Hypertension and cerebrovascular damage.

Hypertension is the most important modifiable factor for cerebrovascular disease. Stroke and dementia are growing health problems that have considerable social and economical consequences. Hypertension causes brain lesions by several mechanisms predisposing to lacunar infarctions, leucoaraiosis, and white matter changes as well as to intracerebral haemorrhages. These parenchymal damages determine evident or silent neurological alterations that often precede the onset of cognitive decline. It is important to recognize cerebrovascular disease and, above all, to correlate typical lesions to hypertension. Antihypertensive therapy has shown clinical benefits in primary and secondary prevention of stroke. These drugs represent important instruments against cerebrovascular disease but their effects on cognition are still matter of debate. Cerebral parenchymal and functional damages have to be considered together to make medical intervention more incisive.

Prolonged QT interval and reduced heart rate variability in patients with uncomplicated essential hypertension.

A prolonged QT interval is a risk factor for ischemic heart disease in hypertensive subjects. Heart rate variability (HRV) is both an index of autonomic function and an important prognostic factor in several diseases. The aim of the present study was to evaluate the relation between a prolonged QT interval and autonomic nervous system function in patients with untreated uncomplicated essential hypertension. Two hundred and fifteen untreated patients with essential hypertension underwent a Holter ECG equipped with software dedicated to HRV and QT analyses. Nine percent of the patients showed a corrected QT (QTc) >or=440 ms. The HRV indexes in the time domain (SDNN, SDNN index, RMSSD, and pNN50) were significantly reduced in the patients with a prolonged QTc compared to those with a normal QTc (SDNN 24 h: 126.4+/-29.9 vs. 143.9+/-35.4 ms, p=0.02; SDNN index [nighttime]: 85.9+/-32.4 vs. 115.5+/-36.7 ms, p=0.0006; RMSSD 24 h: 22.2+/-7.7 vs. 31.2+/-13.0 ms, p=0.0007; pNN50 24 h: 4.4+/-4.9 vs. 9.7+/-8.4%, p=0.0006). The linear correlation analysis between QTc length and HRV parameters showed a significant negative correlation with all the time-domain indexes. Such a correlation was maintained for RMSSD 24 h, pNN50 24 h and SDNN index (nighttime) after correction for gender and age. The present study shows that, even prior to the development of cardiac hypertensive disease, a prolongation of the QTc and a reduced HRV, both markers of cardiovascular risk, coexist in a proportion of patients with untreated essential hypertension. Further studies are warranted to evaluate whether the combination of such markers can identify hypertensive patients at risk for life-threatening arrhythmias and sudden death. (Hypertens Res 2008; 31: 2003-2010).

Hypertension and cognitive function.

Arterial hypertension, cerebrovascular disease, and dementia are related pathologies. This paper has reviewed comparatively the incidence of arterial hypertension and adult-onset dementia disorders. Hypertension is associated with cerebrovascular disease, which is in turn associated with dementia. It is the most important modifiable risk factor for stroke, which is a recognized cause of vascular dementia. In terms of pathophysiology of hypertensive brain damage, several hypotheses were developed, such as that vascular alterations induced by hypertension can induce lacunar or cortical infarcts and leucoaraiosis, that hypertension is responsible for cerebrovascular disease and acts into the contest of a pre-existing subclinic Alzheimer's disease (AD), that hypertension determines neurobiologic alterations (such as beta-amyloid accumulation) resulting in neuropathologic damage, and that aging and cerebrovascular risk factors act together to cause cerebral capillary degeneration, mitochondrial disruption, reduced glucose oxidation, and reduced ATP synthesis. The consequence of these alterations are neuronal death and dementia. Macroscopic results of these mechanisms are the so-called white matter lesions (WML), the significance of which is analyzed. Increasing clinical evidence suggests a close relationship between the reduction of elevated blood pressure and countering of both vascular dementia and AD. Antihypertensive treatment probably influences cognitive performances and prevents cognitive function alterations and the development of dementia. It is therefore important to evaluate as soon as possible cognitive functions of hypertensive patients.

[Arterial hypertension and cognitive deficit]. / Ipertensione arteriosa e deficit cognitivo.

Cognitive impairment and dementia are more and more common in the elderly. The first begins, it advances silently and it leads to dementia in few years. Arterial hypertension represents the most important cerebrovascular risk factor after age. In numerous studies an inverse relationship between blood pressure values and cognitive performance emerges: it is possible that arterial hypertension plays a role in the pathogenesis of cognitive decline. Even in asymptomatic subjects the magnetic resonance signs of cerebral damage accompany cognitive impairment development. Antihypertensive therapy influence on cognitive function represents a subject of actual interest. The most studied drugs are calcium antagonists and ACE-inhibitors; they seem to have a protective effect on cognitive impairment, with regard to diuretics and beta-blockers. It would be important to study hypertensive patients, above all young asymptomatic hypertensives, even about cognitive functions, to prevent and consider cognitive decline and effective organ damage.

Arterial hypertension: a cause of cognitive impairment and of vascular dementia.

Arterial hypertension is a well-documented modifiable risk factor for cerebrovascular disease and for both cerebral infarction and intracerebral hemorrhage. Recent studies indicate a relationship between high blood pressure in midlife and dementia in late life and suggest that arterial hypertension may represent a cause of vascular dementia (VaD). This paper has reviewed the main evidence of a link between arterial hypertension and vascular cognitive impairment or VaD. Brain lesions induced by hypertension, diagnostic procedures for early diagnosis of vascular cognitive impairment in at risk subjects and the need to include cognitive assessment in patient's general visits in hypertension units are discussed.

Bioequivalence study of nicardipine solution versus nicardipine tablets.

The bioequivalence of a solution (investigational product) and a tablet (reference product) formulation of the dihydropyridine-type derivative Ca2+ antagonist nicardipine were investigated by measuring plasma levels of the compound after single randomized administration of 20 mg of the two formulations. Drugs were given orally in a single dose to 24 healthy volunteers (12 males and 12 females) at the beginning of the experiment and after a two weeks wash-out. Nicardipine is available in oral and intravenous formulations, the second being used for the short-term treatment of hypertensive crises. Oral formulations of nicardipine most diffused include immediate release (20 or 30 mg, three times a day administration), sustained release (30 mg, 45 mg or 60 mg, twice a day administration) and modified release (80 mg, once a day administration) tablets. A nicardipine solution is available only in Spain, but no published studies on the kinetics of this formulation are available. In the last 15 years, the main efforts were aimed to develop sustained or controlled release formulations of nicardipine to improve patient compliance by reducing the number of doses required each day. However, the use of twice a day or once a day administration of Ca2+ antagonists should be not overemphasized in particular situations like those of possible risk of cerebrovascular and/or coronary steal effect primarily in the elderly. The oral formulation of nicardipine investigated with a bioequivalence range > 70% compared to nicardipine immediate release tablets may represent an additional resource for treating elderly patients with concomitant cerebrovascular or coronary heart disease.