D. Naso

Antihypertensive drugs and the sympathetic nervous system.

Hypertension has been associated with several modifications in the function and regulation of the sympathetic nervous system (SNS). Although it is unclear whether this dysfunction is primary or secondary to the development of hypertension, these alterations are considered to play an important role in the evolution, maintenance, and development of hypertension and its target organ damage. Several pharmacological antihypertensive classes are currently available. The main drugs that have been clearly shown to affect SNS function are β-blockers, α-blockers, and centrally acting drugs. On the contrary, the effects of ACE inhibitors (ACE-Is), AT1 receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics on SNS function remain controversial. These properties are pharmacologically and pathophysiologically relevant and should be considered in the choice of antihypertensive treatments and combination therapies in order to achieve, beyond optimal blood pressure control, a normalization of SNS physiology and the most effective prevention of target organ damage.

Orthostatic hypotension: evaluation and treatment.

Orthostatic hypotension (OH) may be dependent upon various neurogenic and non-neurogenic disorders and conditions. Neurogenic causes include the main autonomic failure syndromes, primary (multiple system atrophy, pure autonomic failure, and autonomic failure associated with Parkinsons disease) and secondary (central nervous system diseases, peripheral neuropathies and systemic diseases). Non-neurogenic causes of OH include cardiac impairment, fluid and electrolyte loss, vasodilatation, and old age. A number of drugs may also cause OH, through their vasoactive action or by interfering with the autonomic nervous system. Symptoms of OH are debilitating, often confining patients to bed, and longitudinal studies have shown that OH increases the risk of stroke, myocardial ischemia and mortality. The therapeutic goal is to decrease the incidence and severity of postural symptoms, rather than restore normotension. In non-neurogenic OH, treatment of the underlying cause may be curative. In neurogenic OH a combination of non-pharmacological and pharmacological measures is often needed. Patient education and non-pharmacological measures represent the first step; among these interventions, fluid repletion and physical countermanoeuvres have been proven very effective. Pharmacological treatment comprises a number of agents acting on blood vessels, on blood volume or with other pressor mechanisms. The drugs most currently used are fludrocortisone and midodrine. Fludrocortisone expands the extravascular body fluid volume and improves alpha-adrenergic sensitivity. Midodrine is a peripheral, selective alpha1-adrenergic agonist that causes arterial and venous vasoconstriction. Despite the wide use of these drugs, multicentre, randomised and controlled studies for the treatment of OH are still scarce and limited to few agents and groups of patients. Pharmacological management of OH substantially improves the quality of life of patients, although it may be problematic. The development of supine hypertension and subsequent congestive heart failure should be avoided, especially in those patients with a pre-existing cardiovascular risk, such as in diabetes or ischemic heart disease.

Ascending aortic dilatation, arterial stiffness and cardiac organ damage in essential hypertension.

Objectives: The objectives of this study were to evaluate the prevalence of dilatation of proximal ascending aorta (pAA) in essential hypertensive patients and the association between pAA dilatation, arterial stiffness and left ventricular hypertrophy. Background: Few data are available regarding patients with pAA dilatation in arterial hypertension. It is not known whether pAA dilatation may be related to increased left ventricular mass and what the relation with central hemodynamics and arterial stiffness would be. Methods: A total of 345 untreated and treated essential hypertensive patients (mean age, 54.3 ± 11 years) were considered for this analysis. We measured pulsatile hemodynamic parameters directly using tonometry, and the proximal aortic diameters through ultrasound imaging (echocardiography). Results: Prevalence of pAA dilatation was 17%. Peripheral hemodynamic parameters were similar in patients with and without ascending aorta dilatation. We observed a slight increase of central systolic (129.81 ± 15.4 vs. 125.02 ± 14.7 mmHg; P = 0.02) and pulse pressure (45.02 ± 10.4 vs. 42 ± 9.54 mmHg; P = 0.02) in patients with pAA dilatation. Pulse wave velocity (9.26 ± 2.33 vs. 7.70 ± 1.69 m/s; P < 0.0001), as well as the augmentation index (25.86 ± 10.2 vs. 19.41 ± 9.52%; P < 0.0001), was significantly greater in patients with pAA dilatation. Finally, left ventricular hypertrophy was thrice as frequent (32.8 vs. 13.4%; P < 0.0001) compared to hypertensive patients without aortic dilatation. Conclusion: This study shows a high prevalence (17%) of ascending aortic dilatation in patients affected by essential hypertension, without further complications. Dilatation of the ascending aorta is associated both to an increased left ventricular mass and arterial stiffness.

Cognitive Decline and Low Blood Pressure: The Other Side of the Coin

Low blood pressure has been found to be associated with cognitive decline and dementia in cross-sectional studies. Two mechanisms have been proposed to interpret this association: blood pressure levels decrease during the course of the dementia process, and low blood pressure induces or accelerates cognitive decline by lowering cerebral blood flow. Results of the prospective studies are contradictory. Low blood pressure and orthostatic hypotension have been found to predict cognitive impairment in the elderly population in some studies only. While hypotension may play a protective role in healthy elderly people, low blood pressure levels in frail elderly patients with associated diseases may cause cerebral hypoperfusion and accelerate cognitive decline.

Aortic size index enlargement is associated with central hemodynamics in essential hypertension.

The aim of this study was to evaluate the association between brachial and central blood pressure (bBP and cBP) levels and aortic root dilatation (ARD) in essential hypertensive patients. A total of 190 untreated and treated essential hypertensive patients (mean age, 55±11 years) were considered for this analysis. We measured pulsatile hemodynamics and the proximal aortic diameter directly using tonometry, ultrasound imaging (echocardiography) and Doppler. Ninety-one hypertensive patients had an ARD (defined as aortic size index (ASi)>2 cm/m2). Central hemodynamic variables were significantly associated with ASi. Patients with increased ASi were significantly older (60±10 vs. 50±11 years, P<0.0001) and had higher levels of the augmentation index (AIx; 28±10 vs. 21±10 P<0.0001), augmentation pressure (AP; 13±6 vs. 8±5 mm Hg, P<0.0001), and central pulse pressure (cPP; 44±10 vs. 39±8 mm Hg, P<0.0001) compared with patients with normal ASi. In a logistic regression analysis, the AIx was the only significant predictor of ASi. In hypertensive patients, the AIx and cBP were associated with ARD, whereas the bBP was not. Patients with an increased ASi may lose part of the elastic properties of the aorta, demonstrating a strict correlation between ASi and central hemodynamic indexes, in particular, the cPP and AIx.

Baroreflex sensitivity is impaired in essential hypertensives with central obesity.

Recently, much interest has focussed on the potential interaction between sympathetic nervous system and global cardiovascular risk. We investigated how baroreflex sensitivity (BRS), an index of autonomic function, interacts with central obesity (CO) in an essential hypertensive (EH) population. We selected 170 EHs and 43 normotensives (NT), (median age 47.3±11.3 and 49.1±13 years, respectively). Anthropometric parameters were measured for each and BRS was evaluated by a non-invasive method using Portapres TNO. The BRS evaluation was made using the sequences method. Systolic blood pressure (SBP) and heart rate were significantly higher in EH (P<0.001 and P=0.007, respectively). BRS was significantly greater in NT (P=0.02), and was associated inversely with waist circumference (WC) (P=0.005), but not with SBP or with other metabolic risk factors. Body mass index, total and high-density lipoprotein cholesterol, age and WC were not significantly different between the two groups. These results were confirmed by age pounded analysis. Finally, a separate analysis of the hypertensive group with CO (n=84) demonstrated a significantly lower BRS compared with the other hypertensive patients (n=86) (P<0.001). BRS is associated with WC but not with arterial pressure values and metabolic risk factors. Hypertensive subjects with CO show an impairment of BRS. Owing to its association with abdominal fat distribution and subsequently insulin resistance, BRS could represent a further and reliable index for evaluation of global cardiovascular risk in hypertensive patients.

Left atrial enlargement in essential hypertension: Role in the assessment of subclinical hypertensive heart disease

Abstract Background. Arterial hypertension is a common cause of cardiac organ damage, inducing morphofunctional modifications involving left chambers. This is a retrospective study: it was designed to evaluate the additive clinical value of left atrial enlargement (LAe) assessment in the evaluation of cardiac organ damage. Methods. A total of 814 (67% male; aged 50.7 ± 12 years, mean ± SD) essential hypertensive subjects underwent routinely to a complete and extensive clinical and echocardiographic evaluation. Left ventricular morphology, systolic and diastolic function and left atrial dimension (LAD; linear and volumetric) were evaluated. Results. Prevalence of LAe varied between 6.2% and 52.1%, depending on the chosen criteria (left atrial diameter indexed for body surface area (BSA) vs left atrial volume (LAV) indexed for BSA – LAVi). LAVi showed to be the most sensitive parameter in order to detect it (sensitivity 96%, specificity 100%). Left ventricular hypertrophy (LVH) was present in about one fifth of our population (14% and 26%, considering indexation for BSA and for height2.7). Concentric remodelling (CR) was present in 27–35% of cases considering left ventricular mass indexation for BSA and for height2.7, respectively. In one quarter of our population, LAe was the only echocardiographic sign of hypertension, independent of LVH and CR. Conclusions. LAV evaluation in hypertensive population can contribute to the identification of subjects affected by hypertensive heart disease other than the conventionally evaluated terms (LVH and CR).

Echocardiographic Abnormalities in the Assessment of Cardiac Organ Damage in Never-Treated Hypertensive Patients

Hypertension-related cardiac organ damage, other than left ventricular (LV) hypertrophy (LVH), has been described: in particular, concentric remodeling, LV diastolic dysfunction (DD), and left atrial (LA) enlargement are significantly associated with cardiovascular morbility and mortality in different populations. This study evaluated the prevalence of these latter morphofunctional abnormalities, in never-treated essential hypertensive patients and the role of such a serial assessment of hypertensive cardiac damage in improving cardiovascular risk stratification in these patients. A total of 100 never-treated essential hypertensive subjects underwent a complete clinical and echocardiographic evaluation. Left ventricular morphology, systolic and diastolic function, and LA dimension (linear and volume) were evaluated by echocardiography. Left ventricular hypertrophy was present in 14% of the patients, whereas concentric remodeling was present in 25% of the subjects. Among patients free from LV morphology abnormalities, the most frequent abnormality was LA enlargement (global prevalence 57%); the percentage of patients with at least one parameter consistent with DD was 22% in the entire population, but DD was present as the only cardiac abnormality in 1% of our patient. Left atrial volume indexed for body surface area was the most sensitive parameter in identifying hypertension-related cardiac modification. The global prevalence of cardiac alteration reached 73% in never-treated hypertensive patients. Left ventricular remodeling and LA enlargement evaluation may grant a better assessment of cardiac organ damage and cardiovascular risk stratification of hypertensive patients without evidence of LVH after routine examination.

Giant proximal aorta aneurysm: A successfully managed time bomb

Management of aortic aneurismatic disease is often care of specialists, from vascular to cardiac surgeons. However, initial diagnosis and management are not unfrequently responsibility of an emergency staff as the disease presentation may be dramatically acute. Thoracic aortic aneurysms (TAA) in particular have a silent clinical history until they become evident with dissection or rupture with a high global mortality rate. The importance of a rapid diagnosis and of correct management in such a subsetting is clear, but recent guidelines where published with the declared rationale of emphasizing the importance of an early detection of the disease. The goal is to reduce morbidity and mortality and improvement of quality of life of such patients. We present a case of successfully managed asymptomatic giant proximal aortic aneurysm in a healthy young man. On a routine transthoracic echocardiogram, severe dilatation of the proximal aorta was detected, with severe aortic regurgitation in a normal tricuspid valve determining left ventricle (LV) dilatation and impaired contractility. Computed tomography scan was scheduled, confirming the findings and open heart surgery performed within 1 week. Clinical and echocardiographical follow-up was started; after 2 months imaging studies showed good surgical results with well-functioning, non-regurgitant prosthetic aortic valve and initial recovery of left ventricular dilatation; at the last control, 14 months later, LV mass and dimensions where markedly improved, with no more signs of hypertrophy nor dilatation. TAA needs a rapid diagnosis and appropriate management. Clinicians should be aware of proper diagnostic tools and of applicable therapeutic strategies in order to grant the better assistance to the patient. In this setting, the role of echocardiography remains pivotal.

DIASTOLIC FUNCTION IN ARTERIAL HYPERTENSION: IMPACT OF DIFFERENT ECHOCARDIOGRAPHIC CRITERIA ON DIAGNOSIS: PP.22.371

Aim: To evaluate the sensitivity of different echocardiographic parameteres in order to estimate diastolic dysfunction prevalence in arterial hypertension. Methods: We studied 308 essential hypertensives (mean age ± standard deviation 49.8 ± 11 years; SBP/DBP 140.4 ± 15/84.9 ± 10 mmHg). Every subject underwent clinical evaluation, echocardiography with ultrasound systems (ATL 5000) equipped with multiple frequency phased array transducers (2 to 4 MHz) to study left ventricular morphology and function. Transmitralic Doppler (Dopp mitr), Doppler of pulmonary veins (PVarD, Adur) flow, tissue Doppler of mitral annulus (E’ sep, E’ lat) and left atrial volume (LAV ind) were acquired for each patient. Results: Transmitralic Doppler alone (Figure 1), allows the detection of diastolic dysfunction in 34% of hypertensives. When this parameter was combined with Tissue Doppler, Pulmonary veins Doppler and LAV ind, about 40% of subjects previously classified as normal, resulted affected by diastolic dysfunction (p < 0.001). Left atrial volume, indexed for body surface area, appears to be the most sensitive criteria. Conclusion: Prevalence of diastolic dysfunction changes according to limits and criteria used for its detection. Systematic use of recent parameters (e.g. atrial volume or TDI) represents a sensitive tool to identify diastolic dysfunction in hypertensive patients. Figure 1. No caption available.