Arterial stiffness is associated with left atrial size in hypertensive patients.

BACKGROUND: Arterial stiffness is a strong predictor of cardiovascular events and particularly of stroke. A likely explanation is the development of atherosclerotic lesions at the carotid level, favored by increased local stiffness. Another possibility involves cardiac consequences of aortic stiffness and particularly left atrial dilatation with its subsequent risk of atrial fibrillation (AF) and cerebral embolism. AIMS: The present study investigated the link between arterial stiffness, pulse pressure and left atrial size, a determinant of AF risk. METHODS: Arterial stiffness was determined from pulse wave velocity (PWV) and pulse pressure (PP). Left atrial size was also measured. Several potential confounders were taken into account including indices of ventricular remodeling and diastolic function (estimated by NT-Pro brain natriuretic peptide (NT-proBNP) levels). RESULTS: Three-hundred and ten hypertensive patients, aged 53 +/- 13 years, were included. Mean 24-h blood pressure (BP) was 154 +/- 20 over 93 +/- 13 mmHg. Significant relationships were found between left atrial diameter (LAD) and PWV (r=0.27, P<0.001) and between LAD and 24-h PP (r=0.32, P<0.001). LAD was also correlated significantly, although not always tightly, with left ventricular dimensions, geometry and NT-proBNP. In two different multivariate models, LAD remained significantly correlated with PWV or with 24-h PP, independently of classical determinants like age, gender, body mass index, ventricular remodeling (i.e. dimensions and geometry) and filling pressure. CONCLUSION: These results led us to propose AF as a new possible pathophysiological link between arterial stiffness and stroke. These results also emphasize the cardiac consequences of arterial stiffness which can fuel a new approach to AF prevention.

[New treatment strategies for hypertension. Which guidelines and how to apply them]. / Nouvelles stratégies thérapeutiques dans l'hypertension artérielle. Quelles recommandations et comment les appliquer?

The diagnosis of hypertension by blood pressure measurements taken in the physician's office has been called into question by several studies. The onset of cardiovascular events appears to correlate better with ambulatory blood pressure measurements than with those taken during consultation (either "white coat" or masked hypertension). While the US, WHO, French and European guidelines diverge as to the specific antihypertensive drug among the seven classes available should be chosen for first-line treatment, there is a consensus for specific choices as a function of the type of hypertension. In any case, most treatment trials show that more than two antihypertensive drugs are often necessary. Treatment can thus begin with two drugs. The optimal target blood pressure is defined by the US JNC7 according to whether the patient also has diabetes or a nephropathy. When hypertension is uncomplicated, the target level is 140/90 mmHg. In the case of diabetes or nephropathy, it is 130/80 mmHg. In all cases, diet and exercise changes are also necessary and it is essential that patients understand them if they are to comply with them. Diastolic blood pressure remains the most important figure for those younger than 50 years, but afterwards, systolic pressure is more relevant. Aortic pressure may be more closely associated with cardiovascular risk than the blood pressure measured at the brachial artery. The concept of comprehensive management is radically modifying our behavior : the hypertensive patient is now above all a patient at high cardiovascular risk and the treatments to consider must not be limited to antihypertensive drugs but must also include treatment of other cardiovascular risk factors (aspirin, statins, smoking cessation, etc.).

REDD2 gene is upregulated by modified LDL or hypoxia and mediates human macrophage cell death.

OBJECTIVE: Cholesterol accumulation in macrophages is known to alter macrophage biology. In this article we studied the impact of macrophage cholesterol loading on gene expression and identified a novel gene implicated in cell death. METHODS AND RESULTS: The regulated in development and DNA damage response 2 (REDD2) gene was strongly upregulated as THP-1 macrophages are converted to foam cells. These results were confirmed by Northern blot of RNA from human monocyte-derived macrophages (HMDM) treated with oxidized LDL (oxLDL). Human REDD2 shares 86% amino acid sequence identity with murine RTP801-like protein, which is 33% identical to RTP801, a hypoxia-inducible factor 1-responsive gene involved in apoptosis. Treatment of HMDM with desferrioxamine, a molecule that mimics the effect of hypoxia, increased expression of REDD2 in a concentration-dependent fashion. Transfection of U-937 and HMEC cells with a REDD2 expression vector increased the sensitivity of the cells for oxLDL-induced cytotoxicity, by inducing a shift from apoptosis toward necrosis. In contrast, suppression of mRNA expression using siRNA approach resulted in increased resistance to oxLDL treatment. CONCLUSIONS: We showed that stimulation of REDD2 expression in macrophages increases oxLDL-induced cell death, suggesting that REDD2 gene might play an important role in arterial pathology.

[Markers of cardiovascular remodeling in hypertension]. / Marqueurs du remodelage cardiovascularire structural et fonctionnel dans l'hypertension.

UNLABELLED: Our goal was to study the relative influence of systolic blood pressure (SBP) and plasmatic markers of sympathetic and renin-aldosterone systems (RAS) activities to left atrial diameter (LAD), left ventricular posterior wall thickness (LVPWT) and pulse wave velocity (PWV), which reflect cardiovascular remodeling in hypertension. METHODS: In 227 consecutive patients with hypertension (mean age +/- SD: 53.3 years +/- 13.4, 126 men), we measured: PWV, LAD, LVPWT, mean 24-hours SBP, plasma renin activity, and plasma aldosterone and catecholamine levels. Multiples linear regression analyses were performed to test statistical associations between hemodynamic and neurohumoral factors, and cardiovascular remodeling parameters, after adjustment for age, gender and body mass index. RESULTS: LVPWT was positively correlated to SBP as well as to plasma aldosterone and meta-noradrenaline (p < 0.001). LAD and PWV were related to SBP but not to any of the biological variables. Moreover, LAD correlated to PWV independently of SBP (p < 0.05), whereas after SBP inclusion in the model, there was not significant correlation between LAD and LVPWT nor between LVPWT and PWV. CONCLUSION: In hypertension, the development of cardiac hypertrophy depends on SBP and the sympathetic and renin-aldosterone systems activities. The RAS is not involved in the PWV nor LAD modifications. Strong association between LAD and PWV suggest that left atrial enlargement, that may be considered as a marker of diastolic function, may results more from arterial stiffness than from ventricular hypertrophy.