Coronary vasoreactivity is not altered in young people with type 1 diabetes.

BACKGROUND AND AIM: Abnormal coronary microvascular circulation has been demonstrated in diabetes and is associated with increased rate of cardiovascular events. Our objective was to evaluate coronary vasoreactivity in young people with type 1 diabetes with and without microvascular complications. METHODS AND RESULTS: Twenty-five type 1 diabetic patients without microvascular complications (DC-), 23 with microvascular complications (DC+), and 18 control subjects (C) were studied. Coronary vasoreactivity was assessed by means of coronary flow reserve (CFR). Blood flow velocity in the left anterior descending coronary artery was measured at rest and after high-dose dipyridamole using transthoracic color-guided pulsed Doppler echocardiography. CFR was defined as the ratio of hyperaemic to resting diastolic peak flow velocities. The three groups had similar cardiac function parameters, and also systolic and diastolic blood pressure at rest, which remained unchanged during dipyridamole infusion. Resting coronary flow velocity was comparable in C, DC-, and DC+ (p=ns). Dipyridamole infusion produced a threefold increase in coronary diastolic peak velocity, which reached similar values in C (0.69±0.16 m/s), DC- (0.69±0.18 m/s), and DC+ (0.66±0.11 m/s). Mean CFR ratio was similar in C (3.33±0.66), DC- (3.30±0.51), and DC+ (3.24±0.60). At multiple linear regression analysis, no association was found between CFR and age, sex, HbA(1c), duration of diabetes, and complications. CONCLUSION: Coronary vasodilatory function is preserved in young D patients, even those with early microvascular complications, suggesting that coronary vasoreactivity deteriorates at more advanced stages of microvascular complications and/or in the presence of other cardiovascular risk factors.

Extended endoscopic endonasal approach to the midline skull base: the evolving role of transsphenoidal surgery.

The evolution of the endoscopic endonasal transsphenoidal technique, which was initially reserved only for sellar lesions through the sphenoid sinus cavity, has lead in the last decades to a progressive possibility to access the skull base from the nose. This route allows midline access and visibility to the suprasellar, retrosellar and parasellar space while obviating brain retraction, and makes possible to treat transsphenoidally a variety of relatively small midline skull base and parasellar lesions traditionally approached transcranially. We report our current knowledge of the endoscopic anatomy of the midline skull base as seen from the endonasal perspective, in order to describe the surgical path and structures whose knowledge is useful during the operation. Besides, we describe the step-by-step surgical technique to access the different compartments, the "dangerous landmarks" to avoid in order to minimize the risks of complications and how to manage them, and our paradigm and techniques for dural and bony reconstruction. Furthermore, we report a brief description of the useful instruments and tools for the extended endoscopic approaches. Between January 2004 and April 2006 we performed 33 extended endonasal approaches for lesions arising from or involving the sellar region and the surrounding areas. The most representative pathologies of this series were the ten cranioparvngiomas, the six giant adenomas and the five meningiomas; we also used this procedure in three cases of chordomas, three of Rathke's cleft cysts and three of meningo-encephaloceles, one case of optic nerve glioma, one olfactory groove neuroendocrine tumor and one case of fibro-osseous dysplasia. Tumor removal, as assessed by post-operative MRI, revealed complete removal of the lesion in 2/6 pituitary adenomas, 7/10 craniopharyngiomas, 4/5 meningiomas, 3/3 Rathke's cleft cyst, 3/3 meningo-encephalocele. Surgical complications have been observed in 3 patients, two with a craniopharyngioma, one with a clival meningioma and one with a recurrent giant pituitary macroadenoma involving the entire left cavernous sinus, who developed a CSF leak and a second operation was necessary in order to review the cranial base reconstruction and seal the leak. One of them developed a bacterial meningitis, which resolved after a cycle of intravenous antibiotic therapy with no permanent neurological deficits. One patient with an intra-suprasellar non-functioning adenoma presented with a generalized epileptic seizure a few hours after the surgical procedure, due to the intraoperative massive CSF loss and consequent presence of intracranial air. We registered one surgical mortality. In three cases of craniopharyngioma and in one case of meningioma a new permanent diabetes insipidus was observed. One patient developed a sphenoid sinus mycosis, cured with antimycotic therapy. Epistaxis and airway difficulties were never observed. It is difficult todav to define the boundaries and the future limits of the extended approaches because the work is still in progress. Such extended endoscopic approaches, although at a first glance might be considered something that everyone can do, require an advanced and specialized training.

Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight.

OBJECTIVES: This study was designed to determine the most appropriate method to normalize left ventricular mass for body size. BACKGROUND: Left ventricular mass has been normalized for body weight, surface area or height in experimental and clinical studies, but it is uncertain which of these approaches is most appropriate. METHODS: Three normotensive population samples--in New York City (127 adults), Naples, Italy (114 adults) and Cincinnati, Ohio (444 infants to young adults)--were studied by echocardiography. Relations of left ventricular mass to body size were similar in all normal weight groups, as assessed by linear and nonlinear regression analysis, and results were pooled (n = 611). RESULTS: Left ventricular mass was related to body weight to the first power (r = 0.88), to body surface area to the 1.5 power (r = 0.88) and to height to the 2.7 power (r = 0.84), consistent with expected allometric (growth) relations between variables with linear (height), second-power (body surface area) and volumetric (left ventricular mass and body weight) dimensions. Strong residual relations of left ventricular mass/body surface area to body surface area (r = 0.54) and of ventricular mass/height to height (r = 0.72) were markedly reduced by normalization of ventricular mass for height2.7 and body surface area1.5. The variability among subjects of ventricular mass was also reduced (p < 0.01 to p < 0.002) by normalization for body weight, body surface area, body surface area1.5 or height2.7 but not for height. In 20% of adults who were overweight, ventricular mass was 14% higher (p < 0.001) than ideal mass predicted from observed height and ideal weight; this increase was identified as 14% by left ventricular mass/height2.7 and 9% by ventricular mass/height, whereas indexation for body surface area, body surface area1.5 and body weight erroneously identified left ventricular mass as reduced in overweight adults. CONCLUSIONS: Normalizations of left ventricular mass for height or body surface area introduce artifactual relations of indexed ventricular mass to body size and errors in estimating the impact of overweight. These problems are avoided and variability among normal subjects is reduced by using left ventricular mass/height2.7. Simple nomograms of the normal relation between height and left ventricular mass allow detection of ventricular hypertrophy in children and adults.

Supernormal contractility in primary hypertension without left ventricular hypertrophy.

Forty-three subjects with uncomplicated primary hypertension and without echocardiographic left ventricular hypertrophy and 54 normotensive volunteers were studied by two-dimensional targeted M-mode echocardiography to evaluate systolic function and contractility before the development of compensatory hypertrophy. The ratio of peak systolic pressure to end-systolic dimension was used to assess left ventricular performance and was divided for either posterior wall thickness or cross-sectional area to generate hypertrophy-independent indices of inotropic state. Fractional shortening was normal in the hypertensive group, despite the increase in end-systolic stress. Systolic pressure/dimension ratio was higher in hypertensive subjects (p less than 0.001), as were hypertrophy-independent indices of inotropic state (p less than 0.005), which were inversely correlated to left ventricular mass (p less than 0.001). Values in 11 hypertensive subjects were above the upper confidence limit of the normal shortening/stress relation, which provides a load-independent measure of inotropic state. They showed high hypertrophy-independent indices of inotropic state (p less than 0.01), while the other hypertensive subjects did not. High fractional shortening, wall stress, and systolic pressure (p less than 0.01) were found in the subgroup with supernormal performance, while left ventricular mass was not different from that of other subgroups, depicting inadequate left ventricular hypertrophy. The duration of hypertension was the same in the subgroups. Supernormal inotropic state could be considered one form of primary adaptation to high wall stress that serves to maintain systolic ventricular performance.

Effort blood pressure control in the course of antihypertensive treatment.

In 30 patients with mild hypertension (diastolic blood pressure, 95 to 105 mmHg), the antihypertensive effect of rilmenidine 1 mg was compared in a double-blind study, with the effect of hydrochlorothiazide 25 mg. Patients not satisfactorily controlled received a combined therapy on the same doses of the two drugs used. Rilmenidine and hydrochlorothiazide induced a significant reduction (p = 0.01) of supine and erect systolic/diastolic blood pressure 23 hours after drug intake with no change in heart rate. This effect was due to a reduction in cardiac output (bioimpedance method) significant (p = 0.05) only for rilmenidine. Both drugs controlled the increase of effort systolic blood pressure in comparison with placebo on systemic vascular resistance treadmill exercise testing. Effort cardiac output was increased by each treatment in comparison with baseline values. Both at rest and on exertion, there was no effect on systemic vascular resistance induced by the two drugs. In a second group of 10 patients with moderate hypertension (diastolic blood pressure, 105 to 115 mmHg), rilmenidine 1 mg was administered in order to evaluate its efficacy and hemodynamic effects (bioimpedance and radionuclide ventriculography), at rest and during a lying cycloergometer effort test. The drug induced a significant decrease in blood pressure at rest and on exertion four hours after drug intake. This effect was due to a reduction (p = 0.05) in systemic vascular resistance, whereas cardiac output and heart rate remained unchanged. Our results show that the reduction in systolic/diastolic blood pressure induced by rilmenidine 1 mg is comparable with that induced by the well-known antihypertensive drug hydrochlorothiazide in mild hypertension. In moderate hypertension, the 1-mg dose appears to be insufficient in controlling the blood pressure in all patients. The drug exerts its antihypertensive effect through the normalization of the altered hemodynamic parameters of hypertension (high cardiac output and/or increased systemic vascular resistance). Rilmenidine also respects the physiologic increase in blood pressure and cardiac output on exertion.

Is insulin action a determinant of left ventricular relaxation in uncomplicated essential hypertension?

OBJECTIVE: To examine the relation of insulin action and left ventricular diastolic function in uncomplicated essential hypertension. METHODS: Doppler echocardiography and glucose clamping combined with indirect calorimetry were performed in 29, newly diagnosed, hypertensive men, free from cardiac and metabolic drugs. They were divided into two groups according to the clamp-derived whole-body glucose disposal level: 20 with insulin resistance (whole-body glucose disposal < 33 mumol/kg per min) and nine with normal insulin sensitivity. RESULTS: The two groups were comparable in age, body mass index, heart rate and blood pressure. No difference in diastolic function was found except for the isovolumic relaxation time, which was prolonged for patients with insulin resistance (P = 0.02). For the population as a whole, the relaxation time had univariate relations with the left ventricular mass index (r = 0.57, P < 0.001), whole-body glucose disposal (r = -0.56, P < 0.001) and non-oxidative glucose metabolism (r = -0.54, P = 0.002). In a multivariate model including age, body mass index, heart rate, diastolic blood pressure, left ventricular mass index and whole-body glucose disposal as potential determinants, only the left ventricular mass index (beta = 0.39, P = 0.02) and whole-body glucose disposal (beta = -0.38, P = 0.03) were independent predictors of the relaxation time (R2 = 0.43, P < 0.001). CONCLUSIONS: In uncomplicated essential hypertension the insulin resistance is a determinant of abnormalities in isovolumic relaxation, independently from the influence exerted by increased blood pressure levels, being overweight and left ventricular hypertrophy.

Myocardial diastolic impairment caused by left ventricular hypertrophy involves basal septum more than other walls: analysis by pulsed Doppler tissue imaging.

OBJECTIVE: To assess regional diastolic function in patients with hypertension with or without left ventricular hypertrophy using Doppler tissue imaging, a new tool that analyzes myocardial wall motion 'on-line'. METHODS: Ten normotensive subjects, 20 hypertensive patients without hypertrophy and 20 with hypertrophy (left ventricular mass index >50 g/m2.7), all men, underwent Doppler echocardiography and Doppler tissue imaging, which was performed in apical view by placing pulsed sample volume at the level of the basal and middle septum, basal and middle lateral wall, and infero-posterior wall. Peak velocities and time-velocity integrals of myocardial early (Em) and late (Am) waves and their ratios, regional deceleration time and regional relaxation time were measured in each segment. RESULTS: Transmitral peak E/A ratio was 1.37 in normotensive subjects, 1.01 in hypertensive patients without hypertrophy and 0.77 in those with hypertrophy (P < 0.00001). The myocardial diastolic indexes derived by Doppler tissue imaging worsened at all levels in hypertensive patients without hypertrophy compared with normotensive subjects. In hypertensive patients with hypertrophy, the majority of myocardial diastolic indexes were further impaired at the basal septal level, but only marginal differences were found in other regions, compared with indexes in hypertensive patients without hypertrophy. The main diastolic indexes were found, using separate intra-group analyses, to be more compromised at the basal septum than at other levels only in hypertrophic hypertensive patients. The prevalence of regions having peak Em/Am ratios < 1 increased significantly from normotensive subjects to hypertensive patients without hypertrophy, but not significantly from these to the hypertrophic group. Among pooled hypertensive patients, after adjusting for heart rate and diastolic blood pressure using multivariate models, the septal wall thickness was shown to be an independent determinant of the diastolic indexes of the basal and middle septum. CONCLUSIONS: In hypertensive patients without hypertrophy, diastolic dysfunction is uniform along the ventricular walls, whereas in those with hypertrophy it is more evident at the basal septal level than in other walls. Overall among hypertensive patients, the diastolic properties of the interventricular septum worsen as the thickness of the septal wall increases, in the presence and in the absence of hypertrophy.

Impact of ambulatory blood pressure on left ventricular diastolic dysfunction in uncomplicated arterial systemic hypertension.

To determine the relations of 24-hour blood pressure (BP) and its different phases with left ventricular (LV) diastolic filling, 125 subjects (mean age 46 years) not taking cardiac drugs were studied by Doppler echocardiography and ambulatory BP recording. Subjects (excluding those with coronary artery or valvular heart disease, heart failure, or diabetes) were classified into 2 groups according to the level of Doppler-derived ratio of peak early to atrial velocity (E/A ratio): 59 had E/A >1 (normal diastole), 62 had E/A <1 (impaired diastole), and 4 had E/A = 1. Patients with E/A <1 were older and had higher LV mass indexed for height, average 24-hour BP, average nighttime BP, and lower day-night BP decrease, whereas average daytime BP did not differ significantly between the 2 groups. Negative correlations of E/A were found with age, heart rate, office, average 24-hour and average nighttime systolic and diastolic BP, and LV mass index. In a multivariate model that included potentially confounding factors, only age (standardized beta coefficient = -0.52, p<0.00001), nighttime BP (beta = -0.28, p<0.0001), and heart rate (beta = -0.22, p<0.001) were independent predictors of E/A in the pooled population. In conclusion, LV diastolic function is more closely related to ambulatory, rather than to clinic, BP measurements, and high average nocturnal diastolic BP is a powerful marker of LV filling impairment.

Hemodynamic hypertrophied left ventricular patterns in systemic hypertension.

The hemodynamic pattern of hypertrophied left ventricle in systemic hypertension was studied by M-mode echocardiography in 42 untreated hypertensive patients with left ventricular (LV) mass index greater than 2 standard deviations from the sex-specific mean of 114 normal subjects (normal values of our laboratory), and in 45 normotensive volunteers. Hypertensive patients showed cardiac dimensions, relative diastolic wall thickness, ratio of systolic pressure to end-systolic dimension, cardiac index and stroke index greater than normotensive control subjects (0.01 less than p less than 0.0001). Pressure/dimension ratio was correlated to relative wall thickness (p less than 0.005). End-systolic stress/volume ratio was normal as was systolic pressure to dimension ratio normalized for end-diastolic wall thickness. LV hypertrophy was concentric in 26% and eccentric in 74% of patients and suggested 2 different heart adaptations to overload: eccentric hypertrophy was associated with increased cardiac dimensions, high peak stress, normal systolic function and moderately increased LV contractility; concentric hypertrophy was associated with the highest blood pressure values, normal cardiac dimension, normal peak stress, normal systolic function and much increased LV contractility. Because stress/volume ratio and wall thickness-corrected systolic pressure/dimension ratio were normal in hypertensive patients, LV contractile capacity might be supported by the increase in myocardium available for contraction, rather than by increase in inotropic state.

Use of pulsed Doppler tissue imaging to assess regional left ventricular diastolic dysfunction in hypertrophic cardiomyopathy.

In this study, regional diastolic patterns and their relations with transmitral Doppler inflow were investigated in hypertrophic cardiomyopathy (HC) by pulsed Doppler tissue imaging (DTI). Doppler echocardiography and DTI of basal septum and lateral wall (apical 4-chamber view) were performed in 20 patients (15 men and 5 women) with HC and in 10 healthy subjects (7 men and 3 women). Diabetes, hypertension, coronary artery and valvular disease, mitral regurgitation, New York Heart Association functional classes III to IV, sinus tachycardia, atrial fibrillation, and inadequate echocardiograms were exclusion criteria. Peak velocity and time-velocity integral of early and late waves and their ratios, and deceleration and isovolumic relaxation times were determined by standard Doppler and by DTI at the septal and lateral wall levels. The 2 groups were comparable for age, heart rate, blood pressure, and ejection fraction. Transmitral peak velocity and time-velocity integral E/A ratios were reduced (both p <0.05) and deceleration and isovolumic relaxation times prolonged (both p <0.00001) in HC. Septal DTI showed lower peak velocity and time-velocity integral e/a ratios (p <0.00001 and p <0.001, respectively) and lengthened regional deceleration (p <0.01) and isovolumic (p <0.001) relaxation times. DTI of the lateral wall showed a prolongation of deceleration and isovolumic relaxation times (both p <0.01). By dividing HC according to transmitral E/A, 8 patients with E/A <1 had lower DTI septal e/a ratio (p <0.01) and prolonged septal deceleration and isovolumic relaxation times (both p <0.01) but no changes in DTI pattern of lateral wall than 12 patients with E/A > 1. In conclusion, DTI is useful and complementary to standard Doppler imaging to characterize diastolic properties in HC, reflecting a typical pattern of intramyocardial impaired relaxation at the level of hypertrophied septum and also providing information about the degree of this regional impairment. The lateral wall presents minor changes in diastolic times, which indicate how diastolic asynchrony is not confined to the hypertrophied segment in HC.

Impact of heart rate and atrioventricular delay on left ventricular diastolic filling in patients with dual-chamber pacing for sick sinus syndrome or atrioventricular block.

We examined the effect of left ventricular filling on different combinations of programmable heart rate and atrioventricular delay in patients with dual-chamber pacemakers. Pacing mode with heart rates of 60 beats/min and 156 ms of atrioventricular delay induced a diastolic pattern that resembles more than others the one observed in healthy subjects in sinus rhythm.

Effects of short-term reduction in serum cholesterol with simvastatin in patients with stable angina pectoris and mild to moderate hypercholesterolemia.

To evaluate the effects of short-term cholesterol-lowering treatment on myocardial effort ischemia, 22 patients with stable effort ischemia and mild to moderate hypercholesterolemia (low density lipoprotein [LDL] cholesterol 160 to 220 mg/dl) were randomly allocated at baseline (TO) in 2 groups. Group A included 12 patients treated with simvastatin 10 mg bid; group B included 10 patients treated with placebo. All patients underwent a treadmill electrocardiography (ECG) test; total cholesterol, HDL and LDL cholesterol, triglycerides, plasma, and blood viscosity were measured. All tests were repeated after 4 and 12 weeks. For 18 of the same patients (11 taking simvastatin, 7 receiving placebo), forearm strain-gouge plethysmography was performed at baseline and after 4 weeks, both at rest and during reactive hyperemia. At 4 and 12 weeks, group A showed a significant reduction in total cholesterol (p <0.05) and LDL (p <0.05), with unchanged HDL, triglycerides, blood, and plasma viscosity. Effort was unmodified, ST-segment depression at peak effort and ischemic threshold were significantly improved after 4 and 12 weeks (all p <0.05) with unchanged heart rate x systolic blood pressure product. A significant increase in the excess flow response to reactive hyperemia was detected in group A (p <0.03); group B showed no changes in hematochemical and ergometric parameters. These data suggest that cholesterol-lowering treatment is associated with an improvement in myocardial effort ischemia; this might be explained by a more pronounced increase of coronary blood flow and capacity of vasodilation in response to effort.

Desmin-free cardiomyocytes and myocardial dysfunction in end stage heart failure.

Our aim was to evaluate the desmin content in the myocardial tissue of patients with end-stage heart failure of ischaemic origin and to assess its role on cardiac function. We studied 18 explanted hearts from patients transplanted for end-stage heart failure due to ischaemic cardiomyopathy (ICM). Control myocardial tissue was obtained from the cardiac biopsies of six women with breast cancer taken prior to commencing chemotherapy with anthracyclines, four male donors for heart transplantation and two autoptic hearts from patients who died due to non-cardiac events. Myocardial tissue, obtained from the left ventricle (remote zone from infarcted area), was analyzed by light and confocal immunochemistry (desmin) microscopy. The desmin content of myocardial tissue was obtained by real-time PCR. Cardiac function was evaluated by echocardiographic and right heart catheterization data, obtained before heart transplantation. Confocal microscopy evaluation showed a significant decrease in the number of desmin-positive myocytes (P<0.01) in ICM hearts compared to controls. At real-time PCR evaluation, there was a reduction (P<0.01) in desmin content in the ICM patients compared to controls. A negative correlation was found between desmin-free cardiomyocytes and ejection fraction (EF) (r=-0.834; P<0.02) on echocardiogram. A negative relationship (r=-0.688) was also found between desmin-negative myocytes and capillary wedge pressure. In conclusion, the myocardial tissue of patients with end-stage heart failure of ischaemic origin, shows a decreased number in desmin-positive myocytes at immunochemistry evaluation compared to normal individuals. This deficiency in cytoskeletal intermediate filament content is associated with reduced cardiac function.

Influence of nighttime blood pressure on left atrial size in uncomplicated arterial systemic hypertension.

The aim of the study was to determine the relations of 24-h blood pressure (BP) and its different phases with left atrial size. A total of 130 subjects (mean age 46 years) not taking cardiac drugs were studied by M-mode and Doppler echocardiography and ambulatory BP recording. Subjects (excluding those with coronary artery or valvular heart disease, heart failure, or diabetes) were classified into two groups: 25 normotensives and 105 hypertensives (history of antihypertensive treatment and office diastolic BP > 90 mm Hg). The two groups were comparable in terms of sex, age, and heart rate, whereas body mass index, (P < .01), office BP, average 24-h BP, and average daytime and nighttime BP (all P < .00001) were higher in hypertensives. Hypertensives also had increased left atrial dimension, left atrial dimension/aortic root ratio (both P < .001), and left ventricular mass (LV) indexed for height (P < .0001). Positive correlations of left atrial dimension were found with office BP, average 24-h, average daytime and nighttime systolic and diastolic BP, LV mass index, and Doppler-derived E/A ratio. In a multivariate model that included potentially confounding factors, only body mass index (standardized beta coefficient = 0.41, P < .00001), average nighttime diastolic BP (beta = 0.33, P < .00001), and male sex (beta = 0.18, P < .01) were independent predictors of left atrial size in the pooled population. In conclusion, left atrial size is more closely related to ambulatory, rather than office, BP measurements, and high average nighttime BP is a powerful marker of left atrial enlargement in arterial hypertension.

Ambulatory blood pressure monitoring in offspring of hypertensive patients. Relation to left ventricular structure and function.

The relation between 24-h ambulatory blood pressure monitoring and echocardiographic left ventricular (LV) anatomy and function was examined in 30 young, normotensive offspring (16 men, 14 women) of hypertensive, parents and in 20 offspring (12 men, 8 women) of normotensive parents, comparable for age, clinical blood pressure, and gender. Offspring of hypertensive subjects exhibited higher body mass index (P < .01), relative wall thickness, and LV mass/height (both P < .001). No significant difference was found in LV chamber dimensions and in either systolic or diastolic function. The 24-h systolic and diastolic blood pressures were higher in offspring of hypertensive subjects than in controls (P < .001 and P < .0001, respectively), as was the coefficient of variation of 24 h systolic blood pressure (P < .01). In pooled groups, LV mass was positively related to daytime systolic blood pressure (r = 0.48), daytime diastolic blood pressure (r = 0.47) (both P < .001), and the coefficient of variation of 24 h diastolic blood pressure (r = 0.37, P < .01). In a multiple regression model, including as variables, body mass index, daytime systolic and diastolic blood pressures, male gender, and family history of hypertension were the major independent predictors of LV mass (both P < .0001), with an additional contribution of the coefficient of variation of 24 h diastolic blood pressure (P < .05). We conclude that male gender and a family history of hypertension are stronger determinants of early changes in cardiac structure than hemodynamic load in a group of young, normotensive adults.

Plasma leptin concentration, insulin sensitivity, and 24-hour ambulatory blood pressure and left ventricular geometry.

Left ventricular (LV) hypertrophy is an important predictor of cardiovascular morbidity and mortality. Hemodynamic factors, such as 24-h blood pressure (BP) values, are responsible for left ventricular hypertrophy in hypertensives. On the other hand, some metabolic factors have also been suggested to affect LV mass and geometry. In particular, plasma leptin concentrations have been found associated to LV myocardial growth. Because chronic leptin infusion stimulates sympathetic nervous system activity and increases BP levels, the role of 24-h BP values on leptin-related changes in myocardial wall geometry cannot be ruled out. Thus, the aim of our study was to evaluate whether the relationship between plasma leptin levels and LV wall thickness is mediated by 24-h BP values in hypertensive male patients. Thirty-six newly diagnosed hypertensive patients underwent Doppler echocardiographic examination, 24-h ambulatory BP recording, and metabolic (euglycemic hyperinsulinemic glucose clamp and fasting plasma leptin levels) measurements. Left ventricular mass correlated positively only with ambulatory diastolic BP (DBP) values, whereas the indices of myocardial wall growth such as interventricular septum thickness and sum of wall thickness (ie, septal + posterior wall thickness) correlated either with 24 h, daytime, or nighttime DBP, as well as with fasting plasma glucose, fasting plasma leptin, and insulin action after adjustment for age, body mass index (BMI), and waist/hip ratio (WHR). In contrast, plasma leptin concentration did not correlate with clinical and ambulatory BP values. A multiple linear regression analysis allowed to investigate the independent role of main anthropometric and cardiovascular covariates on the sum of wall thickness variability. A model that includes age, BMI, WHR, fasting plasma leptin concentration, plasma Na+ concentration, insulin action, and nighttime DBP explained 68% of the sum of wall thickness variability. In such a model, plasma leptin concentration (P < .001), insulin action (P < .029), and nighttime DBP (P < .002) were significantly and independently associated with myocardial wall thickness. In conclusion, our study demonstrates that in hypertensive men fasting plasma leptin levels are determinant of myocardial wall thickness independently of 24-h BP values.

Independent association of plasma leptin levels and left ventricular isovolumic relaxation in uncomplicated hypertension.

BACKGROUND: On the basis of evidence of plasma leptin (LE) effects on cardiovascular system, we assessed possible association of LE and Doppler-derived left ventricular (LV) diastolic function in arterial hypertension. METHODS: Doppler echocardiography, blood sample for fasting plasma LE levels, and euglycemic hyperinsulinemic glucose clamp were performed on 15 healthy insulin-sensitive men and 40 newly diagnosed hypertensive men, who were divided into two groups according to insulin sensitivity degree: 15 insulin sensitive (IS) and 25 insulin resistant (IR) individuals (whole body glucose disposal >33.3 and <33.3 micromol/kg, respectively). RESULTS: The IR hypertensives had significantly higher body mass index (BMI), waist/hip ratio, LE and LV mass index than the other two groups. IR hypertensives had lower LE (even after adjusting for BMI and waist/hip ratio) and among LV diastolic indexes, lower E peak velocity (P < .05) and longer isovolumic relaxation time (IVRT) (P < .001) in comparison to IR hypertensives. IR hypertensives had the lowest E/A ratio (0.88 +/- 0.2) compared to IS patients (1.03 +/- 0.1 P < .05) and controls (1.31 +/- 10.2 P < .001). By multiple linear regression analyses performed both in the overall population and hypertensives, LV mass index and LE were independently associated to IVRT (R2 = 0.41 in overall population, R2 = 0.42 in hypertensives, both P < .0001), whereas age, heart rate, diastolic and systolic blood pressure (BP), BMI, waist/hip ratio, and insulin action were not significant. CONCLUSIONS: Our study underscores an independent association of increased plasma LE and lengthening of isovolumic relaxation in uncomplicated hypertension. Further studies will need to understand the conditions underlying both these phenomena.

Simvastatin versus pravastatin: efficacy and tolerability in patients with primary hypercholesterolemia.

One hundred patients with primary hypercholesterolemia (total plasma cholesterol greater than or equal to 6.2 mmol/L [240 mg/dl]) were enrolled in an open, randomized, parallel comparative study of simvastatin and pravastatin. All patients started or continued a standard lipid-lowering diet for at least six weeks prior to entry into the four-week placebo baseline period. Fifty patients received simvastatin and 50 patients received pravastatin, both at the recommended starting dose of 10 mg/day, for a treatment period of six weeks. Total cholesterol levels were reduced by 24% (from 7.59 mmol/L to 5.80 mmol/L) with simvastatin, and by 15% (from 7.48 mmol/L to 6.35 mmol/L) with pravastatin. Low-density-lipoprotein cholesterol levels were reduced by 33% and 22% and high-density-lipoprotein cholesterol levels were increased by 10% and 7% with simvastatin and pravastatin, respectively. Plasma total triglyceride levels were reduced by 12% with simvastatin and by 6% with pravastatin. Adverse experiences were similar between treatment groups and both drugs were well tolerated. No patients were withdrawn from the study due to clinical adverse experiences; one patient in the pravastatin group required a reduction in dose to 5 mg/day due to insomnia. At the recommended starting dose, simvastatin had a significantly greater lipid-lowering effect than pravastatin. These results may have implications for the appropriate lipid-reduction therapy for patients at risk of coronary heart disease.

Indapamide and atenolol in the treatment of hypertension: double-blind comparative and combination study.

Fifteen out-patients with moderate hypertension were randomly and sequentially treated with atenolol, indapamide and a combination of the two drugs after a wash-out period of at least 1 week and a 2-week placebo run-in period. The duration of treatment was 4 weeks in each case. The dosage was 2.5 mg indapamide and 100 mg atenolol, in single tablets which were taken at 11.00 hours. All the treatment regimens produced a highly significant (p less than 0.001) reduction in systolic and diastolic, supine and standing blood pressure; these reductions were not significantly different for the single drugs but were significantly greater for the combined therapy. The number of patients reaching the end-point of a diastolic blood pressure of 95 mmHg or less was the same with either atenolol or indapamide, i.e. 7 (46.6%), but was greater with the combined therapy, i.e. 10 (66.6%). A significant (p less than 0.001) reduction in pulse rate was observed with the treatments involving atenolol. Acceptability of the treatments was very good; the number of volunteered and elicited complaints during the different treatments being less compared to the placebo period, particularly for the combined treatment. No significant difference was observed in the blood biochemistry tests. The results are discussed in light of the mechanisms of action of the two drugs, which seem well integrated with each other, and the duration of the antihypertensive effect, which allows a single administration with consequent good treatment compliance.

Favourable interaction of calcium antagonist plus ACE inhibitor on cardiac haemodynamics in treating hypertension: rest and effort evaluation.

The aim of the study was to evaluate the effects of verapamil sustained release (SR) 240 mg, enalapril and their combination on blood pressure (BP) and cardiac haemodynamics at rest and during exercise in 20 patients with moderate essential hypertension (seven men and 13 women, mean age +/- s.d. 53.7 +/- 15.8 years). After a 4 week placebo run-in period, patients were randomly allocated to received verapamil SR 240 mg once daily or enalapril 20 mg once daily for 4 weeks in a double-blind fashion. Patients whose diastolic blood pressure (DBP) was still > or = 95 mm Hg at the end of this period received verapamil SR plus enalapril for an additional 4 weeks. At the end of the placebo, single and combined treatment periods, resting and exercise (bicycle ergometry) haemodynamics were evaluated by radionuclide ventricular angiography (technetium-99m) and the following parameters were assessed: BP, heart rate, double product, systemic vascular resistances (SVR), cardiac output (CO), stroke volume (SV), ejection fraction (EF) mean ejection rate (mER) and peak filling rate (PFR). Both verapamil SR and enalapril monotherapies significantly reduced resting and exercise BP (P < 0.01), with a BP normalisation (DBP < or = 95 mm Hg) of five of 10 and 4 of 10 patients respectively. A greater BP fall and a normalisation of 11 of 11 patients was obtained in non-responders to monotherapy, when treated with verapamil SR and enalapril (P < 0.01). Verapamil SR also reduced heart rate at rest and during exercise (-11.8% and -18.4%, respectively, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)