Arturo Esposito

Different effects of antihypertensive therapies based on losartan or atenolol on ultrasound and biochemical markers of myocardial fibrosis: results of a randomized trial.

Background—In hypertensive left ventricular hypertrophy (LVH), myocardial texture is altered by a disproportionate increase in fibrosis, but there is insufficient clinical evidence whether antihypertensive therapy or individual agents can induce regression of myocardial fibrosis. Methods and Results—We compared the effects of an angiotensin II receptor antagonist with a &bgr;-blocker on myocardial collagen volume (assessed by echoreflectivity and serum collagen markers) in 219 hypertensive patients with echocardiographically documented LVH. Patients were allocated randomly to receive losartan 50 to 100 mg/d (n=111) or atenolol 50 to 100 mg/d (n=99) with or without hydrochlorothiazide 12.5 to 25 mg/d for 36 weeks. Echoreflectivity analysis was conducted on ultrasound tracings of the midapex septum with specifically designed and validated software. A color histogram of reflecting echoes was obtained, and its spread (broadband [BB], previously shown to correlate directly with collagen volume fraction on endomyocardial biopsies) was used as the primary outcome measure. Mean color scale and serum markers of collagen synthesis (PIP, PIIIP) or degradation (CITP) were secondary outcome variables. Echoreflectivity analysis proved feasible in 106 patients (losartan 52, atenolol 54). Losartan reduced BB over 36 weeks (from 114.5 to 104.3 color levels, P<0.02), whereas atenolol treatment was associated with an increase in BB (from 109.0 to 113.6 color levels, P=NS), the difference between treatments being −12.8 color levels (95% CI −23.6 to −2.0, P=0.02). Secondary end points (mean color scale and collagen markers) also changed in the direction of decreased collagen in patients receiving losartan, but differences between groups were not statistically significant. Conclusions—In hypertensive patients with LVH, losartan decreases myocardial collagen content, whereas atenolol does not. The difference between the 2 treatments is statistically significant.

Retinal microvascular changes and target organ damage in untreated essential hypertensives.

Background and purpose The clinical and prognostic significance of initial retinal alterations in hypertensive patients remains controversial. Therefore, we assessed the relationship of microvascular abnormalities with prognostically validated markers of target organ damage (TOD), such as left ventricular mass (LVM), carotid intima–media thickness (IMT) and microalbuminuria, in early stages of untreated essential hypertension. Methods A total of 437 consecutive, never-treated patients with grade 1 or 2 essential hypertension, referred to our outpatient clinic, underwent the following procedures: (1) clinical and routine laboratory examinations, (2) 24-h ambulatory blood pressure monitoring, (3) 24-h urine collection for microalbuminuria, (4) echocardiography, (5) carotid ultrasonography, (6) non-mydriatic retinography. Patients were divided into group I, with either a normal retinal pattern (n = 65, 14.9%) or arteriolar narrowing (n = 185, 42.4%) and group II with arteriovenous crossings (n = 187, 42.7%). Results The two groups were similar for gender, body mass index, smoking habit, heart rate, clinic and ambulatory blood pressure (BP) values, while mean age was slightly but significantly higher in group II than in group I (47.6 ± 10.7 versus 44.5 ± 12.5 years, P = 0.008). No differences occurred between the two groups in LVM index (101.8 ± 18.5 versus 99.9 ± 20.4 g/m2), carotid IMT (0.67 ± 0.12 versus 0.66 ± 0.20 mm), urinary albumin excretion rate (14.4 ± 27.7 versus 13.3 ± 27.7 mg/24 h) as well as in the prevalence of LV hypertrophy (14.3 versus 14.0%), IM thickening and/or plaques (26.5 versus 27.2%) (both defined according to 2003 ESH-ESC guidelines) and microalbuminuria (10.1 versus 8.7%). Furthermore, the three different retinal artery patterns were similarly distributed among tertiles of LV mass index, IMT and urinary albumin excretion rate. Conclusions These results show that: (1) a very large fraction (more than 80%) of untreated, recently diagnosed hypertensive patients have initial retinal microvascular abnormalities detectable by non-mydriatic retinography, (2) the presence of arteriovenous crossings is not associated with more prominent cardiac and extracardiac TOD, (3) fundoscopic examination has a limited clinical value to detect widespread organ involvement in early phases of grade 1 and 2 hypertension.

Ambulatory blood pressure, target organ damage and aortic root size in never-treated essential hypertensive patients.

The relationship between ambulatory blood pressure (ABP), target organ damage (TOD) and aortic root (AR) size in human hypertension has not been fully explored to date. We investigated the relationship between ABP, different markers of TOD and AR size in never-treated essential hypertensive patients. A total of 519 grade 1 and 2 hypertensive patients (mean age 46±12 years) referred for the first time to our outpatient clinic underwent the following procedures: (1) routine examination, (2) 24 h urine collection for microalbuminuria (MA), (3) ambulatory blood pressure monitoring over two 24 h periods within 4 weeks, (4) echocardiography and (5) carotid ultrasonography. AR dilatation was defined by sex-specific criteria (⩾40 mm in men and ⩾37 mm in women). AR diameter was increased in 3.7% of patients. Demographic variables (body mass index, age and male gender), average night-time diastolic blood pressure (BP) (but not clinic or average 48 h BP), left ventricular mass index and carotid intima-media (IM) thickness showed an independent association with AR size in both univariate and multivariate analyses. When TOD data were analysed in a categorical way, a stepwise increase in the prevalence of left ventricular hypertrophy (LVH) (I=17.5%, II=27.6%, III=35.8%) and carotid IM thickening (I=20.9%, II=28.8%, III=34.4%), but not in MA (I=6.8%, II=9.1%, III=8.7%) was found with the progression of AR size tertiles. Our results show that (1) AR enlargement in uncomplicated never-treated hypertensive patients has a markedly lower prevalence than traditional markers of cardiac and extracardiac TOD; (2) night-time BP, LVH and carotid IM thickening are independent predictors of AR dimension.

Metabolic syndrome and biventricular hypertrophy in essential hypertension.

The metabolic syndrome (MS) is associated with structural and functional alterations of the left ventricle (LV); no evidence is available on the impact of the MS on the right ventricle (RV). To assess whether MS, as defined by the ATP III report, is associated with biventricular hypertrophy, a total of 286 hypertensive subjects (mean age 58.7±12.2 years) attending our outpatient clinic underwent the following procedures: (1) physical examination and standard clinic blood pressure (BP) measurement; (2) routine laboratory investigations; (3) M-mode, two-dimensional and Doppler echocardiography. LV hypertrophy (LVH) was defined by LM mass index ⩾51/47 g m−2.7 in men and women, respectively. Right-sided chambers were measured in parasternal long axis at the outflow tract and subcostal view; RV hypertrophy (RVH) was defined by anterior RV wall thickness ⩾6.0/5.5 mm in men and women, respectively. Filling velocities of both ventricles were assessed by pulsed Doppler echocardiography. Structural cardiac alterations were more pronounced in hypertensive men and women with MS than in their non-MS counterparts and involved both ventricles as shown by the differences in continuous variables as well as in prevalence rates of LVH (58 and 48% vs 28 and 30%, respectively, P<0.01) and RVH (48 and 54% vs 25 and 35%, respectively, P<0.01). Both LV and RV filling in MS hypertensives were more dependent on the atrial systole. Our study shows that in human hypertension, structural and functional cardiac changes induced by MS are not limited to the LV but also involve the right one.

Studies on left ventricular hypertrophy regression in arterial hypertension: a clear message for the clinician?

BACKGROUND Evidence-based medicine should provide clear and unbiased information to clinicians. We conducted an analysis on published randomized trials evaluating the effects of antihypertensive therapy on left ventricular (LV) morphology assessed by echocardiography to investigate (i) the consistency of criteria used for definition of LV hypertrophy (LVH) and (ii) the consistency of the way LVH regression and blood pressure (BP) control were reported. METHODS Studies identified by a PubMed search were eligible for inclusion in the analysis, if they fulfilled the following criteria: (i) publication in a peer-reviewed journal within the last 12 years; (ii) double blind, randomized, controlled, parallel-group design; (iii) numerosity of at least 50 adult hypertensive subjects; (iv) follow-up duration of at least 6 months; (v) comparison between single-drugs or association regimens; (vi) LV mass (LVM) or wall thickness measured by echocardiography. RESULTS Thirty-nine trials, including 9,162 hypertensive subjects of both genders in 78 active treatment arms or in 6 placebo arms were identified. Definition of LVH was provided by 34 studies (87.1%) according to 19 different criteria. All trials evaluated LVH regression as the absolute or relative changes of continuous variables such as LVM index (LVMI) or LV wall thickness. Data concerning prevalence rates of LVM normalization were reported in 12 studies (30.7%). The percentage of patients reaching BP target (<140/90 mm Hg) was reported in 11 studies (28.2%). CONCLUSIONS Our findings indicate that (i) definition of hypertensive LVH phenotype is extremely variable, and (ii) no precise information on LVH regression rates or changes in LV geometrical patterns, as well as on target BP, is provided by the majority of papers.

Prevalence and clinical correlates of right ventricular hypertrophy in essential hypertension.

Aim Right ventricular hypertrophy (RVH) has been reported to be a component of cardiac damage in systemic hypertension; this evidence, however, is based on small studies and major determinants of biventricular hypertrophy are still undefined. Thus, the prevalence and clinical correlates of RVH have been investigated in essential hypertension. Methods A total of 330 untreated and treated uncomplicated essential hypertensives consecutively attending a hospital out-patient hypertension clinic were considered for the analysis. All individuals underwent a quantitative echocardiographic examination as well as extensive clinical and laboratory investigations. RVH was defined by an anterior RV wall thickness equal or higher than 3.1/3.0 mm/m2 in men and women, respectively, and left ventricular hypertrophy (LVH) by LV mass index equal or higher than 51/47g/m2.7 in men and women, respectively. Results Overall, 114 (34.5%) patients fulfilled the criteria for LVH and 111 (33.6%) for RVH; normal cardiac morphology was observed in 164 patients (49.6%), isolated RVH in 52 (15.7%), isolated LVH in 55 (16.6%) and bi-ventricular hypertrophy in 59 (17.8%). In a logistic regression analysis, modifiable risk factors such as abdominal obesity (OR 3.41, CI 1.73–6.74, P = 0.0004), LV mid-wall fractional shortening (OR 2.48, CI 1.26–4.85, P = 0.008), fasting blood glucose (OR 2.47, CI 1.25–4.89, P = 0.009) and systolic blood pressure (OR 2.39, CI 1.19–4.82, P = 0.014) were the major independent correlates of biventricular hypertrophy. Conclusion RVH is commonly found in systemic hypertension and is associated with LVH (i.e., biventricular hypertrophy) in approximately one-fifth of the patients seen in a specialist setting. The clinical correlates of biventricular hypertrophy suggest that this phenotype is associated with a profile of very high cardiovascular risk.

Effects of antihypertensive treatment on ultrasound measures of myocardial fibrosis in hypertensive patients with left ventricular hypertrophy: results of a randomized trial comparing the angiotensin receptor antagonist, candesartan and the angiotensin-converting enzyme inhibitor, enalapril

Objective To compare the effects of the angiotensin II receptor antagonist candesartan with the angiotensin-converting enzyme inhibitor enalapril on myocardial fibrosis evaluated by echoreflectivity analysis. Methods Hypertensive patients (n = 196) with echocardigraphically documented left ventricular hypertrophy were randomized to candesartan 8–16 mg/day (n = 91) or enalapril 10–20 mg/day (n = 105) with possible addition of hydrochlorothiazide (12.5–25 mg/day) for 48 weeks. Echoreflectivity analysis was performed on ultrasound two-dimensional tracings of the midapex septum with a specifically designed and validated software. Colour histograms were obtained; the primary outcome variable was the treatment-related change in histogram width (broadband), previously shown to correlate with collagen volume on endomyocardial biopsy; changes in mean colour scale were secondary outcome variable. Results Echoreflectivity analysis was feasible in 84 patients (48 candesartan, 36 enalapril). Broadband decreased significantly in the candesartan (−8.0 colour levels) and in the enalapril group (−12.9 colour levels) with no significant difference between treatments (P = 0.409); no significant changes occurred in mean colour scale. Patients under monotherapy (n = 46) showed similar trends as the larger intention to treat cohort, without significant difference between treatments. Conclusion In hypertensive patients with left ventricular hypertrophy, both candesartan and enalapril induce a moderate but statistically significant reduction in an echoreflectivity index of myocardial fibrosis.

Prevalence and correlates of multiple organ damage in a never-treated hypertensive population: role of ambulatory blood pressure.

AimAvailable evidence on multiple target organ damage (TOD) in the early phases of essential hypertension is scanty. We examined the prevalence and correlates of multiple TOD in never-treated patients with recently diagnosed hypertension. MethodsA total of 602 consecutive outpatients with grades 1 and 2 hypertension underwent the following procedures: (i) routine examination, (ii) 24-h urine collection for microalbuminuria, (iii) ambulatory blood pressure monitoring over two 24-h periods within 4 weeks, (iv) echocardiography, (v) carotid ultrasonography. TOD at cardiac, vascular and renal levels was defined according to major international hypertension guidelines. ResultsPrevalence rates of patients negative for TOD (group I) or positive for one (group II), two (group III), or three (group IV) markers of TOD were as follows: 45, 33, 17 and 5%. In group II, alterations in left ventricular structure and geometry were more frequently present than carotid atherosclerosis and microalbuminuria; a similar trend was found in group III where a close association between cardiac and vascular, but not renal, signs of TOD was observed. In multiple regression analyses the risk of having three TOD was significantly related to age [odds ratio (OR): 2.11, 95% confidence interval (CI): 1.34–3.53], average 48-h systolic blood pressure (OR: 1.81, 95% CI: 1.22–2.95), smoking status (OR: 1.76, 95% CI: 1.22–2.86), male sex (OR: 1.36, 95% CI: 1.24–1.79), reproducible nondipping pattern (OR: 1.27, 95% CI: 1.12–1.61) and metabolic syndrome (OR: 1.16, 95% CI: 1.09–1.74). ConclusionsOur results show that: (i) a cluster of three TOD, namely at cardiac, carotid and renal levels, is not a common finding in a population of untreated essential hypertensive patients; a single TOD is present in about one-third of the patients and the parallel involvement of two organs in one-fifth of the cases; (ii) old age, ambulatory systolic blood pressure and smoking status are the most important predictors of multiple organ involvement.

Ambulatory heart rate and target organ damage in never-treated essential hypertensives

Limited evidence is available about the relationship between ambulatory heart rate (HR) and target organ damage (TOD) in uncomplicated hypertension. We sought to investigate the association between ambulatory HR and subclinical cardiac, vascular and renal markers of TOD in never-treated essential hypertensives. A total of 580 subjects with recently diagnosed (⩽1 year) grade 1 and 2 hypertension, categorized by tertiles of HR levels, assessed by two 24-h ambulatory blood pressure monitoring at 1- to 4-week interval, sex and the presence or absence of TOD were considered for this analysis. All subjects also underwent laboratory and ultrasonographic investigations searching for microalbuminuria (MA), left ventricular hypertrophy (LVH) and carotid atherosclerosis (carotid thickening/plaque). In the whole population, as well as in both genders, LVH, carotid atherosclerosis and MA prevalence rates did not significantly increase with 48-h HR tertiles. When patients were categorized according to the presence or absence of TOD (that is, LVH, carotid atherosclerosis or MA) no significant intergroup differences in 48-h HR were found. Furthermore, average 48-h HR was similar in patients without organ involvement as in those with one, two or three TOD signs. Finally, in a multivariate analysis age, 48-h systolic blood pressure and metabolic syndrome assessed by ATP III criteria, but not HR were independently associated with TOD. Our findings showing that 48-h ambulatory HR is not associated with markers of TOD do not support the view that a faster HR may have an additive value in predicting organ damage in the early phases of essential hypertension.

The translocation of marrow MNCs after experimental myocardial cryoinjury is proportional to the infarcted area

BACKGROUND: The selective homing of peripherally injected marrow MNCs (MMNCs) has recently been demonstrated in a model of cryodamaged heart. However, the mechanism underlying this phenomenon is still unknown. In the hypothesis that this process is related to the necrotic area extension, the infarcted area was correlated with the number of homed MMNCs in a model of experimental cryodamaged heart.