Sympathoadrenergic and metabolic factors are involved in ambulatory blood pressure rise in childhood obesity.

We investigated in a young Italian obese population, the relationship between ambulatory BP (ABP) and several pathophysiological factors linking obesity to hypertension. A total of 89 obese children and adolescents underwent a 24-h ambulatory BP monitoring (ABPM) and an oral glucose tolerance test. The circulating levels of insulin, lipids, uric acid, C-reactive protein, interleukin-6, renin and aldosterone and the 24-h urinary levels of epinephrine, norepinephrine and albumin excretion rate were measured. Nine percent of subjects had daytime sustained hypertension (SH), 26% night-time hypertension and 11% a non-dipping pattern. SH subjects compared to those with sustained normotension (SN) were more obese (P<0.05), with a more frequent family history of hypertension (P<0.05), higher urinary catecholamine (P<0.05) and heart rate values (P<0.05) after adjustment for standard deviation score (SDS) of body mass index (BMI) and sex. Subjects with night-time hypertension compared to those with night-time normotension were more obese (P<0.0001), with a higher prevalence of impaired glucose tolerance (P<0.05) and metabolic syndrome (P<0.05) and higher 2-h glucose (P<0.05), uric acid (P<0.05) and triglycerides (P<0.05). In multivariate regression analysis, daytime systolic BP (SBP) remained independently correlated with urinary norepinephrine and SDS-BMI (P<0.05 for both), daytime diastolic BP (DBP) with waist circumference (P<0.05) and night-time SBP and DBP with SDS-BMI (P<0.01 for both). The risk of having systolic and diastolic hypertension increased with the increase in SDS-BMI and waist circumference, respectively. In conclusion, in our cohort of obese children and adolescents, daytime and night-time hypertension were associated with activation of the sympathoadrenal system and worst metabolic conditions, respectively.

Circadian blood pressure profile in patients with active Cushing's disease and after long-term cure.

Hypertension is a major feature of Cushing's disease, with the attendant increase in the rate of cardiovascular events. The circadian blood pressure profile also impacts cardiovascular risk and a few studies have shown that patients with Cushing's syndrome do not present the expected nocturnal blood pressure decrease and, further, that this alteration persists in short-range disease remission. These studies were performed by conventional discontinuous ambulatory pressure monitoring, a technique not devoid of limitations. Aim of our study was the assessment of blood pressure and heart rate profile by beat-to-beat noninvasive monitoring in twelve patients with active Cushing's disease (9 women and 3 men, age 33.3+/-2.36 years) and the assessment of its possible changes at short- (<1 year) and long-term (2-3 years) follow-up after curative surgery. No nocturnal blood pressure dipping (i.e., decrease by 10% of daytime values) was observed in 50% of patients both during active hypercortisolism and within 1 year from surgery. Recovery of blood pressure dipping profile was detected at long-term follow-up in a minority of patients. Daytime heart rate was higher in patients with active Cushing's disease and decreased over time after cure. In conclusion, patients with Cushing's disease present absent nocturnal blood pressure dipping and abnormal heart rate values which do not resolve after short-term remission of hypercortisolism and show only partial improvement in the long run. These findings identify additional cardiovascular risk factors for patients cured of Cushing's disease.

Autonomic cardiovascular regulation in quiescent ulcerative colitis and Crohn's disease.

BACKGROUND: In inflammatory bowel diseases, changes in autonomic enteric regulation may also affect neural cardiovascular control. However, while cardiac autonomic modulation has been shown to be impaired in active ulcerative colitis, the occurrence of cardiovascular autonomic alterations, also in the quiescent phase of inflammatory bowel diseases, is still a matter of debate. The aim of our study was thus to explore the features of cardiovascular autonomic regulation in ulcerative colitis and Crohn's disease during their remission phase. MATERIALS AND METHODS: Autonomic cardiovascular control was evaluated by time- and frequency-domain indexes of spontaneous heart rate and blood pressure variability and by assessing the baroreflex heart rate control (sequence technique) in 26 patients with ulcerative colitis, in 26 patients with Crohn's disease and in 23 healthy controls. RESULTS: The groups were matched for age, gender and body mass index. They had similar blood pressure mean levels and variability. By contrast, mean heart rate, its overall variability (standard deviation), and baroreflex sensitivity were lower in ulcerative colitis patients than in controls. Moreover, all indexes related to cardiac vagal control were significantly lower in ulcerative colitis patients with respect not only to controls but also to Crohn's disease patients. CONCLUSIONS: Cardiac vagal control is impaired in quiescent ulcerative colitis only, and not in Crohn's disease, while in both bowel diseases vascular control appears preserved. Since cardiovagal modulation seems related to anti-inflammatory mechanisms, the reduced parasympathetic cardiac regulation in apparently quiescent ulcerative colitis suggests that such systemic derangement is accompanied by local subclinical inflammations, even in the absence of clinically active inflammatory processes.

Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. Systolic Hypertension in Europe Trial Investigators.

CONTEXT: The clinical use of ambulatory blood pressure (BP) monitoring requires further validation in prospective outcome studies. OBJECTIVE: To compare the prognostic significance of conventional and ambulatory BP measurement in older patients with isolated systolic hypertension. DESIGN: Substudy to the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial, started in October 1988 with follow up to February 1999. The conventional BP at randomization was the mean of 6 readings (2 measurements in the sitting position at 3 visits 1 month apart). The baseline ambulatory BP was recorded with a noninvasive intermittent technique. SETTING: Family practices and outpatient clinics at primary and secondary referral hospitals. PARTICIPANTS: A total of 808 older (aged > or =60 years) patients whose untreated BP level on conventional measurement at baseline was 160 to 219 mm Hg systolic and less than 95 mm Hg diastolic. INTERVENTIONS: For the overall study, patients were randomized to nitrendipine (n = 415; 10-40 mg/d) with the possible addition of enalapril (5-20 mg/d) and/or hydrochlorothiazide (12.5-25.0 mg/d) or to matching placebos (n = 393). MAIN OUTCOME MEASURES: Total and cardiovascular mortality, all cardiovascular end points, fatal and nonfatal stroke, and fatal and nonfatal cardiac end points. RESULTS: After adjusting for sex, age, previous cardiovascular complications, smoking, and residence in western Europe, a 10-mm Hg higher conventional systolic BP at randomization was not associated with a worse prognosis, whereas in the placebo group, a 10-mm Hg higher 24-hour BP was associated with an increased relative hazard rate (HR) of most outcome measures (eg, HR, 1.23 [95% confidence interval [CI], 1.00-1.50] for total mortality and 1.34 [95% CI, 1.03-1.75] for cardiovascular mortality). In the placebo group, the nighttime systolic BP (12 AM-6 AM) more accurately predicted end points than the daytime level. Cardiovascular risk increased with a higher night-to-day ratio of systolic BP independent of the 24-hour BP (10% increase in night-to-day ratio; HR for all cardiovascular end points, 1.41; 95% CI, 1.03-1.94). At randomization, the cardiovascular risk conferred by a conventional systolic BP of 160 mm Hg was similar to that associated with a 24-hour daytime or nighttime systolic BP of 142 mm Hg (95% CI, 128-156 mm Hg), 145 mm Hg (95% CI, 126-164 mm Hg) or 132 mm Hg (95% CI, 120-145 mm Hg), respectively. In the active treatment group, systolic BP at randomization did not significantly predict cardiovascular risk, regardless of the technique of BP measurement. CONCLUSIONS: In untreated older patients with isolated systolic hypertension, ambulatory systolic BP was a significant predictor of cardiovascular risk over and above conventional BP.

Early and late sympathetic activation in hypertension.

In several experimental animal models of hypertension, sympathetic factors have been shown to be involved in the development and/or maintenance of high blood pressure. Although the information available on this issue in man is more scarce, recent evidence clearly indicates the participation of adrenergic mechanisms in the early and late phases of the hypertensive process. In addition, several cardiovascular risk factors frequently associated with hypertension, such as obesity, insulin-resistance, cigarette smoking, and the atherogenic process, are also characterized by alterations in sympathetic cardiovascular drive. This contributes to a further activation of the sympathetic nervous system thus favoring the development of the end organ damage (e.g. cardiac and vascular hypertrophy) associated with the hypertensive state.

Smoking impairs baroreflex sensitivity in humans.

In 10 healthy smokers, finger blood pressure was recorded continuously for 1 h in a supine control condition and for 1 h while smoking four cigarettes, one every 15 min. Smoking increased average systolic blood pressure (+19%, P < 0.01) and its variability and reduced pulse interval (reciprocal of heart rate, -22%, P < 0.01) and its variability. Baroreflex sensitivity, as assessed by the slope of spontaneous hypertension/bradycardia or hypotension/tachycardia sequences and by the alpha-coefficient (squared ratio between pulse interval and systolic blood pressure spectral powers at 0.1 Hz) was significantly decreased (P < 0.01) during smoking, whereas there were no effects of smoking on the reflex changes in pulse interval induced by carotid baroreceptor stimulation through a neck suction device. Sham smoking by a drinking straw had no effects on any of the above parameters. Thus, when assessed in the absence of laboratory maneuvers in daily life conditions, baroreflex sensitivity is markedly impaired by smoking. This impairment may contribute to the smoking-induced increase in blood pressure and heart rate as well as to the concomitant alterations in their variability.

Diurnal blood pressure profile in older patients with isolated systolic hypertension. The SYST-EUR Investigators.

This study describes the diurnal blood pressure (BP) profile and identifies its correlates in older patients with isolated systolic hypertension (ISH). The ambulatory BP readings of 408 patients, aged > or = 60 years, with ISH on clinic measurement, enrolled in the placebo run-in phase of the Syst-Eur Trial were examined. The time-weighted 24 h BP, daytime and night-time BP and the cusum-derived crest and trough BP were computed to express the BP level. The daily alteration between the high and low BP span was estimated from the day-night BP difference, the cusum derived circadian alteration magnitude and plot height, as well as the amplitude of the Fourier curve. The 24 h SBP and DBP tended to be higher in men (150 +/- 15/82 +/- 9 mm Hg) than in women (147 +/- 17/79 +/- 10 mm Hg), but the sex difference was only significant for DBP. In multiple regression analysis, the 24 h SBP increased (P < 0.05) by 3 mm Hg for each 10 year increment in age and was also 10 mm Hg higher (P < 0.001) in smokers than in non-smokers; the 24 h DBP was 2 mm Hg higher (P < 0.05) in men than in women and decreased (P < 0.05) by 1.5 mm Hg for each 10 year increment in age. The day-night difference in SBP increased with 2 mm Hg for each 10 mm Hg increase in the conventional pressure, decreased with 5 mm Hg for each 10 year increment in age and was 6 mm Hg higher in smokers than in non-smokers; the day-night difference in diastolic pressure was 2 mm Hg greater in women than in men. We conclude that the main determinants of the diurnal BP variation in older patients with isolated systolic hypertension were sex, age, smoking habits and the level of pressure on conventional measurement.

Persistent blood pressure increase induced by heavy smoking.

OBJECTIVE: To test the hypothesis that heavy smoking is associated with a persistent increase in blood pressure. DESIGN: In 10 normotensive smokers asked to smoke one cigarette every 15 min for 1 h, blood pressure and heart rate were continuously monitored during the smoking period and during the preceding non-smoking hour. In six other normotensive smokers asked to smoke two cigarettes per hour throughout the whole day, blood pressure and heart rate were monitored non-invasively in ambulatory conditions for 8 h (0900-1700 h). Blood pressure monitoring was repeated during a non-smoking day. METHODS: Beat-to-beat blood pressure and heart rate were monitored at rest by means of the Finapres device. Blood pressure signal was sampled at 165 Hz by a computer to calculate hourly data. Ambulatory blood pressure and heart rate were measured once every 10 min. RESULTS: In resting conditions, the first cigarette caused an immediate and marked increase in blood pressure and heart rate, and the peak blood pressure and heart rate achieved were similar for the remaining three cigarettes. In each instance, the hemodynamic effects were so prolonged that throughout the smoking hour, blood pressure and heart rate were persistently higher than during the non-smoking hour. The standard deviations of systolic and diastolic blood pressure and heart rate were also higher during the smoking hour, indicating an increase in blood pressure and heart rate variability. In the six ambulant smokers, daytime blood pressure and heart rate were also persistently higher during smoking than during non-smoking. CONCLUSIONS: Heavy smoking is associated with a persistent rise in blood pressure and also with an increase in blood pressure variability. These effects (which may escape clinic blood pressure measurements performed during non-smoking) may account for some of the smoking-related cardiovascular risk.

Blood pressure and heart rate response to repeated smoking before and after beta-blockade and selective alpha 1 inhibition.

In normotensive volunteers who habitually smoked more than 20 cigarettes a day, 1-h beat-to-beat blood pressure recordings were taken. Measurements were made using a non-invasive finger device when the subjects were not smoking (1 h, control) and during an hour in which the subjects were asked to smoke four cigarettes, one every 15 min. The first cigarette smoked produced a marked increase in systolic and diastolic blood pressures and the heart rate. The peak blood pressure and heart rate values observed for the first cigarette did not change when the remaining three cigarettes were smoked, indicating that the responses were neither attenuated nor increased by repeated smoking. However, after each cigarette, the pre-smoking values did not return to baseline, but were successively greater for the second, third and fourth cigarettes, indicating that blood pressure and the heart rate undergo a persistent increase during smoking. Compared with the hour-long non-smoking period, mean values over the smoking period were 18.8%, 14.0% and 29.7% higher for systolic and diastolic blood pressure and the heart rate, respectively. Cigarette smoking also increased the blood pressure and heart rate standard deviations around the mean, thereby increasing the variability. The effects of atenolol and doxazosin on the blood pressure and heart rate responses to smoking were investigated in two placebo-controlled, single-blind, randomly allocated, crossover studies. Compared with placebo, atenolol (50-100 mg given once a day for 4 days) significantly attenuated the smoking-induced increase in the heart rate but not the increase in systolic or diastolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular effects of smoking.

Coronary heart disease (CHD) increases with smoking and this factor interacts with hypercholesterolemia and hypertension in raising the incidence of this condition in a greater than linear fashion. This can be explained by the adverse effect of smoking on plasma fibrogen, platelet turnover and lipid profile. It may also be accounted for, however, by the acute bradycardia, increase in blood pressure and generalized vasoconstriction accompanying smoking, due to a nicotine-dependent activation of the sympathetic nervous system. These effects (which in heavy smokers can raise blood pressure permanently) are only partly offset by beta-blockers and can only be abolished by opposing the cardiac and vascular sympathetic influences by alpha and beta-blockade combined.