Marinobufagenin in hypertensive patients with obstructive sleep apnea.

Although obstructive sleep apnea (OSA) is an independent risk factor for hypertension, the underlying mechanisms are not clearly understood. Apnea and hypopnea episodes during sleep lead to sympathoactivation, decrease plasma pH, and predispose to sodium and volume retention. We hypothesized that, the latter could stimulate digitalis-like natriuretic/vasopressor hormones, endogenous ouabain (EO) and marinobufagenin (MBG). Overnight polysomnography (Embletta) and 24 hrs blood pressure monitoring (SpaceLab 90207) was conducted in 52 consecutive patients with OSA (51 +/- 8 years; 40 males, 12 females) and in 48 age-matched hypertensive subjects without OSA. According to the polysomnography data, 17 patients had a mild degree of OSA (apnea/hypopnea index (AHI) 5-15), 17 patients-moderate (AHI 15-30) and 18 -severe OSA (AHI >30). Levels of MBG excretion co-varied with OSA severity (0.5 +/- 0.1, 0.9 +/- 0.04 and 1.2 +/- 0.06 nmoles per 24 hrs, respectively), while excretion of EO did not differ in patients with different degrees of OSA severity. Our observations suggest that MBG may be involved in the pathogenesis of hypertension in OSA, and may be a marker of OSA severity.

Effect of 24-week treatment with telmisartan on myocardial structure and function: relationship to insertion/deletion polymorphism of the angiotensin-converting enzyme gene.

The aim of the present study was to assess the effect of treatment with the angiotensin II receptor blocker telmisartan for 24 weeks on myocardial structure and function in patients with essential hypertension, and the relationship between this effect and the structural polymorphism of the angiotensin-converting enzyme (ACE) gene. Thirty-five patients with essential hypertension and left ventricular hypertrophy (LVH) without other associated morbidity were included in an open-label, non-comparative study. The patients were treated with telmisartan 40-80 mg once daily. In the final analysis, there were 29 patients who received the full course of treatment and were evaluated echocardiographically before and after treatment by the same blinded investigator, and myocardial structure and function were analysed. The myocardial mass of the left ventricle was determined in M-mode. Assessment of diastolic function of transmitral blood flow was performed using pulsed Doppler echocardiography. All patients were genotyped for insertion/deletion (I/D) polymorphism of the ACE gene. Telmisartan produced a significant reduction in left ventricular mass index from 140.4 +/- 48.6 to 128.7 +/- 40.6 g/m2 that was accompanied by an improvement in characteristics of diastolic function. The decrease in LVH was more significant in the ID genotype group than in the II and DD groups. Thus, prolonged treatment with telmisartan is accompanied by an improvement in myocardial structure, expressed as a reduction in left ventricular mass and function that is more marked in patients with ID genotype of the ACE gene.

Prevalence and determinants of left ventricular hypertrophy and remodelling patterns in hypertensive patients: the St. Petersburg study.

OBJECTIVE: The primary aim of the present study was to determine the prevalence of left ventricular hypertrophy (LVH) in hypertensive patients with the use of different threshold values and also to assess the distribution of left ventricular (LV) geometry patterns verified by two different methods of relative wall thickness (RWT) calculation. The secondary aim was to evaluate the impact of different demographic determinants into prevalence of LVH and remodelling patterns. PATIENTS AND METHODS: A cross-sectional study in a population-based sample of 734 essential hypertensives from the primary care clinic was undertaken. Echocardiography was performed and analysed by trained observers. The LV posterior wall thickness (PWd), interventricular septum (IVSd) and LV mass index (LVMI) were measured. The following criteria for LVH definition were used: LVMI >125 g/m2 and 134/110 g/m2, and >131/110 and 116/104 g/m2 in males/females, respectively. The RWT was calculated as a 2PWd/LVDD or PWd + IVSd/LVDD, where LVDD is the LV internal dimension at the end of diastole. The values exceeding 0.45 were considered evidence for concentric remodelling. RESULTS: Prevalence of LVH ranged from 52.2 to 72.2% by the use of different threshold for LVH definition. It was shown that the LVH estimation without sex-specific criteria underestimates the prevalence of LVH in women and overestimates it in men. The prevalence of concentric LVH and concentric remodelling was higher when the IVSd was included in the RWT calculation. Only one-quarter of patients were free from morphological alterations and eccentric LVH was as frequently observed as concentric LVH. Sex, obesity stage and type as well as hypertension level and duration contributed to LVH level and remodelling pattern. CONCLUSIONS: The use of different threshold values can significantly influence the assessment of prevalence of LVH in hypertension. The "mild" criteria, to our opinion, can overestimate the prevalence of structural LV remodelling, while implementation of sex-specific criteria for the definition of LVH increases the sensitivity of the method. In any way, eccentric LVH is as common for hypertension as a concentric LVH, the proportion of the latter increasing with age and more frequently observed in males. Concomitant obesity, in particular abdominal, significantly increases LVH prevalence.

Lack of association of the renin-angiotensin system genes polymorphisms and left ventricular hypertrophy in hypertension.

OBJECTIVE: The aim of the present study was to determine if there is an association of different gene polymorphisms of renin-angiotensin system and left ventricular hypertrophy (LVH) in patients with essential hypertension (EH) in St Petersburg population. PATIENTS AND METHODS: We examined 156 patients (the mean age 49+/-8 years) with mild-to-moderate EH recruited from the general population of the outpatient clinic. Left ventricular mass was measured by echocardiography and left ventricular mass index (LVMI) was calculated. Subjects were genotyped for I/D polymorphism of the angiotensin-converting enzyme (ACE) gene, A1166C polymorphism of the AT1 receptor gene, M235T polymorphism of angiotensinogen gene and -6G/A polymorphism of its promoter region. RESULTS: Genotype distribution of the sample obeyed Hardy-Weinberg equilibrium and was comparable to that reported previously for hypertensive individuals. Groups of patients with II, ID and DD polymorphism of ACE gene did not differ significantly in their LVMI levels. Furthermore, neither ID ACE-gene polymorphism nor ATI-receptor gene and angiotensinogen gene polymorphism was associated with LVH. Additionally, no any significant gene-gene interactions were found to be associated with LVH in the group studied. CONCLUSIONS: In the light of these observations it seems reasonable to make a preliminary conclusion about lack of association between LVH and distinct polymorphisms of renin-angiotensin system genes in the population studied.