Changes in natriuretic peptide and cytokine plasma levels in patients with heart failure, after treatment with high dose of furosemide plus hypertonic saline solution (HSS) and after a saline loading.

BACKGROUND AND AIMS: Neurohormonal activation and inflammation characterizes heart failure, relates to outcome, and is a therapeutic target. The aim of this study was to evaluate the effects of high-dose furosemide plus small-volume hypertonic saline solutions (HSS) on natriuretic peptides and immuno-inflammatory marker levels and to analyze, after treatment, the response to acute saline loading. METHODS AND RESULTS: 120 patients with heart failure treated with high-dose furosemide+HSS (Furosemide/HSS group) were matched with: 30 subjects with heart failure treated with high-dose furosemide (furosemide group), 30 controls with asymptomatic left-ventricular dysfunction (ALVD) (asymptomatic group) and 30 controls without heart failure or ALVD (Healthy group). We evaluated plasma levels of natriuretic peptides and cytokine levels in baseline, after treatment and after acute saline load. After treatment with high-dose furosemide+HSS compared to treatment with furosemide alone we observed a significant lowering of ANP [96 (46.5-159.5) pg/ml vs 64 (21-150) pg/ml], BNP [215.5 (80.5-487) pg/ml vs 87 (66-141.5) pg/ml], TNF-α [389.5 (265-615.5) pg/ml vs 231.5 (156-373.5) pg/ml], IL-1ß [8 (7-9) pg/ml vs 4 (3-7) pg/ml], IL-6 [5 (3-7.5) pg/ml vs 3 (2-4) pg/ml], plasma values and after an acute saline load, a lower percentage change of ANP (+18.6% vs +28.03% vs +25% vs +29%), BNP (+14.5% vs +29.2% vs +30% vs +29.6%) TNF-α (+10.8% vs +15.8% vs +17.8% vs +11.3%), IL-1ß (+20% vs 34.4% vs 40% vs 34.4%) compared to control groups. CONCLUSIONS: Treatment with HSS could be responsible for a stretching relief that could influence natriuretic and immuno-inflammatory markers.

Efficacy and safety of long-term ezetimibe/simvastatin treatment in patients with familial hypercholesterolemia.

AIM: Patients with heterozygous familial hypercholesterolemia (FH) have an increased risk of premature myocardial infarction, stroke, and surgical revascularization, and an increased rate of progression of carotid intima-media thickness (IMT). The most commonly used drugs for cholesterol lowering, statins, have a limited action in these patients. Ezetimibe, a novel compound, selectively inhibits cholesterol uptake and when associated with statins has an additional low-density lipoprotein cholesterol (LDL-C) reducing effect. The aim of this study is to evaluate the effects of long-term combined Ezetimibe/Simvastatin (EZE/SIMVA) therapy (30 months) on the lipidic pattern, inflammatory markers, and carotid IMT in patients with FH subdivided into two groups: one with a history of acute myocardial infarction (IMA) and the other with carotid atherosclerotic plaques but no history of cardiovascular events. METHODS: All patients enrolled in this study (group A: patients with a history of IMA; group B, patients with carotid lesions but no history of cardiovascular events) were submitted to a 6-week period of isocaloric diet and to a 4-week lipid-lowering wash-out period before study entry. After the wash-out period at baseline (time 0) and then every two months total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B and A1 were determined. LDL-C levels were calculated. Fibrinogen and hs-CRP at baseline and at 6, 18, and 30 months were determined. All patients were submitted to an ultrasonographic evaluation of the carotid intima-media thickness at baseline, 18 and 30 months. The scheduled duration time of the study was 30 months. At the beginning of the study all patients were assigned to receive the combined EZE/SIMVA treatment 10/20 mg per day. After two months, patients who had not reached the respective LDL-C targets proposed by NCEP ATPIII (<70 mg/dL for patients with a history of IMA and <100 mg/dL for patients with carotid lesions) were assigned to receive EZE/SIMVA 10/40 mg per day and, after four months, patients who had not reached the respective LDL-C targets were assigned to receive EZE/SIMVA 10/80 mg per day. RESULTS: At the end-point, significant reductions (P<0.001) of about 70% in LDL-C, of 57% in total cholesterol (TC), of 46% in Apo-B, and of 46% in hs-C-reactive protein (hs-CRP) were observed in both groups compared to baseline. Also, triglyceride and fibrinogen levels were significantly (P<0.01) reduced, respectively by 26% and 15% compared to baseline. The EZE/SIMVA association resulted in significant increases in HDL-C (P<0.01) of 11% and in Apo-A1 (P<0.05) by 9% and in significant (P<0.001) reductions of the mean of the carotid IMT in both groups. The EZE/SIMVA treatment was generally well-tolerated, with a safety profile on laboratory parameters. During the 30-month scheduled period of the study, no patient in either group presented any further cardiovascular events. CONCLUSION: In patients with FH, combined EZE/SIMVA treatment resulted in a significant LDL-C lowering, achieving the goals proposed by NCEP ATP III, in a significant improvement of all the lipidic and inflammatory patterns, and above all in a progressive decrease of the carotid IMT. Although the results of ongoing randomized controlled trials are required before making any definitive conclusions, our results support the hypothesis of stabilizing effect of EZE/SIMVA on the atherosclerotic disease both in primary and in secondary prevention.

Effect of dual blockade of renin-angiotensin system on TGFbeta1 and left ventricular structure and function in hypertensive patients.

The effects of 24 weeks losartan and ramipril treatment, both alone and in combination, on left ventricular mass (LVM), circulating transforming growth factor beta1 (TGFbeta1), procollagen type I (PIP) and III (PIIIP), have been evaluated in hypertensive (HT) patients. A total of 57 HT with stage 1 and 2 essential hypertension were included. After 4 weeks run in, a randomized double-blind, three arms, double dummy, independent trial was used. All HT patients were randomly allocated to three treatment arms consisting of losartan (50 mg/daily), ramipril (5 mg/ daily) and combined (losartan 50 mg/daily + ramipril 5 mg/daily) for 24 weeks. TGFbeta1, PIP and PIIIP, LVM, LVM/h(2.7) and other echocardiographic measurements, blood urea nitrogen, creatinine and clearance and potassium were determined after run in and after 24 weeks. All groups were comparable for gender, age, body mass index, blood pressure and LVM. The prevalence of baseline left ventricular hypertrophy (LVH) was not significantly different among three groups. At the end of treatment, a significant (P<0.05) reduction in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), TGFbeta1, PIP, PIIIP, LVM and LVM/h(2.7) was observed in all groups. The absolute and percent reduction in TGFbeta1 and LVM/h(2.7) were significantly higher in combined than losartan or ramipril groups and also in HT patients with LVH. No significant change in absolute and percent reduction of SBP, DBP and MBP were found. Our data indicate an additional cardioprotective effect of dual blockade of renin-angiotensin in HT patients.

Obesity: a main factor of metabolic syndrome?

The metabolic syndrome (MS) is a common metabolic disorder that has been recently related to the increasing prevalence of obesity. The disorder is defined in various ways, but in the near future a new definition(s) will be applicable worldwide. The pathophysiology has been largely attributed, in the past years, to insulin-resistance, even if several epidemiological and pathophysiological data are attractive to indicate visceral obesity as a main factor in the occurrence of the MS, promoting new definitions and re-evaluation of the pathogenesis of this syndrome. In this review, we have analyzed the role of visceral obesity in the new definition of the MS such as the pathophysiological role of the abnormal fat distribution in the occurrence of this syndrome. In view of this, relationships between visceral obesity, free fatty acids, dyslipidaemia and insulin-resistance have been reported. In addition, the effects of some adipocytokines and other proinflammatory factors produced by fat accumulation on the appearance of the MS have been also emphasized. Finally, according to recommendations of several international societies, the role of the life-style change and of the weight loss in the prevention and treatment both of obesity and of other associated risk factors has been analyzed.

Effects of moderate Sicilian red wine consumption on inflammatory biomarkers of atherosclerosis.

OBJECTIVE: The aim of the study is to evaluate the effect of moderate Sicilian red wine consumption on cardiovascular risk factors and, in particular, on some inflammatory biomarkers. METHODS: A total of 48 subjects of both sexes who were nondrinkers or rare drinkers of moderate red wine were selected and randomly subdivided into two groups assigned to receive with a crossover design a Sicilian red wine (Nero d'Avola or Etna Torrepalino) during meals: Group A (n = 24), in whom the diet was supplemented for 4 weeks with 250 ml/day of red wine, followed by 4 weeks when they returned to their usual wine intake; and Group B (n = 24), in whom the usual wine intake was maintained for 4 weeks, followed by 4 weeks when the diet was supplemented with 250 ml/day of red wine. The following were values measured in all tests: blood glucose, total and HDL-cholesterol and triglycerides, LDL-cholesterol, LDL/HDL ratio, apolipoproteins A1 and B, Lp(a), plasma C-reactive protein, TGFbeta1, D-Dimer, Factor VII , PAl Ag, t-PA Ag, fibrinogen, oxidized LDL Ab, total plasma antioxidant capacity. RESULTS: At the end of the red wine intake period, LDL/HDL, fibrinogen, factor VII, plasma C-reactive protein and oxidized LDL Ab were significantly decreased, while HDL-C, Apo A1,TGFbeta1, t-PA, PAI and total plasma antioxidant capacity were significantly increased. CONCLUSIONS: Our results show a positive effect of two Sicilian red wines on many risk factors and on some inflammatory biomarkers, suggesting that a moderate consumption of red wine in the adult population is a positive component of the Mediterranean diet.

Left ventricular filling abnormalities and obesity-associated hypertension: relationship with overproduction of circulating transforming growth factor beta1.

This study has been designed to evaluate the relationship among transforming growth factor beta1 (TGFbeta1) and some measurements of diastolic function in a population of hypertensive subjects with normal left ventricular ejection fraction. We studied 67 hypertensive outpatients who according to their BMI levels were subdivided into three groups: lean (L), overweight (OW) and obese (OB) hypertensives (HT). Circulating TGFbeta1 and M- and B-mode echocardiography was determined. All hypertensives were further subgrouped, according to European Society of Cardiology Guidelines, into two subsets of patients with normal diastolic function or with diastolic dysfunction. Prevalence of left ventricular hypertrophy (LVH) was determined in all the groups. TGFbeta1, left ventricular mass (LVM), LVM/h(2.7), E-wave deceleration time and isovolumic relaxation time (IVRT) were significantly (P < 0.005) higher and E/A velocity ratio was significantly (P < 0.05) lower in OW-HT and OB-HT than in L-HT. Prevalence of LVH was significantly higher (P < 0.03) in group OB-HT than in L-HT. TGFbeta1 (P < 0.004), LVM/h(2.7) (P < 0.001) and prevalence of LVH were (P < 0.01) significantly higher in hypertensives with diastolic dysfunction than hypertensives with normal diastolic function. TGFbeta1 levels were positively correlated with BMI (r = 0.60; P < 0.0001), LVM/h(2.7) (r = 0.28; P < 0.03), IVRT (r = 0.30; P < 0.02) and negatively with E/A ratio (r = -0.38; P < 0.002) in all HT. Multiple regression analysis indicated that TGFbeta1, BMI and IVRT were independently related to E/A ratio explaining 71% of its variability (r = 0.84; P < 0.0001). This relationship was independent of LVH, age and HR suggesting that TGFbeta1 overproduction may be considered a pathophysiological mechanism in the development of left ventricular filling abnormalities in obesity-associated hypertension.

Early carotid atherosclerosis and cardiac diastolic abnormalities in hypertensive subjects.

Despite the fact that it is known that hypertension may be associated to early atherosclerosis manifestations, few data are to date available on the relationship between early carotid abnormalities and left ventricular diastolic dysfunction. To address this issue, 142 hypertensive patients (64 females and 78 males) younger than 55 years, at the first diagnosis of mild-to-moderate essential hypertension (WHO/ISH criteria), were selected from a database consisting of 3541 subjects referred to ultrasound cardiovascular laboratory in the last 5 years. Carotid intima-media thickness (IMT) was detected by high-resolution vascular ultrasound and left ventricular structure and function by the use of Doppler echocardiography. According to carotid IMT values, all patients were subgrouped into two groups consisting of 89 (62.6%) pts with IMT > or = 1 mm (A) and 53 (37.4%) pts with IMT < 1 mm (B). Our results show that isovolumic relaxation time (IVRT), deceleration time of E velocity (EDT) and left ventricular relative wall thickness (LV-RWT) were significantly (P < 0.05) higher in group A (IVRT 112 +/- 8.9 ms; EDT 288 +/- 21.8 ms; LV-RWT 0.40 +/- 0.08) than in group B (IVRT 92.3 +/- 4.6 ms; EDT 203.3 +/- 27.01 ms; LV- RWT 0.37 +/- 0.06). Moreover, the prevalence of left ventricular hypertrophy (LVH) was significantly (P < 0.01) higher in group A (30/89; 33.7%) than in group B (8/53; 15%). A positive correlation (P < 0.001) between IMT, EDT and IVRT was found only in hypertensives without LVH. These results are consistent with the indication that IMT evaluation has to be recommended both in hypertensive patients with LVH and in those without LVH, but with left ventricular diastolic dysfunction. This approach might improve the prognostic stratification of hypertensive subjects and it might be suitable to recognize the subset of patients at a higher risk of cardiovascular disease or events early.

Relationship between transforming growth factor beta1 and progression of hypertensive renal disease.

In this study the role of circulating transforming growth factor beta1 (TGFbeta1) on progression of renal hypertensive disease has been investigated. Fifty consecutive outpatients with essential hypertension were enrolled and divided into three groups, according to their urinary albumin excretion (UAE). Group A comprised 10 hypertensives with UAE 20 < 300 mg/24 h (microalbuminuric group); Group C encompassed 19 hypertensives with UAE >or= 300 mg/24 h (proteinuric group). In all patients UAE by immunonephelometric assay, circulating TGFbeta1 by a solid phase specific sandwich ELISA technique, BUN and creatinine by routine laboratory methods were determined. In addition, left ventricular telediastolic internal diameter, interventricular septum diastolic (IVSTd), posterior wall thickness, total and normalised to height(2.7) left ventricular mass, relative wall thickness and left ventricular ejection fraction by M-B Mode echocardiography were calculated. Our results indicated that TGFbeta1 levels were significantly (P < 0.05) higher in Group B and C than Group A and in Group C than Group B. In addition IVSTd values were significantly (P < 0.05) higher in both Group B and C than Group A. An evident, but not significant, higher prevalence of subjects with left ventricular hypertrophy were observed in Group C as compared with other groups. In all hypertensive subjects TGFbeta1 correlated directly with UAE (P < 0.0001) but not with BMI, LVM/h(2.7) and mean blood pressure. Our data indicated that TGFbeta1 might be considered a useful marker to evaluate the severity and progression of hypertensive renal disease. Additional long-term clinical data are needed to evaluate whether inhibition of TGFbeta1 system may prolong the time to the ESRD in hypertensive patients.

Effect of long-term losartan administration on renal haemodynamics and function in hypertensive patients.

In this study the efficacy and safety of long-term losartan administration on renal haemodynamics were evaluated in mild to moderate hypertension. After a run-in period with placebo, 18 hypertensives without renal or cardiovascular disease were allocated to losartan (50 mg/die for one year) treatment. Renal haemodynamic measurements included renal plasma flow (ERPF) and glomerular filtration rate (GFR) by standardized radioisotope study. Effective renal blood flow (ERBF), filtration fraction (FF), and renal vascular resistance (RVR) were also calculated. Blood pressure was evaluated monthly, whereas renal haemodynamics and function were detected at baseline and after 6 and 12 months of losartan administration. Losartan induced a significant (p < 0.001) decrease in SBP, DBP, and MBP versus baseline values both at 6 months and at 12 months. In addition a significant decrease in RVR (p < 0.001) and in FF (p < 0.05) was also seen. In addition RVR values at 1 year of treatment were higher than their values at 6 months, but this difference was not significant. Our data indicated that long-term control in blood pressure induced by losartan administration was associated with a maintained renal function after 6 months of treatment, but these favourable effects were attenuated after 1 year of treatment.

Effects of a short-term hypoenergetic diet on morphofunctional left ventricular parameters in centrally obese subjects. An echocardiographic study.

BACKGROUND: We aimed to study centrally obese subjects without other diseases, to establish whether a short-term hypoenergetic balanced regimen is able to positively modify left ventricular (LV) patterns. METHODS: We studied 32 obese subjects (out of 52 recruited for this study) with central fat distribution and without associated diseases. Each subject had undergone a moderately hypoenergetic diet for a four-month follow-up period and had a regular loss in weight. Some relevant clinical and echocardiographic parameters were evaluated. Baseline data and those evaluated at the end of the follow-up period were used for outcome analysis. RESULTS: We found a considerable reduction in LV mass and other LV structural parameters including relative wall thickness (RWT). Moreover, we found an improvement of both LV ejection fraction and filling parameters. As regards the relation ship between parameter changes, LV mass was correlated to LV internal diameter and mainly to LV wall thickness. LV mass change was also correlated to a reduction of diastolic BP and RWT. Only improvements in LV filling were correlated to WHR reduction. None of the changes in cardiac variables resulted significantly correlated to BMI change. Other interesting correlations are reported in the text. CONCLUSIONS: Our study points out that improvements in LV structure and function are rapidly possible with a moderately hypoenergetic regimen in obese otherwise healthy subjects. The main changes were those in LV wall thickness even if a more complex cardiovascular adjustment was recognised. All this could be very important to possibly prevent future cardiovascular events (including heart failure), so largely linked to obesity of central type.

Early markers of cardiovascular damage in obese subjects.

Cardiovascular disease remains a frequent cause of morbidity and mortality in industrialized countries, particularly in subjects with hypertension, diabetes mellitus, and dyslipidemia, conditions frequently associated with central obesity. Identification of early morphological and/or functional alterations of the cardiovascular system may help target individuals most likely to benefit from preventive measures. The literature data and our own experience suggest that parameters that are direct expressions of cardiovascular damage, can be identified at an early stage. For example, diastolic dysfunction may precede the clinical expression of several cardiac diseases, left ventricular hypertrophy is one of the first manifestations of cardiac involvement in hypertension, central obesity and diabetes mellitus, and a carotid plaque may point to concomitant coronary artery disease. Other early manifestations of cardiovascular involvement are microalbuminuria and endothelial dysfunction. Insulin resistance and alterations of the renin-angiotensin-aldosterone system play an important physiopathogenic role in the development of cardiovascular damage in obese subjects, and their association with risk and cardiovascular disease has been confirmed in numerous studies. Since all these changes generally precede overt clinical manifestations and are closely related to cardiovascular morbidity, they may help identify individuals at the highest risk of cardiovascular events.

Micro-albuminuria in obese subjects: relationship among body fat distribution, blood pressure and left ventricular structure and function.

OBJECTIVE: To evaluate the relationships among micro-albuminuria, blood pressure and measurements of left ventricular structure and function in centrally and peripherally obese subjects compared with members of a lean control group. METHODS: Centrally obese subjects were subdivided according to whether they had levels of micro-albuminuria higher than 30 mg/24 h (micro-albuminuric group) or lower than or equal to 30 mg/24 h (normo-albuminuric group). For all the subjects we measured heart rate, casual mean blood pressure (MBP), 24 h MBP, total cholesterol level, high-density lipoprotein cholesterol, lipoprotein (a) level, fasting immunoreactive insulin level, plasma renin activity, plasma aldosterone level and micro-albminuria (UAE) by current methods. Left ventricular mass indexed for body height, left ventricular diastolic and systolic diameters, interventricular septal thickness and left ventricular ejection fraction were measured by echocardiography. Peak filling rate was also calculated by radionuclide study. Family history of cardiovascular disease was evaluated for all the obese subjects.RESULTS: Lipoprotein (a) level, total cholesterol level, 24 h MBP and interventricular septal thickness were significantly (P < 0.05) greater for micro-albuminuric than they were for normo-albuminuric centrally obese subjects, whereas high-density lipoprotein cholesterol level and left ventricular ejection fraction were significantly (P < 0.05 lower. In addition, UAE levels of centrally obese subjects were significantly (P < 0.05) higher than those of peripherally obese subjects. UAE of all the centrally obese subjects was correlated directly to lipoprotein (a) level (r = 0.33, P < 0.009), 24 h MBP (r = 0.41, P < 0.002), interventricular septal thickness (= 0.36, P < 0.005) and family history of cardiovascular disease (r = 0.33, P < 0.007). Multiple regression analysis indicated that UAE was independently related to 24 h MBP and family history of cardiovascular disease. CONCLUSION: Our data indicated that measurement of micro-albuminuria is useful for evaluating cardiovascular risk profiles of obese subjects with a central fat distribution.

Prevalence of obesity and ischaemic heart disease in hypertensive subjects.

In the present study the prevalence of obesity and its association with ischemic heart disease, recognized according to clinical criteria (chest pain or previous infarction) and/or instrumental data, were described in 8,847 normotensive subjects and in 867 hypertensive subjects, hospitalized during a ten years period (1983-1992), through a cross-sectional study. In view of this all the subjects were considered as lean or obese according to their body mass index (BMI) and to sex specific cut-off values reported in the Italian Consensus Conference on Obesity. In particular, according to BMI values, the subjects were grouped as lean, overweight, moderate and severe obese subjects. Our results indicated that 3,982 normotensive subjects (45%) could be considered lean, whereas 2,654 of them (30%) were overweight, 1,769 of them (20%) were moderate obese and 442 of them (5%) were severe obese. On the contrary only 206 hypertensives (23.7%) might be considered lean, whereas 313 (36.1%) were overweight, 302 (34.8%) were moderate obese and 46 (5.3%) were severe obese. According to age subgrouping (lower than or equal to 65 years or higher than 65 years) the distribution of hypertensives within the lean, overweight, moderate and severe obese groups did not change significantly, but, according to sex subgrouping, the distribution of hypertensives within the BMI groups was significantly different (chi 2, p < 0.001). When we considered the degree of hypertension, distribution of hypertensives was significantly different according to c2 test (p < 0.004), suggesting that the percentage of the subjects with severe hypertension increased only in subjects with severe obesity. Concomitant ischaemic heart disease (IHD) was also documented in 350 normotensives (4%) and in 119 hypertensives (13.8%). The prevalence of IHD was not significantly different in lean, overweight, moderate and severe obese hypertensives, also when sex and smoking habits were considered. Our data indicated a strong association between obesity and hypertension. In addition they may be consistent with the suggestion that obese hypertensives were not characterized by a lower risk of ischaemic heart disease (IHD), than lean hypertensives.

Central obesity and hypertension: the role of plasma endothelin.

Hypertension and central obesity are two conditions closely linked, but the mechanisms responsible for obesity-associated hypertension are still unclear. In the last few years, several studies addressed the role of endothelin-1 (ET-1) in the development and maintenance of hypertension. This study was designed to evaluate plasma ET-1 in normotensive and hypertensive central obese subjects compared with a lean healthy group. Our final goal was to analyze the relationship between plasma ET-1, blood pressure, and left ventricular structure and function in central obese subjects (both normotensives and hypertensives). ET-levels have been assessed by the radioimmunoassay method in 20 lean normotensives and in 57 central obese subjects; 30 of them were hypertensives and 27 of them were normotensives. Twenty-four-hour mean blood pressure (MBP/24 h) by noninvasive ambulatory blood pressure monitoring, left ventricular mass/ height (LVM/H), and left ventricular ejection fraction (LVEF) by echocardiography and peak filling rate (PFR) by radionuclide study were also measured. ET levels were significantly (P < .05) higher in obese hypertensives and obese normotensives than in lean normotensives. In addition, ET levels were significantly (P < .05) higher in obese hypertensives than in obese normotensives. ET were directly related to LVM/ H (r = 0.86; P < .001) and MBP/24 h (r = 0.48; P < .009) but only in obese hypertensives. Multiple regression analysis indicated that ET-1 plasma levels remain an independent predictor of MBP/ 24 h and LVM/H also when age was included in the analysis. These data suggest that obesity-associated hypertension is characterized by an endothelial dysfunction that may contribute to the higher cardiovascular risk detectable in these patients.

Echo-Doppler left ventricular filling abnormalities in patients with rheumatoid arthritis without clinically evident cardiovascular disease.

Our investigation aimed at verifying diastolic abnormalities in rheumatoid patients, without clinically evident cardiovascular disease and other confounding complaints, by using pulsed Doppler examination of transmitral blood flow. We selected 40 patients fulfilling revised American Rheumatism Association (ARA) criteria for the diagnosis of rheumatoid arthritis having no symptoms of cardiac disease or clinical findings of other extracardiac diseases. We also studied 40 rheumatoid-matched healthy volunteers as a control group. An echocardiographic examination was carried out on each subject. Left ventricular structural and functional measurements were obtained. Interventricular, septal thickness and left ventricular mass index were significantly higher in rheumatoid patients than in the control group. We also found in rheumatoid patients higher mean values of peak A velocity and A/E ratio. When multiple linear regression analysis was performed on the data of rheumatoid patients we found an independent relationship only between A/E ratio and left ventricular mass. In conclusion, our results confirm diastolic abnormalities in rheumatoid patients and point out that these abnormalities also affect echo-Doppler parameters of left ventricular filling. Moreover, further analysis of our data may suggest the possibility that structural left ventricle changes could be responsible for left ventricular filling impairment.

Effects of cilazapril on renal haemodynamics and function in hypertensive patients: a randomised controlled study versus hydrochlorothiazide.

In this study the efficacy and safety of short-term cilazapril administration on renal haemodynamics were evaluated in mild to moderate hypertensive subjects. Our final goal was to evaluate whether the reduction in blood pressure achieved by treatment was associated with maintained renal function. After a run-in period with placebo, 40 hypertensive subjects without renal or cardiac diseases were randomly allocated to a double-blind 4 week controlled trial with cilazapril 5 mg once a day (20 patients) or hydrochlorothiazide 25 mg once a day (20 patients). Renal haemodynamics measurements included effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) by radionuclide study using 131I-hippuran and 99mTc, according to the methods described by Schlegel and Gates, respectively. Effective renal blood flow [ERBF = ERPF/(1-Ht)], filtration fraction (FF = GFR/ERPF) and renal vascular resistance (RVR = MBP x 80/ERBF) were calculated. At the end of cilazapril and hydrochlorothiazide administration significant decreases (p < 0.001) in SBP, DBP and MBP vs baseline values were observed. In the cilazapril group a significant decrease (p < 0.001) in RVR and FF and a significant increase (p < 0.001) in ERPF and ERBF were also found. In the hydrochlorothiazide group a significant decrease (p < 0.001) in RVR was found. No important side effects were observed with either treatment. In conclusion our data indicate that both cilazapril and hydrochlorothiazide reduced blood pressure equally well but only cilazapril improved renal blood flow and reduced filtration fraction.

Evaluation of regional haemodynamics and alterations of vascular wall of the lower limbs in hypertensive subjects.

This study was designed to analyse the relationship between arterial hypertension and changes in arterial blood flow and vascular wall damage of the lower limbs in hypertensive patients with various degrees of hypertension. Six hundred and fifty-four hypertensive patients (421 males and 233 females) aged 35 to 70 years and 88 healthy subjects (63 males and 25 females) aged 39 to 60 years were studied. Strain-gauge plethysmography of the lower limbs was used to calculate arterial calf blood flow (RF), arterial calf blood flow after post-ischaemic hyperaemia (PF), basal and minimal vascular resistances (BVR and MVR), time to reach peak flow (tPF), time until 50% reduction of peak flow (tT1/2) and total recovery time (tT). In 108 (67 males and 41 females) of the hypertensive patients, a morphological study by echo-Doppler duplex scanning of the popliteal artery was performed to measure medial-intimal thickening and popliteal lumen diameter. Our results indicate that regional haemodynamics of the lower limbs worsened in hypertensives in comparison with control subjects. In addition, the change in peripheral haemodynamics was related to the degree of hypertension. Moreover, medial--intimal thickening was significantly (P < 0.05) higher in severe hypertensives than mild hypertensives. Popliteal lumen diameter was significantly (P < 0.05) lower in severe hypertensives than moderate and mild hypertensives. In all these subjects mean blood pressure was correlated directly (r = 0.31; P < 0.001) with medial-intimal thickening and inversely (r = -0.37; P < 0.001) with popliteal lumen diameter. Multiple regression analysis indicated that mean blood pressure, age and serum cholesterol were independently correlated to medial-intimal thickening. This relationship was not influenced by the diabetic patients and smokers among the groups. Our results indicate that hypertension impairs peripheral flow and encourages the development of medial-intimal thickening.