Midwall mechanics are improved after regression of hypertensive left ventricular hypertrophy and normalization of chamber geometry.

BACKGROUND: It is still unclear whether substantial regression of hypertensive left ventricular hypertrophy (LVH) and normalization of chamber geometry are associated with improved left ventricular (LV) myocardial function. METHODS AND RESULTS: Midwall mechanics were evaluated in 152 patients undergoing 1 year of effective antihypertensive treatment. Two-dimensionally directed M-mode echocardiography was performed as follows: (1) after a 4-week placebo "run-in" period, (2) after 1 year of treatment with 20 mg/d lisinopril (alone or associated with 12.5 to 25 mg/d hydrochlorothiazide), and (3) after a final 1-month placebo period to allow blood pressure (24-hour average ambulatory monitoring) to return to pretreatment levels. Treatment-induced reductions in blood pressure (from 149+/-16/95+/-11 to 131+/-12/83+/-10 mm Hg, P:<0.05) and circumferential end-systolic wall stress (from 84+/-22 to 72+/-19 g/cm(2), P:<0.05) were associated with a marked reduction in LV mass index (from 159+/-30 to 133+/-26 g/m(2), P:<0.05). LVH regression was accompanied by an increase in midwall fractional shortening (from 19.7+/-2.7% to 20.9+/-2.7%, P:<0.05) and by a decrease in relative wall thickness (from 48.2+/-7.7% to 44.1+/-6.7%, P:<0.05). The improvement in midwall function associated with afterload reduction and substantial LVH regression persisted after antihypertensive therapy withdrawal and restoration of the hypertensive state. Despite a significant increase in end-systolic wall stress, further LV chamber remodeling did not occur. The preservation of relative wall thickness was associated with a persistent improvement in midwall systolic function. CONCLUSIONS: Regression of concentric LVH is associated with an improvement of midwall systolic function, which is more dependent on the normalization of LV geometry than on the reduction in LV systolic stress.

Cardiopulmonary receptor modulation of plasma renin activity in normotensive and hypertensive subjects.

Cardiopulmonary receptors modulate renin release in several animals species. However, their involvement in reflex control of this humoral substance in humans is controversial. Furthermore, no information is available on the alteration of this control in hypertension. We studied the modulation of plasma renin activity (radioimmunoassay) in 12 normotensive subjects and in 12 age-matched subjects with untreated hypertension of mild or moderate degree. Cardiopulmonary receptors were stimulated by increasing central venous pressure (right atrial catheter) and cardiac volume (echocardiographic measurement) through passive leg raising and deactivated by reducing central venous pressure and cardiac volume through lower body negative pressure. The stimuli were maintained for 20 to 30 minutes, and their degree was set to avoid changes in blood pressure (indirect or direct measurements) and heart rate, thus avoiding involvement of arterial baroreceptors. In normotensive subjects, deactivation of cardiopulmonary receptors induced a progressive rise in plasma renin activity and stimulation of cardiopulmonary receptors induced a progressive fall. The reflex gain (ratio between plasma renin activity and central venous pressure or cardiac volume changes) was similar for deactivation and stimulation. During cardiopulmonary receptor deactivation, the gain corresponded to that obtained by dividing the increase in plasma renin by the reduction in central venous pressure induced by tilting. Cardiopulmonary receptor deactivation and stimulation also induced clear-cut changes in plasma renin activity in hypertensive subjects, but the percent magnitude of the reflex plasma renin activity excursion was less than that in normotensive subjects. These observations indicate that cardiopulmonary receptors modulate plasma renin activity in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary reflex before and after regression of left ventricular hypertrophy in essential hypertension.

Studies that have examined the cardiopulmonary receptor control of circulation in hypertension have produced conflicting results. In 10 normotensive subjects and in age-matched essential hypertensive subjects without (n = 10) or with left ventricular hypertrophy (n = 12), as well as in seven subjects of the latter group restudied after 1 year of treatment that induced regression of cardiac hypertrophy, we examined the cardiopulmonary reflex by increasing central venous pressure and stimulating cardiopulmonary receptors through passive leg raising and by reducing central venous pressure and deactivating cardiopulmonary receptors through nonhypotensive lower body negative pressure. Reflex responses were measured as changes in forearm vascular resistance (mean blood pressure divided by plethysmographically measured blood flow), plasma norepinephrine concentration, and plasma renin activity. In hypertensive subjects without left ventricular hypertrophy, stimulation and deactivation of cardiopulmonary receptors caused changes in forearm vascular resistance, norepinephrine concentration, and plasma renin activity that were modestly reduced as compared with those in normotensive subjects. However, all these changes were markedly reduced in hypertensive subjects with left ventricular hypertrophy. Following regression of left ventricular hypertrophy, the changes in vascular resistance, plasma norepinephrine, and plasma renin activity induced by cardiopulmonary receptor manipulation all improved markedly. These results demonstrate that cardiopulmonary receptor regulation of peripheral vascular resistance and of neurohumoral variables is impaired in essential hypertension and that the impairment is much more pronounced when this condition is associated with cardiac structural alterations. Therapeutic regression of these alterations, however, leads to a marked improvement of this reflex, with consequent favorable effects on circulatory homeostasis.

Early 24-hour blood pressure elevation in normotensive subjects with parental hypertension.

Subjects with a family history of parental hypertension are reported to have a slightly higher office blood pressure in the prehypertensive stage. Whether this reflects a hyperreactivity to blood pressure measurement or a more permanent blood pressure elevation, however, is not known. In the present study, blood pressure was measured in 15 normotensive subjects whose parents are both hypertensive (FH++), 15 normotensive subjects with one hypertensive parent (FH(+)-), and 15 normotensive subjects whose parents are not hypertensive (FH--); among the three groups, subjects were matched for age, sex, and body mass index. The measurements were made in the office during a variety of laboratory stressors and during a prolonged resting period, and for a 24-hour period (ambulatory blood pressure monitoring). Office blood pressure was higher in the FH++ group than in the FH-- group (p less than 0.05). The pressor responses to laboratory stressors were similar in the two groups, but the FH++ group had higher prolonged resting and 24-hour blood pressure than the FH-- group; the difference was always significant (p less than 0.05) for systolic blood pressure. The FH++ group also had a greater left ventricular mass index (on echocardiographic examination) than the FH-- group (p less than 0.01). The blood pressure values and echocardiographic values of the FH(+)- group tended to be between those of the other two groups. Thus, the higher blood pressure shown by individuals in the prehypertensive stage with a family history of parental hypertension does not reflect a hyperreactivity to stress but an early permanent blood pressure elevation.(ABSTRACT TRUNCATED AT 250 WORDS)

Mineralocorticoid hypertension due to a nasal spray containing 9 alpha-fluoroprednisolone.

The finding of hypokalemia and of low plasma renin activity (PRA) in a hypertensive patient suggests a diagnosis of primary hypermineralocorticoidism. Medications containing compounds with mineralocorticoid-like activity (licorice, carbenexolone) may also cause the same syndrome. Recently, we carried out detailed studies on 10 patients with severe hypertension and hypokalemic alkalosis, suppressed PRA and low aldosterone levels. Plasma levels of cortisol and ACTH were suppressed in most of the cases. Measurement of deoxycorticosterone and corticosterone (and in some patient of 18-hydroxydeoxycorticosterone and 18-hydroxycorticosterone) was not significantly higher than normal. Therapeutic trials of dexamethasone and aminoglutethimide were ineffective. In contrast, spironolactone and amiloride treatment resulted in substantial but incomplete amelioration of both hypertension and hypokalemia. All of the patients share a common history of chronic rhinitis and habitual use of large doses of nasal spray containing 9 alpha-fluoroprednisolone and vasoconstrictor agents. Withdrawal resulted in a complete remission of hypokalemia in one to two weeks in all patients. The hypertension and depressed levels of PRA, aldosterone and cortisol took longer to return to normal, varying from case to case; in all but one patient, the values returned to normal within two months. This report reveals another cause of factitious mineralocorticoid excess which may be considered in the differential diagnosis of hypokalemic hypertensive syndromes.

Similarities and differences in structural and functional changes of left ventricle and carotid arteries in young borderline hypertensives and in athletes.

OBJECTIVE: To investigate the association between increased left ventricular mass and the intima-media thickening of carotid arteries in hypertensive patients and the simultaneous involvement of the heart and the conductance vessels by the hypertensive process. METHODS: Because no data are available concerning the ultrasonographic characteristics of large arteries in athletes with physiological increases in left ventricular mass, we measured the intima-media thickness (IMT) of the common carotid artery (CCA) in 14 normotensive subjects (group I, aged 22 +/- 4 years), in 14 borderline hypertensives (group II, aged 24 +/- 6 years) and in 14 Japanese wrestling players (group III, aged 23 +/- 4 years). The IMT of the posterior wall of the CCA was measured at 5, 10 and 20mm caudally to the bifurcation and the measurements were averaged. Left ventricular diameters and thicknesses of the interventricular septum and posterior wall were obtained from two-dimensionally guided M-mode tracings and measured according to the Penn convention. Left ventricular mass was calculated by the formula of Devereux. Left ventricular filling was measured by a pulsed Doppler technique. RESULTS: Both systolic and diastolic blood pressure values were significantly higher in group II (145 +/- 7/91 +/- 5 mmHg) than they were in group I (116 +/- 11/75 +/- 5 mmHg) and in group III (120 +/- 8/78 +/- 6 mmHg). In athletes and hypertensives both the left ventricular mass index and the IMT of the CCA were significantly greater than they were in control subjects (80 +/- 12 g/m2 and 0.45 +/- 0.05 mm in group I; 106 +/- 15 g/m2 and 0.57 +/- 0.08 mm in group II; and 122 +/- 17 g/m2 and 0.55 +/- 0.05 mm in group III). The mitral early:late peak flow velocity ratio was significantly lower in group II (1.9 +/- 0.58) than it was in the other two groups (2.3 +/- 0.66 in group I and 2.6 +/- 0.64 in group III). CONCLUSIONS: The results of our study suggest that both hypertension and physical training can induce parallel changes in cardiac and in arterial walls, and that physiological left ventricular hypertrophy in athletes is accompanied by a normal diastolic filling pattern in contrast to the pathological pattern found in hypertensives. Further investigation is required to explore possible differences in carotid structure and function between these two conditions.

Left ventricular concentric remodelling and carotid structural changes in essential hypertension.

AIM: Left ventricular concentric remodelling defines a modified left ventricular geometry in the presence of a normal left ventricular mass; it is an early and frequent adaptation in arterial hypertension. The present study was designed to evaluate the extent of carotid structural changes in essential hypertensives with left ventricular remodelling. PATIENTS AND METHODS: Two groups of hypertensive patients, who had never previously received anti-hypertensive treatment, 14 with left ventricular concentric remodelling (group I, relative wall thickness 0.48 +/- 0.02) and 48 with normal left ventricular geometry (group II, relative wall thickness 0.37 +/- 0.04) underwent clinical and laboratory examination, echocardiography, carotid artery ultrasonography and 24 h ambulatory blood pressure monitoring (ABPM). The left ventricular dimensions and mass were obtained according to the Penn convention. The intima-media thickness (IMT) of the posterior wall of both common carotid arteries was measured 5, 10 and 20 mm caudally to the bulb and the average value was used for analysis. RESULTS: In both groups age (group I 44 +/- 9 years; group II 40 +/- 9 years), body surface area (group I 1.85 +/- 0.2 m2; group II 1.80 +/- 0.2 m2), duration of hypertension (group I 4.4 +/- 4; group II 3.8 +/- 3.9 years), metabolic parameters and smoking habits were similar. Both clinic and 24 h ABPM values were higher in group I (clinic 157 +/- 12/102 +/- 5; 24 h ABPM 145 +/- 10/95 +/- 7 mmHg) than they were in group II (clinic 146 +/- 11/97 +/- 5; 24 h ABPM = 134 +/- 10/87 +/- 8 mmHg, P < 0.01). The left ventricular mass index (LVMI) and IMT were found to be slightly but significantly greater in group I than they were in group II (LVMI 106 +/- 7 versus 98 +/- 12 g/m2, P < 0.05; IMT 0.68 +/- 0.13 versus 0.61 +/- 0.10 mm, P < 0.05). A significant correlation was found between LVMI and common carotid IMT in the whole group of hypertensive patients (r = 0.43, P < 0.01). CONCLUSIONS: Our results indicate that left ventricular concentric remodelling does not represent the only early cardiovascular change in arterial hypertension but rather is associated often with carotid intima-media thickening.

Cardiac and carotid structure in patients with established hypertension and white-coat hypertension.

AIM: The introduction of ambulatory blood pressure monitoring in the clinical practice has defined a new subgroup of hypertensive patients called white-coat hypertensives. It has been reported that white-coat hypertensives have less cardiac involvement than established hypertensive patients. This study was designed to examine the extent of cardiac and vascular involvement in patients with white-coat hypertension and established hypertension. PATIENTS AND METHODS: We studied 82 patients with mild essential hypertension, never previously treated, using 24-h ambulatory blood pressure monitoring and an echocardiographic and vascular ultrasonographic study. Left ventricular dimensions and mass were obtained according to the Penn convention. The intima-media thickness of the posterior wall of both common carotid arteries was measured 5, 10 and 20 mm caudally to the flow-divider and the average value was used for analysis. RESULTS: Of the 82 patients, 31 (mean +/- SD age 35 +/- 10 years) had average 24-h systolic/diastolic blood pressure values of below 132/85 mmHg (white-coat hypertensives) and 51 (aged 42 +/- 2 years) had a consistently elevated diastolic blood pressure. Both groups had similar body surface area (1.82 +/- 0.22 versus 1.81 +/- 0.22 m2), sex distribution (20 males and 11 females versus 32 males and 19 females), duration of hypertension, metabolic parameters and smoking habit. The 24-h ambulatory blood pressure monitoring values were, by definition, significantly higher in established hypertensives than in white-coat hypertensives (142 +/- 10/94 +/- 6 versus 127 +/- 6/79 +/- 4 mmHg, P<0.001). The left ventricular mass index and intima-media thickness were significantly higher in the established hypertensives (112 +/- 17 g/m2, 0.67 +/- 0.11 mm, respectively) than in the white-coat hypertensives (98 +/- 18 g/m2, 0.58 +/- 0.09 mm; P<0.001 for both). CONCLUSIONS: The prevalence of left ventricular hypertrophy and cardiac remodeling was significantly more frequent in established hypertensives (51%) compared to white-coat hypertensives (19%). These confirm that structural changes in the left ventricle in white-coat hypertensives are more limited than in established hypertensives and show that in white-coat hypertensives there is significantly less involvement of the conductance vessels than in established hypertensives.

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.

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

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

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

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

Prevalence of target organ damage in treated hypertensive patients: different impact of clinic and ambulatory blood pressure control.

OBJECTIVES: First, to evaluate the prevalence of left ventricular (LV) hypertrophy, LV concentric remodelling and microalbuminuria in a selected sample of treated hypertensive patients with effective and prolonged clinic blood pressure (BP) control (BP < 140/90 mmHg). Second, to compare the prevalence of these markers of organ damage in patients with and without ambulatory BP (ABP) control, defined as average daytime BP < 132/85 mmHg). DESIGN AND METHODS: Fifty-eight consecutive hypertensive patients who attended our hypertension outpatient clinic over a period of 3 months and were regularly followed up by the same medical team were included in the study. Obesity, diabetes mellitus, history or signs of cardiovascular or renal complications and major noncardiovascular diseases were the exclusion criteria from the study. Each patient underwent 24 h ABP monitoring, echocardiography and 24 h urine collection for albumin measurement. RESULTS: The prevalence of LV hypertrophy (LV mass index > 125 g/m2 in both sexes), LV concentric remodelling (relative wall thickness > 0.45) and microalbuminuria (urinary albumin excretion < 300 mg/ 24 h) in this selected group of patients (32 men, 26 women; mean age 53 +/- 9 years; mean clinic BP 122 +/- 9/ 78 +/- 6 mmHg) was markedly low (6.9, 8.6 and 5.1%, respectively). The 26 patients with effective ABP control (group I) were similar to the 32 patients without effective ABP control (group II) in age, gender, body surface area, clinic BP, smoking habit, glucose, cholesterol and creatinine plasma levels. Prevalence of LV hypertrophy, LV concentric remodelling and microalbuminuria was lower in group I than in group II (0 versus 12.9% P< 0.01, 7.7 versus 9.4% NS, 3.8 versus 6.2% NS, respectively). CONCLUSIONS: This study demonstrates that nonobese, nondiabetic hypertensive patients with an effective clinic BP control have a very low prevalence of target organ damage and that LVH is present only in individuals with insufficient ABP control.

Impact of nocturnal fall in blood pressure on early cardiovascular changes in essential hypertension.

OBJECTIVE: To evaluate in a selected population of subjects with a recent diagnosis of hypertension whether a blunted nocturnal fall in blood pressure is associated with more advanced cardiac and vascular damage. METHODS: One hundred and eleven recently diagnosed and never-treated patients with mild essential hypertension underwent 24-h ambulatory blood pressure monitoring (ABPM), echocardiography and carotid ultrasonography. RESULTS: The 78 patients with normal (> 10%) night-time fall in systolic blood pressure (SBP) and diastolic blood pressure (DBP) (dippers) were similar to the 33 patients with a small (< or = 10 %) fall (non-dippers) for age, sex, body surface area, smoking habit, clinic and 24-h blood pressure. There were no differences between dippers and non-dippers in left ventricular mass index (104 versus 105 g/m2), common carotid internal diameter (5.8 versus 5.9 mm), intima-media thickness (0.66 versus 0.64 mm) and carotid plaques prevalence (25 versus 29%). Furthermore, no differences were found in the correlation of daytime and night-time SBP and DBP with left ventricular mass and carotid wall thickness. When the 77 men and 34 women were analysed separately, similar results were obtained. CONCLUSION: These results suggest that a blunted reduction in night-time blood pressure does not play a major role in the development of cardiovascular changes during the early phase of essential hypertension.

Blood pressure control in a hypertension hospital clinic.

OBJECTIVES: First, to evaluate the prevalence of clinic blood pressure (BP) control (BP < or = 140/90 mm Hg) in a representative sample of treated hypertensive patients followed in our hypertension clinic. Second, to assess in a subgroup of these patients: (a) the proportion of BP control with both clinic blood pressure (CBP < or =140/90 mm Hg) and daytime ambulatory blood pressure (ABP) (< or =132/85 mm Hg) criteria, and (b) the prevalence of echocardiographic left ventricular hypertrophy (LVH) (left ventricular mass index, LVMI>125 g/m2 in men and >110 g/m2 in women). DESIGN AND METHODS: Seven hundred consecutive hypertensive patients who attended our hypertension centre clinic during a period of 6 months and who had regularly been followed up by the same medical team were included in the study. BP was taken in the clinic by a doctor using a mercury sphygmomanometer with the participants seated. Seventy-four patients with similar demographic and clinical characteristics to the entire population of participants underwent complete echocardiographic examination and 24 h ABP monitoring. RESULTS: During follow-up, 352 of the treated patients had clinic BP < or =140/90 mm Hg, 198< or =160/95 mm Hg and 150>160/95 mm Hg, indicating that BP control was satisfactory in 50.3%, borderline in 28.3% and unsatisfactory in 21.4% of the cases. In the subgroup of 74 patients, the proportion of individuals with satisfactory clinic BP control (CBP< or =140/90 mm Hg) was higher (50.0 versus 33.6%) than with satisfactory ABP control (daytime ABP values < or =132/85 mm Hg). LVH was found in 21 of the 74 patients (28.3%): 12 of them had unsatisfactory CBP control and 19 had unsatisfactory ABP control. LVMI did not correlate with CBP values but only with ABP values (mean 24 h systolic r = 0.47, diastolic r = 0.40, P<0.001; mean daytime systolic r = 0.45, mean daytime diastolic r = 0.39, P<0.001; mean night-time systolic r = 0.38, mean night-time diastolic r = 0.38, P<0.001). CONCLUSION: This study demonstrates that hypertensive patients managed in a hypertension centre clinic have satisfactory CBP control in 50% of cases, but this rate seems to over-estimate the effective BP control during daily life. A large fraction of patients show persistence of LVH and this evidence of organ damage almost entirely concerns individuals with poor ABP control.

Systolic and pulse blood pressures (but not diastolic blood pressure and serum cholesterol) are associated with alterations in carotid intima-media thickness in the moderately hypercholesterolaemic hypertensive patients of the Plaque Hypertension Lipid Lowering Italian Study. PHYLLIS study group.

OBJECTIVE: The Plaque Hypertension Lipid Lowering Italian Study (PHYLLIS), is the first study in patients with hypertension (diastolic blood pressure (DBP) 95-115 mmHg; systolic blood pressure (SBP) 150-210 mmHg), moderate hypercholesterolaemia (LDL-cholesterol 4.14-5.17 mmol/l (160-200 mg/dl) and initial carotid artery alterations (maximum intima-media thickness (IMT) Tmax > or = 1.3 mm). The primary objective of PHYLLIS is investigating whether in these patients administration of an angiotensin converting enzyme inhibitor, fosinopril, and a statin, pravastatin, is more effective than administration of a diuretic and a lipid-lowering diet in retarding or regressing alterations in carotid IMT. While the study is in progress, baseline data are here reported to clarify the association of various risk factors with carotid IMT in these medium-high risk hypertensive patients. METHODS: Patients numbering 508 have been randomized to PHYLLIS by 13 peripheral units, in Italy. Age was (mean +/- SD) 58.4 +/- 6.7 years, males were 40.2%, current smokers 16.5%, means +/- SD of serum total, low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol and triglycerides concentrations were 6.79 +/- 0.67, 4.69 +/- 0.51, 1.37 +/- 0.38, 1.59 +/- 0.64 mmol/l (262.4 +/- 25.8, 181.3 +/- 19.8, 53.0 +/- 14.6, 141.0 +/- 56.7 mg/ dl). Means +/- SD of clinic sitting SBP/DBP were 159.8 +/- 9.0/98.3 +/- 4.2 mmHg. 483 of the 508 patients also had 24 h ambulatory BP monitoring, edited and read at a centralized unit (mean +/- SD 24 h SBP/DBP averages 136.3 +/- 14.1/84.0 +/- 10.0 mmHg). Quantitative B-mode ultrasound (Biosound 2000 II 5A, Biosound, Indianapolis, Indiana, USA) recordings of carotid arteries were taken by certified sonographers in the peripheral units and tracings were all read at a central unit. CBMmax (mean IMT of eight sites at common carotids and bifurcations) was 1.21 +/- 0.17; Mmax (mean of 12 sites also including internal carotids) 1.16 +/- 0.17, and Tmax (single maximum) 1.85 +/- 0.48 mm. RESULTS: Ambulatory SBP and pulse pressure (PP) (24 h, daytime, night-time averages) and their variability indices (24 h SD) were always significantly correlated with CBMmax and Mmax (P0.01 -0.001), and the correlations remained significant after adjustment for age, gender and smoking. No measurement of DBP was ever associated with any IMT measurement. Likewise, no lipid variable was found associated with any IMT measurement. CONCLUSIONS: Baseline data from PHYLLIS indicate that in this population of hypertensive patients with moderate hypercholesterolaemia, SBP and PP are with age among the most significant factors associated with carotid artery alterations. However, the narrow range of inclusion LDL-cholesterol and DBP values may have obscured an additional role of these variables.

Effect of detraining on the cardiopulmonary reflex in professional runners and hammer throwers.

In professional athletes with marked cardiac hypertrophy, reflex influences originating from cardiopulmonary receptors are impaired. To determine whether the reflex is restored after termination of physical training and regression of cardiac hypertrophy 8 former athletes (age 31 +/- 6 years, mean +/- SD) who stopped agonistic activity for 5 +/- 1 years were compared with 15 sedentary subjects (27 +/- 7 years) and 19 active professional athletes (22 +/- 7 years). Cardiopulmonary receptor stimulation and deactivation were obtained by increasing and reducing left ventricular end-diastolic diameter (echocardiography) through leg raising and nonhypotensive lower body negative pressure, respectively. Left ventricular mass index (echocardiography) was markedly and significantly (p less than 0.01) greater in athletes (135 +/- 6 g/m2) than in former athletes (105 +/- 4 g/m2) whose value was similar to that of sedentary subjects (98 +/- 4 g/m2). The reduction in forearm vascular resistance and plasma norepinephrine induced by increasing left ventricular end-diastolic diameter was 24 and 23% less in athletes than in former athletes whose responses were similar to those of sedentary subjects. This was the case also for the responses induced by reducing left ventricular end-diastolic diameter. In contrast, the hemodynamic responses to cold pressor test were similar in the 3 groups. It is concluded that the impairment of the cardiopulmonary reflex observed in athletes is largely reversible when physical training is terminated. This may be due to regression of left ventricular hypertrophy.

Effect of verapamil on atherosclerosis.

Whether antihypertensive agents exert an antiatherosclerotic effect by blood pressure reduction or independently of their antihypertensive effect is clinically relevant. Animal studies have generally shown that the calcium antagonist verapamil has a preventive rather than a therapeutic antiatherosclerotic effect, which is independent of its antihypertensive effect. However, doses used in animal studies were much higher than those administered to humans and, in animals, the time of administration of verapamil coincided with the application of atherogenic stimulus. Human studies have given controversial results. Verapamil appears to effectively reduce the restenosis rate after coronary angioplasty. However, in patients with coronary stenosis who were undergoing bypass surgery, results were conflicting: a retrospective study provided positive results, while a prospective study gave negative results. An ongoing study investigating the effect of verapamil on the carotid arteries of hypertensive patients could help clarify the relationship between blood pressure reduction and the progression, regression or development of carotid lesions.

Antihypertensive and water and sodium balance effects of felodipine, a new vasodilating calcium antagonist, in hypertensive patients.

Felodipine, a new dihydropyridine derivative with a selective action on vascular smooth muscle, was investigated in 2 short term studies in hypertensive patients. In the first study, oral administration of felodipine 12.5 mg three times daily in a preliminary tablet formulation for 3 days significantly reduced supine and upright blood pressure with only a slight increase in heart rate and no clinically relevant signs of sodium and water retention. By increasing each dose to 25 and 50 mg three times daily, there was a further, but quite moderate, decrease in blood pressure; however, this was accompanied by an increase in heart rate and a tendency towards a reduction of creatinine clearance and urinary sodium output. In the second study, a new oral formulation containing 10 mg felodipine, administered twice daily for 7 days, was effective in lowering blood pressure without a clinically relevant tachycardia. Following the first dose of felodipine, urinary sodium excretion was slightly increased while potassium excretion showed only minor changes. The new calcium antagonist, felodipine, lowers blood pressure without the clinically relevant adverse reactions commonly related to other direct vasodilator antihypertensive drugs.

Lack of correlation between left ventricular mass and diameter of left coronary artery main trunk in hypertensive patients.

The study was designed to evaluate whether the increase in left ventricular (LV) mass in essential hypertensives (H) is associated with a proportional increase in diameter of the left coronary artery (LCA) trunk. Twenty-six hypertensives, 14 with left ventricular hypertrophy (LVH) (left ventricular mass index [LVMI] > or =134 g/m2 in men and > or =110 g/m2 in women) and 12 without LVH, and 10 normotensive controls (C) underwent clinical laboratory and echocardiographic transthoracic examination. LV dimensions were measured according to the Penn convention and LV mass calculated by the formula of Devereux. The LCA main trunk was visualized by two-dimension short axis view at the level of the great vessels section, and the diameter measured as intima-intima distance at end-diastole. Hypertensives with and without LVH and C had similar age, sex, and body surface area distribution. LVMI was, by definition, significantly higher in H with LVH than in H without LVH and in C (144+/-21, 113+/-13, and 98+/-10 g/m2, P<.01), whereas the diameter of the LCA trunk was similar in all groups (0.48+/-0.1, 0.48, and 0.46 cm, respectively). There was no significant correlation between LVMI and LCA diameter in H (r = 0.21, P = not significant). The diameter of LCA trunk was significantly correlated only with BSA (r = 0.5, P<.01), LV end-systolic and end-diastolic diameters (r = 0.5 and r = 0.4, P<.05). Our data suggest that in H the increase in LVM is not associated with a concomitant increase of epicardial coronary artery diameter, and this finding may account in part for the impairment of coronary blood flow reserve in LVH.

Evaluation of the efficacy and safety of enalapril plus hydrochlorothiazide plus methyldopa vs standard triple therapy in the treatment of moderate to severe hypertension: results from a multicentre study.

We report the results of a randomized, double-blind, parallel group multicentre study in 120 patients with moderate to severe hypertension, comparing two different types of antihypertensive treatment: a) the standard 'triple therapy' with hydrochlorothiazide, propranolol and hydralazine, and b) the combination of an ACE inhibitor, enalapril with hydrochlorothiazide (HCTZ) and methyldopa. The two regimens caused similar degrees of blood pressure reductions. The only significant difference between the two groups was heart rate due to the bradycardiac effect of propranolol in the group treated with the standard 'triple therapy'. Only 3.4% of patients receiving the regimen of enalapril, HCTZ and methyldopa were withdrawn from the study for adverse reactions, against 10% of patients on HCTZ, propranolol and hydralazine. Four cases of hypokalaemia in the enalapril group and 19 in the propranolol group were reported: so enalapril seemed to ameliorate the hypokalaemic effect of HCTZ. The overall analysis of the study results shows that the treatment based on enalapril, HCTZ and methyldopa is as efficient and better tolerated than the established regimen of HCTZ, propranolol and hydralazine.