Alicia Megías

Endothelial dysfunction, intima-media thickness and coronary reserve in relation to risk factors and Framingham score in patients without clinical atherosclerosis.

Background Endothelial dysfunction, decreased coronary flow reserve (CFR) and increased intima–media thickness (IMT) are related to atherosclerosis and can be assessed non-invasively by echography. Objectives In order to describe the relationship between these parameters and with cardiovascular risk, this study investigated them simultaneously in patients without clinical atherosclerosis. Methods A total of 106 subjects were studied, 91 with and 15 without cardiovascular risk factors. Cardiovascular disease was excluded in all cases. Doppler ultrasound was used to analyse endothelium-dependent vascular dilation in the brachial artery, IMT in the common carotid artery and CFR in the left anterior artery. Results Patients with cardiovascular risk factors had impaired flow-mediated dilation (FMD; 3.7 ± 3.2 versus 11.6 ± 4.4%, P = 0.000); greater IMT (0.89 ± 0.3 versus 0.56 ± 0.14 mm, P = 0.000) and lower CFR (2.7 ± 0.9 versus 4 ± 1.2, P = 0.000). Correlation was found between IMT and FMD r = −0.240, (P = 0.013), IMT and CFR, r = −0.384 (P = 0.000), and between FMD and CFR of r = 0.289 (P = 0.007). All patients with IMT greater than 1 mm showed depressed FMD, most of them with low values of CFR, but patients with reduced FMD or CFR did not necessarily show increased IMT. There was a significant correlation between the three parameters and the Framingham risk score. Multiple linear regression analysis showed that IMT was the only factor related to the Framingham score. Conclusion In patients without clinical atherosclerotic disease, cardiovascular risk factors are associated with impaired FMD, CFR and increased IMT. Even though a correlation between these changes was found, they showed different dependence on cardiovascular risk factors and with global risk, IMT being the best correlated with the Framingham score.

Effect of candesartan on coronary flow reserve in patients with systemic hypertension.

Background Patients with hypertension have structural and functional changes in conductance and resistance vessels. In the absence of coronary stenosis the coronary microvascular function can be analysed by studying the coronary reserve. The aim of this study was to evaluate, non-invasively, the effect of candesartan on coronary microvascular function in hypertensive patients. Methods Twenty-two hypertensive patients (> 40 years) without clinical coronary disease (age 63.86 ± 10.3 years; women, 59.1%) were studied. In addition to blood pressure (BP), measurement of carotid intima–medial thickness (IMT), left ventricle mass index (LVMI) and the coronary flow reserve (CFR) were evaluated with echography at the beginning, and after 3 months of treatment with 16 mg/day of candesartan. Twelve hypertensive controls (64.50 ± 10.8 years; women, 58.4%) completed the same study without any change in treatment. Results A 15% improvement in CFR (3.10 ± 1.02 to 3.56 ± 1.06; P = 0.001) was observed simultaneously with the BP reduction. There was no change in CFR in the control group (2.9 ± 1.1 to 3.01 ± 0.9; P = 0.23). The IMT was not modified significantly at the end of the follow-up (0.86 ± 0.1 to 0.83 ± 0.1 mm; P = 0.103). Conclusion Candesartan improves the CFR in hypertensive patients. The improvement was not related to BP control or LVMI regression. Patients with a lower CFR show a better response to candesartan. This fact can be demonstrated non-invasively with echography after 3 months of therapy.

Regression of left ventricular hypertrophy by a candesartan-based regimen in clinical practice. The VIPE study.

The VIPE study was a prospective, non-comparative, open-label clinical evaluation of 97 hypertensive patients (69.1% female; 68.9±9.5 years; mean blood pressure (BP) 160±12/90±9 mmHg) with echocardiographic evidence of left ventricular hypertrophy (LVH). Patients were treated for six months with a candesartan-based regimen (8 mg/16 mg + HCTZ 12.5 mg + additional drugs to lower BP < 140/90 mmHg). After six months, systolic/diastolic BP was decreased by 19.3±8/9.4±5 mmHg (p<0.001 for both), and left ventricular mass index (LVMI) decreased 17.01 g/m2 (95%CI: -13.2 to -20.99; p<0.001). During treatment with the candesartan-based regimen all echocardiographic parameters related to LVMI were significantly reduced and 28% achieved a target LVMI [< 134 g/m2 (men) and < 110 g/m2 (women) ]. No significant changes were observed in ejection fraction, shortening fraction or LV diastolic function. Univariate analysis showed that both age (p=0.03) and diabetes (p=0.029) were predictive of LVH regression. Thus, a candesartan-based regimen for six months significantly reduced echocardiographic LVH in hypertensive patients in general practice. The drug was very well tolerated and no serious adverse events were reported.

Noninvasive Assessment of the Effect of Atorvastatin on Coronary Microvasculature and Endothelial Function in Patients With Dyslipidemia

INTRODUCTION AND OBJECTIVES The effect of statins has been monitored mainly in peripheral arteries. It is now possible to study coronary microcirculation by analyzing coronary reserve with transthoracic echocardiography. The aim of this study was to use this noninvasive technique to evaluate the effect of atorvastatin on peripheral endothelial function and on the coronary microvasculature in patients with dyslipidemia. PATIENTS AND METHOD We included 21 patients with dyslipidemia but no clinical antecedents of atherosclerosis. Mean (SD) age was 64.9 (11) years, and women made up 61.9% of the group. All patients were treated with 20 mg atorvastatin during 3 months. Lipid profile, carotid intima-media thickness, endothelium-dependent vasodilation and coronary flow reserve were determined at baseline and at the end of treatment. All studies were performed with echocardiographic techniques. RESULTS Together with improvements in the lipid profile, we found a 43% increase in endothelium-dependent vasodilation (4.3 [4.4] to 6.2 [3.8]; P=.07) and a 25% increase in coronary flow reserve (2.5 [0.6] vs 3.1 [0.8]; P=.002). The increase in endothelium-dependent vasodilatation correlated with age (r=-0.60; P=.004), intima-media thickness (r=-0.47; P=.029), low-density lipoprotein level before treatment (r=-0.43; P=.05), and baseline endothelium-dependent vasodilatation (r=-0.63; P=.002). The increase in coronary flow reserve correlated with low-density lipoprotein level after treatment (r=-0.51; P=.04). CONCLUSIONS Short-term treatment with atorvastatin improved the lipid profile, coronary microvascular function and endothelium-dependent vasodilation in the peripheral circulation. The noninvasive assessment of coronary reserve is feasible with transthoracic echocardiography.

Rendimiento de la ecocardiografía transtorácica con sonda de alta frecuencia en el estudio de la descendente anterior

Introduccion y objetivos Se realizo este estudio conel objetivo de valorar el rendimiento y la utilidad de laecocardiografia transtoracica (ETT) con sonda de altafrecuencia para detectar y analizar el flujo de la descendenteanterior en pacientes con lesiones de la misma yen pacientes con infarto anterior. Material y metodos Se estudiaron 11 pacientes conlesiones mayores del 75% y 10 pacientes con infarto anteriorprevio. Los resultados se compararon con un grupocontrol de 18 sujetos. Se intento localizar la descendenteanterior en el surco interventricular anterior partiendo deuna proyeccion apical de 4 camaras. Se considero quese detectaba la descendente anterior cuando se registrabacon Doppler pulsado un flujo predominante diastolico. Resultados La arteria fue detectada en 37/39 (94,9%)pacientes. Los pacientes con lesiones coronarias presentaronuna disminucion en el limite de la significacion delcociente velocidad pico diastolica/sistolica: 2,5 (desviacionestandar [DE], 0,7) frente a 1,8 (DE, 0,3) (p = 0,024).Los pacientes con infarto anterior presentaron un cocientevelocidad pico diastolica/sistolica mas disminuido respectoa los controles: 2,5 (DE, 0,7) frente a 1,4 (DE, 0,3)(p = 0,001). Conclusiones El flujo de la descendente anterior sepuede analizar con ETT y sonda de alta frecuencia enmas del 90% de los casos. Los pacientes con lesionescoronarias y aquellos con infarto tienen disminucion delcociente de velocidad pico diastolica/sistolica.

Familial Form of Noncompaction Cardiomyopathy Associated With Polycystic Kidney Disease

The isolated form of non-compacted cardiomyopathy (NCC) is a rare disease whose underlying causes are increasingly well-understood due to greater knowledge and the development of imaging tools. It is caused by the interruption of the embryonic process of myocardial compaction, which occurs between the fifth and eighth weeks of intrauterine life. As a result, the myocardium acquires a hypertrabeculated appearance with two layers, an external compacted epicardium and an inner, noncompacted endocardium, with deep intertrabecular recesses which communicate with the ventricular cavity. NCC frequently presents in families. In the series studied, up to 50% of family members are affected to some degree. Mutations have been identified in several genes. The G 4.5, which is involved with mitochondrial function (taffazine protein), and others associated with the cytoskeleton (alpha-dystrobrevin and dystrophin) are inherited as sex-linked recessive genes. By contrast, genes that encode sarcomere proteins such as LDB3 (Cypher / Zaspa protein) on chromosome 10q21-q23, or cytoskeletal proteins such as alpha-actin or beta-myosin heavy chain, are inherited as autosomal dominant genes. Although NCC is classically expressed by the triad of heart failure, arrhythmias and stroke, our current capacity for early detection of incipient forms means that the clinical expression is often oligosymptomatic. It is associated with extracardiac, frequently neuromuscular, manifestations. However, the range is varied and includes facial dysmorphia, hematological disorders and endocrine or kidney disease, including horseshoe kidney, glomerulonephritis or polycystic kidney disease. We report the case of 2 siblings with NCC and hepatorenal polycystosis. The index case was a hypertensive, dyslipemic woman aged 65 years who was on dialysis for renal failure secondary to polycystic disease. The woman was admitted with dyspnea at minimal effort, orthopnea, oliguria, and peripheral edema. The electrocardiogram sinus rhythm indicated left ventricular growth. An echocardiogram was requested and showed dilated left chambers with areas of distal hypertrabeculation. Contrast echocardiography in these areas indicated a mildly depressed ejection fraction and pulmonary pressure, compatible with “non-compaction cardiomyopathy.” The diagnosis was confirmed by magnetic resonance imaging (Figure 1). After treatment with beta blockers and diuretics, the patient showed clinical improvements. A review of the family history identified a 63year-old brother who was also dyslipemic and hypertensive and who had received a kidney transplant for polycystic disease in 1995. Because of his history he had had several echocardiograms, all of which indicated dilation of the left-side cavities with moderate systolic dysfunction and apical hypertrabeculation compatible with NCC (Figure 2). Polycystic kidney disease is a major cause of chronic kidney disease. It is hereditary and is produced by mutations which occur mainly in the PKD 1 and PKD 2 (polycystine 1 and 2) genes located on chromosomes 16 and 4 and which are transmitted as an autosomal dominant and recessive gene, respectively. Kidney cysts are associated with liver cysts. Signs of the disease include renal fossa pain, hematuria, and intercurrent urinary infections. Cardiovascular manifestations typically associated with the disease include hypertension, mitral valve prolapse, and intracranial aneurysms. Only 3 cases of the association between NCC and polycystic kidney disease have been reported in the literature, and all reported the presence of both disorders in just one patient. We present the first concurrent presentation of both diseases LETTERS TO THE EDITOR

Determinación no invasiva del efecto de atorvastatina en la microvasculatura coronaria y la función endotelial periférica de pacientes dislipémicosNoninvasive Assessment of the Effect of Atorvastatin on Coronary Microvasculature and Endothelial Function in Patients With Dyslipidemia

Introduccion y objetivos La monitorizacion del efecto de las estatinas se ha estudiado fundamentalmente en el ambito arterial periferico. Es posible estudiar la microcirculacion coronaria mediante la evaluacion de la reserva coronaria (RC) con ecocardiografia transtoracica. El objetivo del estudio fue evaluar, de forma no invasiva, el efecto de atorvastatina en la funcion endotelial periferica y la microvasculatura coronaria en pacientes dislipemicos. Pacientes y metodo Se incluyo a 21 pacientes dislipemicos sin antecedentes de aterosclerosis clinica (edad, 64,9 ± 11 anos; mujeres, 61,9%). Se valoraron, basalmente y a los 3 meses de tratamiento con 20 mg/dia de atorvastatina, el perfil lipidico, el grosor mediointimal (GMI) carotideo, la vasodilatacion dependiente del endotelio (VDE) y la reserva coronaria (RC) de la arteria descendente anterior (DA). Los estudios se realizaron con ecocardiografia. Resultados Simultaneamente con la mejoria del perfil lipidico se aprecio un incremento del 43% de la VDE (el 4,3 ± 4,4% frente al 6,2 ± 3,8%; p = 0,07) y un 25% de mejoria de la RC (2,5 ± 0,6 frente a 3,1 ± 0,8; p = 0,002). El incremento de la VDE se correlacionaba con la edad (r = –0,60; p = 0,004), el GMI carotideo (r = –0,47; p = 0,029), el colesterol unido a lipoproteinas de baja densidad (cLDL) basal (r = –0,43; p = 0,05) y con la VDE basal (r = –0,63; p = 0,002). El incremento de la RC se correlacionaba con el cLDL final (r = –0,51; p = 0,04). Conclusiones El tratamiento a corto plazo con atorvastatina mejora no solo el perfil lipidico, sino tambien la funcion microvascular coronaria y la vasodilatacion periferica dependiente del endotelio. Es posible su monitorizacion de manera no invasiva con ecocardiografia.