Identification of dietary patterns in a general population of North Italian adults and their association with arterial stiffness. The RoCAV study.

BACKGROUND AND AIMS: The aims of this study were to identify dietary patterns in a general population of North Italian adults and to investigate the cross-sectional association between prevalent dietary patterns and arterial stiffness. METHODS AND RESULTS: Participants to the RoCAV study without chronic diseases at recruitment and with reliable dietary data were included. The food-frequency EPIC questionnaire was used to evaluate dietary habits. Dietary patterns were estimated using principal components analysis and Mediterranean diet adherence score (MedS). Carotid-femoral pulse wave velocity (cfPWV) was used as proxy of arterial stiffness. Basing on data from 2640 subjects (1608 men and 1032 women, mean ± SD 65.5 ± 6.7 years), four principal components (PC) were retained, explaining 24% of the overall variance. Considering 1284 subjects with cfPWV (mean ± SD 10.7 ± 2.5 m/s) data available, adherence to PC1 (Western-like dietary pattern) was associated with higher stiffness values (+0.29 m/s cfPWV for 1 SD increase of PC1, 95% CI:0.08,0.50; p = 0.007) in a multivariate model. Conversely, adherence to PC2 (Mediterranean-like) was not related to cfPWV values (-0.18, 95% CI: -0.36, 0.004; p = 0.06). Likewise, MedS and other PC patterns did not show any significant association with cfPWV. Mediation analysis showed that the association between Western-like dietary pattern and cfPWV is mediated by higher levels of leucocytes (9.2% of the effect, p = 0.047). CONCLUSIONS: Our study in a Southern European population identified a Western-like dietary pattern associated with an increased cfPWV, a proxy of arterial stiffness. The association with cfPWV was in part mediated by inflammatory status.

sRAGE and early signs of cardiac target organ damage in mild hypertensives.

BACKGROUND: Soluble Receptor for Advanced Glycation End Products (sRAGE) may be considered a marker inversely related to inflammation and its participation has been established in patients with advanced atherosclerotic vascular diseases. However, it is still unknown whether sRAGE reduction could be early metabolic change in the first stage of hypertension and initial hypertension-associated cardiac damage. We sought to determine the sRAGE values in otherwise healthy, untreated and recently diagnosed mild hypertensives and evaluate their association with blood pressure (BP) values, metabolic parameters, and with subclinical initial signs of cardiac target organ damage (TOD). METHODS: sRAGE were measured in 100 hypertensive and 100 normotensive subjects matched for age, gender and body mass index (BMI), submitted to a clinic visit and both ambulatory BP monitoring and echocardiography to determine the presence of initial cardiac TOD (presence of signs of left ventricular hypertrophy: left ventricular mass indexed for height2.7 (LVMi) > 48 g/m2.7 for men and > 44 g/m2.7 for women and/or increased left atrial volume 4-chamber indexed for body surface area (LAVi) > 34 ml/m2). RESULTS: sRAGE levels were similar between hypertensive and normotensive subjects and were not significantly correlated with office and 24-h BPs values. However, when subgrouping the hypertensive patients in Hyp-TOD and Hyp-withoutTOD, sRAGE was found to be different among the three groups (p = 0.030), being lower in the Hyp-TOD group than the values of both Hyp-withoutTOD (p = 0.038) and normotensives (p = 0.038). In hypertensive patients sRAGE was negatively related with both LVMi (r = - 0.239, p = 0.034) and LAVi (r = - 0.315, p = 0.005) and was independently related to cardiac TOD also in multivariable analysis. CONCLUSIONS: In this population of mild hypertensives, low circulating sRAGE may be a very early marker of initial TOD, suggesting the possible participation of oxidative stress in initial cardiac changes in human hypertension.

In vitro effects of Apixaban on 5 different cancer cell lines.

BACKGROUND: Cancer is associated with hypercoagulability. However, several data suggest that anticoagulant drugs may have an effect on tumor development and progression mediated by both coagulation dependent processes and non-coagulation dependent processes. Therefore, we investigated the in vitro effects of Apixaban on cell proliferation, mortality, cell migration, gene expression and matrix metalloproteinase in 5 different cancer cell lines. METHODS: The following cancer cell lines, and 2 normal fibroblast cultures (lung and dermal fibroblasts), were studied: OVCAR3 (ovarian cancer), MDA MB 231 (breast cancer), CaCO-2 (colon cancer), LNCaP (prostate cancer) and U937 (histiocytic lymphoma). Proliferation and cell mortality were assessed in control cells and Apixaban treated cultures (dose from 0.1 to 5 µg/ml, 0 to 96-h). Necrosis/Apoptosis (fluorescence microscopy), cell migration (24-h after scratch test), matrix metalloproteinase (MMP) activity and mRNA expression (RT PCR) of p16, p21, p53 and HAS were also assessed. RESULTS: High-dose (5 µg/ml) Apixaban incubation was associated with a significantly reduced proliferation in 3 cancer cell lines (OVCAR3, CaCO-2 and LNCaP) and with increased cancer cell mortality in all, except LNCaP, cancer lines. Apoptosis seems to account for the increased mortality. The migration capacity seems to be impaired after high-dose Apixaban incubation in OVCAR3 and CaCO-2 cells. Data on mRNA expression suggest a consistent increase in tumor suppression gene p16 in all cell lines. CONCLUSIONS: Our data suggest that high-dose Apixaban may be able to interfere with cancer cell in vitro, reducing proliferation and increasing cancer cell mortality through apoptosis in several cancer cell lines.

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.

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.

Neutrophils and clinical outcomes in patients with acute coronary syndromes and/or cardiac revascularisation. A systematic review on more than 34,000 subjects.

Some studies have suggested that high levels of total white blood cell (WBC) count and C-reactive protein (CRP) may be considered as independent prognostic factors in patients with acute coronary syndromes (ACS) and/or after cardiac revascularisation by percutaneous coronary intervention or coronary artery bypass grafting surgery. Evidence on the role of neutrophils in cardiovascular disease is less compelling. Therefore, we conducted a systematic review of the literature with the aim of identifying all the available evidence to clarify the role of neutrophils (absolute or relative count, neutrophil/lymphocyte ratio) as a prognostic risk factor in patients with ACS and/or cardiac revascularisation. All published studies evaluating the role of neutrophils as a risk factor for clinical outcomes were assessed using the MEDLINE and EMBASE databases. Study selection, data extraction and validity assessment was performed independently by two reviewers. Twenty-one studies (17 of which had positive results) for a total of more than 34,000 patients were included. Ten of 13 studies in ACS patients found that neutrophils measured on-admission are related to mortality rate and/or to major adverse clinical events. A predictive value of neutrophils after cardiac revascularisation procedures was reported in seven out of eight studies. Most of the studies showed that neutrophils were independent predictors of cardiovascular outcomes when analysed concomitantly with other markers of inflammation (WBC, CRP). The findings of our systematic review highlight the potential application of this inexpensive and readily available inflammatory marker for risk stratification in patients with ACS and/or cardiac revascularisation.

Lipid targets during statin treatment in dyslipidemic patients affected by nonalcoholic fatty liver disease.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is associated with both dyslipidemia and increased risk for cardiovascular disease. Despite the indication to treat in patients affected by both dyslipidemia and NAFLD, an undertreatment in statin therapy due to the potential liver damage is frequently observed. We sought to evaluate retrospectively the impact of statin on the lipid profile and on the achievement of low-density lipoprotein (LDL) cholesterol targets in relation to the National Cholesterol Education Program--Adult Treatment Panel III-cardiovascular risk in dyslipidemic patients presenting with a clinical--diagnosis of NAFLD and elevated liver enzymes before statin prescription. As a secondary endpoint, the authors investigated whether statin could be associated with changes of liver enzymes. METHODS: Forty-three patients with dyslipidemic NAFLD presenting with increased values of aspartate aminotransferase and/or alanine aminotransferase and/or γ-glutamyl-transferase at baseline were analyzed retrospectively as regard the lipid profile and liver enzymes (values reported before statin and during statin therapy). RESULTS: Total cholesterol, LDL and triglycerides were significantly reduced at follow-up (5.4 ± 5.4 months). The LDL target was achieved at the second visit in 30 patients (69.8%).The number of patients achieving the LDL target was significantly higher in low-risk group compared with moderate- and high-risk subjects. Liver enzyme levels showed no significant changes between baseline and follow-up. CONCLUSIONS: Statin treatment was effective (without changes in liver enzymes) in patients with dyslipidemia and NAFLD and therefore, affected by a profound alteration in lipoprotein metabolism. The number of patients achieving LDL target was related to the Adult Treatment Panel III risk classification, being higher in patients with lower risk.

Cytokine production from peripheral blood mononuclear cells and polymorphonuclear leukocytes in patients studied for suspected obstructive sleep apnea.

PURPOSE: The relationship between obstructive sleep apnea (OSA) and atherosclerosis-related inflammation has been poorly investigated, particularly focusing on functional responses of immune cells playing a key role in atherogenesis and in comparison with control groups with similar cardiovascular risk factors which are known to be themselves associated with inflammation. We sought to determine cellular tumor necrosis factor-alpha (TNF-α) production from peripheral blood mononuclear cells (PBMCs) and interleukin (IL)-8 release from neutrophils (PMNs) in patients studied for suspected OSA. METHODS: Thirty-six consecutive patients who underwent a nocturnal complete cardiorespiratory evaluation for suspected OSA were initially evaluated. Serum, PBMCs, and PMNs were isolated (at baseline and after 12 weeks) from patients with apnea-ipopnea index (AHI) >20 (OSA group, n = 16) and from control patients with AHI <5 (nonOSA group, n = 11). All patients continued the same pharmacological therapy for 12 weeks; the OSA group was additionally treated with nocturnal continuous positive-airway-pressure ventilation (cPAP). RESULTS: The two groups had similar clinical characteristics (prevalence of hypertension, dyslipidemia, diabetes, and cardio-metabolic therapies) except for obesity. Resting and stimulated TNF-α production from PBMCs and IL-8 release from PMNs were similar in the two groups. Serum cytokines resulted within the normal range. In the OSA group, cPAP was not associated with changes in cellular responses. CONCLUSIONS: In patients showing similar prevalence of major cardiovascular risk factors and cardio-metabolic therapies, differing for the presence or absence of OSA, cytokine productions from PBMC and PMN were similar and were not modified during cPAP therapy. Studies designed to investigate OSA-associated inflammation should carefully match the control group subjects.

Prolonged statin-associated reduction in neutrophil reactive oxygen species and angiotensin II type 1 receptor expression: 1-year follow-up.

AIMS: Our study investigated reactive oxygen species (ROS) generation and angiotensin II type 1 receptor (AT(1)-R) expression in primed polymorphonuclear leukocytes (PMNs) of dyslipidaemic subjects over prolonged statin treatment. METHODS AND RESULTS: Sixteen untreated dyslipidaemic subjects with moderately increased cardiovascular risk (National Cholesterol Education Program, Adult Treatment Panel III) were studied before and during long-term (1 year) simvastatin treatment. Neutrophils from dyslipidaemic subjects generated more ROS in comparison with cells from healthy control subjects. After 1 year of simvastatin treatment, ROS production (delta N-formyl-Met-Leu-Phe-induced generation and area under the curve) was significantly reduced. At baseline, AT1-R mRNA expression was also higher in dyslipidaemic subjects than in healthy controls and it was reduced after clinical treatment with simvastatin. In a subgroup of patients, a reduced angiotensin II-induced ROS generation was also observed upon clinical simvastatin treatment. Moreover, a direct effect of statin on the upregulated AT(1)-R expression was demonstrated in vitro in neutrophils of untreated dyslipidaemic subjects. CONCLUSION: A consistent reversion of pro-inflammatory oxidative functional response and reduction of AT(1)-R expression in primed PMNs was observed in patients during long-term statin treatment. The AT1-R reduction over treatment may contribute to the normalization of dysregulated neutrophil activation which occurs in the pre-clinical phase of atherosclerosis.

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.

Pain perception, blood pressure levels, and peripheral benzodiazepine receptors in patients followed for differentiated thyroid carcinoma: a longitudinal study in hypothyroidism and during hormone treatment.

BACKGROUND: Elevated blood pressure levels that are associated with hypalgesia and hypothyroidism have major influences on the cardiovascular system. The potential modulation of pain sensitivity by thyroid hormones is largely undetermined. Moreover, a few experimental studies show that peripheral benzodiazepine receptors (PBRs), which may be altered in hypothyroidism, seem to be related with pain perception. METHODS: Dental pain threshold and tolerance were evaluated in 19 patients followed for differentiated thyroid carcinoma (1) in severe short-term hypothyroidism (phase 1) and (2) during thyroid stimulating hormone-suppressive LT4 treatment (phase 2). PBR expression (cytofluorimetric evaluation) on peripheral blood mononuclear cells was also investigated in the 2 phases. RESULTS: Pain perception differed throughout the study, the dental pain threshold was higher in phase 1 (P<0.05) whereas pain tolerance was higher but not significantly (P=0.07). Although the systolic blood pressure was higher during hypothyroidism (P<0.01), no relationship was found between blood pressure changes and pain sensitivity variations. Moreover, the multiple regression analysis showed an independent association of the clinical phase with pain sensitivity (r=-2.61, P=0.029), while accounting for systolic blood pressure. The intensity of PBRs was significantly higher in the first phase of the study (P=0.047) whereas the ratio did not significantly differ. However, no relationship was observed between pain sensitivity and PBRs. DISCUSSION: In conclusion, in athyreotic patients, the pain sensitivity is related to the thyroid status and is independent of the increase in blood pressure induced by thyroid hormone deprivation. The PBRs do not seem to have major influence on pain sensitivity changes in hypothyroidism.

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-.

Simvastatin treatment modifies polymorphonuclear leukocyte function in high-risk individuals: a longitudinal study.

BACKGROUND: Although extensive experimental evidence supports a primary role of polymorphonuclear leukocytes (PMNs) in atherosclerosis, few data exist concerning the functional properties of these cells and their pharmacological modulation in high-risk individuals. OBJECTIVE: The production of the proinflammatory chemokine interleukin-8 (IL-8), migration and chemotaxis, and reactive oxygen species (ROS) generation were investigated in a longitudinal study in PMNs obtained from high-risk individuals during statin treatment. As a secondary endpoint we compared PMN function of high-risk patients with that of controls. METHODS AND RESULTS: PMNs were isolated from 21 high-risk individuals before treatment and 3 and 30 days after the beginning of simvastatin treatment, and from healthy controls. During treatment a significant reduction was observed both in resting (P = 0.009) and N-formyl-Met-Leu-Phe (fMLP)-stimulated (P = 0.008) IL-8 production, and in the chemotactic index (P = 0.038), whereas ROS generation did not significantly change. In comparison with cells from controls, PMNs obtained from patients before starting simvastatin treatment showed higher resting and fMLP-stimulated IL-8 release (P = 0.007 and P = 0.002, respectively) and ROS generation (resting, P = 0.009; and fMLP-stimulated, P = 0.046), whereas migration and the chemotactic index did not significantly differ. CONCLUSIONS: An activation of neutrophils is present in high-risk individuals, shown by the enhanced production of IL-8, and increased ROS generation. The 4-week statin treatment is able to reduce the cell capability to produce IL-8, and to decrease chemotaxis, thus affecting the proinflammatory properties of PMNs.

Blockade of the renin-angiotensin-aldosterone system: effects on hypertensive target organ damage.

The renin-angiotensin-aldosterone system (RAAS) plays a relevant role not only in the pathophysiology of essential hypertension, but also in the development of hypertensive target organ damage. Different drugs acting on RAAS components are now available: angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II AT1 receptors blockers (ARBs), non-selective and selective aldosterone antagonists. The review will focus on their effects on hypertensive organ damage. In fact, apart from the well known efficacy in reducing blood pressure, all these drugs have been demonstrated to protect against target organ damage, reversing or preventing its development. The main issues addressed will be: effects of the RAAS blockade on heart and kidney disease, protective action against arterial wall damage, with a focus on the endothelial protection. The comparison among ACE inhibitors, ARBs and aldosterone antagonists will be discussed, with specific reference to different class and/or drug effects and to the results of few studies evaluating the effects of combination therapy with different drugs blocking the RAAS.

Mixed cranial nerve neuroma revealing itself as baroreflex failure.

We report here the first case of baroreflex failure due to a mixed cranial nerve neuroma in which the clinical manifestations (recurrent severe hypertensive crisis, hypotension) due to baroreflex arc impairment preceded the clinical diagnosis of brain tumour and neurosurgery by a few months. Given the clinical suspicion of baroreflex failure, even in the absence of iatrogenic clues, we propose that the patient's study should include neuroradiologic evaluation of the ponto-cerebellar angulus.

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.

Effect of glycemic control on left ventricular diastolic function in type 1 diabetes mellitus.

Left ventricular (LV) diastolic dysfunction is a main feature of diabetic heart disease. The aim of this prospective study was to evaluate the influence of glycemic control on diastolic function in type 1 diabetes mellitus. Thirty-six normotensive (24-hour blood pressure <130/80 mm Hg) subjects with inadequately controlled (glycated hemoglobin >7%) type 1 diabetes, without clinically detectable heart disease, were enrolled. After the basal evaluation, insulin therapy was modified to improve glycemic control. Glycated hemoglobin, LV echocardiography, 24-hour blood pressure monitoring, and laboratory tests were repeated after 6 months in all patients and after 12 months in 27 patients. At the basal evaluation, LV anatomy and systolic function were normal in all, and diastolic function was impaired in 14 patients. After 6 months, the mean values of body mass index, 24-hour blood pressure, and LV anatomy and systolic function were unchanged; mean glycated hemoglobin was decreased (p < 0.001), and mean values of diastolic parameters were significantly improved. After 12 months, the mean values of all blood pressure, metabolic, and LV parameters were unchanged. Percent changes of diastolic parameters were inversely correlated with percent changes of glycated hemoglobin, considering changes from the basal to the 6-month evaluation, as well as changes from the 6- to the 12-month evaluation. In conclusion, in normotensive patients with type 1 diabetes, a close relation was found between glycemic control and LV diastolic function, which improves when glycemic control improves. Therefore, diastolic dysfunction can be prevented or reversed, at least partly, by tight glycemic control.

Isolated office hypertension: a 3-year follow-up study.

The study aimed to evaluate, over a 3-year period, the progression towards sustained hypertension and left ventricular (LV) changes in patients with isolated office (IO) hypertension (office BP>140 and/or 90 mmHg, daytime BP<130/80 mmHg). After 3 years from the basal evaluation, 38 subjects with basal normal BP and 42 subjects with basal IO hypertension underwent a second 24-h BP monitoring and echocardiography; 19 patients of the basal IO hypertension group were not revaluated because they had already developed ambulatory hypertension and were on antihypertensive treatment. At the second evaluation, the 38 normotensive subjects had unchanged BP and LV parameters; 25 IO hypertensives have developed sustained hypertension. Considering them together with the 19 patients already treated, 72% of 61 IO hypertensives developed ambulatory hypertension over a 3-year period. The patients who subsequently developed hypertension differed from the group who did not only for lower basal values of LV diastolic parameters; all the patients with basal LV hypertrophy and/or preclinical diastolic impairment subsequently developed sustained hypertension. In conclusion, IO hypertensive patients show a high rate of progression towards sustained hypertension. Basal LV hypertrophy and/or preclinical diastolic dysfunction were the only markers of a greater risk of becoming hypertensives.