Franco Contaldo

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.

Interaction Between Body Size and Cardiac Workload: Influence on Left Ventricular Mass During Body Growth and Adulthood

The development of the left ventricle parallels body growth. During infancy, the relation between body size and left ventricular (LV) mass is very close. With advancing age, variability of LV mass in relation to body size markedly increases. To test the hypothesis that the age-related increase in variability of LV mass is due to the progressive impact of hemodynamic stimuli on LV growth, quantitative M-mode echocardiograms were obtained in 766 normal-weight, normotensive individuals over a range of ages from 1 day to 85 years (330 female subjects, 373 subjects younger than 18 years). LV mass was linearly related to height2.7 (r2=.69). Prediction of values of LV mass by body size was more accurate at birth and progressively less precise with increasing age. Stroke work (stroke volume times systolic pressure) was closely related to LV mass (r2=.74). The explained variance of LV mass increased from 69% in the univariate regression with height2.7 to 82% in a multivariate model including height2.7, stroke work, and gender. In children and adolescents (younger than 18 years), height2.7 was the main determinant of LV mass, whereas during adulthood stroke work and gender were more important predictors of LV mass than height2.7. Thus (1) the influence of body growth on development of LV mass decreases after early infancy because of both the variability of hemodynamic load and the increasing effect of gender; (2) after adolescence, during adulthood, in normotensive, normal-weight individuals, the impact of hemodynamic load and male gender on LV mass is greater than the one of body size; and (3) an appreciable proportion of variability of LV mass remains unexplained with the studied models. This might be due to genotypic variations and/or measurement error.

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.

Link of nonhemodynamic factors to hemodynamic determinants of left ventricular hypertrophy.

Despite current evidence suggesting that hemodynamic load is the fundamental stimulus to begin the sequence of biological events leading to the development of left ventricular hypertrophy, genotype, gender, body size, and less easily recognizable environmental factors may contribute to generate the cascade of molecular changes that eventually yield the increase in protein synthesis needed to increase left ventricular mass. However, even nonhemodynamic factors such as gender and body size eventually regulate the growth of left ventricular mass by at least in part influencing loading conditions. Consideration of measurable factors, such as gender, body size, and hemodynamic load, allows evaluation of individual echocardiographic left ventricular mass as the deviation from the level that would be required to face a gender-specific hemodynamic load at a given body size. Values of left ventricular mass that are inappropriately high for individual gender, body size, and hemodynamic load are associated with a high cardiovascular risk phenotype, even independent of the presence of arterial hypertension. Thus, the condition of inappropriately high left ventricular mass may be recognized as a more advanced stage of pathological structural changes initially induced by overload, going beyond the compensatory needs. The biological process that yields inappropriate left ventricular mass is probably linked to the protracted activity over time of biological mediators of left ventricular hypertrophy, such as proto-oncogenes and other growth factors, neurohormones, and cytokines, inducing structural modifications that initially compensate imposed overload but eventually change the structure of myocardial tissue and the composition of motor units.

Left ventricular filling pattern in uncomplicated obesity

To determine if uncomplicated obesity is associated with systolic dysfunction or impairment of left ventricular (LV) filling, 40 normotensive, white, asymptomatic, obese subjects (16 men and 24 women, mean +/- SD age 35 +/- 13 years; body mass index 36 +/- 6 kg/m2) and 40 normotensive, normal-weight, white volunteers matched for age and sex distribution, were studied by Doppler echocardiography. Endocardial and midwall shortening did not show differences between groups (obese = 33 +/- 4% and 17 +/- 2%; normal weight = 33 +/- 3% and 18 +/- 2%, respectively). LV mass index was higher in obese than in normal-weight subjects (p <0.0001). Obese persons had prolonged isovolumic relaxation time (p <0.0001), lower transmitral peak early diastolic filling wave (E) velocity (p <0.02), higher E velocity deceleration time (p <0.002) and lower E/atrial diastolic filling wave (A) flow velocity ratio (p <0.01) than did normal-weight subjects, even after controlling for age and blood pressure. Between-group differences in E and E velocity deceleration time disappeared when controlling for LV mass index, whereas prolonged isovolumic relaxation time in obesity was independent of LV mass, chamber dimension, and end-systolic stress. LV filling variables were not statistically related to endocardial or midwall shortening, both as absolute value or as a percentage of that predicted from wall stress. We conclude that uncomplicated obesity is associated with primary impairment of LV isovolumic relaxation; abnormalities of early passive filling flow in obesity are associated with increased LV mass.

Nutritional screening and early treatment of malnutrition in cancer patients

BackgroundMalnutrition is a frequent complication in patients with cancer and can negatively affect the outcome of treatments. On the other hand, side effects of anticancer therapies can also lead to inadequate nutrient intake and subsequent malnutrition. The nutritional screening aims to identify patients at risk of malnutrition for prompt treatment and/or careful follow-up.Methods and resultsThis manuscript highlights the need of an interdisciplinary approach (oncologist, nutritionist, dietitian, psychologist, etc.) to empower patients who are experiencing loss of physiological and biological function, fatigue, malnutrition, psychological distress, etc., as a result of cancer disease or its treatment, and maintain an acceptable quality of life.ConclusionsIt is necessary to make all healthcare professionals aware of the opportunity to identify cancer patients at risk of malnutrition early in order to plan the best possible intervention and follow-up during cancer treatment and progression.

Non-Alcoholic Fatty Liver Disease in Young Adult Severely Obese Non-Diabetic Patients in South Italy

Background/Aims: In the absence of other causes, obesity increases the risk of liver disease. We evaluated the prevalence and degree of metabolic and hepatic abnormalities associated with non-alcoholic fatty liver disease (NAFLD) in type II–III obesity in a metropolitan area of South Italy. Methods: 187 (81 M, 106 F) young adult non-diabetic obese patients, age range 18–50 years (mean 31.9 ± 8.8), body mass index (BMI) ≧30 (mean 47.5 ± 9.6), consecutively admitted from January 2000 to April 2003 to the Obesity Outpatients Clinic entered into the study. Patients were divided into two groups: (1) BMI 30.0–39.9, and (2) BMI≧40. Ultrasound detected liver steatosis was classified as: (I) mild; (II) moderate, and (III) severe. Results: All patients, except 4, showed a variable degree of steatosis: mild was more frequent among females, severe steatosis present only in grade III obesi ty, with higher prevalence in males than in females (p < 0.001). Mean serum transaminases, in particular alanine aminotrasferase (ALT), increased according to BMI and degree of steatosis. Homeostasis Model Assessment (HOMA) index, ferritin and fibrinogen levels increased with BMI, particularly in severe steatosis. In group 2, patients with BMI≧40 showed a positive correlation between ferritin, aspartate aminotransferase (AST) (r = 0.46, p < 0.018), ALT (r = 0.41, p < 0.036) and gamma-glutamyltransferase (γGT) (r = 0.51, p < 0.007), between serum triglycerides (TG) and AST (r = 0.28, p < 0.036), ALT (r = 0.30, p < 0.02) and between HOMA and ALT (r = 0.30, p < 0.03) and γGT (r = 0.35, p < 0.012). In group 2 patients with severe steatosis the prevalence of metabolic syndrome according to Adult Treatment Panel III (ATP III) was 40%. Conclusion: These data suggest that, in young adult non-diabetic grade III obese patients, fatty liver is always present and strictly related to insulin resistance which, in the presence of severe liver steatosis, is also related to serum ferritin.

Short-term effects of moderate alcohol consumption on lipid metabolism and energy balance in normal men

The short-term effects of moderate alcohol consumption on energy balance, serum lipids, and lipoproteins were studied in eight healthy middle-aged men (age 30 to 47 years and body mass index 23.1 to 27.7 w/h2). A crossover dietary trial included two isocaloric periods without (20% protein, 50% carbohydrate, 30% fat) or with alcohol (12% protein, 29% carbohydrate, 25% fat, 75 g of alcohol as red wine). Each period lasted 2 weeks. The body weight of the subjects remained stable over the study. Fasting blood glucose, serum insulin, total cholesterol, and LDL cholesterol were similar at the end of both dietary periods. Mean values of serum total triglyceride (108 +/- 18 v 85 +/- 24 mg/dL, P less than 0.05), VLDL-Tg (88 +/- 24 v 73 +/- 16 mg/dL, NS), and total HDL cholesterol (49.4 +/- 6.0 v 43.4 +/- 5.5 mg/dL, P less than 0.05) were higher after the diet with alcohol than without alcohol. The increase of HDL cholesterol was primarily due to that of HDL2 cholesterol (10.4 +/- 5.1 v 5.7 +/- 3.9 mg/dL, P less than 0.05). The concentration of apoprotein A-I, A-II, and B averaged 104 +/- 17 v 89 +/- 16 mg/dL, 33 +/- 4 v 28 +/- 8 mg/dL, P less than 0.02, and 111 +/- 24 v 105 +/- 33 mg/dL after the diets with and without alcohol, respectively. Adipose tissue LPL activity increased in six of the eight volunteers during the diet with alcohol. Resting metabolic rate, postprandial energy expenditure, and postprandial responses of blood glucose, serum insulin, triglyceride, and plasma FFA were similar after the both diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Butyrylcholinesterase as a prognostic marker: a review of the literature

BackgroundButyrylcholinesterase (BChE) is an α-glycoprotein synthesized in the liver. Its serum level decreases in many clinical conditions such as acute and chronic liver damage, inflammation, injury and infections, and malnutrition.Methods and resultsThis review collects the main evidence on the emerging role of butyrylcholinesterase as a prognostic marker of liver and nonliver diseases as well as a marker of protein-energy malnutrition and obesity. In fact, serum concentrations and BChE activity seem to accurately reflect the availability of amino acidic substrates and/or derangement in protein synthesis due to hepatocellular damage. In cancer, with or without liver impairment, serum BChE levels serve as an accurate functional and prognostic indicator, useful for monitoring clinical and therapeutic interventions according to patients’ prognosis. In the absence of inflammation, BChE could also serve as an index of the effectiveness of nutritional support.ConclusionsSerum BChE assessment should be included in routine clinical diagnostic procedures to evaluate patient clinical conditions, in particular in cases of inflammation and/or protein-energy malnutrition.