining the higher risk of the patients with MS of developing DM2 and CVD.

Introduction: Hypertension may increase the risk for stroke and is frequently associated with subcortical and periventricular white matter lesions (WML). This is considered a prognostic factor for the development of stroke and cognitive impairment, particularly in attention processes. Additionally, in elderly subjects, it is known the implications of alterations in the neural cardiovascular regulation and the cardiovascular risk. Aims: To evaluate, in asymptomatic elderly hypertensives, the association of ambulatory blood pressure values and autonomic activity with neurocognitive impairment and WML. In addition, we also evaluated the role of the autonomic nervous system particularly the vagal component, in the pathogenesis of white matter lesions. Methods: We studied 22 elderly essential hypertensive patients (69±1.1y) and as control group, 16 normotensive elderly subjects (age 67±3.2y) were also enrolled. To each one of them, a cerebral MRI was performed to classify them, by a neuro-radiologist blinded of the subject clinical status, using a 0 to 9 scale where 0 denoted no WML and 9 the most severe lesions. Twenty four hours arterial blood pressure monitoring was performed to each one of the subjects under study. Office blood pressure was measured 3 times and the mean value reported. Beat to beat finger arterial pressure monitoring (Finapres) was performed for a 2h period. During the first hour the patient remained lying supine in a quiet darkened room and during the second hour four manoeuvres: stand-up, cold pressor test, handgrip and quiet activity were randomly performed. Mean blood pressure and pulse interval values, from the two periods, and their respective variabilities, baroreflex sensitivity and power spectral analysis were calculated. Regarding neuropsychological assessment: Minimental test, attention evaluation, RAVLT, visual memory, language and executive function, geriatric depression scale, cognitive deficit rate tests were performed in all subject.....

Epidemiological and clinical evidence have shown a close association between hypertension, obesity, IGT or NIDDM, and dyslipidemia. The activation of sympathetic nervous system plays a role in the pathogenesis of essential hypertension and its inhibition is of a therapeutic value. Rilmenidine is an oxazoline compound with antihypertensive properties that acts mainly on the brain stem but also in the kidneys, where it selectively binds to I1 imidazoline receptors, distinguishing it from reference α2-agonists. As a consequence, anti-hypertensive treatments that reduce the sympathetic response could also have effects on the metabolic abnormalities of hypertensive patients with metabolic disorders. The aim of the present study was to evaluate the effect of rilmenidine or placebo on insulin resistance and sympathetic activity, in essential hypertensive patients untreated or non-adequately treated. Our results have shown that Rilmenidine was able to decrease sympathetic activity expressed by both a decrease in SBP variability and an increase in baroreflex sensitivity. Together with these effects a significant improvement of insulin resistance index (HOMA), which was not obtained by the adjusted conventional treatment, was also observed. In conclusion, these beneficial effects observed support the idea that Rilmenidine could be comparable to established drugs for first-line therapy in hypertension.

Hypertension is common in the elderly, and with an increasing ageing population in the industrialised world, has become a major public health issue. Hypertension in the elderly may have many different patterns of presentation such as Systolic-Diastolic Hypertension, Isolated Systolic Hypertension, Nocturnal Hypertension, Hypertension accompanied by Postural Hypotension and Supine Hypertension in the back ground of autonomic dysfunction. Management of hypertension in the elderly is not straightforward due to the presence of a variety of patterns of presentation, Pathophysiological changes associated with hypertension and aging, co-existing medical problems and Polypharmacy. This article deals with the management of commonly encountered problems such as orthostatic hypotension, orthostatic hypotesnion accompanied by supine hypertension, erectile dysfunction and also covers issues such as controversy surrounding the [alleged] association between hypertension and its treatment and the risk of dementia as well as management of hypertension in the very elderly.

The Amlodipine Cohort study by Internet-based research for Evaluation of Efficacy (ACHIEVE) was conducted to assess the efficacy of amlodipine 10mg daily. Hypertensive patients, who were up-titrated from amlodipine 5mg to 10mg daily, were enrolled by medical practitioners using web-based registration between March 9 and July 31, 2009. The primary outcomes were the blood pressure (BP) at clinic and at home, and the secondary outcome was rates of achievement who reached their target BP levels at clinic after 3 months. Seven-hundred and fifty three hypertensive patients were enrolled and 583 patients completed the follow-up study. Mean clinic BP decreased from 156.4/86.3 mmHg at baseline to 137.5/76.5mmHg, whereas mean home BP decreased from 151.5/83.9 mmHg at baseline to 139.6/75.2mmHg after 3 months of treatment. The reduction of these BPs was more pronounced among the patients with higher baseline BP values than among those with lower baseline levels. Sufficiently controlled hypertension, which is defined as a systolic BP <140 mmHg for clinic BP and <135 mmHg for home BP is 1.2% at baseline to 43.1% after 3 months of treatment. The survey showed that among poorly controlled hypertensive Japanese, high-dose titration from 5 mg to 10 mg daily of amlodipine showed marked reduction in both clinic and home BPs.

It has been known for some time that dietary salt intake correlates with the prevalence of cardiovascular disease. However, the molecular link between dietary salt and cardiovascular disease is poorly understood. On this background, it has been observed that there are a class of hormones called cardiotonic steroids whose concentrations increase in response to increases in dietary salt. We have shown that some of these hormones may be natriuretic, but we have also shown that they may also be responsible for progressive renal and cardiac injury. Based on data summarized in this review, we propose cardiotonic steroids may serve as the molecular link between dietary salt and cardiovascular disease.

Prehypertension is known to be a risk factor for hypertension and cardiovascular disease. If prehypertension is left untreated, the blood pressure continues to increase due to multiple accelerators which facilitate the development of hypertension. Studies using animal models of hypertension suggested that interruption of these mechanisms by transient inhibition of the renin-angiotensin system (RAS) attenuates the development of hypertension. The TROPHY study provided clinical evidence that pharmacological intervention in the prehypertensive stage may suppress subsequent development of hypertension. Recently, we reported that high dose angiotensin inhibition in spontaneously hypertensive rats (SHR) with established hypertension caused a significant regression of hypertension, and we have started a prospective, multi-center clinical study (STAR CAST study) to examine if regression from hypertension back to prehypertension may also be feasible in humans. Since prehypertension is increasingly recognized as an important public health issue, further studies to assess strategies for attenuating the progression from prehypertension to hypertension are required.