Mureddu Gf

Usual versus tight control of systolic blood pressure in non-diabetic patients with hypertension (Cardio-Sis): an open-label randomised trial.

BACKGROUND The level to which systolic blood pressure should be controlled in hypertensive patients without diabetes remains unknown. We tested the hypothesis that tight control compared with usual control of systolic blood pressure would be beneficial in such patients. METHODS In this randomised open-label trial undertaken in 44 centres in Italy, 1111 non-diabetic patients with systolic blood pressure 150 mm Hg or greater were randomly assigned to a target systolic blood pressure of less than 140 mm Hg (usual control; n=553) or less than 130 mm Hg (tight control; n=558). After stratification by centre, we used a computerised random function to allocate patients to either group. Observers who were unaware of randomisation read electrocardiograms and adjudicated events. Open-label agents were used to reach the randomised targets. The primary endpoint was the rate of electrocardiographic left ventricular hypertrophy 2 years after randomisation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00421863. RESULTS Over a median follow-up of 2.0 years (IQR 1.93-2.03), systolic and diastolic blood pressure were reduced by a mean of 23.5/8.9 mm Hg (SD 10.6/7.0) in the usual-control group and by 27.3/10.4 mm Hg (11.0/7.5) in the tight-control group (between-group difference 3.8 mm Hg systolic [95% CI 2.4-5.2], p<0.0001; and 1.5 mm Hg diastolic [0.6-2.4]; p=0.041). The primary endpoint occurred in 82 of 483 patients (17.0%) in the usual-control group and in 55 of 484 patients (11.4%) of the tight-control group (odds ratio 0.63; 95% CI 0.43-0.91; p=0.013). A composite cardiovascular endpoint occurred in 52 (9.4%) patients in the usual-control group and in 27 (4.8%) in the tight-control group (hazard ratio 0.50, 95% CI 0.31-0.79; p=0.003). Side-effects were rare and did not differ significantly between the two groups. INTERPRETATION Our findings lend support to a lower blood pressure goal than is recommended at present in non-diabetic patients with hypertension. FUNDING Boehringer-Ingelheim, Sanofi-Aventis, Pfizer.

Stroke volume and cardiac output in normotensive children and adults. Assessment of relations with body size and impact of overweight.

BACKGROUND Relations between organs and body size are not linear but rather follow allometric (growth) relations characterized by their powers (exponents). METHODS AND RESULTS Stroke volume (SV) by M-mode echocardiography was related to height, weight, body surface area (BSA), and ideal BSA (derived from ideal body weight for given height) in 970 normotensive individuals (1 day to 85 years old; 426 < 18 years old; 204 overweight to obese; 426 female). In normal-weight children, adults, and the entire population, SV was related by allometric relations to BSA (power = 0.82 to 1.19), body weight (power = 0.57 to 0.71), and height (power = 1.45 to 2.04) (all P < .0001). Relations of cardiac output to measures of body size had lower allometric powers than those for SV in the entire population (0.41 for body weight, 0.62 for BSA, and 1.16 for height). In overweight adults, observed SVs were 17% greater than predicted for ideal BSA, a difference that was approximated by normalization of SV for height to age-specific allometric powers. Similarly, observed cardiac output was 19% greater than predicted for ideal BSA, a difference that was accurately detected by use of cardiac output/height to age-specific allometric powers but not of BSA to the first power. CONCLUSIONS Indices of SV and cardiac output for BSA are pertinent when the effect of obesity needs to be removed, because these indices obscure the impact of obesity. To detect the effect of obesity on LV pump function, normalization of SV and cardiac output for ideal BSA or for height to its age-specific allometric power should be practiced.

Cardiac abnormalities in young women with anorexia nervosa.

OBJECTIVE--To identify the characteristics of cardiac involvement in the self-induced starvation phase of anorexia nervosa. METHODS--Doppler echocardiographic indices of left ventricular geometry, function, and filling were examined in 21 white women (mean (SD) 22 (5) years) with anorexia nervosa according to the DSMIII (Diagnostic and Statistical Manual of Mental Disorders) criteria, 19 women (23 (2) years) of normal weight, and 22 constitutionally thin women (21 (4) years) with body mass index < 20. RESULTS--13 patients (62%) had abnormalities of mitral valve motion compared with one normal weight woman and two thin women (p < 0.001) v both control groups). Left ventricular chamber dimension and mass were significantly less in women with anorexia nervosa than in either the women of normal weight or the thin women, even after standardisation for body size or after controlling for blood pressure. There were no substantial changes in left ventricular shape. Midwall shortening as a percentage of the values predicted from end systolic stress was significantly lower in the starving patients than in women of normal weight: when endocardial shortening was used as the index this difference was overestimated. The cardiac index was also significantly reduced in anorexia nervosa because of a low stroke index and heart rate. The total peripheral resistance was significantly higher in starving patients than in both control groups. The left atrial dimension was significantly smaller in anorexia than in the women of normal weight and the thin women, independently of body size. The transmitral flow velocity E/A ratio was significantly higher in anorexia than in both the control groups because of the reduction of peak velocity A. When data from all three groups were pooled the flow velocity E/A ratio was inversely related to left atrial dimension (r = -0.43, p < 0.0001) and cardiac output (r = -0.64, p < 0.0001) independently of body size. CONCLUSIONS--Anorexia nervosa caused demonstrable abnormalities of mitral valve motion and reduced left ventricular mass and filling associated with systolic dysfunction.

Relation of Left Ventricular Diastolic Properties to Systolic Function in Arterial Hypertension

BACKGROUND It is unclear whether impairment of left ventricular (LV) diastolic characteristics is independent of systolic dysfunction. METHODS AND RESULTS To address this issue, 159 consecutive hypertensive patients (44+/-11 years, 78 obese, 96 women) and 165 normotensive subjects (32+/-11 years, 84 obese, 110 women) were studied with the use of Doppler echocardiography. After adjustment for age, body mass index (BMI), and sex, we found that ejection fraction (EF; M-mode, z-derived) was higher in hypertensive (66. 6+/-5.2%) than in normotensive (63.9+/-4.4%, P<0.0001) subjects, whereas midwall shortening (MS) was lower (hypertensive patients 16. 9+/-2.0%, normotensive subjects 17.8+/-2.2%, P<0.02), even after correction for end-systolic wall stress (P<0.05). Isovolumic relaxation time (IVRT) was greater in hypertensive patients (103+/-14 ms) than in normotensive subjects (78+/-19 ms), as was deceleration time of E velocity and peak A velocity (all P<0.0001). In multivariate analysis, IVRT was unrelated to EF, but a negative relation was found with MS (P<0.001), independent of age, BMI, presence of arterial hypertension, LV geometry, and load (multiple R(2)=0.58). For comparable age, sex distribution, BMI, and blood pressure values, hypertensive patients with lower afterload-adjusted MS exhibited longer IVRT than patients with normal MS (P<0.005). However, IVRT remained higher than in normotensive control subjects after control for LV geometry and load. CONCLUSIONS Doppler indices of delayed LV relaxation can be detected in the presence of normal or supranormal EF but are independently related to impaired MS. A less severely abnormal relaxation, however, can be also detected in the presence of normal midwall function, independent of LV geometry and load. Thus, diastolic abnormalities may occur before systolic dysfunction even when it is measured at the midwall.

Age-related changes in total arterial capacitance from birth to maturity in a normotensive population

We evaluated the effect of body growth and aging on the ratio of echocardiographic (Teichholz) stroke volume to pulse pressure (SV/PP ratio) in 373 normal-weight, normotensive children to adolescents (1 day to 17 years old; 166 girls, 87 nonwhite) and 393 normal adults (17 to 85 years old; 164 women, 112 nonwhite). Stroke volume increased with age in children (r = .64, P < .0001) and was stable in adults; pulse pressure decreased slightly with age in children (r = -.10, P = .06) and increased in adults (r = .29, P < .0001). As a consequence, SV/PP ratio increased with age in children (r = .51, P < .0001) and decreased in adults (r = -.18, P = .0004). To control for changes in body size that influence the size of the arterial tree, we used ANCOVA to adjust SV/PP for body size. Body size-adjusted SV/PP ratio was no longer related to age in children, whereas the negative relation with aging in adults remained statistically significant (r = -.19, P < .0002). Heart rate was negatively related to SV/PP ratio in both children and adolescents and adults, but this relation did not influence the relation with age. In multivariate analysis, high SV/PP ratio was predicted by greater height (P < .002) and weight (P < .04) and nonwhite race (P < .001) in children and adolescents and by younger age (P < .0001), greater weight (P < .0001), and low heart rate (P < .001) in adults. Sex did not enter the regression models. Thus, (1) SV/PP ratio is a measure of increasing capacity of the arterial tree during growth, whereas it depends on arterial compliance during adulthood through old age; (2) arterial compliance decreases progressively with aging; (3) the apparent difference between males and females might be due to their different body sizes.

Relation of insulin resistance to left ventricular hypertrophy and diastolic dysfunction in obesity

OBJECTIVE: To assess relations of left ventricular (LV) geometry and function to insulin resistance in obesity – a condition associated with volume overload and abnormal LV relaxation.DESIGN: Cross-sectional relational study.SUBJECTS: 27 healthy overweight–obese subjects (18 women, body mass index (BMI)=35.0±4.0 kg/m2) and 31 age-matched normal-weight controls (21 women, BMI=22.6±2.4 kg/m2).MEASUREMENTS: Subjects were studied by Doppler-echocardiography the same day and hour (08.00 h) as measurements of fasting insulin and blood glucose were made. Insulin resistance was determined by the ‘Homeostasis Assessment Model’.RESULTS: Twelve obese subjects with insulin resistance (IR) had higher body size than 15 patients without IR and higher blood pressure than normal-weight controls (all P<0.01). Relative IR was related to isovolumic relaxation time. This relation was not maintained after controlling for age, blood pressure, weight and height. Isovolumic relaxation time was, however, positively related to diastolic blood pressure, a measure of load, in normal controls (r=0.44) and obese without IR (r=0.62) but not in insulin resistant subjects (r=0.14).CONCLUSION: IR does not independently influence myocardial relaxation in uncomplicated obesity, but modulates the effect of load on active diastole.

Assessment of cardiac autonomic control by heart period variability in patients with early‐onset familial obesity

Abstract. For quantitative assessment of cardiac autonomic control, time and frequency domain measures of heart period variability were calculated by 24 h Holter recording in 10 young obese women with early‐onset familial obesity and in 10 control subjects. Ultra low frequency and very low frequency power were lower in obese subjects than in controls (P < 0.05). High frequency power, a pure measure of vagal tone, was comparable between the two groups. However, low frequency power, which analysed over a 24 h Holter recording reflects parasympathetic more than sympathetic activity, was slightly lower in obese subjects than in controls (P= 0.06). Body mass index showed an inverse correlation with total power (r= ‐0.62; P < 0.05) and separately with ultra low (r=‐0.59; P < 0.01), very low (r= ‐0.64; P < 0.005), low (r= ‐0.61; P < 0.005) and high frequency power (r=—0.53; P < 0.05). These results demonstrate a parasympathetic withdrawal increasing body weight. The reduction of ultra low frequency and very low frequency power, which are associated with sudden death, may help to explain the higher cardiovascular risk in obesity.

Impact of aortic or mitral valve sclerosis and calcification on cardiovascular events and mortality: a meta-analysis.

a Department of Statistics and Quantitative Methods, Section of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy b Cardiology Division, Spedali Civili di Brescia and University of Brescia, Italy c Department of Cardiovascular Diseases, S. Giovanni-Addolorata Hospital, Roma, Italy d Department of Medicine, Section of Cardiology, University of Verona, Italy e Echocardiography Laboratory, Villa Bianca Hospital, Trento, Italy f Cardiology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy

Effect of canrenone on left ventricular mechanics in patients with mild systolic heart failure and metabolic syndrome: the AREA-in-CHF study.

BACKGROUND AND AIM We analyzed the effect of the mineralocorticoid receptor antagonist canrenone on LV mechanics in patients with or without metabolic syndrome (MetS) and compensated (Class II NYHA) heart failure (HF) with reduced ejection fraction (EF≤45%) on optimal therapy (including ACE-i or ARB, and β-blockers). METHODS AND RESULTS From a randomized, double-blind placebo-controlled trial (AREA-in-CHF), patients with (73 on canrenone [Can] and 77 on placebo [Pla]), based on modified ATPIII definition (BMI≥30kg/m(2) instead of waist girth) or without MetS (146 by arm). In addition to traditional echocardiographic parameters, we also evaluated myocardial mechano-energetic efficiency (MME) based on a previously reported method. At baseline, Can and Pla did not differ in age, BMI, blood pressure (BP), metabolic profile, BNP, and PIIINP. Compared with MetS-Pla, and controlling for age, sex and diabetes, at the final control MetS-Can exhibited increased MME, preserved E/A ratio, and decreased atrial dimensions (0.04<p<0.0001). At baseline, degree of diastolic dysfunction was similar in MetS-Can and MetS-Pla but after 12 months, diastolic function improved in MetS-Can, compared to MetS-Pla (p<0.002): moderate-to-severe diastolic dysfunction decreased from 26% to 12% with canrenone whereas it was unchanged with placebo (both 26%). Can, but not Pla, reduced BNP in both patients with or without MetS (p<0.0001). CONCLUSIONS Treatment with canrenone given on the top of optimal therapy in patients with MetS and chronic, stabilized HF with reduced EF, protects deterioration of MME, improves diastolic dysfunction and maximizes the decrease in BNP.

Global cardiovascular risk management in different Italian regions: An analysis of the evaluation of final feasible effect of control training and ultra sensitisation (EFFECTUS) educational program

BACKGROUND AND AIM The Final Evaluation Feasible Effect of Ultra Control Training and Sensitization (EFFECTUS) is an educational program, aimed at improving global CV risk stratification and management in Italy. The present study evaluates differences on clinical approach to global CV risk among physicians involved in the EFFECTUS program and stratified in three geographical macro-areas (North, Center, South) of our Country. METHODS AND RESULTS Physicians were asked to submit data already available in their medical records, covering the first 10 adult outpatients, consecutively seen in the month of May 2006. Overall, 1.078 physicians (27% females, aged 50 ± 7 years) collected data of 9.904 outpatients (46.5% females, aged 67 ± 9 years), among which 3.219 (32.5%) were residents in Northern, 3.652 (36.9%) in Central and 3.033 (30.6%) in Southern Italy. A significantly higher prevalence of major CV risk factors, including obesity, physical inactivity, hypertension and diabetes, was recorded in Southern than in other areas. Accordingly, Southern physicians more frequently prescribed antihypertensive, glucose and lipid lowering agents than other physicians, who paid significantly more attention to life-style changes in their clinical practice. CONCLUSIONS This analysis of the EFFECTUS study demonstrates a high prevalence of CV risk factors in Italy, particularly in Southern areas, and indicates some important discrepancies in the clinical management of global CV risk among physcians working in different Italian regions.