Anorexia nervosa and heart disease: a systematic review.

Anorexia nervosa (AN) is an eating disorder that most frequently afflicts females in adolescence. In these subjects, cardiovascular complications are the main cause of morbidity and mortality. Aim of this review is to analyze the hemodynamic, pro-arrhythmic and structural changes occurring during all phases of this illness, including re-feeding. A systematic literature search was performed on studies in the MEDLINE database, from its inception until September 2017, with PUBMED interface focusing on AN and cardiovascular disease. This review demonstrated that the most common cardiac abnormalities in AN are bradycardia and QT interval prolongation, which may occasionally degenerate into ventricular arrhythmias such as Torsades des Pointes or ventricular fibrillation. As these arrhythmias may be the substrate of sudden cardiac death (SCD), they require cardiac monitoring in hospital. In addition, reduced cardiac mass, with smaller volumes and decreased cardiac output, may be found. Furthermore, mitral prolapse and a mild pericardial effusion may occur, the latter due to protein deficiency and low levels of thyroid hormone. In anorectic patients, some cases of hypercholesterolemia may be present; however, conclusive evidence that AN is an atherogenic condition is still lacking, although a few cases of myocardial infarction have been reported. Finally, refeeding syndrome (RFS), which occurs during the first days of refeeding, may engender a critically increased risk of acute, life-threatening cardiac complications.

Sub-clinical organ damage in hypertension and obesity.

BACKGROUND: The development of sub-clinical organ damage precedes and predicts the occurrence of cardiovascular (CV) events in hypertensive as well as in obese patients. AIM AND METHODS: We investigated the prevalence and clinical correlates of organ damage (OD), namely carotid atherosclerosis (US scan) and urine albumin to creatinine ratio (three non-consecutive first morning samples) in a group of 164 obese patients and in an age- and gender-matched group of non-obese hypertensive patients. RESULTS: There was a significantly greater prevalence and severity of OD in obese patients as compared to non-obese hypertensive patients. In particular obese patients more frequently had microalbuminuria (16 vs 7%, χ(2) 5.8, P=0.0157) and carotid abnormalities (53 vs 10%, χ(2) 69.5, P<0.0001) as well as higher urinary albumin excretion rate (-0.05 ± 0.52 vs -0.28 ± 0.43log ACR, P<0.0001) and carotid intima-media thickness (0.955 ± 0.224 vs 0.681 ± 0.171, <0.0001). Notably, the coexistence of hypertension and obesity did not entail a greater prevalence and severity of OD. Moreover, after adjusting for potentially confounding factors including blood pressure levels, diagnosis of diabetes, and lipid profile, morbidly obese patients showed a 5-fold, and 22-fold higher risk of having microalbuminuria, and carotid atherosclerosis, respectively. CONCLUSIONS: Sub-clinical OD is highly prevalent in obese patients, even in the absence of high blood pressure. Hypertension and obesity seem to exert an independent, possibly non-additive role on the occurrence of organ damage.

Hypoadiponectinemia in lipodystrophic HIV individuals: a metabolic marker of subclinical cardiac damage.

BACKGROUND AND AIM: To evaluate cardiovascular abnormalities in highly active antiretroviral therapy (HAART) treated HIV patients with no signs or symptoms of cardiovascular impairment, and to assess the relative role of multiple concomitant risk factors. METHODS AND RESULTS: Forty-four consecutive HIV subjects (mean age 41+/-6 yrs) were enrolled. Inclusion criteria were HIV infection, CD4+cell count>150/ml, HAART treatment for at least 4 years. Metabolic serum levels, morphological and functional echocardiographic parameters were assessed in all subjects. Sixteen healthy age and sex matched subjects with no cardiovascular risk factors were recruited as controls. HIV patients showed increased left ventricular mass index with reduced mid-wall fractional shortening (mFS) when compared to controls (50.2+/-10.5 vs. 38.6+/-14.4, p=0.05 and 18.3+/-0.6 vs. 21.9+/-0.7, p<0.05, respectively). Twenty-nine patients were lipodystrophic (LD) and showed a longer HAART period (p=0.0004) and greater use of protease inhibitors (PI) (p=0.001). Coronary flow reserve (CFR) was significantly reduced in HIV patients as compared to controls (p<0.0001), as it was in LD subjects when compared to non-lipodystrophic ones (NLD) (p<0.001). Adiponectin concentrations were found to be significantly lower in LD subjects than in NLD ones (7.8+/-0.8 vs. 13.8+/-1.2 microg/ml, p=0.01), and showed a direct correlation with CFR. In multiple regression analysis, insulin, HDL and adiponectin accounted for 63% of CFR variations. CONCLUSIONS: Left ventricular hypertrophy, depressed mFS and reduced CFR represent the main signs of subclinical cardiac damage in HIV subjects treated with HAART. Hypoadiponectinemia in these subjects seems to be a metabolic risk factor of cardiovascular impairment.

Metabolic syndrome is associated with left ventricular dilatation in primary hypertension.

Metabolic syndrome (MS) has been shown to predict cardiovascular events in hypertension. Recently, a new four-group left ventricular (LV) hypertrophy classification based on both LV dilatation and concentricity was proposed. This classification has been shown to provide a more accurate prediction of cardiovascular events, suggesting that the presence of LV dilatation may add prognostic information. We investigated the relationship between MS and the new classification of LV geometry in patients with primary hypertension. A total of 372 untreated hypertensive patients were studied. Four different patterns of LV hypertrophy (eccentric nondilated, eccentric dilated, concentric nondilated and concentric dilated hypertrophy) were identified by echocardiography. A modified National Cholesterol Education Program definition for MS was used, with body mass index replacing waist circumference. The overall prevalence of MS and LV hypertrophy (LVH) was 29% and 61%, respectively. Patients with MS showed a higher prevalence of LVH (P=0.0281) and dilated LV geometries, namely eccentric dilated and concentric dilated hypertrophy (P=0.0075). Moreover, patients with MS showed higher LV end-diastolic volume (P=0.0005) and prevalence of increased LV end-diastolic volume (P=0.0068). The prevalence of LV chamber dilatation increased progressively with the number of components of MS (P=0.0191). Logistic regression analysis showed that the presence of MS entails a three times higher risk of having LV chamber dilatation even after adjusting for several potential confounding factors. MS is associated with LV dilatation in hypertension. These findings may, in part, explain the unfavourable prognosis observed in patients with MS.

Infective endocarditis in hypertrophic cardiomyopathy: prevalence, incidence, and indications for antibiotic prophylaxis.

BACKGROUND: The literature on infective endocarditis in hypertrophic cardiomyopathy (HCM) is virtually confined to case reports. Consequently, the risk of endocarditis in HCM remains undefined. METHODS AND RESULTS: We assessed the occurrence of endocarditis in 810 HCM patients evaluated between 1970 and 1997. Endocarditis was diagnosed in 10 patients, 2 of whom were excluded from analysis of prevalence and incidence because they were referred for acute endocarditis. At first evaluation, echocardiographic features consistent with prior endocarditis were identified in 3 of 808 patients, a prevalence of 3.7 per 1000 patients (95% CI, 0.8 to 11). Of 681 patients who were followed, 5 developed endocarditis, an incidence of 1.4 per 1000 person-years (95% CI, 0.5 to 3.2); outflow obstruction was present in each of these 5 patients and was associated with the risk of endocarditis (P=0.006). In the 224 obstructive patients, incidence of endocarditis was 3.8 per 1000 person-years (95% CI, 1.6 to 8.9) and probability of endocarditis 4. 3% at 10 years. Left atrial size was also associated with the risk of endocarditis (P=0.007). In patients with both obstruction and atrial dilatation (>/=50 mm), incidence of endocarditis increased to 9.2 per 1000 person-years (95% CI, 2.5 to 23.5). Analysis of all 10 patients with endocarditis identified outflow obstruction in each and atrial dilatation in 7. CONCLUSIONS: Endocarditis in HCM is virtually confined to patients with outflow obstruction and is more common in those with both obstruction and atrial dilatation. These results indicate that antibiotic prophylaxis is required only in patients with obstructive HCM.

Left ventricular geometry and function in patients with essential hypertension and microalbuminuria.

BACKGROUND: Microalbuminuria has recently emerged as a strong, independent predictor of cardiovascular mortality in patients with essential hypertension, yet the pathophysiological mechanisms underlying this association remain to be elucidated. OBJECTIVE: To study the relationship between microalbuminuria and left ventricular geometry and function and extra-cardiac vascular changes in a group of 211 untreated hypertensive patients. METHODS: Albuminuria was evaluated as albumin-to-creatinine ratio in three non-consecutive first morning urine samples. Left ventricular mass index and function were assessed by M-B mode echocardiography and carotid wall thickness by high-resolution ultrasound scan. RESULTS: The prevalences of microalbuminuria and left ventricular hypertrophy were 14 and 47% respectively. Patients in the top quartile of albuminuria showed a higher left ventricular mass index (57 +/- 1.8, 55 +/- 2, 47 +/- 1.4 and 48 +/- 1.6 g/m2.7, respectively; P< 0.0001) as well as a higher prevalence of left ventricular hypertrophy (72, 65, 26 and 25%, respectively; P< 0.001) and especially concentric hypertrophy (56, 47, 17 and 21%, respectively; P< 0.0001) in the four quartiles of albuminuria. Microalbuminuric patients showed depressed left ventricular performance as indicated by a reduced midwall fractional shortening (15.7 +/- 0.3, 15.9 +/- 0.3, 16.7 +/- 0.4 and 16.8 +/- 0.3%, respectively; P< 0.02). Furthermore patients in the top quartile of albuminuria showed increased carotid wall thickness as compared to normoalbuminuric patients (0.78 +/- 0.03, 0.7 +/- 0.04, 0.65 +/- 0.03 and 0.6 +/- 0.03 mm, respectively; P < 0.001). CONCLUSIONS: Hypertensive patients with microalbuminuria show a higher prevalence of unfavourable left ventricular geometric patterns, depressed left ventricular function and early signs of extra-cardiac vascular damage. These findings strengthen the role of microalbuminuria as an indicator of subclinical cardiovascular disease and may account for the worse outcome that is usually associated with increased urinary albumin excretion in essential hypertension.

Detection of acute myocardial infarction by 99mTc-labeled D-glucaric acid imaging in patients with acute chest pain.

UNLABELLED: Definitive diagnosis of acute myocardial infarction early in the process is often difficult. An imaging agent that localized quickly and specifically in areas of acute necrosis could provide this critical diagnostic information. To determine whether imaging with 99mTc-labeled D-glucaric acid (GLA) could provide this information, we imaged a group of patients presenting with symptoms suggestive of acute infarction. METHODS: Twenty-eight patients presenting to the emergency department with symptoms highly suggestive of acute infarction were injected with 99mTC-GLA and imaged about 3 h later. RESULTS: The sensitivity of lesion detection was remarkably time dependent. Fourteen patients with acute infarction injected within 9 h of onset of chest pain had positive scans, even in the presence of persistent occlusion. The remaining 14 patients had negative scans. Nine patients with negative scans had acute infarction but were injected more than 9 h after onset of chest pain. The final diagnosis in the remaining 5 patients was unstable angina (3 injected <9 h and 2 injected >9 h after onset of chest pain). Six patients were reinjected with 99mTc-GLA 4-6 wk after their initial study to determine whether persistent positive scans occurred with this agent. All 6 had negative scans. CONCLUSION: This study suggests that 99mTc-GLA localizes in zones of acute myocardial necrosis when injected within 9 h of onset of infarction.

Perfusional and metabolic effects of nisoldipine as shown by positron emission tomography after acute myocardial infarction.

After myocardial infarction, regional dysfunction can occur in viable myocardial regions because of the presence of baseline hypoperfusion. Recent evidence suggests that these areas may maintain a residual perfusion reserve. The aim of the present study was to evaluate whether oral nisoldipine can increase regional myocardial blood flow (MBF) in dyssynergic but viable myocardium after myocardial infarction. Patients with isolated left anterior descending coronary stenosis were studied 1 month after the first myocardial infarction. Patients underwent [18F]fluorodeoxyglucose imaging, and MBF was measured, using positron emission tomography and [13N]ammonia, at baseline and following dobutamine administration (10 micrograms/kg/min over 5 minutes). MBF measurements were repeated 24 hours after nisoldipine (10 mg twice daily). Preliminary results suggest that necrotic areas showed the largest reduction in baseline MBF. Dyssynergic-viable regions showed a reduced resting MBF but maintained a residual perfusion reserve in response to inotropic stimulation. Thus, nisoldipine selectively improved basal perfusion in dyssynergic-viable myocardium.

Ventricular septal rupture after myocardial infarction. Detection by transesophageal echocardiography.

Acute rupture of the interventricular septum is a relatively unusual complication following acute myocardial infarction. The echocardiographic features depicted by transthoracic echocardiography are well described. However, transesophageal echocardiographic description of a ruptured septum has not been previously reported. This brief report illustrates the transesophageal features of such a defect.

Microalbuminuria is an early marker of target organ damage in essential hypertension.

Microalbuminuria has been associated with a cluster of metabolic and nonmetabolic risk factors, suggesting that it might indicate the presence of generalized microvascular damage in patients with essential hypertension. To explore whether microalbuminuria is associated with early target organ damage, two groups of essential hypertensive patients, with (n = 17) (HtAlb+) and without (n = 16) (HtAlb-) microalbuminuria, and a control group (C) of healthy normotensive subjects (n = 20) were studied. The study groups, selected among participants of a large epidemiologic trial, were carefully matched for several potentially confounding variables such as gender, age, duration of hypertension, and body mass index. Albumin excretion rate was evaluated by radioimmunoassay in three nonconsecutive timed overnight collections after 3 weeks of pharmacologic wash-out. Left ventricular mass was assessed by M-B-mode echocardiography, carotid wall thickness by a high resolution ultrasound scan, and renal vascular impedance by Doppler scan. Office as well as 24-h ambulatory pressure monitoring (Takeda TM-2420) were also evaluated. There was no difference between the two hypertensive groups for office and 24-h blood pressure levels except for a lower daytime/nighttime systolic blood pressure ratio in the group with microalbuminuria. Microalbuminuric patients showed signs of early organ damage as compared to normoalbuminuric patients and normal subjects, namely greater left ventricular mass indices (LVMI 167+/-7 g/m2 in HtAlb+; 139+/-9 g/m2 in HtAlb-; 118+/-5 g/m2 in C, P < .001) and increased wall thickness of common carotid arteries (intima plus media thickness 12.5+/-0.2 mm in HtAlb+; 11.7+/-0.3 mm in HtAlb-; 11.2+/-0.2 mm in C, P < .001) as well as higher intrarenal vascular resistance (mean resistive index 0.62+/-0.01 in HtAlb+; 0.59+/-0.01 in HtAlb-; 0.59+/-0.01 in C, P < .05). In conclusion, microalbuminuria is an early marker of diffuse target organ damage in essential hypertension and therefore can be useful to identify patients for whom more aggressive preventive strategies or additional treatment measures are advisable.

5,10-Methylenetetrahydrofolate reductase polymorphism and early organ damage in primary hypertension.

Hyperhomocyst(e)inemia is a known risk factor for the development of atherosclerotic vascular damage. Plasma homocyst(e)ine levels are influenced by nutritional and hereditary factors. A point mutation (cytosine to thymidine substitution; C677T) in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) makes the enzyme thermolabile and has been associated with elevated homocyst(e)ine levels in homozygous carriers (TT genotypes). We evaluated the relationship between the T allele encoding for the thermolabile variant of MTHFR and several biochemical risk factors and early signs of hypertensive and atherosclerotic organ damage in 206 untreated patients with primary hypertension. The MTHFR genotype was evaluated by polymerase chain reaction. Albuminuria was measured as albumin-to-creatinine ratio in three nonconsecutive first morning urine samples (negative urine culture). Persistent Mi (Alb+) was defined as an average albumin-to-creatinine ratio between 2.38 and 19 (men) and 2.96 and 20 (women). Left ventricular (LV) mass index (LVMI) was assessed by M-B mode echocardiography (LV hypertrophy, LVH = LVMI > or = 125 g/m2), carotid geometry by high-resolution ultrasound scan, and retinal vascular changes by direct ophthalmoscopy (Keith-Wagener classification). The prevalence of Mi, LVH, and retinopathy was 14%, 45%, and 42%, respectively. The prevalence of carotid plaque was 25%. Allele frequencies for C (wild-type allele) and T allele (mutant allele) were 56% and 44%, respectively. Genotype frequencies were CC 29%, CT 54%, TT 17% according to Hardy Weinberg equilibrium. There were no differences as for age, sex, body mass index, blood pressure levels, lipid profile, smoking habits, and alcohol intake, and LVMI and urinary albumin excretion on the basis of MTHFR genotype. Patients with TT polymorphism showed a higher prevalence of retinal vascular changes (TT, 61% v CT + CC, 38%; P < .02) and carotid plaque (TT, 42% v CT + CC, 21%; P < .05) compared to patients with CC and CT polymorphism. Moreover, patients with T allele showed increased carotid artery size as demonstrated by intima plus media thickness (IT, 0.79 +/- 0.05 mm v CT + CC, 0.67 +/- 0.02 mm; P < .02), relative wall thickness (TT, 0.23 +/- 0.01 mm v CT + CC, 0.20 +/- 0.005 mm; P < .02), and surface area (TT, 19 +/- 1.9 mm2 v CT + CC, 15 +/- 0.55 mm2; P < .05). Multiple linear regression analysis demonstrated that MTHFR genotype and systolic blood pressure independently influence intima-media thickness and together account for about 11% of its variations (r2 = 0.11, F = 9.7, dF = 1-205, P < .0001). Homozygosity for the T allele of the MTHFR gene is an independent risk factor for the development of early atherosclerotic organ damage in hypertensive patients.

Microalbuminuria: a marker of cardiovascular risk and organ damage in essential hypertension.

Microalbuminuria (Mi) is thought to reflect diffuse vascular damage and to predict cardiovascular morbidity and mortality in essential hypertension, although its pathogenesis remains to be fully elucidated. The relationship between microalbuminuria and several cardiovascular risk factors and target organ damage was evaluated in a large cohort of untreated essential hypertensive patients. Albuminuria was measured as the albumin to creatinine ratio in three non consecutive first morning urine samples. Cardiac damage was evaluated by ECG and retinal vascular changes by direct ophtalmoscopy. In a subgroup of 23 patients with Mi and in a control group of 22 normoalbuminurics, selected from the entire cohort of patients and carefully matched for age, gender, body mass index (BMI) and duration of disease, we also measured left ventricular mass index by M-B mode echocardiography, common carotid wall thickness by high resolution US-scan, and renal vascular resistances by US-doppler of interlobar arteries. K-means cluster analysis performed on the entire cohort of patients showed that microalbuminuria is associated with the presence of an unfavorable risk profile and target organ damage. Furthermore, microalbuminuric hypertensive patients have a larger left ventricular mass index, increased intima media thickness of carotid arteries and higher intrarenal vascular resistances as compared to a well matched group of normoalbuminuric patients. We conclude that in essential hypertension increased urinary albumin excretion can be useful to identify patients for whom more aggressive preventive strategies and/or additional treatment measures are advisable.

Hemodynamic effects of microbubble echo contrast.

The dose-related hemodynamic effects of an active (bubble-rich) echo contrast agent were compared with those of a bubble-free contrast agent and saline solution to determine whether the microbubbles contained in the echo contrast agent are truly passive indicators in the circulation or whether they actively alter the hemodynamic state independent of the volume and osmotic loading associated with such injections. The study population consisted of 13 fully instrumented open-chest mongrel dogs. Four hundred ninety-two bolus injections were made of three different types: active contrast agent (Levovist, Schering AG, Berlin) (n = 333), saline solution (n = 112), and bubble-free contrast agent (n = 47). Levovist was administered in five dose ranges spanning 0.013 to 0.341 gm/kg and, like the saline solution, was administered in bolus volumes of 0.053 to 1.136 ml/kg. For each injection type, the percent change in hemodynamic parameters after administration of the bolus were calculated on the basis of the dose or volume of the injectate. Audio Doppler signal intensity was used to document the presence of bubbles in the injectate. Statistical significance was defined at the p = 0.05 level; clinical significance was defined as a greater than 15% change in a hemodynamic parameter. Statistically, but not clinically, significant changes were noted in almost all hemodynamic parameters regardless of injection type, and at all dose and volume ranges. Although statistically significant, injection of an active contrast agent in the human dose range resulted in a < 5% change in hemodynamic parameters. High doses of a contrast agent (active or bubble-free) increased the left atrial pressure and had associated changes in peripheral vascular hemodynamics because of the osmotic load. Clinically significant increases (> 15%) in pulmonary artery pressure and pulmonary vascular resistance were unique to the active contrast agent at high dose ranges. Standard doses of the active contrast agent changed the hemodynamics by less than 5% in healthy dogs. Transient clinically significant increases in pulmonary artery pressure and pulmonary vascular resistance are a unique side effect to high dose bolus injections of microbubble echo contrast agent.

Contrast harmonic color Doppler left ventriculography: machine-interpreted left ventricular ejection fraction compared with equilibrium-gated radionuclide ventriculography.

BACKGROUND: Multi-gated acquisition (equilibrium-gated radionuclide ventriculography) (MUGA) is considered the gold standard for measuring left ventricular ejection fraction (LVEF) because it is accurate, machine interpreted, and reproducible. Echocardiographic LVEF measurements are subject to variability in image acquisition and interpretation and to the limitations of 2-dimensional (2D) versus 3-dimensional imaging. GOAL: The shortcomings of traditional echocardiography may be addressed by combining multiplane 2D harmonic imaging, echocardiographic contrast, color Doppler ultrasonography, and digital image processing to create a new imaging modality: contrast harmonic color Doppler left ventriculography. METHODS: We compared the accuracy of a new method for measuring LVEF that allows for machine interpretation and uses contrast-enhanced intermittent harmonic color Doppler ultrasonography (CHCD). Quantitative LVEF measurements by hand-traced harmonic 2D echocardiography, contrast-enhanced harmonic 2D echocardiography, CHCD, and machine-interpreted CHCD were compared with MUGA in 35 patients. RESULTS: Contrast-enhanced intermittent harmonic color Doppler provided images with vivid endocardial definition in all patients, but hand-traced harmonic 2D echocardiography and contrast-enhanced harmonic 2D echocardiography had inadequate images in 9% of patients. The MUGA LVEF range was 0. 09 to 0.70. All echocardiographic methods showed excellent correlation with the MUGA LVEF (R (2) > 0.96), but the CHCD method had the best limits of agreement. CONCLUSIONS: Contrast-enhanced intermittent harmonic color Doppler LVEF correlates with MUGA at least as well as traditional noncontrasted echocardiography, but it provides diagnostic images in a greater proportion of patients. The CHCD images have vivid endocardial delineation and can be machine interpreted.

Microalbuminuria is an integrated marker of subclinical organ damage in primary hypertension.

Increased urine albumin excretion is associated with an unfavourable cardiovascular risk profile and prognosis in primary hypertension, even though its pathogenesis is currently unknown. Microalbuminuria (Mi) has been proposed as an integrated marker to identify patients with subclinical organ damage, but its routine use is still too often neglected in clinical practice. The aim of our study was to evaluate the relationship between urinary albumin excretion and early signs of subclinical target organ damage (TOD), namely left ventricular hypertrophy and carotid atherosclerosis in a large group of non diabetic hypertensive patients. A group of 346 never treated patients with primary hypertension (212 men, 134 women, mean age 47 +/- 9 years) referred to our clinic were included in the study. They underwent the following procedures: (1) family and personal medical history and physical examination; (2) clinical blood pressure measurement; (3) routine blood chemistry and urine analysis including determination of urinary albumin excretion (ACR); (4) electrocardiogram; (5) ultrasound evaluation of left ventricular mass (LVMI) and carotid artery thickness (IMT). The overall prevalence of Mi, left ventricular hypertrophy, and carotid plaque was 13, 51, and 24% respectively. Mi was significantly correlated with LVMI (P < 0.0001), IMT (P < 0.0001) and several metabolic and non-metabolic risk factors (blood pressure, body mass index, serum lipids). Cluster analysis identified three subgroups of patients who differ significantly with regards to TOD and albuminuria (P < or = 0.001 for each of the examined variables). Patients with higher IMT and LVMI values also showed increased ACR levels. Furthermore, patients with microalbuminuria were more likely to have both LVH and IMT values above the median for the study population (OR 21, C.I. 4.6-99.97, P < 0.0001). Mi is an integrated marker of subclinical organ damage in patients with primary hypertension. Evaluation of urinary albumin excretion is a specific, cost-effective way to identify patients at higher risk for whom additional preventive and therapeutic measures are advisable.

Long term effect of nifedipine GITS and lisinopril on subclinical organ damage in patients with essential hypertension.

BACKGROUND: Preventing subclinical organ damage is currently a major issue in the management of patients with essential hypertension. Antihypertensive drugs which act through different pathophysiological mechanisms might confer specific target organ protection beyond what is already provided by their blood pressure lowering effect. METHODS: Thirty-one patients with essential hypertension were randomized to receive long-term treatment with either a calcium channel blocker (nifedipine GITS, 90 mg/day) or an ACE-inhibitor (lisinopril, 20 mg/day). Blood pressure, left ventricular mass, carotid wall thickness and timed urinary albumin excretion were measured at baseline and over the course of 24 months of treatment. RESULTS: Both regimens significantly lowered mean blood pressure over the 24 months (from 124+/-2 to 103+/-2 mmHg in the lisinopril group and from 122+/-2 to 104+/-1 in the nifedipine group). Overall, end-organ damage improved with persistent blood pressure control. However, the two treatments had different specific effects. Lisinopril induced a more pronounced reduction of the left ventricular mass index (from 56+/-3 to 52+/-2 g/m2.7, P< 0.05) and urinary albumin excretion (from 34+/-15 to 9+/-2 microg/min, P< 0.01), while nifedipine achieved a greater reduction of carotid intima plus media thickness (from 0.8+/-0.06 to 0.6+/-0.06 mm, P< 0.01). CONCLUSIONS: Blood pressure control does help reduce the severity of organ damage in patients with essential hypertension. Different antihypertensive treatments may confer additional specific cardiorenal and vascular protection regardless of blood pressure control. These data could be useful when devising individualized therapeutic strategies in high-risk hypertensive patients.

When can Doppler be used in place of integrated backscatter as a measure of scattered ultrasound intensity?

The purpose of this work was to determine under what circumstances the intensity of Doppler audio signals can be used as a substitute for the more direct and complex measure of ultrasonic backscatter (integrated backscatter) which requires radio-frequency ultrasound signals. Using a rotating rubber disk phantom and a microbubble echo-contrast flow phantom, we have shown that the intensity of audio Doppler signals is independent of the constraints typically associated with Doppler ultrasound (velocity and angle), but like integrated backscatter depends on the transmit intensity, gain of the ultrasound receiver, attenuation and the nature of the scatterers. Using Doppler ultrasound for backscatter measurements is ideally suited for the expected application of the technique: the assessment of echo contrast in cardiac chambers, blood vessels and tissue perfusion (i.e., any flow system). Compared to integrated backscatter, the Doppler audio method has the advantage of using standard clinical ultrasound machines, requires less sophisticated data storage and processing equipment and the positioning system for the region of interest (the Doppler sample volume) is built into all pulsed-wave Doppler machines. Further, the low-velocity filter removes all nonmoving scatterers (like the intense echoes from heart valves and the walls of blood vessels), thus allowing study of only those echoes originating from the blood pool. This combination of features is what attracted us to the Doppler method for quantitating ultrasonic backscatter in flow systems.

Quantitative echo contrast concentration measurement by Doppler sonography.

The hypothesis investigated in this study is that Doppler ultrasound can be used to make quantitative echo contrast concentration measurements in flow systems. Our motivation was to demonstrate the utility and some of the pitfalls of using scattered ultrasound intensity to quantify echo contrast in chambers and vessels. Doppler ultrasound was used rather than conventional imaging techniques because of its natural association with the assessment of flow in chambers and vessels. We compared the intensity of audio Doppler to various steady-state concentrations echo contrast in a carefully controlled in vitro flow system. A total of 62 paired audio Doppler intensity and echo contrast concentration measurements were made. A weak positive correlation was found between the absolute echo contrast concentration and audio Doppler intensity (r = 0.510, p = 0.001). The correlation was weak because of the many unknowns and effervescent nature of microbubble echo contrast agents. However, audio Doppler intensity was shown to correlate strongly with the relative concentration of echo contrast over short time periods (r = 0.958, p = 0.0001). The results show that Doppler intensity can be used to quantitatively measure the relative, but not the absolute concentration of echo contrast in in vitro flow systems.

Volumetric arterial flow quantification using echo contrast. An in vitro comparison of three ultrasonic intensity methods: radio frequency, video and Doppler.

The two hypotheses presented in this paper are: (1) absolute and relative volumetric flow rates in vessels can be measured by echo contrast time-intensity curves; and (2) echo contrast time-intensity curves generated by different ultrasound backscatter intensity techniques have equivalent capability for flow measurements. A nonpulsatile flow system was built for quantitative ultrasound backscatter measurements from bolus echo contrast injections using two different volumes of mixing. A total of 49 echo contrast bolus injections were made at various flow rates (0.44-2.59 L/min). Ultrasound backscatter time-intensity curves were generated by ultrasound radio frequency, video and Doppler techniques. The rate of backscattered ultrasound intensity washout for each technique (WASHOUT RATE), and relative change in WASHOUT RATE (delta WASHOUT RATE) were compared to the volumetric flow rate (FLOW) and changes in flow rate (delta FLOW), respectively. The relationship between WASHOUT RATE, FLOW and the volume of contrast mixing was studied. A linear relationship was demonstrated between WASHOUT RATE and delta WASHOUT RATE and the corresponding FLOW and delta FLOW by all three methods (r > 0.90 for all comparisons). The WASHOUT RATE was found to depend on the FLOW and the volume of contrast mixing, but the delta WASHOUT RATE was equal to the delta FLOW and independent of the volume of mixing. Time-intensity curves can be generated from different ultrasound backscatter intensity techniques and the WASHOUT RATE correlates well with FLOW. delta FLOW can be determined directly from the corresponding delta WASHOUT RATE. Doppler ultrasound, because of its natural association with the assessment of flow in chambers and vessels, is uniquely suited to assessment of arterial volumetric blood flow in vitro.

The Doppler kinetics of microbubble echo contrast.

The right and left heart kinetics of a saccharide-based microbubble echo contrast agent were measured in 11 anesthetized dogs using Doppler intensity as a measure of microbubble concentration while controlling for the dose administered, weight of the subject and cardiac output. A two-phase Doppler time-intensity curve was noted in all vascular regions. A brief first pass effect (phase 1) was found to depend on the contrast dose, cardiac output and subject size. This was followed by a much longer nearly steady-state elevation in the Doppler intensity compared with baseline (phase 2). The kinetics of phase 2 were found to be the same in all vascular distributions and independent of cardiac output. The phase 2 kinetics depend on the contrast dose, subject size and elimination characteristics of the contrast agent. The clinically important conclusions are: (1) the magnitude of Doppler enhancement and duration of the contrast effect can be predicted using the simple formulas presented; (2) the flow-dependent portion of the arterial contrast effect is effectively over only a few seconds after intravenous injection; and (3) the kinetics of phase 2 are the same throughout the body.