Effects of atorvastatin and rosuvastatin on thromboxane-dependent platelet activation and oxidative stress in hypercholesterolemia.

OBJECTIVES: We examined the time-dependent effects of atorvastatin and rosuvastatin on in vivo oxidative stress and platelet activation, to assess whether these phenomena are related to any pleiotropic effect of any statin or to their LDL-lowering effect. We also asked whether the presence of specific allele frequencies in carriers of the 3'UTR/lectin-like oxidized LDL receptor-1 (LOX-1) polymorphism may influence the effect of either statin. METHODS: We included 60 hypercholesterolemic subjects, previously screened for LOX-1 3'UTR polymorphism, randomized, according to genetic profile (15 T and 15 C carriers for each arm), to atorvastatin 20mg/day or rosuvastatin 10mg/day. RESULTS: After 8 weeks, atorvastatin and rosuvastatin were associated with comparable, significant reductions in LDL cholesterol (40.8% and 43.6%, respectively), plasma hs-CRP (9.5% vs. 13.8%), urinary 11-dehydro-thromboxane (TX) B(2) (38.9% vs. 27.1%) and 8-iso-prostaglandin (PG) F(2α) (39.4% vs. 19.4%). The impact of rosuvastatin or atorvastatin on CRP, 8-iso-PGF(2α), and 11-dehydro-TXB(2) did not differ according to the LOX-1 haplotype. On multiple regression analyses, only CRP and LDL were independent predictors of 11-dehydro-TXB(2), and only LDL was a significant predictor of 8-iso-PGF(2α). CONCLUSIONS: Both atorvastatin and rosuvastatin cause comparable reductions of thromboxane-dependent platelet activation, lipid peroxidation and inflammation. The presence of 3'UTR/LOX-1 polymorphism does not affect the changes induced by either statin.

Pro/Anti-inflammatory cytokine imbalance in postischemic left ventricular remodeling.

OBJECTIVES: Cytokines play an important role in left ventricular remodeling consequent to myocardial ischemia. The aim of this study was to correlate cytokine production and lymphocyte apoptosis to post-ischemic left ventricular remodeling in patients affected by acute myocardial infarction (AMI) undergoing primary cutaneous angioplasty (PCI). METHODS: In 40 patients, affected by AMI and undergoing PCI, we evaluated peripheral blood mononuclear cells (PBMCs), tumor necrosis factor-alpha (TNF-alpha) and interleukin 10 (IL10) production and apoptosis on day 1, day 3, day 7, 1 month and 6 months after PCI. Patients were divided into two subgroups of remodeling or not remodeling by echocardiographic criteria. RESULTS: In the subgroup of remodeling patients, at each timepoint TNF-alpha production was increased significantly in comparison with the subgroup of not remodeling patients. IL10 production was statistically lower in remodeling subjects than in not remodeling ones 1 and 6 months after reperfusion. There were no differences between the two groups as regards lymphomonocyte apoptosis. CONCLUSIONS: We found an increased production of pro-inflammatory cytokine TNF-alpha and a corresponding decrease of anti-inflammatory/regulatory cytokine IL10 in remodeling patients and we concluded that this cytokine imbalance resulted in pro-inflammatory effects which might contribute to the progression of left ventricular remodeling.

Cardiac dysautonomia and arterial distensibility in essential hypertensives.

INTRODUCTION: The central nervous system plays an important role in the regulation of blood pressure: the sympathetic nervous system may be a primary contributor to the development of some forms of essential hypertension. Hypertension is also associated with reduced distensibility of large arteries. The aim of our study is the evaluation of a correlation between cardiac dysautonomia (evaluated by means of heart rate variability [HRV]) and altered artery distensibility (evaluated by means of measurement of the time interval from the onset of the QRS wave and the detection of the last Korotkoff sound [QKD interval]). MATERIALS AND METHODS: HRV and QKD interval were evaluated in 23 patients (60.9+/-8.7 years) with untreated hypertension and in 20 control subjects (53.2+/-16.8 years). QKD interval and QKD(100-60) (that is QKD for a 100 mm Hg systolic blood pressure and 60 bpm heart rate) were measured during a 24-hours blood pressure monitoring. HRV was evaluated by means of a spectral method. Three main spectral components were distinguished: very low frequency (VLF), low frequency (LF) and high frequency (HF) component. RESULTS: Patients with reduced QKD(100-60) interval show reduced total power and spectral components values, with higher LF/HF ratio in basal conditions in comparison with control group. In patients with hypertension, QKD(100-60) values correlated significantly with LF/HF ratio (Spearman r=-0.551; p=0.006), HF spectral component (Spearman r=0.630; p=0.001) and total power (Spearman r=0.426; p=0.004). CONCLUSIONS: Our results suggest that sympathetic overactivity may be the contributor of reduced arterial distensibility observed in patients with essential hypertension.

Brain natriuretic peptide and other risk markers for outcome assessment in patients with non-ST-elevation coronary syndromes and preserved systolic function.

Several emerging cardiac markers constitute strong predictors among patients with coronary artery disease. In particular, brain natriuretic peptide (BNP), troponin T (TnT), and C-reactive protein (CRP) are related to increased risk of recurrent ischemic events and death. However, little is known about the utility of these biomarkers in combination. This study examined risk assessment in patients with coronary artery disease and preserved systolic function. We studied 208 consecutive patients (138 men, 70 women) with stable angina, unstable angina, and non-Q-wave myocardial infarction whose plasma BNP, TnT, and CRP levels were measured at hospital admission. All recruited patients underwent echocardiographic examination, and selective coronary angiography was performed. After adjusting for clinical presentation, age, gender, and common risk factors, BNP was demonstrated as a strong predictor of heart failure (6 months, odds ratio [OR] 2.03, 95% confidence interval [CI] 1.24 to 2.9, p <0.01; 12 months, OR 2.65, 95% CI 1.69 to 3.5, p <0.001) and mortality at 3, 6, and 12 months (p <0.001). BNP was also significantly related to extent of coronary artery disease and left anterior descending artery involvement (p <0.01). Patients with a BNP level >80 pg/ml in all 3 groups had a significantly poorer prognosis with increased incidence of heart failure and death. CRP was related to recurrent ischemic events (infarct or recurrent angina, OR 1.4, 95% CI 1.14 to 2.08, p <0.01) and was associated with major cardiac revascularization at 12 months (OR 1.51, 95% CI 1.29 to 1.73, p <0.001). TnT demonstrated a mild correlation with recurrent infarct or angina at 12 months (OR 1.1, 95% CI 0.96 to 1.22, p <0.05) but appeared related to multivessel coronary artery disease (OR 1.47, 95% CI 1.05 to 1.99, p <0.01). In conclusion, BNP appears to be associated with a long-term increased risk of mortality and heart failure in patients with apparently mild risk. BNP is also associated with a larger extent and greater severity of myocardial ischemia. Early BNP measurement could provide incremental information to TnT and CRP, and it may be the strongest independent predictor of cardiac outcome in subjects without left ventricular dysfunction or enlargement.

Takayasu's arteritis: a review of the literature.

Takayasu's arteritis is a rare, idiopathic, chronic inflammatory disease with cell-mediated inflammation, involving mainly the aorta and its major branches. It leads to stenosis, occlusion or aneurysmal degeneration of large arteries. The clinical presentation is characterised by an acute phase with constitutional symptoms, followed, months or years later, by a chronic phase in which symptoms relate to fibrosis or occlusion of vessels. Angiography is the gold standard for diagnosis and for topographical classification and it correlates with symptoms and prognosis. Here we focus on the pathophysiology, clinical and angiographical classification, diagnostic assessment and therapeutic approach of Takayasu's arteritis.

3'UTR/T polymorphism of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is associated with modified anti-platelet activity of atorvastatin in hypercholesterolemic subjects.

Oxidized-low density lipoproteins (ox-LDL) and the specific receptor LOX-1 are involved in atherogenesis and atherothrombosis. LOX-1 downregulation is associated with the anti-platelet action of atorvastatin. 3'UTR/T LOX-1 polymorphism has been associated with increased risk of coronary artery disease. This study was planned to determine whether LOX-1 genetic variations could affect anti-platelet action of atorvastatin. We studied by platelet P-selectin (P-sel), CD36 and LOX-1 expression (cytofluorimetric detection) whether differences in cellular activation could be suitable in 109 3'UTR/T carriers out of 201 hypercholesterolemic subjects treated with atorvastatin 20mg/day. Hyperactivated platelets (P-sel in resting cells and % variation upon thrombin activation, p<0.001) were detected at baseline in patients without significant differences between T or C carriers. P-sel and platelet-associated ox-LDL, were significantly decreased (all p<0.001) in C carriers after one week of treatment before LDL reduction. In 3'UTR/T carriers P-sel was reduced (p<0.01) after 6 weeks of treatment according to LDL and ox-LDL reduction. In 3'UTR/T carriers atorvastatin reduced platelet activity by LDL and ox-LDL lowering and not by rapid CD36 and LOX-1 downregulation as in C carriers. Such data suggest that in T carriers LDL lowering is needed to achieve anti-platelet action.

Different effect of statins on platelet oxidized-LDL receptor (CD36 and LOX-1) expression in hypercholesterolemic subjects.

Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular mortality by decreasing cholesterol as well as by non-lipid-related actions. Oxidized low-density lipoproteins (ox-LDL) are pro-atherogenic molecules and potent platelet agonists. CD36 and lectin-like ox-LDL receptor-1 (LOX-1) are specific ox-LDL receptors also expressed in platelets. This study was planned to address whether treatment with atorvastatin 10 mg/day, pravastatin 40 mg/day or simvastatin 20 mg/day could affect platelet CD36 and LOX-1 expression. Twenty-four patients for each treatment were evaluated after 3, 6, and 9 days and at 6 weeks for complete lipid profile (chromogenic), ox-LDL (ELISA), platelet P-selectin (P-sel), CD36, LOX-1 (FACS), and intracellular citrullin recovery (iCit) (HPLC). Data show hyperactivated platelets (P-sel absolute values, percent variation in activated cells, all p < 0.001), and CD36 and LOX-1 overexpression (all p < 0.001) in patients at baseline. P-sel, CD36, and LOX-1 were significantly decreased by atorvastatin and simvastatin (all p < 0.01) and related with iCit increase (r = 0.58, p < 0.001) and platelet-associated ox-LDL (r = 0.51, p < 0.01) at 9 days. Pravastatin reduced LOX-1 and P-sel (p < 0.05) at 6 weeks in relation with decreased LDL and ox-LDL (r = 0.39, p < 0.01 and r = 0.37, p < 0.01, respectively). These data suggest that atorvastatin and simvastatin reduce platelet activity by exposure of CD36 and LOX-1 before significant LDL reduction, whereas pravastatin action is detected later and in relation with LDL and ox-LDL lowering. Rapid and consistent reduction of CD36 and LOX-1 could be considered a direct anti-atherothrombotic mechanism related to the role of ox-LDL in platelet activation, platelet-endothelium interactions, and NO synthase activity.

[Immune factors in atherosclerosis]. / I mediatori della risposta immunitaria nell'aterosclerosi.

Immune cells play an important role in atheromatous plaque formation and progression and in the phase of "active plaque" and of the consequent clinical manifestations. Endothelial dysfunction is the first determinant step in atherogenesis by inducing the alteration of vasodilating and antithrombotic properties of the endothelium and of its permeability to lipoproteins. Circulating monocytes are recruited and internalized and lipoproteins are stored in the subendothelial area where they undergo oxidation (oxidized LDL) and are removed by macrophages by means of non-autoregulated scavenger receptors (foam cells). Foam cells are able to express surface receptors and to produce soluble mediators (interleukin-1, tumor necrosis factor-alpha, monocyte chemotactic protein 1) which attract other monocytes, activate endothelial cells and smooth muscle cells. Lymphocytes too are present in these first stages of atherogenesis. If the injurious agents are not removed or nullified by the inflammatory response and the inflammation progresses, the response changes from a protective to an injurious response. Recruitment of monocytes and lymphocytes occurs as a result of the up-regulation of adhesion molecules on both the endothelium and the leukocytes and the plaque progresses to an advanced lesion. Finally the activation of monocytes and T cells induces the plaque activation and rupture in presence of inducing agents such as oxidized LDL. CD4 lymphocytes are common components of atheroma and are mainly localized at the sites of rupture in strict contact with macrophages and smooth muscle cells which express activation surface molecules and which are able to process and to present the antigen to T cells. Activated lymphocytes produce proinflammatory cytokines as interferon-gamma which is able to amplify the inflammatory response but also interleukin-10 which seems to possess a regulatory effect. Activated macrophages release metalloproteinases and other proteolytic enzymes which cause degradation of the matrix, thinning of fibrous cap and plaque destabilization. Both T cells and macrophages produce cytotoxic factors which contribute to the apoptosis. The process may be potentiated by the activation of platelets, tissue factor, coagulation-fibrinolytic system which can contribute to thrombus formation, plaque rupture and artery occlusion.

[Hypogammaglobulinemia and thymoma (Good's syndrome): a case report and a literature review]. / Ipogammaglobulinemia associata a timoma (sindrome di Good): descrizione di un caso clinico e revisione della letteratura.

Good's syndrome is a rare adult-onset immunodeficiency disease characterized by hypogammaglobulinemia and thymoma. A 61-year-old male patient was diagnosed with Good's syndrome after a 2-year history of recurrent respiratory infections. Chest X-ray and chest computed tomography scan showed a mediastinal mass which was surgically removed. Histology revealed a thymoma. Following surgery he presented with recurrent respiratory and urinary tract infections and with esophageal candidiasis, even though his overall conditions dramatically improved after starting treatment with an appropriate dosage of intravenous immunoglobulins. Laboratory tests showed hypogammaglobulinemia, mild neutropenia, lymphopenia with no B cells, decreased CD4+ lymphocytes with an inverted CD4/CD8 ratio and increased interleukin-4-producing CD4+ lymphocytes, suggestive of an excessive Th2 response.

Mechanisms for antiplatelet action of statins.

Hydroxymethyl-glutaryl coenzyme A reductase inhibitors (statins) offer important benefits for the large populations of individuals at high risk for coronary heart and cerebrovascular disease. the overall clinical benefits observed with statin therapy appear to be greater than what might be expected from changes in lipid profile alone, suggesting that the beneficial effects of such drugs may extend beyond their effects on serum cholesterol. Platelet hyperactivity is a key step in atherothrombosis and experimental data suggest that statins could exert an antiplatelet effect which could be involved in their protective action. In the present review we report of the major studies in humans showing the effect of statins on platelets, especially by the more sensitive methods to explore platelet function such as cytofluorymetric detection of specific proteins. Moreover we describe the putative mechanisms involved in platelet deactivation with particular regard to the effects related to cholesterol reduction or beyond lipid-lowering. Indeed, data from several studies suggest some differences among compounds in terms of timing of action by modulation of several activating pathways which could take part either in the early, cholesterol-lowering independent, effects in the acute phase of vascular disease or during chronic treatment.

Takayasu's arteritis: case report of a patient with recurrent subclavian steal syndrome.

Takayasu's arteritis is a chronic inflammatory disease of unknown origin in which cell-mediated inflammation involves large arteries progressing from the adventitia to the intima, until the lumen of the vessel is narrowed. Here we report a case of a 48-year-old female patient who was diagnosed with Takayasu's arteritis 6 years ago. At that time, because of severe involvement of both the right and left carotid arteries, she underwent application of a Hemashield vascular prosthesis, including the ascending aorta, left common carotid artery, and right common carotid artery. Due to the fact that there were also bilateral subclavian artery stenoses, the application of the prosthesis induced bilateral subclavian steal syndrome. This year she developed stenosis of the prosthesis and the bilateral subclavian steal syndrome disappeared until she underwent percutaneous transluminal angioplasty, which restored cerebral flow through the carotid arteries after which the subclavian steal syndrome reappeared.

Effects of carvedilol therapy on restrictive diastolic filling pattern in chronic heart failure.

BACKGROUND: Carvedilol therapy during congestive heart failure demonstrated a good efficacy in mortality rate reduction and in improvement of left ventricular (LV) systolic performance. However, currently there is not any finding about the drug's effect on diastolic filling. The aim of this study was to evaluate the effects of beta-blocker treatment on LV diastolic function with an eco-pulsed Doppler ultrasound scanning examination at transmitral level in a group of patients who were affected by heart failure with a restrictive filling pattern. METHODS: We studied 27 patients with idiopathic or ischemic dilated cardiomyopathy with LV severe systolic disfunction (ejection fraction <35%). Fourteen patients were randomized to receive carvedilol treatment (carvedilol group), and 13 patients continued to receive standard therapy with angiotensin-converting enzyme inhibitors, diuretics, and vasodilators (placebo group). All patients underwent an echo-Doppler ultrasound scanning examination at the beginning of the study and after 4 and 12 months of treatment. RESULTS: In the carvedilol group, we found a progressive improvement of Doppler ultrasound scanning parameters after 4 months, with a significant increase of A wave (P <.005), deceleration time (DT; P <.02) and isovolumetric relaxation time (IVRT; P <.02). These improvements were confirmed after 1 year of follow-up, whereas patients in the placebo group did not shown any significant modifications. After 1 year, the differences in these groups were more significant for A wave (39 +/- 4 cm/sec carvedilol group vs 30 +/- 4 cm/sec placebo group; P <.0001), for E/A ratio (1.8 +/- 0.2 carvedilol group vs 2.6 +/- 0.5 placebo group; P <.0002), for DT 1(40 +/- 16 msec carvedilol group vs 112 +/- 13 msec placebo group; P <.001), and for IVRT (74 +/- 8 msec carvedilol group vs 57 +/- 7 mesc placebo group; P <.0002). These changes seem to happen before systolic and morphological modifications. CONCLUSION: Our results show that carvedilol therapy is a means of modifying parameters of diastolic filling favorably in patients with heart failure. These effects seem to be independent of those of systolic function. The improvement of systolic performance occurs after 1 year of treatment. The restrictive filling pattern, related to an unfavorable prognosis, changes toward pseudonormal or altered relaxation pattern during carvedilol therapy. Further investigations with a greater sample size will be necessary to confirm our findings.

[Lymphocyte apoptosis in non-ST segment elevation acute myocardial infarction ]. / L'apoptosi linfocitaria nell'infarto miocardico acuto senza sopraelevazione del tratto ST.

It is well known that lymphocytes play a major role in coronary plaque destabilization in acute coronary syndromes. The aim of this study was to evaluate circulating lymphocyte apoptosis in patients with non-ST elevation myocardial infarction (NSTEMI) in comparison with subjects with stable angina and with healthy controls. We considered spontaneous lymphomonocyte apoptosis (evaluated by ELISA), interleukin (IL)-2 production (evaluated by ELISA), Fas expression on T cells (evaluated by flow cytometry) and Fas ligand mRNA (evaluated by reverse transcriptase polymerase chain reaction), as well as Fas functionality. To evaluate T-cell activation, we also investigated T-cell subpopulations (CD4/CD8 ratio), T-cell surface HLA-DR and CD69 expression (evaluated by flow cytometry) in blood taken within 6 hours from onset of NSTEMI. Spontaneous apoptosis was significantly increased in NSTEMI patients in comparison with the two control groups and it was associated with an increased expression of Fas, an increased susceptibility to the Fas agonist (CH-11) and a normal production of IL-2 in cell cultures. We also found a significant increase of HLA-DR+ CD3+ and CD69+ CD4+ cells in NSTEMI patients. These data suggest that the enhanced apoptosis is due to a mechanism of "active" antigen-driven death, induced by the expression of death cytokines and not by the failure of cell growth factors. We conclude that in case of NSTEMI peripheral lymphocytes are activated and undergo an enhanced programmed cell death due to activation mechanisms. It is likely that lymphocyte activation occurs before the onset of acute ischemia and contributes to the plaque rupture and to the myocardial ischemic insult.

Platelet hyperactivity after statin treatment discontinuation.

Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular events by cholesterol lowering as well as by non-lipid related actions. Among them, the modulation of platelet activity could play a relevant role in vascular protection. Furthermore withdrawal of statins has been associated with increased cardiovascular event rate. The aim of our study was to evaluate platelet activity after cerivastatin discontinuation in eighteen subjects that did not accept other drugs and in sixteen subjects continuing treatment with simvastatin. Fourteen subjects at the end of the discontinuation period decided to receive other drugs (simvastatin) and they were evaluted six weeks later. We measured complete lipid profile by the chromogenic method (LDL-C was calculated); oxidized-LDL (ox-LDL; ELISA), platelet P-selectin (P-sel) expression (flow cytometry detection), platelet aggregation (% change of transmitted light), intracellular citrullin production (iCit; HPLC) as an indicator of intracellular NO synthase activity at baseline and 7, 14, 28, 60 days after statin discontinuation. P-sel expression and platelet aggregation were increased at 14 days (p < 0.001 and p < 0.05) in association with raised ox-LDL (r = 0.30, p < 0.05) and decreased iCit (r = 0.53, p < 0.01). Increased LDL-C was related to P-sel and platelet aggregation at 28 days (r = 0.30, p < 0.05). Subjects continuing statin treatment had no significant changes of P-sel at 28 (p = 0.221) and 60 days (p = 0.238). Subjects treated with simvastatin after 60 days of diet showed a significant reduction of P-sel and platelet aggregation after six weeks of treatment (p < 0.01). Our data suggest a platelet hyperactivation state in the second week after statin discontinuation which is partially related to raised LDL-C. Such a finding could participate in the increased cardiovascular event rate after statin discontinuation.

Dyslipidemias and fibrinolysis.

BACKGROUND: The relation between fibrinolysis and cardiovascular disease is an open debate. Fibrinolysis is related to endothelial function and presents many molecular links with platelet and coagulation activity. Furthermore, reduced fibrinolysis has been reported in several dysmetabolic conditions. METHODS: To detect mechanisms linking dyslipidemias and fibrinolysis we evaluated 75 subjects (42 males, 33 females, 20 hypercholesterolemic, 20 hypertriglyceridemic or 20 with mixed hyperlipoproteinemia, 15 with isolated low HDL-cholesterol). Plasminogen activator inhibitor (PAI)-1, tissue-type plasminogen activator activity and plasmin-antiplasmin complexes (PAP) were determined at baseline and after the venous occlusion test. We also measured D-dimer, lipid pattern, soluble E-selectin, platelet surface P-selectin, prothrombin fragments 1 + 2 (F1 + 2), lipoprotein(a), factor VII, von Willebrand factor, plasma insulin, fibrinogen, homocysteine, thrombin activable fibrinolysis inhibitor (TAFI) activity, thrombomodulin, factor XIII, urokinase-type plasminogen activator. RESULTS: Hypertriglyceridemic patients were found to have lower PAP and D-dimer and higher PAI-1 serum levels (baseline and venous occlusion test, p < 0.001 and p < 0.01) compared to hypercholesterolemic and control subjects (p < 0.01, p < 0.001). P-selectin, F1 + 2 and TAFI were significantly increased only in hypercholesterolemic subjects (p < 0.001) and associated with reduced PAP and D-dimer, showing a linear relation with LDL-cholesterol levels (p < 0.01, r = -0.62 and p < 0.01, r = -0.59). PAI-1 activity was not different with respect to controls (baseline p = 0.59, venous occlusion test p = 0.42). Serum levels of von Willebrand factor were significantly increased in hypertriglyceridemic/low HDL subjects compared to hypercholesterolemics (p < 0.01). CONCLUSIONS: Impaired fibrinolysis in subjects with hypertriglyceridemia/low HDL-cholesterol is associated with increased serum levels of PAI-1 whereas enhanced thrombin generation and TAFI hyperactivity are the main findings in hypercholesterolemia. Such data may suggest the opportunity of evaluating several fibrinolytic factors when studied as prognostic factors in diverse dyslipidemias.

Transmitral and pulmonary venous flow study in elite male runners and young adults.

BACKGROUND: Even if diastolic function has been assessed in athletes by analysis of transmitral Doppler flow, no one has studied pulmonary venous flow in this population. The aim of this study was to establish if the physiological adaptations following a prolonged physical training could influence the diastolic function in a professional Olympic male runner group. METHODS: From February to December 1999 we studied 25 athletes (Group I) during the period of maximal training compared with 18 age- and sex-matched healthy sedentary subjects (Group II). We used mono- and bidimensional Echocardiography to assess left ventricular structure and systolic function. The diastolic function was evaluated by Doppler method assessing transmitral and venous pulmonary flow. RESULTS: From the comparison between the two groups, we found great differences in the interventricular septum and the posterior wall thickness; the analysis of the systolic function demonstrated a significant increase in ejection fraction, stroke volume, left ventricular mass, and end diastolic volume in the athletes' population. Fluximetric study showed that ventricular diastolic function is not influenced by hypertrophy: indeed, Doppler evaluation of the transmitral flow showed a bigger velocity of the E wave, similarly, when we assessed pulmonary venous flow, we found faster retrograde Ar wave in group I. CONCLUSIONS: Our data indicate that diastolic function remains normal or improves in some cases after physical training; left ventricular hypertrophy and concentric remodeling do not involve diastolic changes like hypertrophic and hypertensive heart diseases.