B Severgnini

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 ⩽ 125/79 mmHg), all patients with RH were subjected to 24-hour ambulatory BP monitoring. Results Both groups were similar for age, gender, body surface area, smoking habit and duration of hypertension, glucose, creatinine and lipid levels. By definition, clinic BP was significantly higher in RH than C (161 ± 19/96 ± 9 versus 127 ± 6/80 ± 5 mmHg, respectively, P < 0.01). The increased prevalence of left ventricular hypertrophy (LVH) and carotid intima–media (IM) thickening (40 versus 12%, P < 0.01, according to a non-gender-specific partition value of 125 g/m2 ; and 36 versus 14%, P < 0.01, according to IM thickness ⩾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.

Metabolic syndrome and target organ damage in untreated essential hypertensives

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/m2 in men and 110 g/m2 in women; (ii) 51 g/h2.7 in men and 47 g/h2.7 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.

Cardiovascular target organ damage in essential hypertensives with or without reproducible nocturnal fall in blood pressure

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) ⩾ 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 ⩽ 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/m2, 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/m2 in men and > 110 g/m2 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.

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 ⩽10% nocturnal fall (non-dippers) in both sessions. The prevalence of left ventricular hypertrophy (LVH) (defined by two criteria: (1) LV mass index ⩾ 125 g/m2 in both genders; (2) LV mass index ⩾ 120 and 100 g/m2 in men and women, respectively) and that of carotid intima–media (IM) thickening (IM thickness ⩾ 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.

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.

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

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

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.

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 ⩽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) ⩾125 g/m2 in both genders; (b) LVMI ⩾134 gm2 in men and ⩾110 in women; (c) LVMI⩾125 g/m2 in men and ⩾110 g/m2 in women; (d) LVMI⩾51 g/m2.7 in men and ⩾47 g/m2.7 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.

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 outpatients hypertension unit. LVH was diagnosed using six different criteria, when left ventricular mass index (LVMI) exceeded (a)100 g/m 2 in women and 120 g/m 2 in men, (b) 110 g/m 2 in women and 125 g/m 2 in men, (c) 110 g/m 2 in women and 134 g/m 2 in men, (d) 125 g/m 2 in both sexes, (e) 47 g/h 2.7 in women and 51 g/h 2.7 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) S 0.8 mm; (b) S 0.9 mm; (c) S 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/height 2.7 , 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.

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.