Lidia Sada

Vascular inflammation and endothelial dysfunction in experimental hypertension.

Essential hypertension is characterized by increased peripheral vascular resistance to blood flow. The endothelium is a crucial regulator of vascular tone. Its function is impaired in patients with hypertension, with reduced vasodilation, increased vascular tone associated with a proinflammatory and prothrombotic state. Low-grade inflammation localized in vascular tissue is therefore recognized as an important contributor to the pathophysiology of hypertension, to the initiation and progression of atherosclerosis as well as to the development of cardiovascular diseases.

Pulmonary embolism in pregnancy

Venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality during pregnancy or early after delivery, remaining a diagnostic and therapeutic challenge in both states. The absolute incidence of pregnancy-associated VTE has been reported as 1 in 1,000 to 1 in 2,000 deliveries. With 5–6 million new births computed in Europe in 2010, the potential clinical relevance of diagnosing and treating gravidic VTE is immediately evident. Fivefold higher in a pregnant as compared with a non-pregnant woman, VTE risk is also higher in postpartum than antepartum period. Ranked absolute and relative thrombotic risk may be described in the several thrombophilic conditions experienced by women at risk, according to which specific prophylactic and therapeutic recommendations have been formulated by recent guidelines. The main purpose of the present review article was to emphasize the most recent findings and recommendations in diagnostic strategies, discussing thrombophilic risk evaluation, as well as risks and benefits of various diagnostic techniques for both mother and fetus.

Effects of a Long-Term Treatment With Aliskiren or Ramipril on Structural Alterations of Subcutaneous Small-Resistance Arteries of Diabetic Hypertensive Patients

Structural alterations of subcutaneous small-resistance arteries are associated with a worse clinical prognosis in hypertension and non–insulin-dependent diabetes mellitus. The effects of the direct renin inhibitor aliskiren on microvascular structure were never previously evaluated. Therefore, we investigated the effects of aliskiren in comparison with those of an extensively used angiotensin-converting enzyme inhibitor, ramipril, on peripheral subcutaneous small-resistance artery morphology, retinal arteriolar structure, and capillary density in a population of patients with non–insulin-dependent diabetes mellitus. Sixteen patients with mild essential hypertension and with a previous diagnosis of non–insulin-dependent diabetes mellitus were included in the study. Patients were then randomized to 1 of the 2 active treatments (aliskiren 150 mg once daily, n=9; or ramipril 5 mg once daily, n=7). Each patient underwent a biopsy of the subcutaneous fat from the gluteal region, an evaluation of retinal artery morphology (scanning laser Doppler flowmetry), and capillary density (capillaroscopy), at baseline and after 1 year of treatment. Subcutaneous small arteries were dissected and mounted on a pressurized micromyograph, and the media-to-lumen ratio was evaluated. A similar office blood pressure–lowering effect and a similar reduction of the wall-to-lumen ratio of retinal arterioles were observed with the 2 drugs. Aliskiren significantly reduced media-to-lumen ratio of subcutaneous small-resistance arteries, whereas ramipril-induced reduction of media to lumen ratio was not statistically significant. No relevant effect on capillary density was observed. In conclusion, treatment with aliskiren or ramipril was associated with a correction of microvascular structural alterations in patients with non–insulin-dependent diabetes mellitus.

The direct renin inhibitor aliskiren improves vascular remodelling in transgenic rats harbouring human renin and angiotensinogen genes

In the present study, we tested the hypothesis that chronic treatment with the direct rennin inhibitor aliskiren improves the remodelling of resistance arteries in dTGR (double-transgenic rats). dTGR (5 weeks) were treated with aliskiren (3 mg/kg of body mass per day) or ramipril (1 mg/kg of body mass per day) for 14 days and compared with age-matched vehicle-treated dTGR. BP (blood pressure) was similarly reduced in both aliskiren-treated and ramipril-treated rats compared with control dTGR (167±1 and 169±2 mmHg compared with 197±4 mmHg respectively; P<0.05). The M/L (media-to-lumen) ratio assessed on pressurized preparations was equally reduced in aliskiren-treated and ramipril-treated rats compared with controls (6.3±0.5 and 6.4±0.2% compared with 9.8±0.4% respectively; P<0.05). Endothelium-dependent and -independent relaxations were similar among the groups. L-NAME (N(G)-nitro-L-arginine methyl ester) significantly reduced acetylcholine-induced dilation in drug-treated dTGR. This effect was significantly more prominent in aliskiren-treated rats. eNOS (endothelial NO synthase) expression showed a 2-fold increase only in aliskiren-treated dTGR as compared with controls (P<0.01) and ramipril-treated dTGR (P<0.05). Plasma nitrite, as an index of NO production, was significantly increased in dTGR treated with either aliskiren or ramipril compared with controls. Only aliskiren induced a 2-fold increase in plasma nitrite, which was significantly greater than that induced by ramipril (P<0.05). gp91(phox) expression and ROS (reactive oxygen species) production in aorta were significantly and similarly reduced by both drugs. In conclusion, equieffective hypotensive doses of aliskiren or ramipril reduced the M/L ratio of mesenteric arteries and improved oxidative stress in dTGR. However, only aliskiren increased further NO production in the vasculature. Hence, in dTGR, direct renin inhibition induces favourable effects similar to that induced by ACE (angiotensin-converting enzyme) inhibition in improving vascular remodelling through different mechanisms.

Blood pressure control versus atrial fibrillation management in stroke prevention.

Hypertension is one of the major risk factors for atrial fibrillation which in turn is the most prevalent concomitant condition in hypertensive patients. While both these pathological conditions are independent risk factors for stroke, the association of hypertension and atrial fibrillation increases the incidence of disabling strokes. Moreover, documented or silent atrial fibrillation doubles the rate of cardiovascular death. Lowering blood pressure is strongly recommended, particularly for primary stroke prevention. However, a relatively small percentage of hypertensive patients still achieve the recommended blood pressure goals. The management of atrial fibrillation with respect to stroke prevention is changing. New oral anticoagulants represent a major advancement in long-term anticoagulation therapy in non valvular atrial fibrillation. They have several benefits over warfarin, including improved adherence to the anticoagulation therapy. This is an important issue since non-adherence to stroke prevention medications is a risk factor for first and recurrent strokes.