L Talarico

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.

Increased echodensity of myocardial wall in the diabetic heart: An ultrasound tissue characterization study

OBJECTIVES We sought to characterize myocardial echodensity in asymptomatic patients with insulin-dependent diabetes and normal conventional two-dimensional echocardiographic findings to determine whether ultrasound tissue characterization can detect ultrastructural changes in myocardium, such as an increase in collagen content. BACKGROUND Fibrosis alters the acoustic properties of the heart in animals and humans, and these changes are detectable by cardiac tissue characterization with ultrasound. Early changes detected in the diabetic heart include increased interstitial collagen deposition. METHODS Using two-dimensional echocardiography, we evaluated 26 asymptomatic patients with insulin-dependent diabetes with normal regional and global rest function, and 17 age- and gender-matched control subjects. By selection, all diabetic patients were normotensive and had negative maximal exercise stress test results to avoid the confounding effects of hypertension and coronary artery disease. Using an echocardiographic instrument implemented at the Institute of Clinical Physiology, we performed an on-line radiofrequency analysis to obtain quantitative operator-independent measurements of the integrated back-scatter signal of the ventricular septum and posterior wall. The integrated values of the radiofrequency signal from the myocardial wall were normalized for those from the pericardial interface and were expressed as percentages (integrated backscatter index). RESULTS Diabetic patients showed a significant increase in myocardial echodensity both in the septum ([mean +/- SD] 36.6 +/- 8.1 vs. 23.6 +/- 4.4, p < 0.0001) and posterior wall (21.2 +/- 5.3 vs. 18.4 +/- 3.7, p < 0.001). By individual patient analysis, 17 patients exceeded the 95% confidence limits for normal myocardial echocardiographic reflectivity found in normal subjects, and only 3 had a relatively abnormal transmitral Doppler filling pattern (E/A ratio), mainly consisting of an abnormally increased late peak flow velocity (65% vs. 11%, p < 0.001). The increased myocardial intensity was similar in patients with (n = 16) and without (n = 10) noncardiac complications, such as retinopathy or nephropathy (37.5 +/- 7.9% vs. 35.0 +/- 8.3%, p = 0.35). CONCLUSIONS Abnormally increased myocardial echodensity, possibly related to collagen deposition, can be detected in asymptomatic diabetic patients with normal rest function. Theoretically, this finding might be considered a very early preclinical alteration potentially related to subsequent development of diabetic cardiomyopathy.

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)

Incremental diagnostic value of dobutamine stress echocardiography and dobutamine scintigraphy (technetium 99m-labeled sestamibi single-photon emission computed tomography) for assessment of presence and extent of coronary artery disease

BackgroundThe incremental diagnostic value of dobutamine stress echocardiography (DSE) and 99mTc-labeled sestamibi single-photon emission computed tomography for the evaluation of the presence and extent of coronary artery disease (CAD) was assessed with ordered logistic regression and receiver-operating characteristic curves.Methods and ResultsForty-five consecutive patients (33 men and 12 women; 53±6.8 years) underwent exercise electrocardiography and simultaneous DSE and sestamibi single-photon emission computed tomographic imaging. Coronary angiography was performed in all patients (significant coronary stenosis >50%). On the basis of the results of exercise electrocardiography, the pretest probability for CAD (Diamonds algorithm) was low (45.6%±12.7%). According to ordered logistic regression analysis, some models were estimated that performed a diagnostic accuracy level for CAD. In particular, we evaluated a clinical model (model 1) determined by the following parameters: sex, age, presence of chest pain, and positivity of electrocardiogram during dobutamine stress test. This model was 64.3%±10.7% accurate for the prediction of CAD. The addition to model 1 of DSE parameters (wall motion stress and rest score index and relative difference) (model 2) yielded a diagnostic accuracy of 81.4%±4.3% (p<0.045), whereas the addition to model 1 of single-photon emission computed tomographic parameters (the difference between perfusional stress and rest score index) (model 3) improved diagnostic accuracy to 92.3%±5.5% (p<0.003), a level that appeared significantly higher than that of model 2 (p<0.016).ConclusionBoth noninvasive methods for the detection of CAD showed a good diagnostic accuracy, especially when test-derived parameters were combined with clinical data. Nevertheless, the single-photon emission computed tomographic model showed a higher sensitivity compared with the DSE model.

Myocardial and forearm blood flow reserve in mild-moderate essential hypertensive patients

Background Structural readaptation of systemic resistance-sized arterioles in response to an elevated blood pressure reduces the forearm vasodilator reserve in patients with essential hypertension. The development of a similar process at the coronary microvascular level has frequently been hypothesized, but little information about coronary remodeling during the uncomplicated stage of hypertension has been obtained, and the relationship with concomitant changes in forearm blood flow reserve is not known. Objective To assess the minimal myocardial resistance and its relationship with the minimal forearm resistance in a group of male patients with mild-to-moderate uncomplicated hypertension and carefully matched controls. Material and methods The minimal myocardial resistance (Rminmyocardial, the mean arterial pressure: hyperemic myocardial flow ratio after administration of 0.84 mg/kg dipyridamole, measured by using positron emission tomography and [13N]-ammonia), minimal forearm vascular resistance (Rminforearm, a hemodynamic index of arteriolar structure derived from the mean blood pressure and maximal postischemic forearm blood flow by venous plethysmography), echocardiographic cardiac mass and wall thickness were measured in 25 male patients with mild-to-moderate uncomplicated essential hypertension, most of whom had previously been treated, and in seven sex- and age-matched normotensive controls. Results Rminmyocardial (and hyperemia: baseline myocardial flow ratios) did not differ significantly between the two groups, whereas Rminforearm was significantly higher in hypertensives. There was no significant intraindividual correlation between the two parameters. The left ventricular mass index was greater in patients and was related positively to Rminforearm but not to Rminmyocardial for the overall sample. In a subgroup analysis, Rminforearm values were 2SD above control values in nine patients and within the normal range in the remaining 16. The myocardial reserve was very similar in the two subgroups. Conclusions The myocardial vasodilator reserve appeared to be preserved in these mild-to-moderate uncomplicated hypertensive patients, whereas the forearm vasodilator capacity was reduced, suggesting that the hypertensive readaptation process was not distributed homogeneously over the two vascular beds.

Increased Myocardial Ultrasonic Reflectivity is Associated With Extreme Hypertensive Left Ventricular Hypertrophy A Tissue Characterization Study in Humans

We assessed myocardial reflectivity pattern in a large spectrum of left ventricular mass values, covering the extremes from absent to severe myocardial hypertensive hypertrophy. Quantitatively assessed ultrasonic backscatter is an index of ultrasonic tissue characterization directly related to the morphometrically evaluated collagen content in humans. We enrolled 88 essential hypertensives. With an echo prototype implemented in our Institute, integrated values of the radiofrequency signal of myocardial walls were obtained and normalized for those of the pericardium (Integrated Backscatter Index, IBI, %). Left ventricular mass index (LVMI) was measured by Devereux formula. There was a weak correlation between septal IBI and LVMI (r = 0.35; P < .001). On the basis of LVMI values, three groups of hypertensives were identified, with absent (Group I, n = 23; LVMI < 125 g/m2), mild to moderate (Group II, n = 44; LVMI from 125 to 174 g/m2), or severe (Group III, n = 21; LVMI > 175 g/m2) left ventricular hypertrophy. The Integrated Backscatter Index in the septum was lower in patients of Group I (IBI = 23.3% +/- 3.6%) and II (IBI = 26.5 +/- 7.6; P = NS v Group I), in comparison with patients of Group III (IBI = 31.1 +/- 5.9; P < .02 v II; P < .0001 v I). An increased myocardial wall reflectivity is detectable only in the presence of extreme forms of hypertensive left ventricular hypertrophy.

Increased myocardial echo density in left ventricular pressure and volume overload in human aortic valvular disease: an ultrasonic tissue characterization study.

Quantitatively assessed ultrasonic backscatter is an index of ultrasonic tissue characterization directly related to morphometrically evaluated collagen in human beings. Our objective was to assess myocardial reflectivity pattern of patients with severe left ventricular hypertrophy caused by either aortic stenosis (AS) or aortic regurgitation (AR). Ten patients with AS, 10 patients with AR, and 10 closely age- and gender-matched healthy controls were studied by two-dimensional Doppler echocardiography. By using an echocardiographic prototype, we performed a radiofrequency analysis to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and the posterior wall (integrated backscatter index: IBI, expressed in percentage). All patients with stenosis or aortic insufficiency showed a normal regional and global resting systolic function (fractional shortening: AS = 36.0 +/- 6.6 versus AR = 40.3 +/- 6.2 versus control = 40.2 +/- 8.7; p = not significant [NS]) Left ventricular mass index (Devereuxs formula) was markedly increased in patients with stenosis or aortic insufficiency (AS = 199.3 +/- 18 versus AR = 208.8 +/- 60 versus control = 97.3 +/- 11 g/m2; p < 0.0001). Myocardial echo density was increased in patients with stenosis or aortic insufficiency in comparison with controls, both in the septum (IBI%: AR = 40.7 +/- 7.9 versus AS = 33.4 +/- 4.2 versus control = 23.0 +/- 6.2; p < 0.0001) and in the posterior wall (IBI%: AR = 27.1 +/- 4.3 versus AS = 23.0 +/- 2.6 versus control = 15.0 +/- 4.2; p < 0.0001). No significant correlations were found between septal and posterior wall IBI and their thickness. Abnormally increased myocardial echo density--possibly related to disproportionate collagen deposition--can be detected in patients with pressure or volume overload caused by aortic valve disease and without overt systolic dysfunction.

Microalbuminuria and Erythrocyte Sodium-Hydrogen Exchange in Essential Hypertension

Microalbuminuria (urinary albumin excretion between 20 and 200 micrograms/min) and abnormalities of red blood cell sodium-hydrogen exchange coexist in essential hypertensive patients. To evaluate how the two phenomena relate, we recruited 10 untreated microalbuminuric male essential hypertensive patients without diabetes to be compared with an equal number of matched essential hypertensive patients excreting albumin in normal amounts as well as 10 healthy control subjects. Sodium-hydrogen exchange values were increased to a comparable extent in microalbuminuric and normoalbuminuric hypertensive patients. Systolic and mean blood pressures were higher in microalbuminuric patients. Fasting insulin was greater and high-density lipoprotein cholesterol lower in patients than control subjects. Urinary albumin excretion correlated positively with both mean blood pressure and left ventricular mass values in the absence of a relationship with circulating lipid and insulin levels. In contrast with microalbuminuria, sodium-hydrogen exchange covaried only with high-density lipoprotein cholesterol and insulin levels. Thus, microalbuminuria and an abnormal sodium-hydrogen exchange are unrelated phenomena in essential hypertensive patients. Microalbuminuria appears to be a hemodynamically driven biological variable, while an accelerated sodium-hydrogen exchange seems primarily conditioned by the metabolic abnormalities of hypertension, possibly in the context of an insulin-resistant syndrome.