Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension.

To determine the prognostic significance of ambulatory blood pressure, we prospectively followed for up to 7.5 years (mean, 3.2) 1187 subjects with essential hypertension and 205 healthy normotensive control subjects who had baseline off-therapy 24-hour noninvasive ambulatory blood pressure monitoring. Prevalence of white coat hypertension, defined by an average daytime ambulatory blood pressure lower than 131/86 mm Hg in women and 136/87 mm Hg in men in clinically hypertensive subjects, was 19.2%. Cardiovascular morbidity, expressed as the number of combined fatal and nonfatal cardiovascular events per 100 patient-years, was 0.47 in the normotensive group, 0.49 in the white coat hypertension group, 1.79 in dippers with ambulatory hypertension, and 4.99 in nondippers with ambulatory hypertension. After adjustment for traditional risk markers for cardiovascular disease, morbidity did not differ between the normotensive and white coat hypertension groups (P = .83). Compared with the white coat hypertension group, cardiovascular morbidity increased in ambulatory hypertension in dippers (relative risk, 3.70; 95% confidence interval, 1.13 to 12.5), with a further increase of morbidity in nondippers (relative risk, 6.26; 95% confidence interval, 1.92 to 20.32). After adjustment for age, sex, diabetes, and echocardiographic left ventricular hypertrophy (relative risk versus subjects with normal left ventricular mass, 1.82; 95% confidence interval, 1.02 to 3.22), cardiovascular morbidity in ambulatory hypertension was higher (P = .0002) in nondippers than in dippers in women (relative risk, 6.79; 95% confidence interval, 2.45 to 18.82) but not in men (P = .91). Our findings suggest that ambulatory blood pressures stratifies cardiovascular risk in essential hypertension independent of clinic blood pressure and other traditional risk markers including echocardiographic left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Asymmetric left ventricular remodeling due to isolated septal thickening in patients with systemic hypertension and normal left ventricular masses.

Early identification of left ventricular (LV) structural changes may have an impact on the outlook of patients with essential hypertension. Of 669 untreated hypertensive subjects, 496 (74%) with normal LV mass at echocardiography (< 125 g/m2) were grouped according to normal LV geometry (n = 303; 61%), asymmetric LV remodeling due to isolated septal thickening (n = 111; 22%), asymmetric LV remodeling due to isolated posterior wall thickening (n = 5; 1%), or concentric LV remodeling due to septal and posterior wall thickening (n = 77; 16%). Remodeling was defined as twice the thickness of septum or posterior wall divided by the internal diameter at end diastole > 0.45. Twenty-four-hour noninvasive ambulatory blood pressure (BP) monitoring was performed in all subjects. Compared with subjects with normal LV geometry, those with asymmetric LV remodeling due to isolated septal thickening showed increased clinic BP (158/100 vs 153/97 mm Hg, both p < 0.05), mean daytime ambulatory BP (144/95 vs 138/90 mm Hg, both p < 0.01), mean nighttime ambulatory BP (128/80 vs 122/76 mm Hg, both p < 0.01), LV mass (99 vs 89 g/m2, p < 0.001), total peripheral resistance (1,881 vs 1,562 dynes s cm-5, p < 0.01) and known duration of hypertension (5.5 vs 3.6 years, p < 0.01) and decreased stroke index (39 vs 47 ml/m2, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Blunted nocturnal fall in blood pressure in hypertensive women with future cardiovascular morbid events.

BACKGROUND: In essential hypertension, a blunted or absent nocturnal fall in blood pressure (BP) may be associated with increased target organ damage. In this case-control study, we tested the hypothesis that an association exists between a blunted or absent nocturnal fall in BP and future cardiovascular morbid events in patients with essential hypertension. METHODS AND RESULTS: Case subjects were 32 hypertensive patients with a first fatal or nonfatal major cardiovascular event who had off-therapy ambulatory BP monitoring 1 to 5 years earlier in the context of a registry of morbidity and mortality in hypertensive patients. Control subjects were 49 hypertensive patients free from cardiovascular events. The groups were matched with regard to date of baseline ambulatory BP monitoring, age, sex, clinic systolic and diastolic BP, and daytime ambulatory systolic and diastolic BP. At their baseline evaluation, cases and controls did not differ, in either sex, with respect to clinic BP (men, 164/100 vs 162/99 mmHg; women, 178/96 vs 180/93 mmHg), mean daytime ambulatory BP (men, 151/94 vs 147/95 mm Hg; women, 156/90 vs 158/89 mm Hg), age (men, 55 vs 56 years; women, 69 vs 68 years), sex, body weight, serum cholesterol, known duration and family history of hypertension, smoking habits, renal function, or prevalence of diabetes. Echocardiographic left ventricular mass, determined in a subset of patients, was greater in cases than in controls in men (145 vs 115 g/m2, P = .038) and women (137 vs 102 g/m2, P = .032). The time interval between baseline ambulatory BP monitoring and subsequent cardiovascular event (cases: mean, 2.1 years) or last contact with our center (controls: mean, 2.5 years) did not differ between the groups. In the baseline ambulatory BP profile, the nocturnal reductions of systolic and diastolic BP in men were 9% and 11%, respectively, in cases vs 9% and 12% in controls (all P = NS), whereas in women they were 3% and 8% in cases vs 11% and 16% in controls (P = .002/.004). CONCLUSIONS: This retrospective case-control study suggests an association between the reduction or absence of the usual nocturnal fall in BP and future cardiovascular morbid events in white women with essential hypertension.

[Noninvasive ambulatory monitoring of arterial pressure in hypertensive patients: inside or outside the hospital?]. / Monitoraggio ambulatoriale non invasivo della pressione arteriosa in pazienti ipertesi: fuori o dentro l'ospedale?

To investigate whether hospitalization may influence the circadian rhythm of blood pressure (BP), 15 untreated patients with essential hypertension underwent noninvasive ambulatory blood pressure monitoring twice, at home and in the hospital, in a random order, 11 days apart. During the hospital session, which took place on the ninth day of hospitalization, patients were allowed to move freely in the hospital area, to receive visits by friends and relatives and to engage in social activities with other inpatients. Home sessions were performed during a usual working day in 14 of 15 patients. Average 24-hour systolic/diastolic BP was 151/93 mmHg (DS 19/10) at home and 154/93 mmHg (DS 21/7) in the hospital; average daytime (6am-10pm) values were 155/97 mmHg (DS 19/10) at home and 157/96 mmHg (DS 20/5) in the hospital; average night-time (10pm-6am) values were 146/88 mmHg (DS 21/12) at home and 150/89 mmHg (DS 23/10). These values did not show any statistical differences (analysis of variance) due to status (home vs hospital), period or sequence. The hourly BP averages of the hospital recording did not differ significantly from the corresponding averages of the home recording. The correlation between hospital and home 24-hour averages of systolic and diastolic BP was close (r = 0.87 and r = 0.78, respectively; p less than 0.01). The chronobiological analysis (single cosinor) showed a statistically significant circadian rhythm of systolic BP in 10/15 patients at home and in 8/15 patients in the hospital (p = NS), and a statistically significant rhythm of diastolic BP in 9/15 patients at home and in 10/15 patients in the hospital (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

[Sex differences in echocardiographic indices of left ventricular hypertrophy in arterial hypertension. Influence of age and pressure levels over 24 hours]. / Differenze tra i sessi negli indici ecocardiografici di ipertrofia ventricolare sinistra nell'ipertensione arteriosa. Influenza dell'età e dei livelli pressori nelle 24 ore.

To evaluate the difference between the sexes in the echocardiographic indices of left ventricular hypertrophy in essential hypertension, we analysed the results of 24-hour non invasive ambulatory blood pressure monitoring and echocardiography in 195 consecutive untreated hypertensive patients (101 males, 94 females). Patients were divided into 3 age groups: up to 40 years, 41-60 years, and greater than 60 years of age. Clinical blood pressure did not differ between sexes in any of the three groups, while average 24-hour ambulatory systolic and diastolic blood pressure levels were higher in males than in females up to 40 years of age (140/93 vs 129/87 mmHg, p less than 0.01), but not between 41 and 60 years (142/93 vs 141/90 mmHg) nor in those over 60 years of age (151/92 vs 145/91 mmHg). LV mass index was higher in males than in females up to 40 years (93 vs 68 g/m2, p less than 0.01), and between 41 and 60 years (115 vs 90 g/m2, p less than 0.01), but not dissimilar between the sexes over 60 years of age (102 vs 107 g/m2, p = n.s.). In females, LV mass index increased with age (r = 0.33) and body weight (r = 0.38; both p less than 0.01), but none of these relationships was significant in males (r = 0.01 and r = 0.19, respectively). Moreover, all the relations of LV mass to either clinical or ambulatory BP were closer in females than in males. None of the echocardiographic indices of left ventricular systolic function showed statistically significant differences between the sexes in any of the three age groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk stratification of left ventricular hypertrophy in systemic hypertension using noninvasive ambulatory blood pressure monitoring.

Twenty-four-hour noninvasive ambulatory blood pressure (BP) monitoring and echocardiography were performed in 165 consecutive untreated hypertensive patients and in 92 healthy subjects. In the hypertensive group, left ventricular (LV) mass index showed closer correlations (all p less than 0.01 in the comparisons between the r coefficients) with average 24-hour ambulatory systolic (r = 0.47) and diastolic (r = 0.33) BP than with casual systolic (r = 0.35) and diastolic (r = 0.28) BP. Hypertensive patients were classified according to the difference between their observed and predicted levels of ambulatory BP (the latter assessed by regressing the observed ambulatory BP on the casual BP). When compared to those with lower than predicted ambulatory BP (less than or equal to 10 mm Hg systolic, less than or equal to 6 mm Hg diastolic), patients with higher than predicted ambulatory BP (greater than or equal to 10 mm Hg systolic and greater than or equal to 6mm Hg diastolic) had higher values of LV mass index and other indexes of LV hypertrophy (all p less than 0.01) but had similar values of casual BP. Prevalence of LV hypertrophy was 6 to 10% in the former and 35 to 39% in the latter (p less than 0.001). None of the indexes of LV structure differed between the group with low ambulatory BP and the normotensive group. It is concluded that hypertensive patients whose ambulatory BP readings are notably higher than one would predict from clinical BP readings are at highest risk of LV hypertrophy, an independent prognostic marker.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence and determinants of left ventricular diastolic filling abnormalities in an unselected hypertensive population.

The independent contribution of age, sex, duration of hypertension, heart rate, clinic and ambulatory blood pressure and echocardiographic left ventricular mass to left ventricular diastolic filling abnormalities in essential hypertension was investigated in 250 subjects (145 untreated and unselected hypertensives and 105 healthy normotensive controls) undergoing Doppler and standard echocardiography and non-invasive 24-h ambulatory blood pressure monitoring. Late and early diastolic transmitral peak flow velocities and their ratio (all P less than 0.01), the rate of deceleration of early diastolic mitral flow (P less than 0.01) and the time of deceleration of early diastolic mitral flow (P = 0.018) were abnormal in the hypertensive group vs controls. None of these parameters significantly varied in the presence vs absence of LV hypertrophy. In the hypertensive group, the prevalence of abnormal age-corrected Doppler values varied up to 46% (up to 45.4% and 50% in the absence and presence of left ventricular hypertrophy, respectively; P = n.s.). In a stepwise multivariate regression analysis, age and average daytime or night-time ambulatory blood pressure showed a significant independent relationship with each of these Doppler indexes of left ventricular diastolic filling. Late transmitral peak flow velocity and the ratio of late to early peak flow velocity were also independently affected by the heart rate. Sex, duration of hypertension, clinic systolic and diastolic blood pressure and left ventricular mass index did not show any independent relationship to these Doppler parameters of left ventricular filling. In conclusion, Doppler abnormalities of diastolic transmitral blood flow were detected in up to 46% of patients in an unselected hypertensive population with a low prevalence (14.5%) of left ventricular hypertrophy. Age and ambulatory blood pressure, but not sex, duration of hypertension, clinic blood pressure and left ventricular mass itself, were the major independent determinants of these abnormalities.

Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension.

The effects of circadian blood pressure (BP) changes on the echocardiographic parameters of left ventricular (LV) hypertrophy were investigated in 235 consecutive subjects (137 unselected untreated patients with essential hypertension and 98 healthy normotensive subjects) who underwent 24-hour noninvasive ambulatory blood pressure monitoring (ABPM) and cross-sectional and M-mode echocardiography. In the hypertensive group, LV mass index correlated with nighttime (8:00 PM to 6:00 AM) systolic (r = 0.51) and diastolic (r = 0.35) blood pressure more closely than with daytime (6:00 AM to 8:00 PM) systolic (r = 0.38) and diastolic (r = 0.20) BP, or with casual systolic (r = 0.33) and diastolic (r = 0.27) BP. Hypertensive patients were divided into two groups by presence (group 1) and absence (group 2) of a reduction of both systolic and diastolic BP during the night by an average of more than 10% of the daytime pressure. Casual BP, ambulatory daytime systolic and diastolic BP, sex, body surface area, duration of hypertension, prevalence of diabetes, quantity of sleep during monitoring, funduscopic changes, and serum creatinine did not differ between the two groups. LV mass index, after adjustment for the age, the sex, the height, and the daytime BP differences between the two groups (analysis of covariance) was 82.4 g/m2 in the normotensive patient group, 83.5 g/m2 in hypertensive patients of group 1 and 98.3 g/m2 in hypertensive patients of group 2 (normotensive patients vs. group 1, p = NS; group 1 vs. group 2, p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

[Echocardiographic analysis of the left ventricle in patients with type II diabetes mellitus]. / Analisi ecocardiografica del ventricolo sinistro in pazienti con diabete mellito di tipo II.

Left ventricular involvement in type II diabetes mellitus is poorly understood. We performed a cross-sectional, M-mode and pulsed Doppler echocardiographic study on 27 diabetic patients and 27 controls accurately matched for age, sex, weight and height. All subjects also underwent 24-hour non-invasive ambulatory blood pressure monitoring. Left ventricular wall thicknesses and dimensions in diastole and systole, left ventricular mass index (82.7 g/m2 vs 78.4 g/m2) and the echocardiographic indices of left ventricular contractility did not show any statistical differences between diabetics and controls. Clinic and 24-hour ambulatory blood pressure did not show important differences between diabetics and controls. Doppler parameters for transmitral flow velocity (including peak A and peak E velocity and their ratio, pressure half time and pressure half slope) were the same in diabetics and controls. A stepwise multivariate regression analysis showed a significant positive independent relationship of peak A/peak E ratio with age (peak A/peak E = 0.0087 + 0.20 x age; F = 18.7; p = 0.0001), but not with diabetes or glycosylated haemoglobin (Hb 1 AC). Compared with non-diabetics, diabetics showed a slight increase in aortic peak flow velocity (0.83 m/sec vs. 0.70 m/sec; p = 0.011) and a very slight increase in peak aortic gradient. Peak aortic velocity showed a highly significant positive independent relation with the duration of diabetes (Vmax = 0.572 + 0.0028* diabetes duration (months); F = 92.6; p less than 0.0001), but not with age, systolic or diastolic blood pressure of HB 1 AC.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory blood pressure monitoring during sustained treatment with conventional and extended-release felodipine in mild-to-moderate hypertension.

To assess the duration of the antihypertensive effect of the dihydropiridine calcium antagonist felodipine in conventional (C-F) and slow-release (ER-F) formulations, 12 patients with essential hypertension underwent ambulatory blood pressure monitoring (ABPM) at the end of a 2-week treatment period with C-F 5 mg b.d., ER-F 10 mg once daily (o.d.) and placebo. C-F, ER-F and placebo were given in a double-blind 3 x 3 latin square design 4 times replicated. There was no systematic change in the ABP profile over the three study periods regardless of the treatment. In comparison to placebo, the mean 24-h systolic and diastolic blood pressures showed a significant and similar reduction after both formulations of F. Compared to placebo, C-F and ER-F induced a significant reduction in systolic blood pressure for 15 and 21 h, respectively, and of diastolic blood pressure for 16 and 21 h, respectively. Three patients complained of headache (mild in 2, moderately severe in 1), and two patients of nocturia, with either formulation of F.

Increased exercise tolerance and reduced electrocardiographic ischaemia 3 and 12 hours after oral felodipine in effort angina.

The antianginal properties and the duration of action of two doses of felodipine, a dihydropyridine calcium antagonist with a vascular:myocardial potency ratio approximating 100:1, were investigated in 15 patients suffering from disabling effort angina pectoris with reproducible exercise tolerance. Felodipine (5 mg, 10 mg) and placebo were administered once in the morning on three different days, with a 24 h interval between them, according to a double-blind 3 x 3 latin square design, 5 times replicated. Symptom-limited cycloergometric exercise tests were performed 3 and 12 h after administration. Duration of exercise to ST segment depression of 1 mm and to peak exercise was increased (all P less than 0.01) by both doses of felodipine in comparison with placebo. Twelve hours after administration, the 10-mg dose induced a significant improvement in the exercise time and a smaller ST segment depression (all P less than 0.01) in comparison with the 5-mg dose. The relationship between ST segment depression and the pressure-rate product during exercise was favourably influenced by the 10-mg dose at 3 and 12 h after intake, and by the 5-mg dose only at 3 h after intake. These findings suggest an increase in coronary blood flow induced by felodipine. Apart from mild headache there were no other unwanted effects. In conclusion, felodipine improves exercise tolerance and reduces electrocardiographic ischaemia for up to 12 h after single oral administration in patients with effort angina. Increasing the dose from 5 mg to 10 mg produces a more prolonged effect, with increased exercise tolerance 12 h after intake.

Home ambulatory blood pressure readings do not differ from clinic readings taken at the same time of day.

In most hypertensives clinic blood pressure (BP) is variably higher than home BP, but the underlying mechanisms are uncertain. We investigated whether the 24-hour ambulatory home BP profile as well as the office-home BP discrepancy could vary with the time of day of application of the recording system (from 08.00 h to 19.00 h) in 135 untreated hypertensives who underwent non-invasive home BP monitoring (ICR 5200). Neither systolic nor diastolic 24-hour home BP (average of daily readings, area-under-the-curve) varied significantly with the time of day of application of the system. Clinic BP was about 12% higher than 24-hour home BP in the whole population, mean values being 161.4/102.9 mmHg (office BP) vs 141.2/90.8 mmHg (average 24-hour home readings), as well as in each of the subcohorts based on the time of day of application of the system (all P less than 0.01). However, in none of the subcohorts were there any statistically significant differences between clinic BP and home BP readings taken at the same time of day as the clinic readings. No correlation was found between clinic heart rate and clinic-home discrepancy. We conclude that in essential hypertension 24-hr non-invasive ambulatory BP monitoring can begin indifferently from 08.00 h to 19.00 h with no expected influence of time of application on results and that clinic BP is not dissimilar from home BP at the same time of day.

Duration of the antihypertensive action of atenolol, enalapril and placebo: a randomized within-patient study using ambulatory blood pressure monitoring.

Atenolol (A) and enalapril (E), two agents widely used as first-line monotherapy in arterial hypertension, have never been compared in their potency and duration of action by using 24-h ambulatory blood pressure monitoring (ABPM). Twelve out-patients (mean age 48.6 years - SD 7) with mild-to-moderate hypertension and supine diastolic blood pressure (Hawksley Random Zero Manometer) greater than 100 mmHg at the end of a 3-week placebo wash-out received, in double-blind and random order, A 100 mg daily, E 20 mg daily and placebo for 4 weeks each, according to a 3 x 3 latin square design. A 24-hour non-invasive ABPM (Spacelabs ICR 5200) was performed at the end of each of the 3 periods. In respect to placebo, both A and E produced a 24-h antihypertensive effect. The frequency of diastolic blood pressure values above 90 mmHg was 50.0% after placebo, 24.5% after A and 28.9% after E (a 51% reduction after A and a 42.3% reduction after E in respect to placebo - both p less than .05). Systolic blood pressure profiles differed less than 5 mmHg between placebo and A, as well as between placebo and E, between 9:30 and 10:30. Diastolic blood pressure profiles differed less than 5 mmHg between placebo and A over 2 h (between 2:30 and 3:30, and between 10:30 and 11:30), and between placebo and E over 2 other h (between 9:30 and 10:30, and between 11:30 and 12:30). None of the routine hematochemical parameters differed between placebo, A and E.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythrocyte concentration of glycolytic phosphorylated intermediates and adenosine nucleotides in subjects with diabetes mellitus.

We determined erythrocyte concentration of phosphorylated glycolytic intermediates and adenosine nucleotides in 9 non-ketotic diabetics under different conditions of glycemic control. We showed a significant increase of G6P, F6P and FDP levels in the 9 diabetics with poor glycemic control, whereas other phosphorylated glycolytic intermediates were in the normal range. After achieving fair glycemic control G6P, F6P and FDP fell to normal value. G6P, F6P and FDP were well correlated with simultaneously determined plasma glucose. Another 5 diabetics with poor glycemic control were connected to Biostator in order to determine the time relationship between blood glucose and erythrocyte levels of G6P, F6P and FDP. We demonstrated a prompt decrease to the normal values of the phosphorylated glycolytic intermediates where blood glucose fell to normal 60-90 minutes after automatic insulin delivery. Finally, we determined RBC glycolytic intermediates in 5 subjects with normal OGTT and in 5 subjects with normal fasting plasma glucose but abnormal OGTT. In this group we observed a prompt and persistent increase of G6P, F6P and FDP levels over the three hours hyperglycemia phase which has been induced by glucose load. No significant increase was found in subjects with normal OGTT. Our results demonstrate that erythrocyte glycolytic metabolism in abnormal in diabetics, depending strictly on the degree of glycemic control.