Alejandro Hita

Local and Systemic Cellular Immunity in Early Renal Artery Atherosclerosis

BACKGROUND AND OBJECTIVES Modern imaging techniques have increased the incidental detection of renal atherosclerotic disease (RAD). Because immune activation may hasten RAD progression, identifying cellular immune markers might provide clues to clinical activity. In this study, cellular immune markers were assessed in early RAD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Immune cell markers in peripheral blood of two groups of hypertensive patients with normal carotid and coronary arteries were evaluated: 28 patients had incidental RAD and 22 patients had normal renal arteries; 21 renal arteries obtained at necropsy from individuals with history of hypertension and tissue evidence of RAD were examined and matched with 21 individuals with normal renal arteries. Cell subpopulations were measured by flow cytometry in peripheral blood and direct cell count, respectively, using T and dendritic cells monoclonal antibodies. RESULTS Peripheral blood of RAD patients showed increased numbers of cells expressing CD3, CD4, CD83, and CD86. CD4 to CD8 ratio was 8.3 ± 1.4 (RAD) to 3.4 ± 0.9 (normal; P<0.001). No differences were found in CD25, CD8, and S100 among groups. Postmortem samples from RAD showed increased CD3+, CD4+, CD86+, and S100+ cells, whereas CD25+ and CD8+ were unmodified between groups. CD4+ to CD8+ ratio was higher in the RAD(PM) group. CONCLUSIONS These results are consistent with an increased expression of immune cell markers in early RAD. Additional studies will explore if they may potentially turn into treatment targets to prevent disease progression.

Sodium Intake Is Associated With Parasympathetic Tone and Metabolic Parameters in Mild Hypertension

BACKGROUND Although the impairment of parasympathetic cardiac control was described in hypertensives submitted to a high salt diet, the impact of this autonomic abnormality on metabolic and inflammation markers in patients with mild hypertension has not been explored. METHODS Four hundred and ninety mild essential hypertensive patients (144 ± 9/94 ± 9 mm Hg, 49.5 ± 13.9 years, 67.9 % male) were studied. Dietary sodium intake was estimated by measuring 24-h urinary sodium excretion (UNa), and the patients were classified according to UNa levels as follows: low (<50 mEq/l), medium (50-99 mEq/l), and high UNa (≥100 mEq/l). Parasympathetic tone was evaluated by assessing heart rate recovery (HRR) after an exercise stress test. HRR, plasma lipids, glucose metabolism, and inflammatory biomarkers were compared across UNa groups. RESULTS HRR and high-density lipoprotein (HDL)-cholesterol were progressively lower, and insulin (INS), homeostasis model assessment of insulin resistance (HOMAir), ultrasensitive-C-reactive protein (usCRP) were progressively higher across increasing UNa groups. In the low and medium UNa groups, HDL-cholesterol was higher and CRP was lower than that in high UNa (P < 0.01 and P < 0.05, respectively) (Dunnett post-hoc test). In the low UNa group, triglycerides (TGs), INS, and HOMAir were lower than that in high UNa (P < 0.05). Multiple linear regression analysis showed that UNa, HOMAir, and heart rate (HR) were negatively associated with HRR (P < 0.0001, P < 0.0001, and P = 0.001, respectively). CONCLUSIONS In the essential hypertensive patients studied high sodium intake is associated with parasympathetic inhibition, lipid disturbances, and inflammation. Studies designed to assess causality between sodium intake and metabolic and autonomic status are needed to evaluate the relevance of controlling sodium intake, especially in hypertensive patients.

Clinical value of the tissue Doppler s wave to characterize left ventricular hypertrophy as defined by echocardiography.

Left ventricular hypertrophy (LVH) may be a physiological finding and may also be associated with different disease entities and hence, with different outcomes. Regional myocardial function can be assessed with color Doppler tissue imaging, specifically by the waveform of the isovolumic contraction (IC) period and the regional systolic wave (“s”). Methods and Results: We studied five groups (G): healthy, sedentary young volunteers (G1, n:10); healthy sedentary adult volunteers (G2, n:8); and subjects with LVH (left ventricular mass index >125 g/m2) including: high performance athletes (G3, n:21), subjects with hypertension (G4, n:21), subjects with hypertrophic cardiomyopathy (HCM) (G5, n:18). We measured peak “s” wave velocity (cm/sec) at the basal and mid septum, the IC/s ratio, and basal to mid‐septal velocity difference (BMVD) of the “s” wave. Regional “s” wave values (cm/sec) were G1 = 5.6 ± 1; G2 = 5.4 ± 0.8; G3 = 5.7 ± 0.6; G4 = 5.3 ± 1.1; G5 = 4.2 ± 1.1 (P < 0.0001). The IC/s ratio was G1 = 0.28 ± 0.18; G2 = 0.39 ± 0.21; G3 = 0.23 ± 0.10; G4 = 0.42 ± 0.15; G5 = 0.64 ± 0.15 (P < 0.0001). The BMVD (cm/sec) was G1 = 2 ± 0.51; G2 = 1.71 ± 0.29; G3 = 1.78 ± 0.44; G4 = 1.26 ± 0.96; G5 = 0.45 ± 0.4 (P < 0.0001). IC/s < 0.38 discriminated physiological from pathological forms of hypertrophy (sensitivity 90%; specificity 88%). Peak “s” wave velocity discriminated HCM from other causes of hypertrophy, with a cutoff value of 4.46 cm/sec (sensitivity 72%; specificity 90%). BMVD <0.98 cm/sec detected HCM with 89% sensitivity and 86% specificity. Conclusions: Peak “s” wave velocity and two indices: IC/s and BMDV are novel parameters that may allow to discriminate physiological from pathological forms of hypertrophy as well as different subtypes of hypertrophy. (ECHOCARDIOGRAPHY 2010;27:370‐377)

Loss of dystrophin is associated with increased myocardial stiffness in a model of left ventricular hypertrophy

Transition from compensated to decompensated left ventricular hypertrophy (LVH) is accompanied by functional and structural changes. Here, the aim was to evaluate dystrophin expression in murine models and human subjects with LVH by transverse aortic constriction (TAC) and aortic stenosis (AS), respectively. We determined whether doxycycline (Doxy) prevented dystrophin expression and myocardial stiffness in mice. Additionally, ventricular function recovery was evaluated in patients 1 year after surgery. Mice were subjected to TAC and monitored for 3 weeks. A second group received Doxy treatment after TAC. Patients with AS were stratified by normal left ventricular end-diastolic wall stress (LVEDWS) and high LVEDWS, and groups were compared. In mice, LVH decreased inotropism and increased myocardial stiffness associated with a dystrophin breakdown and a decreased mitochondrial O2 uptake (MitoMVO2). These alterations were attenuated by Doxy. Patients with high LVEDWS showed similar results to those observed in mice. A correlation between dystrophin and myocardial stiffness was observed in both mice and humans. Systolic function at 1 year post-surgery was only recovered in the normal-LVEDWS group. In summary, mice and humans present diastolic dysfunction associated with dystrophin degradation. The recovery of ventricular function was observed only in patients with normal LVEDWS and without dystrophin degradation. In mice, Doxy improved MitoMVO2. Based on our results it is concluded that the LVH with high LVEDWS is associated to a degradation of dystrophin and increase of myocardial stiffness. At least in a murine model these alterations were attenuated after the administration of a matrix metalloprotease inhibitor.

[PP.29.21] IMPAIRED HEART RATE VARIATION WHEN STANDING: A SIMPLE MARKER OF EARLY VASCULAR AGING AND AUTONOMIC DYSFUNCTION

Objective: a- To evaluate associations between heart rate variation when standing (HRVS) and vascular stiffness in hypertensives and normotensives. b-To determine independent predictors of impaired HRVS (I-HRVS) in these populations. Design and method: 396 consecutive subjects who attended to the Champagnat Cardiometabolic Center of Austral Hospital were evaluated. The exclusion criteria were: age below 18/above 80 years, secondary hypertension, heart disease, anaemia, diabetes, sympatholitics, and chronotropic drugs. HR, BP (OMROM HEM-781CPINT) and PWV (Mobil-O-Graph, IEE) were measured in supine position after 5 minute rest, and HR was determined again then of 3 minutes of standing position. HRVS was calculated between standing and supine positions. PWV was evaluated according to sextiles of HRVS in hypertensive and normotensive patients (ANOVA, Student Newman Keuls). I-HRVS was defined as those HRVS values contained in the first sextile (lower HRVS). Independent predictors of l-HRVS, adjusted for age, sex, BP, anthropometric factors and medications, were determined. (MEDCALC v12.5.0.0). Results: 314 patients were included: 162 treated hypertensives (54.7 ± 10.6 years, 134 ± 19/86 ± 13 mm Hg, 58.0% males) and 152 normotensives (47.7 ± 10.2 years, 119 ± 10/77 ± 8 mm Hg, 41.4% males). PWV presented a negative relationship across sextiles of HRVS in hypertensives (p = 0.03) and normotensives (p = 0.01). l-HRVS resulted below 2 beats in hypertensives and below 5 beats in normotensives. In univariate analysis, supine HR, sex, PWV and calcium channel blockers were different according to sextiles of HRVS in hypertensives. Supine HR and PWV were also different among sextiles of HRVS in normotensives. In logistic regressions, only supine HR and PWV were independent predictors of I-HRVS in hypertensives (HR: p = 0.0009, and PWV: p = 0.03) and normotensives (HR: p = 0.0002, and PWV: p = 0.03). Figure. No caption available. Conclusions: Across the broad spectrum of BP, I-HRVS was related independently with increased arterial stiffness and higher basal HR. This findings may be explained through a lower baroreceptor functioning secondary to vascular stiffness, as a cause of the lesser parasympathetic cardiac control observed in this subjects. Thus, I-HRVS would be a simple marker of early vascular aging and autonomic dysfunction both in normotensive and hypertensive patients.

Obstructive Membrane at the Base of the Left Atrial Appendage, a Multi‐Imaging Approach

The left atrial appendage (LAA) is a small muscular extension that grows from the anterolateral wall of the left atrium, in the proximity of the left pulmonary veins. The presence of a membrane in the LAA is a rare clinical entity whose origin is not known. Its clinical implication in the genesis of atrial arrhythmias and thromboembolic risk remains unknown. We report a case of an obstructive membrane located at the base of the LAA, found incidentally in a young patient who was initially undergoing a transesophageal echocardiogram prior to an invasive treatment for atrial fibrillation.

HUMORAL MARKERS, CONVENTIONAL DOPPLER ECHOCARDIOGRAM AND BIDIMENSIONAL STRAIN IN THE DETECTION OF MYOCARDIAL TOXIC EFFECT SECONDARY TO CHEMOTHERAPY

Aim: Analyze the usefulness of humoral markers (quantitative troponin T (TT), BNP, NT pro-BNP), conventional and the two-dimensional longitudinal strain (LS), and radial strain (RS) in the prediction of ventricular systolic dysfunction in patients treated with cardiotoxic chemotherapy. Thirty six

EFFECTS OF VENTRICULAR GEOMETRY ON VENTRICULAR ARTERIAL COUPLING IN ESSENTIAL HYPERTENSION: PP.8.341

Introduction: Echocardiography is used to assess ventrículo-arterial coupling (VAC) determined by the balance between the contractile properties of left ventricle (LV) and the pressure load. However ventricular geometry (VG) and cardiac hypertrophy (LVH) may modulate the VAC in hypertension (HT). Adaptative variations of aortic (Eal) and ventricular (Ees) elastances may be related with VAC changes within normal systolic function (SF). Objective: To characterize non-invasively the interaction between VG and VAC in HT within normal range of SF and VAC. Methods: We evaluated 23 consecutives hypertensive patients, age 53,3 ± 9,8, male 12(52,2%) female 11 (47,8%), SBP 134,78 ± 12,8 mmHg, DBP 82,47 ± 8,21 mmHg, with Doppler Echocardiography (Vivid 7,GE), using simple pulse method modified for the calculation of Ees and the ratio of end systolic pressure to stroke volume for Eal. VAC is the ratio Eal/Ees.Elastances were normalized to 100 g of ventricular mass. The following measurements were also determined: Mesoparietal fractional shortening, normalized systolic stress (MFS/STRESS), left atrial diameter (LA), correlation E/A (E/A), diastolic isovolumic relaxation time (Tau), systolic work index (SWI), systolic volume index (SVI) and peripheral vascular resistance index (PVRI). The VG was classified as: normal (Nor), concentric remodeling (Rem), concentric LVH (Conc) and eccentric LVH (Exc). Results: Significative differences on the VG were found in Nor with Rem: Ees(p < 0,05); Conc: LA(p < 0,01), Eal(p < 0,01), E/A(p < 0,01), SWI(p < 0,05); Exc: SWI(p < 0,05), SVI(p < 0,05), LA(p < 0,05), Eal(p < 0,01). Conclusions: In HT with SF and VAC within normal ranges, VG seems to affect VAC, contractility and ventricular performance. The noninvasive measurement of VG and related VAC, may be useful for diagnostic and therapeutic porpoises in early stages in hypertensive patients. Figure 1. No caption available.

IMMUNOLOGICAL ACTIVATION IN EARLY PHASES OF ATHEROSCLEROTIC RENOVASCULAR DISEASE: - A NEW THERAPEUTIC TARGET?: 1C.03

Introduction: An autoimmune component is present in atherosclerotic disease, cellular and humoral immunity are involved in its development. However most of the reports describing the presence of immune markers in clinical settings came from individuals with severe symptomatic carotid or coronary plaques and no previous reports described it in asymptomatic lesions from renovascular atherosclerosis (RVD). Basis in this unexplored field we examined the presence of immune markers in hypertensive patients with asymptomatic RVD. Aims: to identify immune activation in hypertensive patients with asymptomatic RVD. Methods: A prospective, controlled study was conducted including 50 patients with hypertension that underwent an evaluation of their renal arteries by digital arteriography. According to its results they were classified in 2 groups; a)RVD (n: 28); b) Normal arteries (NA, n: 22). Basal characteristics, cardiovascular risk factors distributions and blood pressure values(table 1) were similar between both groups, no carotid or coronary atherosclerotic lesions were found in any patient included. All patients were asymptomatic for RVD (as defined by AHA,2000: RVD not accompanied by severe, malignant or refractory hypertension, nor renal function impairment). Peripheral blood samples were obtained and incubation for primary and secondary antibodies were performed. Immunophenotyping was done using the following monoclonal antibodies: anti-CD4, anti-CD3, anti-CD83; anti-CD86; anti-CD8; anti-CD25 and all the appropriates isotypes controls. Results (table1): In the RVD group, CD3+ and CD4 T cell counts were approximately 2 times (P < 0.0001) and 3 times (P < 0.0001) higher respectively, the CD4+/CD8+ ratio was 2.4 times higher (P < 0.0001) and CD86+ and CD83+ cell count was approximately 5.15 times and 1.4 times higher (P < 0.0001, respectively). Conclusions: An increased significative immune activation was found in asymptomatic hypertensives with RVD suggesting that an active immune reaction is already present in these early phases. Further research would be necessary in interventions targeting this activation to reduce disease progression. Figure 1. No caption available.