V. Di Bello

Microalbuminuria and endothelial dysfunction in essential hypertension

Microalbuminuria (urinary albumin excretion between 20 and 200 micrograms/min) and endothelial dysfunction coexist in patients with essential hypertension. To evaluate whether the two phenomena are related and the determinants of that association, we recruited 10 untreated males with essential hypertension and microalbuminuria without diabetes to be compared with an equal number of matched patients with essential hypertension excreting albumin in normal amounts and 10 normal controls. The status of endothelial function was inferred from circulating von Willebrand Factor antigen (vWF), a glycoprotein secreted in greater amounts when the vascular endothelium is damaged. vWF concentrations were higher in hypertensive patients with microalbuminuria than in hypertensive patients without and controls. Individual vWF and urine albumin-excretion values were correlated (r = 0.55, p < 0.002). Blood pressure correlated with both urinary albumin excretion and vWF. Left ventricular mass index and minimal forearm vascular resistances were comparable in patients with hypertension and higher than in controls; total and low-density lipoprotein cholesterol, triglycerides, lipoprotein-a, Factor VII, and plasminogen activator inhibitor-1 did not differ. Fibrinogen was higher and creatinine clearance lower in microalbuminurics. Albuminuria in essential hypertension may reflect systemic dysfunction of the vascular endothelium, a structure intimately involved in permeability, haemostasis, fibrinolysis, and blood pressure control. This abnormality may have important physiopathological implications and expose these patients to increased cardiovascular risk.

Microalbuminuria, an integrated marker of cardiovascular risk in essential hypertension

This paper reviews the existing epidemiological and clinical evidence about the relationships of non-diabetic microalbuminuria with cardiovascular risk factors such as elevated blood pressure (BP), systolic particularly, cardiac hypertrophy, adverse metabolic status, smoking habits, elevated angiotensin II levels, endothelial dysfunction, acute and perhaps subclinical inflammation. Because of that unique property of reflecting the influence of so many clinically relevant parameters, microalbuminuria may legitimately be defined as an integrated marker of cardiovascular risk, an unique profile among the several prognostic predictors available to stratify risk in hypertensive patients. Recent cohort studies also showed associations with cardiovascular morbidity and mortality independently from conventional atherogenic factors. This behaviour, whose understanding still needs further elucidation, suggests to measure albuminuria and to screen patients at a higher absolute risk in whom preventive treatment is expected to be more beneficial than in those with a lower absolute risk.

Microalbuminuria and Pulse Pressure in Hypertensive and Atherosclerotic Men

To identify the biological covariates of microalbuminuria (albuminuria >/=15 microg/min) in nondiabetic subjects, brachial blood pressure, echocardiographic left ventricular mass, and other cardiovascular and metabolic parameters were evaluated in 211 untreated males (38 normal controls, 109 uncomplicated stage 1 to 3 essential hypertensives, and 64 patients with clinically stable atherosclerotic peripheral vascular disease either with [n=44] or without [n=20] essential hypertension) with normal cardiac and renal function. Compared with normoalbuminuric subjects, microalbuminuric subjects (n=67) were characterized by higher systolic blood pressure, comparable diastolic blood pressure, and, therefore, wider pulse pressure. Greater prevalence of hypertension, peripheral vascular disease, left ventricular hypertrophy, and reduced HDL cholesterol values further distinguished microalbuminuric from normoalbuminuric subjects in univariate comparisons. The risk of microalbuminuria increased by ascending pulse pressure quintiles in age-corrected logistic regression models, in which pulse pressure was more predictive than systolic pressure and was independent of mean pressure. When microalbuminuric status was regressed against a series of dichotomous (vascular and active smoker status) and continuous (age, pulse and mean pressure, left ventricular mass index, and HDL and LDL cholesterol) variables, only pulse pressure, left ventricular mass index, and smoking status were independent predictors. The association of increased albuminuria with wider pulse pressure, a correlate of the pulsatile hemodynamic load and conduit vessel stiffness as well as an important cardiovascular risk factor, may explain why microalbuminuria predicts cardiovascular events in nondiabetic subjects. The independence from concomitant vascular disease also suggests that wider pulse pressure, rather than representing a simple marker for atherosclerotic disease, influences albuminuria directly.

Normal ultrasonic myocardial reflectivity in athletes with increased left ventricular mass. A tissue characterization study.

BackgroundUltrasonic integrated backscatter of myocardial walls is directly related to the morphometrically evaluated collagen content. The integrated backscatter is also increased in hypertrophic cardiomyopathy, probably because of fiber disarray. The purpose of this study was to investigate myocardial tissue reflectivity in subjects with physiological hypertrophy caused by intense physical training and to assess the relation between the acoustic properties of myocardial tissue and left ventricular wall thickness assessed by conventional two-dimensional echocardiography. Methods and ResultsTwenty-four young male athletes (14 professional cyclists and 10 weight lifters, all in full agonistic activity) were studied together with 10 normal age-matched controls with sedentary life. By means of a commercially available two-dimensional echocardiograph, standard measurements were obtained according to the recommendations of the American Society of Echocardiography. With a prototype implemented in our Institute, an on-line radiofrequency analysis of ultrasound signals was also performed to obtain quantitative operator-independent measurements of the integrated backscatter of the myocardial walls. The integrated values of the radiofrequency signal were normalized for the pericardial interface and expressed in percent integrated backscatter (%IB). Compared with control subjects, athletes showed greater thickness values of septum (controls, 9±1; cyclists, 14±2; weight lifters, 15±1 mm, mean± SD; p < 0.01) and posterior wall (9±1, 12±2, and 12+1 mm, respectively; p < 0.01) but similar values of %IB for both septum (23±4%, 21±7%, and 23±8%, p = NS) and posterior wall (10±2%, 9±2%, and 11±2%, p = NS). In athletes, no correlation was found between septal and posterior wall thickness and the corresponding regional myocardial reflectivity (r = 0.23, p = NS and r = 0.01, p = NS, respectively). Furthermore, we compared the quantitative ultrasonic data between two subsets of 10 athletes and 10 patients with hypertrophic cardiomyopathy and similar degrees of septal thickness (16±1 versus 17±1 mm, respectively, p = NS). Septal and posterior wall %IB results were significantly higher in patients with hypertrophic cardiomyopathy (53±13% and 36±9%o, respectively) than in athletes (21±7% and 10±3%, respectively; p < 0.01 for both). ConclusionsWe conclude that 1) endurance athletes show a normal pattern of quantitatively assessed ultrasonic backscatter despite of a marked left ventricular hypertrophy and 2) athletes and patients with hypertrophic cardiomyopathy and similar degrees of myocardial wall thickness can be differentiated on the basis of quantitative analysis of backscattered signal.

Left ventricular function during exercise in athletes and in sedentary men.

Aim of this study was to evaluate left ventricular function during exercise in 10 male elite runners and in 10 sedentary males. End-diastolic (EDV) and end-systolic volume (ESV), left ventricular ejection fraction (EF), early peak transmitral flow velocity (peak E), time-velocity integral of mitral inflow (m-TVI); mitral cross sectional area (m-CSA); mitral stroke volume (SV), and cardiac output (CO) were measured by echo-Doppler. We simultaneously analyzed: VO2max by spirometric method, mean arterial blood pressure (MAP) by sphygmomanometer, and heart rate (HR) by ECG. The parameters were measured under basal conditions (level 1), at 50% of maximal aerobic capacity (level 2), at peak of exercise (level 3) and during recovery. Ejection fraction in athletes increased significantly at peak of exercise through Frank-Starling mechanism. Stroke volume and cardiac output increased significantly in athletes at peak of exercise. Left ventricular diastolic function was superior in athletes versus controls: in fact, higher peak E in athletes enhanced early diastolic ventricular filling. Therefore, the athletes showed complex cardiovascular adjustments induced by training, which allowed an higher peak working power, a greater cardiac output, and VO2max when compared with an untrained control population.

Microalbuminuria is a marker of left ventricular hypertrophy but not hyperinsulinemia in nondiabetic atherosclerotic patients.

Microalbuminuria predicts cardiovascular events in diabetic and nondiabetic patients. For a better understanding of the physiopathological importance of microalbuminuria in atherosclerotic disease, we evaluated the relation between urinary albumin excretion and arterial blood pressure, left ventricular mass, insulin, and lipid levels. The studies were conducted in patients with atherosclerotic peripheral vascular disease. Urinary albumin excretion (studied by nephelometry; an average of triplicate collections from 8 PM to 8 AM), causal blood pressure, echocardiographic left ventricular mass index and wall thickness, plasma immunoreactive insulin and C-peptide (both basally and after a 75-g oral glucose load), blood lipids, and fibrinogen were studied in eight normal subjects and 20 nonobese, nondiabetic male patients with angiographically documented atherosclerotic peripheral vascular disease and preserved renal function, 12 of whom were either hypertensive or on antihypertensive treatment. Eight patients were microalbuminuric (urinary albumin > 20 micrograms/min) and 12 were not. Ankle-arm index and calf and foot transcutaneous oxygen tension were reduced in comparison with normal control subjects but superimposable between the two patient groups to indicate a comparable clinical progression of the vascular disease. In the microalbuminuric subjects, left ventricular mass index was greater, interventricular septum was thicker, and cardiac hypertrophy was more frequent than in nonmicroalbuminuric patients. The prevalence of hypertension tended to be greater and systolic blood pressure values were higher in the presence of microalbuminuria. Overall, a highly significant relation existed between urinary albumin excretion and left ventricular mass. Systolic blood pressure was greater and a history of arterial hypertension was more frequent among microalbuminurics, whereas diastolic blood pressure values showed a statistically significant correlation with both variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between preclinical abnormalities of global and regional left ventricular function and insulin resistance in severe obesity: a Color Doppler Imaging Study

Background:The aim of this study was to evaluate the relationship between insulin resistance and preclinical abnormalities of the left ventricular structure and function detected in severe obesity by Color Doppler Myocardial Imaging (CDMI). Forty-eight consecutive severely obese patients (Group O) (11 males, 37 females, mean age 32.8±7 years) were enrolled. Forty-eight sex- and age-matched non-obese healthy subjects were also recruited as controls (Group C). All subjects underwent conventional 2D-Color Doppler echocardiography and CDMI. The homeostasis model assessment insulin resistance index (HOMA-IR) was used to assess insulin resistance results. Obese subjects had a greater left ventricular mass index (by height) (58.8±14 g/m2.7) than controls (37±8 g/m2.7) (P<0.0001), owing to compensation response to volume overload caused by a greater cardiac output (P<0.02). Preload reserve was increased in obese subjects, as demonstrated by a significant increase in left atrial dimension (P<0.0001). Obese patients had a slightly reduced LV diastolic function (transmitral E/A ratio: Group O, 1.1±0.8 vs Group C, 1.5 ±0.5; P<0.002). Cardiac deformation assessed by regional myocardial systolic strain and strain rate (SR) values was significantly lower (abnormal) in obese patients than in controls, both at the septum and lateral wall level. These strain and SR abnormalities were significantly related to body mass index. In addition, the early phase of diastolic function, evaluated using SR, was compromised in obese patients (P<0.001). The HOMA-IR values in obese patients were significantly higher (3.09±1.6) than those determined in the control group (0.92±0.5) (P<0.0001). The HOMA-IR values, in the obese group, were significantly related to systolic strain and SR values sampled at the septum level (P<0.0001).Conclusion:In conclusion, this study has demonstrated that obese patients pointed out systolic structural and functional abnormalities at a preclinical stage, in particular through strain and SR analysis; on the other hand, those altered CDMI parameters well distinguish obese subjects as compared with the control group. Furthermore, another main finding of the study was that myocardial deformation (systolic strain) could have a correlation with insulin resistance level.

Effects of anabolic-androgenic steroids on weight-lifters' myocardium : an ultrasonic videodensitometric study

BACKGROUND Recent bioptical data have shown that in weight-lifters (WL) under the pharmacological effects of anabolic-androgenic steroids (AAS), a focal increase in myocardial collagen content might occur as a reparative mechanism against a myocardial damage. OBJECTIVE The aim of this study was to investigate whether by using videodensitometry an early identification of the changes in myocardial texture is possible or a potential sign of myocardial damage, which can potentially occur in WL who have used AAS. METHODS Ten males WL (mean age: 32+/-6 yr) who had regularly used AAS (users), were compared with 10 male WL at same training level (nonusers), who had not used any drugs and with 10 healthy sedentary controls (controls). The three groups were age and sex-matched. Echocardiographic parietal, septal thickness, and left ventricular mass (LVMbs) were evaluated. Left ventricular systolic and diastolic functions were evaluated with Doppler examination. Quantitative analysis of echocardiographic digitized data was carried out with a calibrated 256 gray level digitization system, in order to calculate the mid-septum and the mid-posterior mean gray level (MGL) and to derive the cyclic variation index (CVI), i.e., the percent MGL variation during cardiac cycle. RESULTS The weight and relative body mass index were significantly higher in WL (P<0.001); also the diastolic blood pressure was slightly but significantly higher in users in comparison both with nonusers and controls (P<0.01). Systolic and diastolic functional parameters overlapped in the three groups. LVMbs was significantly higher in users (145+/-17) and in nonusers (122+/-27) vs. C (104+/-18 g x m(-2)) (p<0.001). CVI at septum level showed significant differences: users: (2.3+/-31%) vs nonusers: (23+/-8) and controls (29+/-5) (P<0.005); although no significant difference was found between nonusers and controls. CVI at posterior wall level followed a similar pattern. No relationship was found between CVI and LVMbs or wall thickness. DISCUSSION As brought out by videodensitometry, despite an increase in septal and parietal thickness and consequently in LVMbs, the physiological pressure overload that happens in WL during sport activities, in absence of any drugs, does not modify the myocardial ultrasonic texture. The abuse of AAS in WL, on the other hand, determines some alterations of the myocardial textural parameters. The real significance of these changes of myocardial texture detected with videodensitometry in WL who use anabolic-androgenic steroids, present also in the absence of other systolic and diastolic left ventricular functional indexes alterations, needs to be further explored with a larger population through the comparison with endobioptical data and with a follow-up study approach.

Transvascular and Urinary Leakage of Albumin in Atherosclerotic and Hypertensive Men

Increased urine albumin is associated with atherosclerotic disease and predicts cardiovascular morbidity and mortality in nondiabetic populations. This finding is frequently postulated to reflect the impact of atherosclerotic damage on glomerular and systemic capillary permeability, an interesting but as yet untested hypothesis. The transcapillary escape rate of albumin (TERalb, the 1-hour decline rate of intravenous 125I-albumin, a measure of capillary macromolecular permeability), albuminuria, lipid levels, echocardiographic wall thickness, and insulin responses to oral glucose were measured in 30 untreated dipstick-negative lean men and clinically stable atherosclerotic peripheral vascular disease; tolerance to oral glucose was a requirement for inclusion in the study. Because hypertension per se might influence TERalb, the sample included either normotensive (n=18, 118+/-6/72+/-7 mm Hg) or hypertensive (n=12, 141+/-7/84+/-6 mmHg by 24-hour blood pressure monitoring) arteriopathic patients; 11 normal age- and gender-matched subjects (121+/-7/76+/-5 mmHg) were used as control subjects. TERalb was higher in patients (10.7+/-3.2 versus 7.4+/-1.7%/h, P<0.013), a difference that persisted after postload glucose, insulin, and lipid levels were accounted for by covariance analysis; atherosclerosis and hypertension together did not further impair vascular permeation to albumin. In contrast with TERalb, albuminuria was elevated only in the hypertensive subgroup; the 2 variables showed no relationship, even when the data were analyzed separately in normotensive and hypertensive subgroups. Urine albumin correlated positively with 24-hour blood pressure and wall thickness. Thus, systemic capillary permeability is altered in nondiabetic atherosclerotic patients independently from blood pressure levels, but this abnormality is not reflected by proportionate changes in albuminuria.

Ultrasonic myocardial texture versus Doppler analysis in hypertensive heart : A preliminary study

-Doppler-derived parameters of transmitral flow are useful indices of diastolic dysfunction in the hypertensive heart. Different degrees of myocardial involvement in hypertensive heart can be detected by videodensitometric myocardial textural analysis. The aim of this study was to compare Doppler-derived and ultrasonic videodensitometric parameters in the differentiation of healthy hearts from hypertensive hearts. We compared a group of age-matched (59+/-9 years) male essential hypertensive patients (n=53) with normotensive healthy subjects as controls (n=32). All subjects provided ambulatory blood pressure measurements for the evaluation of 24-hour mean systolic and diastolic blood pressure. A transmitral flow Doppler analysis was performed on all subjects. A quantitative analysis of the echocardiographic digitized imaging was performed with the help of a calibrated digitization system to calculate the septum and the posterior wall textural parameters. The myocardial mean gray level (MGL) was calculated to derive the cyclic variation index (CVI): (MGLend-diastolic-MGLend-systolic)/MGLend-diastolic x100. When compared with controls, the hypertensive patients showed a significantly lower CVI for both septum (-11.1+/-26.8% versus 34. 7+/-16.3%; P<0.001) and posterior wall (-11.2+/-27.6% versus 38. 2+/-15.4%; P<0.001). Individual analyses for the ratio of peak transmitral flow velocity in early diastole to the peak transmitral flow velocity in late diastole showed that only 24% of the patients (13/53) were discriminated from normal subjects by this parameter. Individual analyses for CVI, however, at both septum and posterior wall levels, showed that 74% of the patients (39/53) were discriminated from normal subjects by this second parameter. In comparison with Doppler-derived indices of diastolic filling, the videodensitometric parameters showed a significantly higher ability to discriminate between hypertensive subjects and normal controls.