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Early evaluation of cardiovascular (CV) risk in hypertensive patients is of primary importance and studies of retinal vessels can be helpful. The aim of this study is to assess the correlation between retinal vessel changes and target organ damage (TOD), expressed as left ventricular remodelling (LVR) or hypertrophy (LVH). We evaluated 60 treated hypertensive individuals (mean age 60.9±13.3 years). On the basis of echocardiographic results, we divided the subjects showing the presence of TOD and subjects without TOD into Groups A and B, respectively. Both groups underwent a non-mydriatic digital retinography. The obtained vessel images were analysed using dedicated software in order to calculate AVR (arteriovenular ratio), index of the retinal arteriolar narrowing. The data analyses confirmed a mean AVR value of 0.86 in Group B and a mean value of 0.77 in Group A. AVR index was also analysed in a subgroup of A with evidence of LVR, and mean value was 0.76. The same procedure was carried out with subgroup of A with LVH and AVR index resulted 0.77. In all comparisons, P-value was statistically significant (P<0.05). Our findings provide evidence that in hypertensive patients retinal AVR correlates with the presence of TOD, in this study in the context of LVR and LVH. In conclusion, AVR offers a direct vision retinal microcirculation and, also, indirectly, provides information of the left ventricular geometric pattern in hypertensive patients; thus, AVR may have an important role in global CV risk stratification and could possibly be used for optimising the hypertensive patient management.

Background and Objectives: Information on ambulatory blood pressure monitoring (ABPM) in children is scarce. While in adults office BP (OBP) is higher than ABP and the difference increases as OBP increases, information in children suggests that at this young age ABP is no lower and often higher than OBP. This study was aimed at describing OBP-ABP differences in a cohort of children of different ages and BPs, and investigating whether OBP-ABP differences are dependent on age or OBP level., Methods: We retrospectively compared OBP and 24-h, daytime and night-time ABP in 433 children and adolescents aged 4-18 years, referred to our hospital clinic., Results: OBP was found to be significantly lower than 24-h and daytime ABP in the low age tertile (4-10 years) but not in the medium and high tertiles. OBP was also lower than ABP in normotensive patients (n = 182), but higher than ABP in untreated hypertensive patients (n = 92) despite similar ages. Continuous analyses showed a weak correlation of OBP-ABP differences with age, and a much stronger correlation with OBP so that 24-h ABP was higher than OBP at OBP values less than 117/73 mmHg and lower than OBP at higher OBP values. Logistic regression analysis indicates that also in children OBP accounts for most of the OBP-ABP difference., Conclusion: There is a common relation both in children and adults between OBP and ABP. It is only because high OBP is common in the elderly, and the lowest OBP is usually found in young children that large positive OBP-ABP differences have been associated with old age, and negative differences with childhood. OBP-ABP differences, often defined as white-coat effect, can have different directions and are likely to be largely due to regression to the mean.

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.

Background: The optimal time at rest before clinic blood pressure (BP) measurement is still undefined. In this study in patients with essential hypertension, the time course of the hemodynamic changes during a 16-min rest in the chair-seated position was evaluated and compared with that observed in a stabilized postural condition, such as after a prolonged supine rest., Methods: In 55 untreated essential hypertensive patients, BP, heart rate, stroke volume (impedance cardiography), and systemic vascular resistances were measured every other minute during a 16-min rest in the chair-seated position and, in random sequence, in the last 16 min of a 60-min supine rest., Results: Overall, systolic BP (SBP) and diastolic BP (DBP) decreased by 11.6 and 4.3 mm Hg, respectively, during the chair-seated rest; only a 1.8-mm Hg decrease in SBP was observed in the control supine study. The chair-seated fall in BP was associated with a decrease in systemic vascular resistances, in the absence of significant changes in cardiac index. From the logarithmic curve of SBP and DBP decrements, a half-time of 5.8 and 5.5 min respectively, was calculated. Decrements in SBP, but not DBP, were inversely related to the corresponding baseline values., Conclusions: In untreated essential hypertensive patients a significant decrease in SBP and DBP associated with a systemic vasodilation was observed during a 16-min rest in the chair-seated position. Because approximately 75% of the spontaneous fall in BP occurred within 10 min, it appears that this time at rest before clinic BP evaluation could improve the precision and accuracy of the measurement.

Objective: In the European Lacidipine Study on Atherosclerosis (ELSA), against a similar antihypertensive effect, a significantly greater effect of lacidipine was found on carotid intima-media thickness (IMT) progression, indicating a specific anti-atherosclerotic effect of lacidipine. However, not only the extent but also the composition of an atherosclerotic plaque is a determinant of subsequent events., Design and Methods: Among the 2334 patients enrolled in ELSA, 420 with 4-year treatment were chosen, videodensitometric analysis of their ultrasound carotid scan was performed and the maximum wall lesion (Tmax) was classified as lipidic, fibrolipidic and fibrotic by means of software previously validated against histology. Of the 420 patients, 244 had scans suitable for videodensitometry., Results: Excellent reproducibility of videodensitometry analysis was found using the Bland-Altman and other methods. At baseline, ELSA hypertensive patients had predominantly fibrolipidic walls (70%), with an echoreflectivity indicating a mean collagen content of 25%. After 4 years of antihypertensive treatment, little change in the frequency distribution of carotid lesions (fibrolipidic 73%) was found, with no significant differences between patients randomized to lacidipine or atenolol., Conclusions: Our study provides previously unavailable information that carotid wall composition changes to an extremely small extent during 4-year effective blood pressure lowering. With lacidipine, stable composition is associated with a lower IMT progression than with atenolol.

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.

Background: The cardiac effects of hypertension include a variety of structural changes such as increases in left ventricular mass (LVM) and left atrium (LA) size. Although data on hypertension-induced left ventricular changes are extensive, relatively little information is available on LA size from large-scale studies., Objective: We sought to assess the prevalence of LA enlargement in a large selected hypertensive population and to determine the relations of LA size to several biologic variables including left ventricular hypertrophy (LVH) and metabolic disturbances., Methods: A total of 2500 untreated and treated uncomplicated essential hypertensives consecutively attending, for the first time, our hospital out-patient hypertension clinic and included in the Evaluation of Target Organ Damage in Hypertension, an observational ongoing registry of hypertension-related target organ damage (TOD), were considered for this analysis. All patients underwent extensive clinical, laboratory and ultrasonographic investigations searching for cardiac (and extracardiac) TOD. The LA was considered enlarged when its anteroposterior diameter exceeded 3.7 cm in women and 4.1 cm in men. LVH was defined according to two different criteria: >/= 125 g/m in men and >/= 110 g/m in women; or >/= 51 g/m in men and >/=47 g/m in women., Results: Enlarged LA diameter was present in 24.5% of women and in 21.5% of men. Compared with 1925 patients with normal LA size, the 575 patients with enlarged LA were older, more frequently overweight, had higher systolic blood pressure and included a greater proportion of subjects under antihypertensive treatment, with diabetes and metabolic syndrome. Both LA size and prevalence of LA enlargement differed significantly in relation to left ventricular geometry and LVM, being greater in patients with concentric or eccentric LVH than in those with left ventricular concentric remodeling or normal geometry. The prevalence of LA enlargement was similar in patients with concentric and eccentric LVH. According to a logistic regression analysis, overweight, LVH, fasting blood glucose > 7.0 mmol/l and metabolic syndrome were the main independent predictors of LA enlargement in the overall population as well as in both untreated and treated hypertensive subgroups., Conclusions: Our study suggests that: LA enlargement is a common echocardiographic finding in selected essential hypertensive patients with different left ventricular geometric patterns; LA size and LA enlargement is related to LVM rather than the type of LVH; and, in addition to LVH, overweight, high fasting glucose and metabolic syndrome are associated with LA dimensions.

Background: In clinical practice, blood pressure (BP) is frequently measured at the end of the visit in patients sitting on one side of the bed and not on a chair according to guidelines., Methods: In 540 consecutive subjects with essential hypertension (EH) attending a hospital outpatient clinic, BP was measured in the following sequence: 1) patient seated on chair for at least 5 min, 2) patient supine, 3) patient seated on bed, and 4) patient standing for a few minutes., Results: We found that mean (+/-SEM) BP was 143.5/87.2 +/- 0.9/0.5, 153.4/89.7 +/- 1.0/0.5, 148.9/90.9 +/- 1.0/0.5, and 144.8/91.7 +/- 1.0/0.6 mm Hg, respectively (P < .05 v position 1 for all). In 14% of patients, either systolic BP (SBP) or diastolic BP (DBP) was above the conventional upper limits of normality in the seated-on-bed but not in the recommended seated-on-chair position ("false" high clinic BP), whereas SBP and DBP were "false" normal (below limit for bed-seated and above limit for chair-seated position) in only 6% and 2% of patients, respectively. Overall, SBP and DBP increments from the chair- to the bed-seated position were inversely related to the baseline chair-seated values; systolic increments were directly related to age, in particular in the subgroup of untreated EH (n = 70), and to body mass index. A gender-related difference was apparent, as female subjects had more pronounced increments in SBP (+7.4 +/- 0.8 v +3.5 +/- 0.7 mm Hg) and DBP (+4.4 +/- 0.5 v 2.9 +/- 0.4 mm Hg) than did male subjects (P < .05 for both)., Conclusions: Clinic SBP and DBP are overestimated in the bed-seated position at the end of the visit compared with the recommended chair-seated position in treated and untreated patients with EH, in particular in elderly obese women with mild hypertension.

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.

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/m), 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.

Background: The prevalence and the relationship between metabolic syndrome, and target organ damage (TOD) in essential hypertensive patients has not been fully explored to date., Objective: To investigate the association between metabolic syndrome, as defined by the ATP III report, and cardiac and extracardiac TOD, as defined by the 2003 ESH-ESC guidelines for management of hypertension, in a large population of never-treated essential hypertensives., Methods: A total of 447 grade 1 and 2 hypertensive patients (mean age 46 +/- 12 years) who were attending a hypertension hospital outpatient clinic for the first time underwent the following procedures: (i) physical examination and repeated clinic blood pressure measurements; (ii) routine examinations; (iii) 24-h urine collection for microalbuminuria; (iv) 24-h ambulatory blood pressure monitoring; (v) echocardiography; and (vi) carotid ultrasonography. Metabolic syndrome was defined as involving at least three of the following alterations: increased waist circumference, increased triglycerides, decreased high-density lipoprotein cholesterol, increased blood pressure, or high fasting glucose. Left ventricular hypertrophy (LVH) was defined according to two different criteria: (i) 125 g/m in men and 110 g/m in women; (ii) 51 g/h in men and 47 g/h in women., Results: The 135 patients with metabolic syndrome (group I) were similar for age, sex distribution, known duration of hypertension and average 24-h, daytime and night-time ambulatory blood pressure to the 312 patients without it (group II). The prevalence of altered left ventricular patterns (LVH and left ventricular concentric remodelling) was significantly higher in group I (criterion a = 30%, criterion b = 42%) than in group II (criterion a = 23%, criterion b = 30%, P < 0.05 and P < 0.01, respectively). A greater urinary albumin excretion (17 +/- 35 versus 11 +/- 23 mg/24 h, P = 0.04) was also found in group I compared to group II. There were no significant differences between the two groups in the prevalence of carotid intima-media thickening and plaques., Conclusions: These results from a representative sample of untreated middle-aged hypertensives show that: (i) the metabolic syndrome is highly prevalent in this setting and (ii) despite similar ambulatory blood pressure values, patients with metabolic syndrome have a more pronounced cardiac and extracardiac involvement than those without it.

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.

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 beta-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.

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.

Objective: The clinical significance of classifying patients as dippers and non-dippers on the basis of a single period of ambulatory blood pressure monitoring (ABPM) has been questioned. The aim of this study was to evaluate the relationship between nocturnal dipping status, defined on the basis of two periods of ABPM, and cardiac and extracardiac target organ damage in essential hypertension., Methods: A total of 375 never-treated essential hypertensive patients [mean 24-h blood pressure (BP) > or = 125/80 mmHg; mean +/- SD age 45.9 +/- 11.9 years] referred for the first time to our outpatient clinic underwent the following procedures: (i) repeated clinic BP measurements; (ii) blood sampling for routine chemistry examinations; (iii) 24-h urine collection for microalbuminuria; (iv) ABPM over two 24-h periods within 4 weeks; (v) echocardiography; and (vi) carotid ultrasonography., Results: A reproducible nocturnal dipping (decrease in BP > 10% from mean daytime BP in both ABPM periods) and non-dipping profile (decrease in BP < or = 10% in both ABPM periods) was found in 199 (group I) and 79 patients (group II), respectively; 97 patients (group III) had a variable dipping profile. The three groups did not differ with regard to age, gender, body mass index, clinic BP, 48-h BP and heart rate. Left ventricular mass index, interventricular septum thickness, left atrium and aortic root diameters were significantly higher in group II compared with group I (mean +/- SD 108.5 +/- 19.5 versus 99.7 +/- 19.6 g/m, P < 0.05; 9.3 +/- 0.9 versus 9.1 +/- 0.9 mm, P < 0.05; 33.6 +/- 3.6 versus 32.2 +/- 3.7 mm, P < 0.01; 36.9 +/- 4.6 mm versus 35.5 +/- 4.6, P < 0.05, respectively). The smaller differences seen between groups II and III and between groups I and III were not statistically significant. The prevalence of left ventricular hypertrophy (defined as a left ventricular mass index > 134 g/m in men and > 110 g/m in women) was greater in group II (19%) than in group I (6%) (P < 0.05), whereas the differences between groups II and III and between groups I and III did not reach statistical significance. Differences among the three groups in the prevalence of carotid structural alterations (such as carotid plaques or intima-media thickening) were not statistically significant, and microalbuminuria had a similar prevalence in all three groups., Conclusions: Despite similar clinic and 48-h BP values, never-treated hypertensive patients with a persistent non-dipper pattern showed a significantly greater extent of cardiac structural alterations compared with subjects with a reproducible dipping pattern, but not those with a variable BP nocturnal profile. A non-dipping pattern diagnosed on two concordant ABPM periods instead of a single monitoring therefore represents a clinical trait associated with more pronounced cardiac abnormalities. Finally, in non-dipping middle-aged hypertensives, echocardiography appears to provide a more accurate risk stratification than carotid ultrasonography or microalbuminuria.

Objective: The aim of this study was to examine whether an impaired reduction in nocturnal blood pressure (BP), defined on the basis of two periods of ambulatory BP monitoring (ABPM), is present in hypertensive patients with metabolic syndrome, as defined by the NCEP criteria., Methods: 460 grade 1 and 2 untreated essential hypertensives (mean age 45.9 +/- 11.9 years) referred for the first time to our outpatient hospital clinic underwent the following procedures: 1) medical history and physical examination; 2) repeated clinic BP measurements; 3) routine examinations; 4) ABPM over two 24-hour periods within 4 weeks. Metabolic syndrome was defined as at least three of the following alterations: increased waist circumference, increased triglycerides, decreased HDL-cholesterol, increased BP, or high fasting glucose. Nocturnal dipping was defined as a night-time reduction in average SBP and DBP >10% compared to average daytime values., Results: The 135 patients with metabolic syndrome (group I) were similar for age, gender and known duration of hypertension to the 325 patients without it (group II). There were no significant differences between the two groups in average 48-hour, daytime, night-time SBP/DBP values and the percentage nocturnal SBP and DBP decrease (-17.7 / -15.7 vs. -18.4 / -16.2, p = ns). A reproducible nocturnal dipping (decrease in BP >10% from mean daytime in both ABPM periods) and non-dipping profile (decrease in BP < or =10% in both ABPM periods) was found in 74 (54.8%) and 29 (21.4%) in group I and in 169 (52.1%) and 73 (22.4%) in group II, respectively (p = ns); 32 patients (23.7%) in group I and 83 patients (25.5%) in group II had a variable dipping profile (p = ns)., Conclusions: This study shows that no significant difference exists in nocturnal BP patterns, assessed by two ABPMs, in untreated essential hypertensive patients with metabolic syndrome compared to those without it.

Background: The 2003 European Society of Hypertension/European Society of Cardiology (ESH-ESC) guidelines have recently proposed a new risk stratification scheme for estimating absolute risk for cardiovascular disease. At variance from the previous 1999 World Health Organization-International Society of Hypertension (WHO/ISH) guidelines, the new criteria include some additional risk factors such as obesity, abnormal high-density (HDL) or low-density lipoprotein (LDL) cholesterol levels and define a slight increase in creatinine and microalbuminuria as signs of target organ damage (TOD)., Objective: The aim of the study was to assess overall cardiovascular risk in uncomplicated hypertensives according to the 2003 ESH-ESC guidelines comparing this approach with the stratification scheme of the 1999 WHO/ISH guidelines., Methods: Four hundred and twenty-five never-treated grade 1 and 2 essential hypertensive patients, referred for the first time to our outpatient clinic without diabetes mellitus, were included in the study. They underwent the following procedures: (i) repeated clinical blood pressure measurements; (ii) routine blood chemistry and urine analysis; (iii) electrocardiogram; (iv) 24-h urine collection for microalbuminuria; (v) echocardiogram; and (vi) carotid ultrasonogram. Risk was assessed according to both stratification schemes suggested by the 2003 ESH-ESC and 1999 WHO/ISH guidelines., Results: According to the 2003 ESH-ESC guidelines, 15.5% of the 425 patients were considered at low added risk, 47.8% at medium added risk and 36.7% at high added risk; 146 patients (34.3%) were classified in the high-risk stratum because of at least one manifestation of TOD and 5.6% having three or more risk factors. The accuracy in detecting TOD of the combined approach with ultrasound procedures and microalbuminuria was approximately 10-fold higher than that provided by routine investigation. As a result of the 1999 WHO/ISH stratification scheme, 34.5% were low-risk, 34.4% medium-risk and 31.1% high-risk patients., Conclusions: Our findings show that: (i) more than one-third of uncomplicated grade 1 and 2 hypertensives seen in a outpatient hypertension hospital clinic have a high added risk according to the ESH-ESC scheme; (ii) classification of the patients in the high stratum is mainly influenced by the presence of TOD; (iii) the routine diagnostic work-up is a highly insensitive approach for the detection of TOD; (iv) the 2003 ESH-ESC guidelines stratify a higher proportion of hypertensive patients in the medium and high-risk groups than do the 1999 WHO/ISH guidelines.

Background: The clinical significance of stratifying cardiovascular risk in hypertensive patients on the basis of retinal changes such as arteriolar narrowing or arterio-venous crossing has been criticized., Aim: Objectives of the study were: (i) to compare the prevalence of retinal abnormalities detected by non-mydriatic retinography with that of other quantitative markers of target organ damage (TOD), such as echocardiographically determined left ventricular hypertrophy (LVH), carotid structural abnormalities and microalbuminuria in recently diagnosed and never treated hypertensives; (ii) to assess the inter- and intra-observer reproducibility in evaluating retinal microvascular changes., Methods: One hundred ninety-seven grade 1 (73%) and grade 2 essential hypertensives (119 males; mean age 46.8 +/- 12.0 years, duration of hypertension: 2.3 +/- 1.8 years) referred for the first time to our outpatient hypertension hospital clinic were subjected to the following procedures: (i) repeated clinic blood pressure (BP) measurements; (ii) electrocardiogram; (iii) routine blood chemistry and urinalysis; (iv) 24-h urine collection for microalbuminuria; (v) 24-h ambulatory BP monitoring; (vi) non-mydriatic retinography; (vii) echocardiogram; (viii) carotid ultrasonography. Retinal changes were evaluated according to a modified Keith, Wagener and Barker (KWB) classification by two physicians, who had no knowledge of the patients' characteristics. These following markers of TOD were considered: (i) left ventricular mass index > or = 125 g/m2 in men and > or = 110 g/m2 in women; (ii) at least one carotid plaque (focal thickening > 1.3 mm) or diffuse common carotid thickening (> or = 0.9 mm); (iii) microalbuminuria (urinary albumin excretion > or = 30 and < 300 mg/24 h)., Results: The prevalence rates of LVH, carotid structural alterations and microalbuminuria were 12.9, 26.0 and 8.6% respectively; while the distribution of patients in the different degrees of hypertensive retinopathy made by two independent readers (1 and 2) was: 0 = 15.2, I = 25.4, II = 58.9, III = 0.5% (1); 0 = 14.7, I = 27.9, II = 56.8, III = 0.5% (2), p = NS. The overall prevalence of retinal changes was 84.3% and 84.7%, respectively, and the inter- and intra-observer reproducibility 89.1, 91.6 (1) and 90.2% (2), respectively., Conclusions: Our data indicate that: (i) the prevalence of initial retinal changes is far higher than that of other prognostically validated quantitative markers of cardiac and extracardiac TOD; (ii) the inter- and intra-observer reproducibility between two skilled readers in detecting these abnormalities with non-mydriatic retinography is excellent; (iii) the high prevalence of retinal changes in untreated subjects with mild hypertension offers a new piece of evidence that they cannot be considered a proof of TOD.

Objective: The aim of the study was to evaluate the prevalence of left ventricular hypertrophy (LVH) in treated patients with good blood pressure (BP) control during multiple home BP (HBP) measurements and during 24-h ambulatory BP monitoring (ABPM), but with unsatisfactory BP control in the clinic. These patients were compared with treated hypertensives whose BP was well controlled under the three circumstances., Methods: Seventy-two treated consecutive patients (group I, age 56 +/- 10 years) with clinic BP values > or = 140/90 mmHg, and a difference between clinic and self-measured HBP > 10 mmHg for diastolic blood pressure (DBP) and/or > 20 mmHg for systolic blood pressure (SBP), underwent the following procedures: (1) clinic BP measurement; (2) routine diagnostic work-up; (3) HBP monitoring; (4) 24-h ABPM; (5) echocardiography. Thirty-five hypertensive patients with satisfactory BP control according to clinic (< 140/90 mmHg), HBP (< or = 131/82 mmHg) and ABP criteria (< or = 125/79 mmHg) were included as the control group (group II, age 55 +/- 9 years)., Results: In group I, 33 subjects out of the 72 (46%) with clinic BP > 140/90 mmHg had BP values controlled outside the clinic (23 according to HBP criteria and 22 according to ABP criteria). The prevalence of LVH (LV mass index > 134 g/m2 in men and > 110 g/m2 in women) was significantly higher in these patients (15.1 versus 2.8%, P < 0.01) than in group II (BP also controlled in the clinic), despite the fact that HBP and ABP were reduced to similar levels in the two groups. CONCLUSIONS Our data provide evidence that treated hypertensive patients with good BP control at home or during ambulatory monitoring, but incomplete BP control in the clinic, have more pronounced cardiac alterations than patients with both clinic and out of the clinic BP control. This finding offers a new piece of information about the diagnostic value of BP measurement in the clinic to assess BP control during antihypertensive treatment.

Unsatisfactory blood pressure (BP) control so often described in treated hypertensive populations is also explained by insufficient physicians' awareness of experts' guidelines. We assessed awareness of current recommendations about hypertension management in a general practice setting, using the World Health Organization/International Society of Hypertension (WHO/ISH) 1999 guidelines as reference. In a regionwide survey, a total of 5133 physicians (three-quarters of all active general practitioners in Lombardy, a region of north-western Italy) were contacted by letter and received a multiple choice 10-item questionnaire. Data on physicians' demographic characteristics, information on hypertension prevalence and their perception of BP control among their patients were also requested in an additional form. The number of answers in agreement with WHO/ISH guidelines was used as an awareness measure. This was considered adequate if correct answers to six out of 10 questions, including an appropriate definition of hypertension, were provided. Of the 1256 returned questionnaires (a 24.5% response rate), 1162 were suitable for analysis. The mean score of correct answers was 5.3 points and only 20.1% of the study population correctly answered at least six of the questions (including that on the definition of hypertension in the elderly). Guidelines awareness was negatively related to increase in physicians' age and duration of clinical practice and by the male gender. Finally, the physicians reported a high rate of achieved BP control, and those who were considered to have achieved highest rates (>75%) of control in their patients had a lower rate of adequate knowledge than those who reported less-successful therapeutic results (18 vs 25%, P<0.01), suggesting that they ignored or disregarded the goal BP recommended by the guidelines. This large regional survey shows that a sufficient degree of guidelines awareness is present in a minority of primary-care physicians in the Italian region of Lombardy. Therefore, further efforts are required to intensify information strategies for improving professional education, training and practice organization aimed at achieving therapeutic goals. Physicians with longer duration of clinical practice represent a particularly relevant target group for these interventions.

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.

Background: Non-dipping pattern in hypertensive patients has been shown to be associated with an excess of target organ damage and with an adverse outcome. The aim of our study was to assess whether a reduced nocturnal fall in blood pressure (BP), established on the basis of a single 24-h BP monitoring, in treated essential hypertensives is related to more prominent cardiac alterations., Methods: We enrolled 229 treated hypertensive patients attending the out-patient clinic of our hypertension centre; each patient was subjected to the following procedures : 1) clinic BP measurement; 2) blood and urine sampling for routine blood chemistry and urine examination; 3) standard 12-lead electrocardiogram; 4) echocardiography; 5) ambulatory BP monitoring (ABPM). For the purpose of this study ABPM was carried-out in three subgroups with different clinic BP profile: 1) patients with satisfactory BP control (BP < 140/90 mmHg; group I, n = 58); 2) patients with uncontrolled clinic BP (clinic BP values > or = 140 and/or 90 mmHg) but lower self-measured BP (< 20 mmHg for systolic BP and/or 10 mmHg for diastolic BP; group II, n = 72); 3) patients with refractory hypertension, selected according to WHO/ISH guidelines definition (group III, n = 99). Left ventricular hypertrophy (LVH) was defined by two gender-specific criteria (LV mass index > or = 125/m2 in men and 110 g/m2 in women, > or = 51/gm2.7 in men and 47/g/m2.7 in women)., Results: Of the 229 study participants 119 (51.9%) showed a fall in SBP/DBP < 10% during the night (non-dippers). The prevalence of non-dippers was significantly lower in group I (44.8%) and II (41.6%) than in group III (63.9%, p < 0.01 III vs II and I). The prevalence of LVH varied from 10.3 to 24.1% in group I, 31.9 to 43.1% in group II and from 60.6 to 67.7% in group III (p < 0.01, III vs II and I). No differences in cardiac structure, analysed as continuous variable as well as prevalence of LVH, were found in relationship to dipping or non-dipping status in the three groups., Conclusions: In treated essential hypertensives with or without BP control the extent of nocturnal BP decrease is not associated with an increase in LV mass or LVH prevalence; therefore, the non-dipping profile, diagnosed on the basis of a single ABPM, does not identify hypertensive patients with greater cardiac damage.

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.

Background: It has been shown that aging and arterial hypertension are both associated with an increased prevalence of carotid structural abnormalities, such as intima-media (IM) thickening or plaques, which are a powerful independent predictor of cardiovascular (CV) events. We investigated the impact of carotid IM thickening in profiling the absolute CV risk stratification according the 1999 World Health Organization/International Society of Hypertension (WHO/ISH) guidelines in elderly hypertensive patients., Methods: Two hundred and thirty untreated elderly patients (>65 years) referred to our outpatient hospital clinic were included in the study. They underwent the following procedures: (i) medical history, physical examination and clinic blood pressure measurement; (ii) routine blood chemistry and urine analysis; (iii) electrocardiogram. The risk was initially stratified according to the routine procedures indicated by WHO/ISH guidelines and subsequently reassessed by adding the results of carotid ultrasonography (IM thickening as diffuse IM thickness >0.9 and <1.3 mm)., Results: According to routine classification 56% (=129) were medium-risk patients, 29% (n = 67) high-risk and 15% (n = 34) very-high-risk patients. The overall prevalence of carotid IM thickening was 54% (49% in medium-risk vs 60% in high or very high-risk patients, p < 0.05). A marked change in risk stratification was observed when IM thickening was taken in consideration: medium-risk patients decreased to 29% and high-risk rose to 56% (p < 0.01)., Conclusions: Ultrasound assessment of large artery damage is extremely useful for a more accurate estimate of global CV risk in elderly hypertensives, because stratification based on diagnostic routine procedures can underestimate the overall risk in a large fraction of medium-risk subjects.

The aim of this study was to investigate the diagnostic approach to recently diagnosed hypertensive patients by primary care physicians in Italy and to find out whether general practitioners manage these patients according to 1999 WHO/ISH guideline recommendations. In total, 228 consecutive patients (117 men and 111 women, mean age 51+/-12 years) with recently diagnosed hypertension (<2 years) referred for the first time to six outpatient hypertension centres throughout Italy were included in the study. The primary care physicians' approach was evaluated during the specialist visit by a specific questionnaire containing detailed questions about diagnostic work-up and treatment made at the time of the first diagnosis of hypertension. At the study visit, 71% of the patients were on treatment with antihypertensive drugs and 18.7% of them had blood pressure (BP) values lower than 140/90 mmHg. A complete clinical and laboratory evaluation according to the minimum work-up suggested by the guidelines had been carried out in only 10% of the patients. A full physical examination had been performed in 60% of the patients, electrocardiogram in 54%, serum total cholesterol in 53%, glucose in 49%, creatinine in 49%, urine analysis in 46%, potassium in 42%, and fundus oculi in 19%. Additional investigations such as ambulatory BP monitoring, echocardiogram, carotid ultrasonogram, and microalbuminuria had been carried out in a minority of patients (21, 18, 9, and 3%, respectively). The impact on hypertension guidelines on patients' management in everyday primary care practice appears marginal. Thus, our findings indicate that the majority of general practitioners manage hypertensive patients according to a simple BP-based approach rather than a more integrated approach based on global risk stratification.

Background: The aim of this study was to describe trends in blood pressure (BP) control and in the prevalence of left ventricular hypertrophy (LVH) during 3 years of follow-up in a representative sample of treated hypertensive patients seen in our out-patient hypertension hospital clinic., Methods: Four hundred and sixty-four hypertensive treated patients who took part in a clinical survey at our out-patient clinic during the year 1997 and who had been submitted to a routine follow-up visit 3 years later were included in the study. All patients were subjected to the following procedures: an accurate medical history, physical examination, electrocardiogram, clinical BP measurement. For the diagnosis of LVH we used two different ECG criteria: the Solokow-Lyon voltage and the gender-specific Cornell voltage., Results: During the first survey, 15% of treated patients had a clinical BP < 130/85 mmHg, 25.1% > or = 130/85 mmHg and < 140/90 mmHg, 33.6% > or = 140/90 and < 150/95 mmHg, 26.3% > or = 150/95 mmHg. The corresponding figures in the second survey were 19, 26.7, 33.2 and 21.1%, respectively. Overall, from the first to the second survey the prevalence of an effective BP control (< 140/90 mmHg) rose from 40.1 to 46.7% (p < 0.01). At baseline, 40 patients had ECG LVH (8.6%); at the second visit, LVH was found to have regressed in 19 of these patients. Among the 424 patients with a normal baseline electrocardiogram, 3 developed LVH during follow-up. Hence, the prevalence of LVH decreased from 8.6 to 5.1% (p < 0.01). In terms of treatment, the prevalence of combination therapy regimens increased from 68.6 to 79.7% (p < 0.05)., Conclusions: This study demonstrates that in hypertensive patients managed in a hypertension hospital clinic, BP control improved during the long-term follow-up and that this trend was associated with a significant regression in ECG LVH.

Objective: Ultrasonic tissue characterization of epi-aortic vessels may be useful to define the composition of atherosclerotic plaques. Videodensitometry provides a histogram representing the frequency distribution of gray levels corresponding to different compositions of the carotid wall. However, lack of standardization limits the clinical application of this technique. In the present study, the echoreflectivity (ER) pattern of atherosclerotic plaques in vivo was compared with their histological pattern after surgical removal, and the reproducibility of measurement was tested., Design and Methods: We studied 19 hypertensive patients with a carotid artery stenosis >or= 70%, eligible for carotid thromboendarterectomy (TEA). Before TEA, all patients underwent standard high-resolution B-mode carotid ultrasound. ER parameters (mean gray level, broad band, skewness, and kurtosis) were obtained in a region of interest selected along the whole plaque, between the intima-blood and the media-adventitia interfaces. The plaques removed during TEA were examined by a histologist and classified into three groups on the basis of fibrous tissue (FT) content: lipidic (FT < 20%), fibrolipidic (20 50%). Discriminant function analysis was used to evaluate classification efficacy of different histological groups based on ER parameters., Results: Histologically, five lesions were classified as lipidic, six as fibrolipidic and eight as fibrous. Analysis of variance showed significant between group differences in all ER parameters. The combined use of all ER parameters provided correct classification of plaques in 94.73% of cases (P < 0.0001), improving the classification made using single parameters. Intra-observer and inter-observer variabilities (Bland-Altman method) of mean gray level measurements were small., Conclusions: Videodensitometry can discriminate between tissue composition of carotid lesions and complement the quantitative assessment of intima-media thickness by additionally providing a well-reproducible semiquantitative evaluation of vascular wall constituents.

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.

Background: An adequate knowledge of hypertension guidelines by primary care physicians is a fundamental step for the improvement of the diagnosis and treatment of hypertension in the general population. The aim of this study was to evaluate, in a local survey in the northern area of Lombardy, the general practitioners' knowledge of the WHO/ISH guidelines., Methods: A 10-item mail questionnaire based on the 1999 WHO/ISH hypertension guidelines was sent to a sample of 280 primary care physicians. The number of answers in agreement with the guidelines was used as a measure of guidelines knowledge, that was considered adequate if a correct answer to 6 out of 10 questions, in addition to an adequate definition of hypertension, was provided., Results: The analysis was based on 83 returned questionnaires, that means a 29% response rate. Guidelines knowledge was adequate in 23.5% of the total study population and the mean score of correct answers was 5.5 points. A significant negative correlation (r = 0.27, p < 0.05) was observed between the mean score of knowledge and the physician's age., Conclusions: In a sample of primary care physicians from a northern region of Italy, the hypertension guidelines knowledge is inadequate; the reasons and the extent of this poor awareness will require further studies.

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.

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.

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.

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.

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.

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.

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.

Background: It has been generally accepted that educational programs can be beneficial in the treatment of a number of chronic diseases such as diabetes mellitus as well as of cardiovascular risk factors and hypertension. We organized a structured educational intervention aimed at 1) assessing the patient's baseline knowledge of hypertension, 2) verifying the short and long-term impact of this initiative on patient's education., Methods: We invited 174 consecutive patients referred to our hypertension outpatient clinic to participate in an educational meeting on hypertension. For organizational reasons, patients were divided into two groups, each attending a single meeting. Each meeting included four sessions: 1) in the first session a multiple choice questionnaire (nine questions, with answers collected by an interactive electronic system) was administered in order to evaluate patients' baseline knowledge of hypertension, 2) a traditional teaching session, 3) an interactive phase aimed at assessing the improvement of knowledge in which the same questions as in the first session were assessed again, 4) a general discussion session. At the end of the meeting a booklet on principal issues related to hypertension was given to each patient. In order to evaluate the long-term impact of this initiative on the patient's knowledge, 6 months later we invited the patients to answer to the same questions in a questionnaire sent to their home address., Results: One hundred thirty-three patients of the 174 invited attended the meeting and 111 (57 males, 54 females, mean age 53 +/- 13 years) completed the questionnaire after 6 months. The answers to the questions in the initial session were correct in a percentage ranging from 60 to 80% (mean 68%) and immediately after the teaching session this rate increased significantly (range 75-98%, mean 90%, p < 0.05 at least, in all questions). A similar good level of knowledge was maintained in the long term (percentage of exact answers ranging from 78 to 97%, mean 88%, p < 0.05 or p < 0.01 compared to baseline)., Conclusions: The findings of the present study show a positive short and long-term impact of a structured educational intervention on the patient's knowledge of issues related to arterial hypertension. The beneficial role on clinical outcomes such as blood pressure control and cardiovascular events will need future controlled trials.

Echocardiographic image texture has been demonstrated to reflect the physical properties of the tissue under examination. To evaluate the role of collagen in determining the echo pattern of the left ventricular wall, we studied nine hypertensive patients with left ventricular hypertrophy (left ventricular mass index > 125 gm/m2) and biopsy-proven different degrees of myocardial fibrosis by analyzing the echocardiographic examinations performed before the biopsy. Myocardial tissue was sampled under fluoroscopy and two-dimensional echo guidance in the interventricular septum. Collagen volume fraction (CVF; normal range up to 2%) was taken as an index of fibrosis. The echo patterns were assessed by analyzing standard two-dimensional parasternal long-axis echocardiograms recorded on videotape. Images were color-coded at 256 levels (0 = yellow, 256 = black) and digitized off-line onto a personal computer. The region of analysis was set using a selection tool (20 x 10 mm) in the general area of septum where the specimen was taken. For each selection a color-level histogram, representing the frequency distribution, was derived with estimates of the average pixel intensity (mCS), skewness (SK), kurtosis (K), and the broad band (Bb) of the echoes about the distribution. Echo-derived parameters in each patient were compared with corresponding CVF values. CVF was out of range in all patients, ranging from 2.6% to 7.6% (mean 4.3% +/- 1.6%). No correlation was found between CVF and mCS, whereas a significant correlation was found at end diastole between CVF and the parameters describing histogram morphology, respectively, SK (r = 0.73), K (r = 0.69), Bb (r = 0.72). These findings for the first time demonstrate in vivo in hypertensive patients with left ventricular hypertrophy an agreement between echo amplitude and histologically assessed collagen volume. Thus in our studied patients collagen content appears to be the major determinant of regional echo intensity, its increase resulting in a significant and progressive wider asymmetrical left shift (yellow) of the color histogram.

The aim of this investigation was to study the coronary pressure-flow relationship in 60 patients with chronic arterial hypertension of diverse aetiologies and in 14 normotensive subjects (control group). The hypertensive cohort included 6 patients with isolated systolic hypertension (ISH), 7 renovascular hypertensive patients with abnormally elevated angiotensin II plasma levels but without electrocardiographic and/or echocardiographic evidence of left ventricular hypertrophy (LVH) and 47 subjects with essential hypertension (EH), 21 of whom had LVH by electrocardiogram and/or echocardiogram. In the hypertensive cohort a Frank-Starling-like curve was found to describe the coronary pressure-flow relationship when the baseline values for coronary sinus blood flow (CBF, intravascular Doppler technique) were plotted against mean aortic pressure (intra-arterial blood pressure). In particular, the descending limb of such a curve represented a critical region where CBF was "inappropriately" low with respect to perfusion pressure. It was thus concluded that this inability of the heart to adapt CBF to its needs might account for the higher propensity to develop myocardial ischaemia encountered in severe essential hypertensive subjects with concomitant LVH and renovascular hypertensive patients.

1. The present investigation was carried out to elucidate the possible role of the renin-angiotensin system in modulating coronary vasomotor responses in eight patients with uncomplicated mild essential hypertension with no electrocardiographic-echocardiographic evidence of left ventricular hypertrophy. 2. Systemic and coronary haemodynamics were monitored at baseline and during intravenous infusion of angiotensin II at a subpressor dose (3 ng min-1 kg-1 for 15 min) and at a pressor dose (13 ng min-1 kg-1 for 15 min) both at rest and during handgrip exercise. Infusion of the subpressor dose of angiotensin II decreased coronary sinus blood flow at rest (207 +/- 10 versus 182 +/- 9 ml/min, P less than 0.05) without a significant change in mean arterial pressure, heart rate or mean right atrial pressure. The performance of handgrip at baseline and during infusion of the subpressor dose of angiotensin II resulted in 55% (321 +/- 13 versus 207 +/- 10 ml/min) and 44% (263 +/- 16 versus 182 +/- 9 ml/min) increases in coronary sinus blood flow, respectively, in response to comparable increments in the rate-pressure product. At rest, infusion of the pressor dose of angiotensin II increased both coronary sinus blood flow (235 +/- 11 versus 207 +/- 10 ml/min, P less than 0.01) and the rate-pressure product (134 +/- 5 versus 111 +/- 8 mmHg beats/min, P less than 0.01). The increase in coronary sinus blood flow during isometric exercise was less than control (309 +/- 18 versus 321 +/- 13 ml/min, P less than 0.01). 3. It is thus concluded that (1) the opposite effects of angiotensin II on coronary blood flow are dose-dependent, and that (2) angiotensin II competes with the ability of the coronary arteries to dilate during handgrip exercise.

The purpose of this study was to evaluate whether the heart can induce high blood pressure by maintaining an inappropriately elevated cardiac output/body weight ratio during growth. Direct (femoral artery) mean arterial pressure (MAP), heart rate, cardiac output/body weight ratio (as defined by M-mode echocardiography), and total peripheral vascular resistance were measured and calculated every 2 months in nine conscious dogs during development from 2 to 10 months of age. In four dogs a J-shaped catheter for atrial pacing was chronically implanted at the age of 3 months, and their hearts were permanently paced at 130 beats/min until maturity. The aim of atrial pacing was to prevent the natural slowing of the heart rate and, consequently, to maintain a cardiac output/body weight ratio that was inappropriately high in relation to age during growth. Five dogs were studied as controls. No hemodynamic differences were observed until the age of 4 months. From the age of 5 to 10 months heart rate was kept at 130 beats/min by atrial pacing in the atrially paced group, and the mean cardiac output/body weight ratio did not decrease (196 +/- 24 vs 191 +/- 34 [SE] ml/min/kg). MAP rose from 62 +/- 4 to 116 +/- 8 mm Hg, and total peripheral resistance increased from 0.34 +/- 0.07 to to 0.61 +/- 0.09 mm Hg/ml/min/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied the hemodynamic mechanism responsible for the antihypertensive effect of indapamide in eight patients with mild essential hypertension. Systemic and pulmonary hemodynamics were measured using direct techniques (right heart catheterization and thermodilution method), before and 7-10 days after oral treatment with indapamide (2.5 mg/day). Indapamide reduced mean arterial blood pressure from 120 +/- 1.6 (mean +/- SE) to 101 +/- 1.4 mm Hg (p less than 0.01), and mean pulmonary artery pressure from 21 +/- 0.59 to 17 +/- 1.05 mm Hg (p less than 0.01). Total peripheral vascular resistance (TPR) and pulmonary vascular resistance were reduced from 36 +/- 0.85 to 29 +/- 0.72 U/m2 (p less than 0.01) and from 4.3 +/- 0.17 to 3.8 +/- 0.18 U/m2 (p less than 0.01), respectively. Indapamide did not change cardiac index (CI) (3,311 +/- 61.6 vs. 3,325 +/- 72.1 ml/min/m2), heart rate (HR) (75 +/- 1.7 vs. 75 +/- 9 beats/min), mean rate of left ventricular ejection index 140 +/- 2.04 vs. 139 +/- 1.99 ml/s/m2, and stroke index (44 +/- 5.6 vs. 43 +/- 5.8 ml/m2). Mean pulmonary wedge pressure decreased from 7 +/- 0.6 to 5 +/- 0.5 mm Hg (p less than 0.05). Body weight, 24-h urinary volume, and hematocrit were unchanged after treatment. We conclude that the hemodynamic mechanism responsible for the antihypertensive action of indapamide is a reduction in TPR without changes in CI and HR.

Angiotensin is a potent coronary vasoconstrictor, but little is known of the effects of long-term activation of the renin-angiotensin system on coronary reserve in humans. The effects of exercise on coronary hemodynamics were determined in eight patients with mild essential uncomplicated hypertension, before and after treatment with furosemide (50 mg, to ensure activation of the renin-angiotensin system). Coronary sinus blood flow was measured by thermodilution technique, intra-arterial blood pressure was measured from the ascending aorta, and plasma renin activity was determined by radioimmunoassay. Oxygen supply and demand were derived (using coronary sinus blood flow multiplied by the arteriovenous oxygen difference to equal oxygen supply and heart rate multiplied by the mean systolic blood pressure to equal oxygen demand) both at rest and during isometric exercise (handgrip to 50 percent of maximal effort for three minutes). The study was a single-blind crossover (furosemide versus placebo) design. Furosemide produced a significant reduction in coronary sinus blood flow, associated with an increase in coronary vascular resistance. Changes in mean arterial pressure and heart rate were insignificant. Slight reductions in plasma volume and mean right atrial pressure were observed. During isometric exercise, the increase in oxygen supply for a given increment in oxygen demand was attenuated by furosemide. The contribution of the renin-angiotensin system to this effect was determined by the short-term administration of 25 mg of the angiotensin converting enzyme inhibitor captopril. Forty-five minutes after oral captopril, coronary reserve was restored to pretreatment values. In conclusion, furosemide modulates coronary reserve, and it is likely that this is because furosemide mediates activation of renin-angiotensin system, thus reducing the vasodilatory capacity of the coronary arteries.

1. Propranolol, when used for treating arterial hypertension, may influence determinants of both cardiac and vascular function; the consequent changes in cardiac performance may result from the interaction of different and possibly opposite effects. 2. Cardiac funtion was investigated in fifty-four primary hypertensive men in the pretreatment state and after 3 weeks of propranolol therapy at a daily dose of 320 mg. 3. beta-Receptor blockade caused depression of pre-injection left ventricular function, which was unrelated to the direction and the extent of changes in peripheral circulation. 4. The ejection left ventricular function could be either depressed or improved depending on the direction to which treatment shifted the vascular resistance, and consequently, the impedance to left ventricular ejection. 5. Withdrawal of the adrenergic support is probably the major factor responsible for the poor ventricular adaptation to an augmented impedance.

1. In 27 severe primary hypertensive patients nifedipine (10 mg), administered orally, induced prompt (-21% of control at 30 min) and persistent (-17% at 120 min) fall of mean arterial pressure mediated through reduction of peripheral vascular resistance with rise of cardiac output. 2. The sublingual route (nine cases) showed more rapid onset of action and equal antihypertensive effectiveness. 3. In five patients with hypertensive crisis and acute left ventricular failure, the drug strikingly reduced systemic and pulmonary arterial pressures and relieved pulmonary oedema. 4. Prompt efficacy, ease of administration, absence of important side effects indicate that nifedipine may be a useful therapeutic agent in severe hypertension and in critical conditions that require rapid lowering of blood pressure.