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.

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.

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.

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-.

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.

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.

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.

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.

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.

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.

Global link between heart rate and blood pressure oscillations at rest and during mental arousal in normotensive and hypertensive subjects.

UNLABELLED: Complex phenomena modulate the interplay between heart rate and blood pressure variability, in particular after adjustments induced by stimuli or in pathophysiological conditions. This study sought to investigate in 25 hypertensive and 16 normotensive male subjects whether relationships operating at rest may be preserved after a central nervous system arousal induced by a mental stress test. As a secondary endpoint, we evaluated the potential changes of the components of heart rate and blood pressure variability during stress. RESULTS: A significant correlation was observed between components of RR and systolic blood pressure (SBP) variability (p<0.0001), after controlling for the subject's status (normotensive vs. hypertensive) and for stress-steps (baseline condition, during stress test and recovery). Moreover, the multiple regression model accounted for the potential effects of the baseline alpha(LF) value and for the baseline heart rate and systolic blood pressure. The relationship operating between the LF/HF(RR) ratio and LF/HF(SBP) ratio was not different either at the different steps of stress test (interaction: p=0.87) or in the two groups of normotensive and hypertensive subjects (interaction: p=0.76). The variables of RR and SBP variabilities were modified during stress and recovery. In particular, the LF/HF(RR) ratio and LF/HF(SBP) ratio increased during stress and decreased during recovery. CONCLUSIONS: The association between heart rate and blood pressure oscillations was preserved during central nervous system arousal by mental stress both in normotensives and hypertensives. A central integration may account for this constant relationship, the correlation being independent from baseline heart rate, blood pressure and baroreflex sensitivity.

Circadian blood pressure variability is associated with autonomic and baroreflex-mediated modulation of the sinoatrial node.

OBJECTIVE: The day-night variability of blood pressure (BP) is of interest in the analysis of ambulatory blood pressure monitoring (ABPM). The aim of this study was to investigate whether the nocturnal BP reduction was associated with the autonomic and baroreflex-mediated modulation of the sinoatrial node in normotensive and hypertensive subjects. METHODS AND RESULTS: 63 consecutive untreated male subjects (40 hypertensive and 23 normotensive) were studied. Spectral parameters of RR interval variability and the alphaLF index (a measure of baroreflex gain) were calculated at rest. Then all the subjects performed a 24-h ABPM. RESULTS: As regards the relationships involving 24-h BP and resting heart rate (HR) and HR variability parameters, a significant correlation was found between mean RR and both systolic and diastolic nocturnal BP falls (r = 0.40, p < 0.001, r = 0.32, p < 0.01, respectively); moreover, a significant correlation was found between the nocturnal fall of systolic BP and both the LF/HF ratio and absolute power of HF (r = -0.25, p < 0.05 and r = 0.29, p < 0.05, respectively). The alphaLF index was significantly associated with the nocturnal diastolic BP fall (r = 0.26, p < 0.05) whereas the association with the systolic fall did not reach statistical significance (r = 0.23, p = 0.07). CONCLUSIONS: The relationship found between the nocturnal reduction of BP and both the LF/HF ratio and HF power of RR variability suggests that factors influencing the sympatho-vagal modulation to the heart are associated with the day-night variability of blood pressure. Moreover, the relationship between BP fall and the spontaneous baroreflex sensitivity index alphaLF, may indicate a role of the baroreflex-mediated arc function in the BP adjustments occurring during the night.

Changes in pain perception during treatment with angiotensin converting enzyme-inhibitors and angiotensin II type 1 receptor blockade.

OBJECTIVES: Besides the well-known role of the angiotensin system in blood pressure control, an interaction of angiotensin and pain perception has been suggested. This study sought to investigate whether an angiotensin converting enzyme inhibitor, which facilitates bradykinins, algesic peptides, and/or an AT1 receptor antagonist may modify hypertension-related hypoalgesia in humans. The study was approved by the ethical committee of our Department. METHODS: A total of 22 hypertensive patients were submitted to dental pulp stimulation to obtain the dental pain threshold and tolerance, and to 24 h blood pressure monitoring together with a control group of 55 normotensives. Then the hypertensives were randomized to enalapril or losartan treatment and were re-evaluated (dental pain perception and ambulatory monitoring) after 8 weeks of the first treatment and after an additional 8 weeks of the second treatment. RESULTS: Untreated hypertensives showed a reduced perception to painful stimuli when compared with normotensives. A significant reduction of both pain threshold and tolerance was observed during the anti-hypertensive treatments (Friedman test: P = 0.007 and P = 0.006, respectively). Pain sensitivity was similar during the two treatments and it did not differ from pain sensitivity values of normotensive controls. ANCOVAs were computed to evaluate the relationship between anti-hypertensive agents and pain sensitivity, after controlling for blood pressure. A 24 h mean pressure served as covariate, removing any effect of blood pressure; a significant difference was observed entering both pain threshold and tolerance as dependent variables (F = 5.28, P = 0.0076; F = 8.16, P = 0.0007, respectively). CONCLUSIONS: Both the angiotensin converting enzyme inhibitor enalapril and the AT1 receptor blocking agent losartan acted similarly on pain threshold and tolerance, pain sensitivity being increased during the two anti-hypertensive treatments. The blood pressure reduction during drug assumption could not account for the pain sensitivity changes observed. The latter may be due to a specific pharmacodynamic mechanism mediated through angiotensin II AT1 receptors.

Relation of extent of nocturnal blood pressure decrease to cardiovascular remodeling in never-treated patients with essential hypertension.

The clinical significance of the extent of a decrease in nocturnal blood pressure (BP) and the resulting classification of hypertensives as "dipper" (decrease in BP >10% day BP) or "nondipper" (decrease in BP <10% day BP) has been questioned recently. The aim of our study was to evaluate if the extent of a nocturnal BP decrease, established on the basis of a single 24-hour BP monitoring, is related to cardiovascular remodeling in essential hypertension. We enrolled 253 never-treated essential hypertensives (24-hour BP > or = 140 and/or 90 mm Hg); for each patient we recorded 24-hour BP, left ventricular (LV) echocardiogram, Doppler transmitral flow velocities, and carotid-femoral pulse-wave velocities. A dipper BP profile was found in 161 patients, whereas 92 patients were nondippers. The 2 groups did not differ with regard to age, gender, body mass index, 24-hour and daytime BP, and 24-hour, daytime, and nighttime heart rate. All LV morphologic characteristics LV systolic and diastolic functional parameters, mitral Doppler-derived diastolic indexes, as well as carotid-femoral pulse-wave velocity, and aortic index distensibility were not significantly different between dippers and nondippers. The prevalence of LV hypertrophy and diastolic dysfunction was also similar between the 2 groups. The extent of a decrease in nocturnal BP did not correlate with any cardiovascular parameter. In conclusion, in never-treated hypertensives, the extent of a nocturnal BP decrease is not related to LV morpho-functional characteristics and aortic distensibility; therefore, the nondipping status established on the basis of a single 24-hour BP monitoring does not identify hypertensive patients with greater cardiovascular damage.

Hypertension-related hypoalgesia, autonomic function and spontaneous baroreflex sensitivity.

OBJECTIVE: The mechanisms involved in the relationship between pain perception and hypertension are poorly understood. This study has sought to investigate whether the spontaneous baroreflex sensitivity and the autonomic nervous system balance are related to hypertension-associated hypoalgesia. METHODS: In the morning, 73 untreated male subjects (45 hypertensives, 28 normotensives) were submitted to a simultaneous recording of electrocardiographic and blood pressure signals in resting condition. The tracings were analysed off-line to evaluate the spectral components of the low frequency (LF) and high frequency (HF) powers (autoregressive algorithm; LF/HF ratio used in subsequent analysis as an index of sympathovagal balance), and the alphaLF (alphaLF), an index of baroreflex sensitivity. After the rest period, the subjects underwent dental pain perception evaluation (pulpar tester: test current increasing from 0 to 0.03 mA, expressed in relative Units) to determine the dental pain threshold and tolerance. Afterwards, a 24-h ambulatory blood pressure monitoring was performed. RESULTS: A significant relationship was observed between alphaLF and pain threshold (r = -0.34; p = 0.003). When a multivariate analysis was computed to control for age, 24-h systolic pressure and LF/HF ratio, alphaLF was a predictive independent factor associated with pain threshold (model p = 0.019; r = -0.31; p = 0.025). Moreover, the 24-h systolic pressure was independently associated with pain threshold (model p = 0.019; r = 0.30, p = 0.031). The relationship between alphaLF and relative tolerance was not statistically significant. When the association between the LF/HF ratio and pain sensitivity was assessed as a secondary endpoint, no significant relationship was observed. Since no significant interaction was found, the effect of alphaLF and LF/HF ratio on pain perception was assumed to be similar in normotensive and hypertensive subjects. CONCLUSIONS: The relationship found between unstimulated baroreflex sensitivity and pain threshold suggests a modulation of pain perception by baroreflex pathways in hypertension-associated hypoalgesia. In a baseline condition, the autonomic nervous system balance does not seem to influence pain sensitivity.

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.