Malten, a new synthetic molecule showing in vitro antiproliferative activity against tumour cells and induction of complex DNA structural alterations.

BACKGROUND: Hydroxypyrones represent several classes of molecules known for their high synthetic versatility. This family of molecules shows several interesting pharmaceutical activities and is considered as a promising source of new antineoplastic compounds. METHODS: In the quest to identify new potential anticancer agents, a new maltol (3-hydroxy-2-methyl-4-pyrone)-derived molecule, named malten (N,N'-bis((3-hydroxy-4-pyron-2-yl)methyl)-N,N'-dimethylethylendiamine), has been synthesised and analysed at both biological and molecular levels for its antiproliferative activity in eight tumour cell lines. RESULTS: Malten exposure led to a dose-dependent reduction in cell survival in all the neoplastic models studied. Sublethal concentrations of malten induce profound cell cycle changes, particularly affecting the S and/or G2-M phases, whereas exposure to lethal doses causes the induction of programmed cell death. The molecular response to malten was also investigated in JURKAT and U937 cells. It showed the modulation of genes having key roles in cell cycle progression and apoptosis. Finally, as part of the effort to clarify the action mechanism, we showed that malten is able to impair DNA electrophoretic mobility and drastically reduce both PCR amplificability and fragmentation susceptibility of DNA. CONCLUSION: Taken together, these results show that malten may exert its antiproliferative activity through the induction of complex DNA structural modifications. This evidence, together with the high synthetic versatility of maltol-derived compounds, makes malten an interesting molecular scaffold for the future design of new potential anticancer agents.

Prevalence and correlates of advanced retinopathy in a large selected hypertensive population. The Evaluation of Target Organ Damage in Hypertension (ETODH) study.

OBJECTIVE: To describe the prevalence of advanced retinal microvascular lesions and their associations with cardiac and extracardiac signs of target organ damage (TOD) in a large selected hypertensive population. METHODS: A total of 2172 non-diabetic untreated and treated uncomplicated essential hypertensives consecutively attending for the first time our hospital outpatient hypertension clinic and included in the Evaluation of Target Organ Damage in Hypertension (ETODH), an observational ongoing registry of hypertension-related TOD, were considered for this analysis. Advanced hypertensive retinopathy was defined by the presence of any of the following lesions: flame-shaped haemorrhages, soft exudates or cotton wool spots and papilloedema. Left ventricular hypertrophy (LVH), carotid structural abnormalities, such as plaques and intima media (IM) thickening, and microalbuminuria were diagnosed according to the 2003 ESH/ESC guidelines criteria. RESULTS: Among the whole study population, 33 patients (1.5%) were found to have advanced hypertensive retinopathy. Patients with these retinal lesions were similar to those without for age, body mas index, known duration of hypertension, smoking habit, total serum cholesterol, fasting blood pressure and prevalence of antihypertensive treatment; whereas mean systolic and diastolic blood pressures were higher in the former group. The prevalence rates of LVH, carotid plaques, carotid IM thickening and microalbuminuria in patients with and without retinopathy were 57%, 67%, 69%, 19% and 25%, 47%, 44%, 12%, respectively. In a multivariate logistic regression analysis, advanced retinopathy was significantly associated with LVH (OR = 4.0), carotid IM thickening (OR = 2.9), carotid plaques (OR = 2.8), but not with microalbuminuria. CONCLUSIONS: Our study indicated that: (i) advanced retinopathy is a rare finding in non-diabetic hypertensive patients seen in a specialist setting; (ii) a strong relation exists between retinal microvascular lesions and cardiac and macrovascular markers of TOD.

Isolated ambulatory hypertension and changes in target organ damage in treated hypertensive patients.

Isolated ambulatory hypertension is a condition characterized by elevated ambulatory but normal clinic blood pressure (BP), and has been reported to be associated with increased cardiovascular risk in untreated subjects. However, little is known about the relationship between this condition and intermediate end points such as target organ damage (TOD) in treated hypertensives. We investigated the impact of isolated ambulatory hypertension on left ventricular hypertrophy (LVH) and microalbuminuria (MA) in a selected sample of treated nondiabetic hypertensives with effective and prolonged clinic BP control (BP<140/90 mmHg). Clinic BP measurements, routine diagnostic procedures, echocardiography and 24-h urine collection for MA, were undertaken in 80 patients (mean age 53+/-8 years) with essential hypertension attending our hospital outpatient centre at baseline and after an average follow-up of 30 months. At follow-up evaluation BP status was assessed by self-measurement of BP and ambulatory BP monitoring (ABPM). At the follow-up visit, 51 out of 80 patients (63.7%) reached a BP control according to ABP (average daytime BP<132/85 mmHg) criteria (group I) whereas the remaining 29 did not (group II); home BP was controlled (BP<135/85 mmHg) in all members of group I and in 86% of group II. In the overall study population, mean Sokolow voltage, LV mass index (LVMI) and urinary albumin excretion (UAE) decreased compared to baseline from 24.1+/-5.0 to 18.9+/-5.1 mm (P<0.05), 115.6+/-24.1 to 97.7+/-21.6 g/m(2) (P<0.01), 11.8+/-23.7 to 5.8+/-14.9 mg/24 h (P<0.05), respectively. The prevalence of ECG LVH, altered LV patterns and MA fell from 7.5 to 2.5% (P=NS), from 45 to 25 (P<0.01) and from 13.7 to 5.1% (P<0.05), respectively. However, when data were analysed separately for the two groups a significant decrease of echo LVH and MA was found only in patients with controlled ABP. LVMI and MA decreased from 117.1+/-23.1 to 95.9+/-22.1 g/m(2) (P<0.01) and 12.8+/-24.7 to 4.1+/-5.7 mg/24 h (P<0.05) in group I, and from 114.1+/-24.8 to 102.3+/-20.3 (P=NS) and 11.9+/-22.1 to 6.3+/-18.1 mg/24 h (P=NS) in group II. In conclusion, in the present study isolated ambulatory hypertension in treated patients is associated with a lack of regression in cardiac and extracardiac TOD, suggesting that a tight BP control throughout the 24 h plays a key role in lowering hypertension-induced structural and functional alterations at cardiac and renal level.

Home blood pressure measurement and its relationship with blood pressure control in a large selected hypertensive population.

Despite the impressive increase of home blood pressure monitoring (BPM) among hypertensive patients over the last few years, a limited number of studies have analysed the rate of home BPM and its relationship with target blood pressure (BP) control, in representative samples of the hypertensive population. The objectives of the study were first to evaluate the prevalence of home BPM in a large selected group of treated hypertensive patients referred to our outpatient hypertension hospital clinic. Second, to assess the rate of satisfactory clinic BP control in patients with or without familiarity with home BPM. In all, 1350 consecutive hypertensive patients who attended our hypertension centre during a period of 12 months and were regularly followed up by the same medical team were included in the study. After informed consent all patients underwent the following procedures: (1) accurate medical history (implemented by a structured questionnaire on demographic and clinical characteristics, including questions concerning home BPM); (2) physical examination; (3) clinic BP measurement; (4) routine examinations; and (5) standard 12-lead electrocardiogram. A total of 897 patients (66%) out of 1350 (687 men, 663 women, age 58.6 +/- 12.3 years, mean clinic BP 141 +/- 16/87 +/- 9 mmHg ) were regularly practising home BPM. In this group of patients, home BPM was associated with a significantly greater rate of satisfactory BP control (49.2 vs 45.6%, P < 0.01). Patients performing home BPM were more frequently men (54 vs 46%, P < 0.02 ) younger (average age 57.8 +/- 12.0 vs 60.3 +/- 12.7 years, P < 0.001) and with a higher educational level (defined by more than 8 years of school, 71 vs 55%, P < 0.05) than their counterparts. There were no significant differences in duration of hypertension, hypercholesterolaemia, obesity, smoking, diabetes, associated cardiovascular diseases, left ventricular hypertrophy and compliance with drug treatment. This study demonstrates that: (1) home BPM is widely performed by hypertensive patients managed in a hypertension hospital clinic; (2) this practice is associated with a significantly higher rate of clinic BP control; and (3) age, male gender and educational level influence the adoption of home BPM.

Reproducibility of nocturnal blood pressure fall in early phases of untreated essential hypertension: a prospective observational study.

A number of studies have shown that a smaller than normal nocturnal blood pressure (BP) decrease is associated with cardiovascular disease. However, no large prospective studies have examined the reliability of nocturnal dipping within individuals. The aim of our study was to investigate the short-term variability of nocturnal BP fall in a large cohort of patients with recently diagnosed essential hypertension. In all, 414 uncomplicated never treated hypertensive patients referred to our outpatient hypertension hospital clinic (mean age 46+/-12 years; 257 M, 157 F) prospectively underwent: (1). repeated clinic BP measurements; (2). routine examinations recommended by WHO/ISH guidelines; and (3). ambulatory BP monitoring (ABPM) twice within a 4-week period. Dipping pattern was defined as a reduction in the average systolic and diastolic BP at night greater than 10% compared to average daytime values. Overall, 311 patients (75.1%) showed no change in their diurnal variations in BP. Of the 278 patients who had a dipping pattern on the first ABPM, 219 (78.7%) confirmed this type of profile on the second ABPM, while 59 (21.3%) showed a nondipping pattern. Among 37 dipper patients with >20% of nocturnal systolic BP decrease (extreme dippers), only 16 (43.2%) had this marked fall in BP on the second ABPM. Of the 136 patients who had a nondipping pattern on the first ABPM, 92 (67.6%) confirmed their initial profile on the second ABPM, while 44 (32.4%) did not. Patients with reproducible nondipping profile were older (48+/-12 years) than those with reproducible dipping profile (44+/-12 years, P<0.05). These findings indicate that: (1). short-term reproducibility of nocturnal fall in BP in untreated middle-aged hypertensives is rather limited: overall, one-fourth of patients changed their initial dipping patterns when they were studied again after a few weeks; (2). this was particularly true for extreme dipping and nondipping patterns; (3). abnormalities in nocturnal BP fall, assessed by a single ABPM, cannot be taken as independent predictors of increased cardiovascular risk.

Reduced nocturnal fall in blood pressure, assessed by two ambulatory blood pressure monitorings and cardiac alterations in early phases of untreated essential hypertension.

To investigate whether in recently diagnosed essential hypertensives a reduced nocturnal fall in blood pressure (BP), established on the basis of two 24-h ambulatory blood pressure monitorings (ABPM) is related to a greater cardiovascular damage. In all, 355 consecutive, recently diagnosed, never-treated essential hypertensives referred for the first time to our outpatient clinic were included in the study. Each patient underwent the following procedures: (1) two 24-h ABPMs performed within 3 weeks, (2) 24-h urinary collection for microalbuminuria, (3) nonmydriatic photography of ocular fundi, (4) echocardiography, (5) carotid ultrasonography. We defined nondipping profile as a night-day systolic and diastolic fall < or =10 % (mean of two ABPMs). A dipper BP profile was found in 238 patients, whereas in 117 patients a nondipper profile was present. The two groups were similar for age, gender, body mass index, smoking habit, clinic BP, 48-h BP and heart rate, while, by definition, night-time systolic and diastolic BP were significantly higher in nondippers than in dippers (130/81 vs 121/74 mmHg, P < 0.0001).The prevalence of left ventricular hypertrophy (LVH) defined by four different criteria: (a) LV mass index (LVMI) > or = 125 g/m(2) in both genders; (b) LVMI > or = 134 gm(2) in men and > or = 110 in women; (c) LVMI> or = 125 g/m(2) in men and > or = 110 g/m(2) in women; (d) LVMI > or = 51 g/m(2.7) in men and > or = 47 g/m(2.7) in women was significantly higher in nondippers than in dippers (a: 12 vs 7%, P < 0.05; b: 16 vs 7%, P < 0.01; c: 20 vs 11%, P < 0.01; d: 35 vs 23% P < 0.02) and this finding was associated with a significant increase in aortic root and left atrium dimensions. There were no differences between the two groups in the prevalence of carotid and retinal changes and microalbuminuria. In conclusion our findings suggest that never-treated hypertensives with a reduced BP fall in the night time, defined on the basis of two ABPMs, have a higher prevalence of TOD than dippers, in terms of echocardiographic LVH. In this population setting, cardiac structural alterations are a more sensitive marker of the impact of the nocturnal BP load on cardiovascular system than other extracardiac signs of TOD.

Change in cardiovascular risk profile by echocardiography in medium-risk elderly hypertensives.

It has been clearly demonstrated that ageing and arterial hypertension are both associated with an increased prevalence of left ventricular hypertrophy (LVH), which is a powerful risk factor for cardiovascular (CV) events. The objective of this study was to assess the impact of echocardiographic LVH in profiling the absolute CV risk stratification according to the 1999 World Health Organization-International Society of Hypertension (WHO/ISH) guidelines in elderly hypertensive patients. A total of 223 never-treated elderly patients (> or =65 years) with essential hypertension (98 men, 125 women, mean age 72+/-5 years) referred to our outpatient hospital clinic were included in the study. They underwent the following procedures: (1) medical history, physical examination, and clinic blood pressure; (2) routine blood chemistry and urine analysis and (3) electrocardiogram. The risk was initially stratified according to the routine procedures suggested by WHO/ISH guidelines and subsequently reassessed by adding the results of echocardiography (LVH as left ventricular mass index >51 g/m(2.7) in men and >47g/m(2.7) in women). According to routine classification, 56% (n=125) were medium-risk patients, 29% (64) high-risk and 15% (34) very-high-risk patients. The overall prevalence of LVH was 56% (48% in medium-risk and 62% in high-risk or very-high-risk patients, P<0.01). A marked change in risk stratification was observed when echocardiographic LVH was taken into consideration: medium-risk patients decreased to 29% and high-risk patients rose to 56% (P<0.01). In conclusion, ultrasound assessment of cardiac target organ damage is extremely useful in obtaining a more valid assessment of global cardiovascular risk in elderly hypertensives, because stratification based on diagnostic routine procedures can underestimate the overall risk in a large fraction (48%) of medium-risk subjects.

A comparison of blood pressure control in a hypertension hospital clinic between 1997 and 2000.

AIMS: (1) To evaluate the prevalence of clinic blood pressure (BP) control in a large sample of treated hypertensives followed in our hypertension clinic during the year 2000, and to compare it with our 1997 data. (2) To investigate the prevalence of left ventricular hypertrophy (LVH) according to different levels of BP control. METHODS AND RESULTS: One thousand consecutive hypertensive patients who attended our hypertension hospital clinic in a period of 7 months during the year 2000 and who had regularly been followed by the same medical team were included in the study. LVH was assessed using two different electrocardiographic criteria (Sokolow-Lyon and Cornell). This population had similar clinical characteristics of a cohort including 700 patients seen at our centre during 1997 in which BP control rate was 34% (Cuspidi et al., J Hypertens 1999; 17: 835-41). During follow-up, 441 of the treated patients had clinic BP < 140/90 mmHg, 283 < 150/95 mmHg and 276 > or = 150/95 mmHg, indicating that BP control was satisfactory in 44.1%, borderline in 28.3% and unsatisfactory in 27.6% of the cases. Thirty-five patients (3.6%) had LVH according to Cornell criteria and 25 (2.6%) according to Sokolow criteria. A significantly lower prevalence of LVH was detected in patients with optimal BP control (< 130/ 85 mmHg) compared to those with unsatisfactory BP (2.3% vs 9.4%, respectively, p < 0.01). CONCLUSION: The study demonstrates that: (1) hypertensive patients in a hypertension clinic have satisfactory BP control in 44.1% of cases, indicating a significant improvement of BP control in this clinical setting during the last 3 years; (2) prevalence of LVH is significantly related to BP control.

Short-term reproducibility of nocturnal non-dipping pattern in recently diagnosed essential hypertensives.

OBJECTIVE: To investigate in a selected population of patients with a recently diagnosed essential hypertension the short-term intrasubject variability of diurnal changes in blood pressure (BP). METHODS: Two hundred and eight consecutive, recently diagnosed, never treated essential hypertensives (119 men, 89 women, 46 +/- 12 years) underwent 24-h ambulatory BP monitoring (ABPM) twice within 3 weeks. Dipping pattern was defined as a reduction in average systolic and diastolic BP at night greater than 10% compared to average daytime values. RESULTS: 177 subjects (85%) showed no change in their diurnal variations in BP. Of the 159 subjects who had a dipping pattern on first ABPM, 134 (90.6%) confirmed this type of profile on the second ABPM, while 15 (9.4%) showed a non-dipping pattern. Of the 59 subjects who had a non-dipping pattern on the first ABPM, 43 (72.2%) confirmed their initial profile on the second ABPM, while 16 (28.8%) did not. CONCLUSION: These findings indicate that short-term reproducibility of diurnal changes in BP in early phases of untreated essential hypertension, characterized by a large prevalence of dipping pattern, is overall satisfactory. However, our study underlines that also in this particularly selected population of hypertensives the definition of non-dipping status on the basis of a single ABPM remains unreliable in about one-third of patients.

Left ventricular concentric remodelling and extracardiac target organ damage in essential hypertension.

Left ventricular (LV) concentric remodelling is an adaptive change in cardiac geometry frequently observed in arterial hypertension. This study was addressed to investigate the extent of extracardiac target organ damage (TOD) in patients with LV concentric remodelling. Two groups of never-treated essential hypertensives, 31 with normal LV geometry (group I, relative wall thickness: 0.39) and 31 with LV concentric remodelling (group II, relative wall thickness: 0.47) matched for age, sex, body mass index and mean 24-h systolic blood pressure (BP), were included in the study. They underwent clinical and laboratory examination, 24-h ambulatory BP monitoring (ABPM), 24-h urinary collection for microalbuminuria, non-mydriatic photography of ocular fundi, echocardiography and carotid ultrasonography. In both groups age (I: 51 +/- 11 years; II: 51 +/- 11 years), body mass index (I: 25 +/- 3 kg/m(2); II: 26 +/- 3 kg/m(2)), clinic and 24-h ABPM values (I: 149 +/- 11/95 +/- 8, 142 +/- 11/91 +/- 7 mm Hg; II: 150 +/- 11/98 +/- 9, 142 +/- 12/92 +/- 9 mm Hg) were similar by design. There were no differences between patients with normal LV geometry and with LV concentric remodelling in LVM index (97 +/- 16 vs 99 +/- 16), carotid intima-media thickness (0.7 +/- 0.02 vs 0.7 +/- 0.02) and carotid plaques prevalence (35% vs 35%). Furthermore, no significant differences among the two groups were found in the prevalence of retinal changes and microalbuminuria. These results suggest that in hypertensive patients with similar BP and LVMI levels, LV concentric remodelling is not associated with more prominent TOD.

Prevalence of left ventricular hypertrophy and carotid thickening in a large selected hypertensive population: impact of different echocardiographic and ultrasonographic diagnostic criteria.

BACKGROUND: Left ventricular hypertrophy (LVH) and increased carotid intima-media thickness (IMT) represent independent risk factors for cardiovascular disease. OBJECTIVE: To evaluate the prevalence of echocardiographic LVH and common carotid artery (CCA) intima-media (IM) thickening by different criteria in a large sample of hypertensive patients referred to our Hypertension Clinic. METHODS: Echocardiograms and ultrasonographic carotid examinations have been performed in 640 consecutive hypertensives referred to our outpatient's hypertension unit. LVH was diagnosed using six different criteria, when left ventricular mass index (LVMI) exceeded (a) 100 g/m2 in women and 120 g/m2 in men, (b) 110 g/m2 in women and 125 g/m2 in men, (c) 110 g/m2 in women and 134 g/m2 in men, (d) 125 g/m2 in both sexes, (e) 47 g/h2.7 in women and 51 g/h2.7 in men, (f) 105 g/h in women and 126 g/h in men. Thickening of CCA IM was identified using three partition values; when IMT was (a) > or =0.8 mm; (b) >0.9 mm: (c) > or = 1.0 mm in both sexes. RESULTS: Echocardiographic and ultrasonographic examinations of sufficient quality to be analysed were obtained in 611 patients (95.2%). Prevalence of LVH ranged from 18.6% (d) to 42.2% (f) and was significantly higher in men than in women by criteria (d) and (e), but slightly higher in women when using criteria (a) and (c). Eccentric hypertrophy was the most frequent type of LVH independently of the criteria used. Prevalence of IM thickening ranged from 14.7% (c) to 44.2% (a). Significant correlations between left ventricular mass (LVM)/body surface area, LVM/height and LVM/height2.7, and carotid IM thickness were found (r=0.41; p <0.0001; r=0.31; p <0.0001; r = 0.30; p <0.0001, respectively). CONCLUSION: The prevalence of LVH and CCA IM thickening in hypertensive patients is markedly dependent on the partition values used to define these markers of target organ damage. Considering the pivotal role of LVH and CCA IM thickening in assessing the global cardiovascular risk profile in hypertensives, improved standardization in defining LVH and carotid IM thickening is needed.

Coordination properties of a polyamine cryptand with two different binding moieties. A case of a pH-modulated antenna device based on a new Eu(III) cryptate complex.

Protonation and alkali- and alkaline-earth-metal coordination by the dipyridine-containing cryptand L have been studied by means of potentiometric and spectroscopic (UV-vis, (1)H NMR) measurements in aqueous solutions. This ligand is constituted by an aliphatic polyamine chain and a coordinating cleft, delimited by two dipyridine units, where the metal ion is lodged. The resulting complexes are characterized by an unusually high stability. The polyamine chain is not involved, or weakly involved, in metal coordination, and facile protonation can occur on the nitrogen atoms of this moiety. Similar coordination features are found in the Eu(III) complex. A fluorescence emission study reveals that the Eu(III) cryptate shows the characteristic visible emission of the metal, due to the intramolecular energy transfer to the metal ion mainly from the lower energy triplet state of the cryptand. On the other hand, the emission intensity is modulated by pH, giving a maximum at neutral pH and decreasing at both acidic and alkaline pH values.

Addition of small molecules by Zn(II) and Cu(II) dinuclear complexes obtained by an amino-phenolic ligand. Crystal structures of the dinuclear zinc complex assembling butanolate and azide anions.

The coordination properties of the ligand 2,6-bis-[[bis-(2-aminoethyl)-amino]methyl]-phenol (L) toward the zinc ion were determined by means of potentiometric measurements in aqueous solution (298.1 +/- 0.1 K, I = 0.15 mol dm(-3)). L forms mono- and dinuclear complexes with zinc; the stable dinuclear complexes are practically the only existing species using L/Zn(II), molar ratio of 1:2. In these species, each dien subunit binds one zinc ion, while the phenolate moiety bound to both ions allows the two metal centers to be in close proximity with an incomplete coordination environment. The role of this metal-metal distance in binding secondary ligands was investigated for the dinuclear systems 2Zn/L and 2Cu/L by potentiometric (298.1 +/- 0.1 K, I = 0.15 mol dm(-3)) and NMR experiments in aqueous and methanol solution with a series of small guests having nitrogen donor atoms. The coordination sphere of the two metals was completed by adding 1 equiv of only those guests, which showed at least two contiguous donor atoms or two lone pairs on the same atom, to exactly fit the metal-metal distance without modifying the metal cluster. To do this, the imidazole molecule which shows the highest addition constants to the [M(2)H(-1)L](3+) species probably forms a mu-1,1-amino. These results are in agreement with the two crystal structures reported herein [Zn(2)(H(-1)L)(CH(3)CH(2)CH(2)CH(2)O)](ClO(4))(2) (space group P2(1)nb, a = 11.483(5), b = 14.166(5), c = 18.279(5) A, V = 2973(19) A(3), Z = 4, R = = 0.0701, wR2 = 0.1611) and [Zn(2)(H(-1)L)N(3)](ClO(4))(2) (space group C 2/c, a = 14.460(3), b = 12.814(3), c = 14.875(3) A, beta = 105.35(2) degrees, V = 2658(10) A(3), Z = 4, R = 0.0783, wR2 = 0.1806). In fact, these structures display a butanolate or azide guest linked to both Zn(II) ions of the dinuclear complex, resulting in a mu-1,1-oxo and mu-1,1-azido bridge, respectively.

High prevalence of cardiac and extracardiac target organ damage in refractory hypertension.

OBJECTIVE: Target organ damage (TOD) in chronically treated hypertensives is related to effective blood pressure (BP) control. The aim of this study was to evaluate the prevalence of cardiac and extracardiac TOD in patients with refractory hypertension (RH) compared with well-controlled treated hypertensives (C). METHODS: Fifty-four consecutive patients with RH (57 +/- 10 years), selected according to WHO/ISH guidelines definition, and 51 essential hypertensives (55 +/- 10 years) with satisfactory BP control obtained by association therapy, underwent the following procedures: (1) clinic BP measurement; (2) blood sampling for routine chemistry examinations; (3) 24 h urine collection for microalbuminuria; (4) non-mydriatic retinography; (5) echocardiogram; (6) carotid ultrasonogram. In order to exclude 'office resistance' (defined as clinic BP > 140/90 mmHg and average 24 h BP or =1.0 mm, respectively); a higher prevalence of carotid plaques (65 versus 32%, P < 0.05), a more advanced retinal involvement (grade II and III, 73 and 5% versus 38 and 0%, P < 0.01) and a greater albumin urinary excretion (22 +/- 32 mg/24 h versus 11 +/- 13 mg/24 h, P < 0.01) were found in RH compared to C. CONCLUSIONS: Our study suggests that RH is a clinical condition associated with a high prevalence of TOD at cardiac, macro- and microvascular level and consequently with high absolute cardiovascular risk, which needs a particularly intensive therapeutic approach aimed to normalize BP levels and to induce TOD regression.

Evaluation of target organ damage in arterial hypertension: which role for qualitative funduscopic examination?

BACKGROUND: The objective of this study was to compare the prevalence of quantitative markers of target organ damage, such as echocardiographically documented left ventricular hypertrophy (LVH), carotid structural changes and microalbuminuria with that of retinal abnormalities detected by qualitative funduscopic examination in a large selected population of patients with essential hypertension. METHODS: Eight hundred consecutive untreated (n = 232) and treated (n = 568) hypertensive patients (386 men, 414 women, mean age 52.7 +/- 11.8 years) referred for the first time to our out-patient clinic were included in the study. In order to search for target organ damage, they were submitted to the following procedures: 1) amydriatic retinography, 2) 24-hour urine collection for microalbuminuria, 3) echocardiography, and 4) carotid ultrasonography. Retinal changes were evaluated according to the Keith, Wagener and Barker (KWB) classification by two physicians, who had no knowledge of the patients' characteristics. Microalbuminuria was defined as a urinary albumin excretion > 30 and < 300 mg/24 hours, LVH as a left ventricular mass index > or = 134 g/m2 in men and > or = 110 g/m2 in women; finally carotid plaque was defined as a focal thickening > 1.3 mm. RESULTS: Hypertensive retinopathy was the most frequent (KWB grade I 46%, II 32%, III-IV < 2%) marker of target organ damage, followed by carotid plaques (43%), LVH (22 %, eccentric LVH was the prevalent type and was 1.8 times as frequent as the concentric one) and microalbuminuria (14%). CONCLUSIONS: At variance with the markers of cardiac, macrovascular and renal damage, an extremely high prevalence of retinal abnormalities (narrowings and initial arterio-venous crossings) were found in our population. If, as suggested by the WHO/ISH guidelines, these retinal abnormalities were considered as a reliable marker of target organ damage, then almost all patients would be affected by hypertensive vascular disease. Based on this evidence it is suggested that retinal abnormalities included in funduscopic grades I and II of the KWB classification should not be considered among the criteria for the quantitative detection of target organ damage.

Influence of different echocardiographic criteria for detection of left ventricular hypertrophy on cardiovascular risk stratification in recently diagnosed essential hypertensives.

BACKGROUND: Hypertensive patients with left ventricular hypertrophy (LVH) need a prompter and more intensive pharmacological treatment than subjects without evidence of cardiac involvement. So the detection of LVH plays an important role for decision-making in hypertensives. OBJECTIVE: To evaluate the impact of different echocardiographic criteria to define LVH in a more precise stratification of absolute cardiovascular risk in hypertensives without target organ damage (TOD) as assessed by routine investigations. METHODS: A total of 100 never treated patients with grade 1 and 2 essential hypertension (53 men, 47 women, age 44 +/- 12 years) referred for the first time to our outpatient clinic were included in the study. They underwent the following procedures: (1) family and personal medical history, (2) clinic blood pressure (BP) measurement, (3) routine blood chemistry and urine analysis, (4) electrocardiogram, (5) echocardiogram. Risk was stratified according to the criteria suggested by the 1999 WHO-ISH guidelines. TOD was initially evaluated by routine procedures only, and subsequently reassessed by using six different echocardiographic criteria to recognise LVH: (a) left ventricular mass index (LVMI) >120 g/m(2) in men and 100 g/m(2) in women; (b) 125 g/m(2) in men and 110 g/m(2) in women; (c) 134 g/m(2) in men and 110 g/m(2) in women; (d) 125 g/m(2) in men and 125 g/m(2) in women; (e) 51 g/m(2.7) in men and 47 g/m(2.7) in women; (f) 126 g/m in men and 105 g/m in women. RESULTS: According to the first classification based on routine investigations, 46% were low risk and 54% were medium risk patients. Significant changes in risk stratification were obtained when LVH was assessed by echocardiography. A percentage of patients, ranging from 9 (f) to 25% (d), were found to having LVH according to different criteria, and consequently moved from low and medium risk strata to high risk stratum. CONCLUSIONS: The detection of LVH by echocardiography allowed a much more accurate identification of high risk patients. In particular our results suggest that: (1) cardiovascular risk stratification only based on a simple routine work-up can often underestimate overall risk; (2) a better standardisation in defining LVH is needed, considering that the impact of cardiac hypertrophy on risk stratification is markedly dependent on the echocardiographic criteria used to diagnose it.

Target organ damage and non-dipping pattern defined by two sessions of ambulatory blood pressure monitoring in recently diagnosed essential hypertensive patients.

OBJECTIVE: To evaluate in a selected population of patients with a recent diagnosis of hypertension whether a reduced nocturnal fall in blood pressure, confirmed by two 24 h ambulatory blood pressure monitoring (ABPM) sessions is associated with more prominent target organ damage (TOD). METHODS: The study was structured in two phases: in the first, 141 consecutive, recently diagnosed, never-treated essential hypertensives underwent 24 h ABPM twice within 3 weeks; in the second phase, 118 of these patients showing reproducible dipping or non-dipping patterns underwent the following procedures: (1) routine blood chemistry, (2) 24 h urinary collection for microalbuminuria, (3) amydriatic photography of ocular fundi, (4) echocardiography and (5) carotid ultrasonography. RESULTS: The 92 patients with (>10%) night-time fall in systolic blood pressure (SBP) and diastolic blood pressure (DBP) (dippers) in both monitoring sessions were similar for age, gender, body surface area, smoking habit, clinic BP, 24 h and 48 h BP to the 26 patients with a < or = 10% nocturnal fall (non-dippers) in both sessions. The prevalence of left ventricular hypertrophy (LVH) (defined by two criteria: (1) LV mass index > or = 125 g/m2 in both genders; (2) LV mass index > or = 120 and 100 g/m2 in men and women, respectively) and that of carotid intima-media (IM) thickening (IM thickness > or = 0.8 mm) were significantly higher in non-dippers than in dippers (23 versus 5%, P < 0.01; 50 versus 22%, P < 0.05; and 38 versus 18%, P < 0.05, respectively). There were no differences among the two groups in the prevalence of retinal changes and microalbuminuria. The strength of the association of LV mass index with night-time BP was slightly but significantly greater than that with daytime BP. CONCLUSIONS: This study suggests that a blunted reduction in nocturnal BP, persisting over time, may play a pivotal role in the development of some expressions of TOD, such as LVH and IM thickening, during the early phase of essential hypertension, despite similar clinic BP, 24 h and 48 h BP levels observed in non-dippers and dippers.

Cardiovascular risk stratification in hypertensive patients: impact of echocardiography and carotid ultrasonography.

BACKGROUND: Decision about the management of hypertensive patients should not be based on the level of blood pressure alone, but also on the presence of other risk factors, target organ damage (TOD) and cardiovascular and renal disease. OBJECTIVE: To evaluate the impact of echocardiography and carotid ultrasonography in a more precise stratification of absolute cardiovascular risk. METHODS: Never-treated essential hypertensives (n = 141; 73 men, 68 women, mean age 46 +/- 11 years) referred for the first time to our out-patient clinic were included in the study. They underwent the following procedures: (1) family and personal medical history, (2) clinical blood pressure (BP) measurement, (3) routine blood chemistry and urine analysis, (4) electrocardiogram, (5) echocardiogram, (6) carotid ultrasonogram. Risk was stratified according to the criteria suggested by the 1999 WHO/ISH guidelines. TOD was initially evaluated by routine procedures only, and subsequently reassessed by using data on cardiac and vascular structure obtained by ultrasound examinations (left ventricular hypertrophy (LVH) as left ventricular mass index (LVMI) > 134 g/m2 in men and > 110 g/m2 in women; carotid plaque as focal thickening > 1.3 mm). RESULTS: According to the first classification 20% were low-risk patients, 50% medium-risk, 22% high-risk and 8% very-high-risk patients. A marked change in risk stratification was obtained when TOD was assessed by adding ultrasound examinations: low-risk patients 18%, medium-risk 28%, high-risk 45%, very-high-risk patients 9%. CONCLUSIONS: The detection of TOD by ultrasound techniques allowed a much more accurate identification of high-risk patients, who represented a very large fraction (45%) of the patient population seen at our hypertension clinic. In particular, a large proportion of patients classified as at moderate risk by routine investigations were instead found to be at high risk when ultrasound examinations were added. The results of this study suggest that cardiovascular risk stratification only based on simple routine work-up can often underestimate overall risk, thus leading to a potentially inadequate therapeutic management especially of low-medium risk patients.

Improvement of patients' knowledge by a single educational meeting on hypertension.

OBJECTIVES: A poor therapeutic compliance is a major cause of insufficient control of hypertension. As education of patients is fundamental in order to improve their compliance, we organised two pilot educational meetings aimed at (1) assessing the support of patients to this kind of meetings, and (2) verifying the impact on patient's education. METHODS: We invited 225 consecutive patients referred to our Hypertension Clinic (some of them regularly followed up and some referred for the first time) to participate to an educational meeting on hypertension. Patients were divided in two groups, for organising reasons each attending a single meeting. Each meeting included four sessions: (1) the first session included a multiple choice questionnaire (nine questions, with answers collected by an interactive electronic system) in order to evaluate the degree of patient's information about hypertension (definition, prevalence, aetiology, complications and treatment), (2) a traditional teaching session, (3) an interactive phase aimed to assess the improvement of knowledge in which the same questions as in the first session have been asked again, and (4) a general discussion session. RESULTS: A total of 144 patients (mean age 54 +/- 12 years; 76 M, 68 F) of the 225 invited attended the meeting. The answers to our questions in the initial session were correct in a percentage ranging from 60% to 80%. During the third phase immediately after the teaching session, the percentage of correct answers increased significantly (range: 75--98%, P < 0.05 at least in all questions). CONCLUSIONS: This study shows: (1) a satisfactory adherence of patients to this educational initiative; (2) a positive impact of a single educational meeting on patient's knowledge about issues related to hypertension. The potential role of improving patient's education on clinical outcomes such as blood pressure levels and the rate of blood pressure control requires future controlled studies. Journal of Human Hypertension (2001) 15, 57-61