Eleonora Nicolini

Plasma levels of matrix metalloproteinases and their inhibitors in hypertension: a systematic review and meta-analysis.

Background Hypertension is a major cause of cardiovascular remodeling. In the cardiovascular system, the remodeling of the extracellular matrix is controlled by the matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs). The aim of this meta-analysis is to elucidate the behavior of plasma MMP and TIMP levels in hypertension and their relationship to cardiovascular remodeling. Methods MEDLINE and EMBASE databases were searched up to July 2011. Studies were considered eligible if they provided values of plasma MMPs and TIMPs in hypertensive patients. Given the high variability of the plasma biomarker values among studies, the standardized mean difference (SMD) was calculated. Results Ten studies provided plasma MMP-9; the SMD between 778 hypertensive patients and 669 controls was 1.95 units (P < 0.05). Thirteen studies provided plasma TIMP-1; the SMD between 851 hypertensive patients and 646 normotensive individuals was 1.92 units (P < 0.01). Three studies investigated whether plasma TIMP-1 predicted left ventricular (LV) remodeling; the SMD between 92 hypertensive patients with and 88 hypertensive patients without LV hypertrophy was 5.81 units (P < 0.05). As for diastolic heart failure (HF), five studies provided data for plasma MMP-2; the SMD between 321 hypertensive patients with and 334 hypertensive patients without HF was 2.36 units (P < 0.01). The heterogeneity among studies was high. Conclusions These results suggest that MMP-2, MMP-9 and TIMP-1 may have a role as biomarkers of cardiovascular remodeling in hypertension. If these results are confirmed in prospective clinical studies, they could provide new tools to stratify cardiovascular risk in hypertensive patients.

Effects of dual blockade of Renin-Angiotensin system on concentric left ventricular hypertrophy in essential hypertension: a randomized, controlled pilot study.

BACKGROUND The renin-angiotensin system (RAS) plays a major role in promoting left ventricular (LV) remodeling in essential hypertension. We designed a controlled, randomized pilot study aimed to test the hypothesis that the dual RAS blockade with angiotensin-converting enzyme (ACE) inhibitor (ACEi) + angiotensin II receptor blocker (ARB) can be more effective in decreasing LV hypertrophy and improving diastolic function than a largely employed association such as ACEi + calcium-antagonist (Ca-A). METHODS Twenty-four never-treated hypertensive patients with LV concentric hypertrophy were randomized to ramipril + candesartan or ramipril + lercanidipine. Before and after the 6-month treatment they underwent a 24-h blood pressure (BP) monitoring and echocardiographic examination. RESULTS At baseline, age, body mass index (BMI), 24-h BP, and LV morpho-functional parameters were similar between the two groups. The 6-month treatment induced in both groups a significant decrease of 24-h BP, septal and posterior wall thickness, and LV mass index (LVMi) (ACEi + ARB 155 +/- 19 to 122 +/- 17 g/m(2), P < 0.0001; ACEi + Ca-A 146 +/- 18 to 127 +/- 20 g/m(2), P < 0.0001). Systolic function remained unchanged; LV diastolic parameters increased significantly in both groups. The extent of 24-h BP decrease was similar between the two groups (-13.3/16.3% vs. -12.3/15.8%, P = 0.63/P = 0.71), whereas the decrease of LV mass (-22% vs. -12.8%, P < 0.005) and the improvement of diastolic function were greater in ACEi + ARB group. CONCLUSIONS In comparison with ACEi + Ca-A, ACEi + ARB treatment showed a greater antiremodeling effect, that can be reasonably ascribed to a BP-independent effect of the dual RAS blockade.

OSA, metabolic syndrome and CPAP: Effect on cardiac remodeling in subjects with abdominal obesity

BACKGROUND We evaluated whether obstructive sleep apnoea (OSA) and continuous positive airway pressure (CPAP) treatment influence left ventricular (LV) remodelling independently of abdominal obesity and metabolic syndrome (MetS). METHODS Cardiorespiratory examination, 24-h BP monitoring and echocardiogram were performed in overweight/obese patients with increased abdominal adiposity and symptoms suggesting OSA : OSA/MetS (n.50), OSA/noMetS (n.22), noOSA/MetS (n.29), noOSA/noMets (n.16). The evaluation was repeated in 41 patients after ≥18 months of CPAP. RESULTS Despite similar age, gender, BMI and 24-h BP, the 2 groups with MetS had greater LV remodelling (LV hypertrophy and diastolic dysfunction) than the 2 groups without MetS. From multiple regression analysis independent determinants for LV mass were MetS, 24-h systolic BP and age, for LV diastolic function were LV mass index, MetS and age. After CPAP, the 20 patients with decreased body weight showed diastolic BP decrease, LV hypertrophy regression and diastolic function improvement, whereas, despite similar respiratory improvement, BP and LV parameters were unchanged in the 21 patients with body weight unchanged/increased. CONCLUSION In patients with increased abdominal adiposity, LV remodelling is not associated to OSA per se; chronic CPAP treatment does not influence LV remodelling whose regression is mainly linked to body weight decrease.

Venous and Arterial Thrombosis Associated with HIV Infection

The advent of highly active antiretroviral therapy (HAART) and the appropriate use of prophylactic strategies to prevent opportunistic infections have drastically decreased human immunodeficiency virus (HIV) infection-related mortality. However, there is growing evidence that metabolic abnormalities associated with HIV infection and with its treatment may lead to an increased risk of cardiovascular (CV) events. Several studies showed an increased risk of symptomatic and subclinical CV events in these patients. On the other hand, the association with venous thromboembolic events is less compelling. This increased risk is possibly explained by the coexistence in this population of different risk factors determined by the HIV infection per se, by the higher prevalence of traditional CV risk factors such as obesity, smoking, hypertension, hyperlipidemia, and glucose intolerance, as compared with the general population, and by the effects of HAART. Thus, systematic identification and aggressive treatment of traditional risk factors seem to be necessary to prevent the development of cardiovascular disease in this population.

Angiotensin-converting enzyme inhibitors influence left ventricular mass and function independently of the antihypertensive effect.

In our retrospective study, we evaluated whether ACE inhibitors can influence left ventricular (LV) morphofunctional characteristics in essential hypertension independently of the antihypertensive effect. We studied 21 hypertensive patients (group 1) before and after at least 18 months of treatment with ACE inhibitors that did not induce any blood pressure (BP) reduction; as a control group, we evaluated 19 hypertensive patients (group 2) not treated with antihypertensive drugs during the same period. At baseline, the 2 groups, neither one previously treated with antihypertensive drugs, were not significantly different with regard to sex, age, body mass index, 24-hour BP, and heart rate; LV mass index was similar between the groups, whereas LV diastolic indices were significantly lower in group 1. At the second evaluation, body mass index, 24-hour BP, and heart rate were unchanged in both groups; LV mass index was significantly decreased in group 1 and increased in group 2. LV diastolic parameters were significantly improved in group 1, whereas in group 2, diastolic function was significantly deteriorated. In conclusion, our clinical study shows that ACE inhibitors can induce LV hypertrophy regression and improvement of diastolic function also in the absence of any antihypertensive effect.

Dyslipidemia in HIV-positive patients: a randomized, controlled, prospective study on ezetimibe+fenofibrate versus pravastatin monotherapy

We designed a randomized, controlled prospective study aimed at comparing efficacy and tolerability of ezetimibe+fenofibrate treatment versus pravastatin monotherapy in dyslipidemic HIV‐positive (HIV+) patients treated with protease inhibitors (PIs).