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

INTRODUCTION: 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). METHODS: We consecutively enrolled 42 HIV+ dyslipidemic patients on stable PIs therapy (LDL cholesterol >130 mg/dl or triglycerides 200-500 mg/dl with non-HDL cholesterol >160 mg/dl). After basal evaluation, patients were randomized to a six-month treatment with ezetimibe 10 mg/day+fenofibrate 200 mg/day or with pravastatin 40 mg/day. Both at the basal evaluation and after the six-month treatment, the patients underwent blood tests for lipid parameters, and muscle and liver enzymes. RESULTS: At baseline, the two groups (21 patients each) were similar with regards to gender, age, BMI, blood pressure and virologic and metabolic parameters. After the six-month therapy, total cholesterol, LDL cholesterol and non-HDL cholesterol decreased significantly (p<0.01) in both groups. high-density lipoprotein (HDL) cholesterol increased (44 ± 10 to 53 ± 12 mg/dl, p<0.005) and triglycerides decreased (from 265 ± 118 mg/dl to 149 ± 37 mg/dl, p<0.001) in the ezetimibe+fenofibrate group, whereas both parameters remained unchanged in the pravastatin group. Mean values of creatine kinase (CK), alanine aminotransferase and aspartate aminotransferase were unchanged in both groups; only one patient in the pravastatin group stopped the treatment after two months, due to increased CK. CONCLUSIONS: In dyslipidemic HIV+ patients on PI therapy, the association of ezetimibe+fenofibrate is more effective than pravastatin monotherapy in improving lipid profile and is also well tolerated.

Evaluation of right ventricular function in patients with a previous episode of pulmonary embolism using tissue Doppler imaging.

New echocardiographic techniques including tricuspid annular plane systolic excursion (TAPSE) and pulsed tissue Doppler imaging (TDI) of the right ventricular wall have been assessed to better define right ventricular dysfunction (RVD) during the acute phase of pulmonary embolism (PE) in patients without significant tricuspidal insufficiency. Their application in patients with a previous history of PE may provide a better estimation of the incidence and clinical significance of long-term functional impairment of the right ventricle. In a case-control study, we compared the prevalence of RVD in a cohort of consecutive patients with previous PE and in age and sex-matched controls without PE. Exclusion criteria were moderate-severe left heart failure, moderate-severe mitral valve regurgitation, severe tricuspid insufficiency, or other causes of chronic pulmonary hypertension. Systolic and diastolic right ventricular functions were evaluated by measuring TAPSE and TDI of the right ventricular wall. Twenty-five patients with a previous first episode of PE and 25 controls were enrolled. Mean value of TAPSE was similar between patients with previous PE and controls (2.58 ± 0.33 and 2.53 ± 0.35 cm, P = ns). In patients with PE, the mean value of E″/A″ was significantly lower than in controls (0.89 ± 0.24 vs. 1.30 ± 0.39, P < 0.001), with 14 out of 25 cases having diastolic dysfunction as compared to only 3 out of 25 controls (P < 0.002). A high proportion of patients with previous PE have echocardiographic signs of RV diastolic dysfunction 6 months after the acute phase, even in the absence of symptoms, and in the presence of normal pulmonary pressures.

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.

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.

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.

Masked hypertension in type 2 diabetes mellitus. Relationship with left-ventricular structure and function.

BACKGROUND: To evaluate in type 2 diabetes mellitus the relationship between masked hypertension (MH) and left ventricular (LV) morpho-functional characteristics. METHODS: Using 24-hour BP monitoring and echocardiography, we evaluated 71 type 2 diabetic patients, without overt cardiac disease and never treated with antihypertensive drugs: 45 normotensive subjects with clinic BP <130/85 mmHg and 26 sustained hypertensives (SH)(clinic BP > or = 140 and/or 90 mmHg and 24-hour BP > or =125 and/or 80 mmHg), matched for age, gender, BMI and duration of diabetes with clinically normotensive patients. MH was diagnosed with clinic BP <130/85 mmHg and 24-hour BP > or =125 and/or 80 mmHg. RESULTS: Among clinically normotensive patients, 21 (47%) had MH and 24 were true normotensive (NT, 24-hour BP <125/80 mmHg). LV mass increased from NT to MH to SH (p < 0.001); the parameters of LV diastolic function were similar between MH and SH and significantly lower than in NT. CONCLUSION: In type 2 diabetic patients with clinic BP <130/85 mmHg, MH is frequent and is associated with LV remodelling characterized by increased myocardial mass and preclinical impairment of LV diastolic function; the remodelling is qualitatively and for some aspects also quantitatively similar to that found in sustained hypertensive patients. Therefore it would be useful to look for MH in diabetic subjects with clinic BP <130/85 mmHg, who, following the guidelines, are not entitled to antihypertensive treatment: the finding of MH could identify a subgroup of patients at higher cardiovascular risk and therefore needing a prompt antihypertensive treatment.

Family history of hypertension influences left ventricular diastolic function during chronic antihypertensive therapy.

BACKGROUND: Genetic factors play an important role in linking insulin resistance and hypertension, also influencing insulin sensitivity changes during antihypertensive treatment. This study was aimed to evaluate whether genetic predisposition to hypertension can also influence left ventricular (LV) changes during antihypertensive treatment. METHODS: We enrolled 36 never-treated hypertensives: 18 with both parents hypertensive (F+) and 18 with both parents normotensive (F-), matched for age, gender, and body mass index (BMI). The patients were evaluated twice, before and after 2.5 years of treatment with enalapril. At both evaluations the patients underwent: 24-h blood pressure (BP) monitoring, LV echocardiogram, and oral glucose tolerance test, with measurements of glucose and insulin levels. RESULTS: At basal evaluation the two groups were not different with regard to gender, age, BMI, 24-h BP, and fasting glucose; glucose metabolic clearance rate was significantly lower in F+. The LV mass index was similar between the groups, whereas diastolic parameters were significantly lower in F+. At second evaluation, 24-h BP and LV mass were decreased to the same extent in both groups; glucose metabolic clearance rate significantly increased in F- and remained unchanged in F+. The improvement of LV diastolic function, found in both group, was significantly greater in F-. CONCLUSIONS: Genetic predisposition to hypertension, in addition to affecting insulin sensitivity, influences LV functional changes during antihypertensive treatment. Despite a similar extent of 24-h BP and LV mass decrease, F+ patients showed no changes in insulin sensitivity and a smaller improvement in LV diastolic function than F-.

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.

Metabolic syndrome and morphofunctional characteristics of the left ventricle in clinically hypertensive nondiabetic subjects.

BACKGROUND: The study was aimed to evaluate the impact of the metabolic syndrome on left ventricular (LV) structure and function in nondiabetic patients, never treated with antihypertensive or lipid-lowering drugs. METHODS: Eighty-eight patients, with recent finding of clinic BP >140 or 90 mm Hg, underwent 24-h blood pressure (BP) monitoring, echocardiogram, evaluation for metabolic syndrome (Adult Treatment Panel III criteria). RESULTS: Metabolic syndrome was diagnosed in 38 subjects (43.2%) (metabolic syndrome+). Age, gender, 24-h systolic and diastolic BP were similar between metabolic syndrome+ and metabolic syndrome- groups, whereas body mass index, clinic and 24-h heart rate, fasting glycemia, and triglycerides were significantly higher and HDL-cholesterol lower in metabolic syndrome + subjects. The prevalence of sustained hypertension (24-h BP >125 or 80 mm Hg) was similar between the two groups. Relative wall thickness and LV mass were significantly greater in the metabolic syndrome+ group, also after correction for body mass index. The LV systolic function was similar between the two groups, whereas all the parameters of diastolic function, but the mitral E/A ratio, were significantly lower in the metabolic syndrome+ group. From multiple regression analysis the main independent determinant of LV mass index was the presence of metabolic syndrome, followed by the 24-h systolic BP. CONCLUSIONS: Nondiabetic patients with metabolic syndrome showed more pronounced alterations of LV geometry and function compared with subjects without metabolic syndrome. These greater preclinical myocardial abnormalities were not accounted for by difference in age, gender, or 24-h BP and can be reasonably ascribed to the interplay of the metabolic syndrome components, making the metabolic syndrome in itself a relevant clinical problem, possibly a cardiovascular disease equivalent, that deserves aggressive treatment.