Circadian variation of blood pressure and endothelial function in patients with essential hypertension:a comparison of dippers and non-dippers

OBJECTIVES: The purpose of this study was to evaluate the relationship between the circadian blood pressure (BP) rhythm and endothelial function in patients with essential hypertension. BACKGROUND: Hypertension is associated with alterations in resistance artery endothelial function. Patients with a non-dipper circadian pattern of BP have a greater risk of cerebrovascular and cardiovascular complications than do patients with a dipper circadian pattern. METHODS: We evaluated the forearm blood flow (FBF) response to intra-arterial acetylcholine (ACh), an endothelium-dependent vasodilator, and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, infusion in 20 patients with non-dipper hypertension and 20 age- and gender-matched patients with dipper hypertension. The FBF was measured using a mercury-filled Silastic strain-gauge plethysmograph. RESULTS: The 24-h systolic BP, as well as nocturnal systolic and diastolic BPs were higher in non-dipper patients than in dipper patients. The 24-h urinary excretion of nitrite/nitrate and cyclic guanosine monophosphate was lower in non-dippers than in dippers. The response of FBF to ACh was smaller in non-dippers than in dippers (25.1 +/- 3.1 vs. 20.2 +/- 3.0 ml/min/100 ml tissue, p < 0.05). The FBF response to ISDN was similar in dippers and non-dippers. The FBF response to ACh was similar in the two groups following intra-arterial infusion of the nitric oxide (NO) synthase inhibitor N(G)-monomethyl-L-arginine. CONCLUSIONS: These findings suggest that endothelium-dependent vasodilation is blunted through a decrease in NO release in non-dippers compared with patients who have dipper hypertension.     

Effect of the angiotensin-converting enzyme inhibitor perindopril on haemostasis in essential hypertension.

Endothelial damage, platelet hyperactivity and other changes of blood coagulation may play a role in the vascular complications of essential hypertension. Undesirable changes of haemostasis induced by some anti-hypertensive drugs can encourage the acceleration of atherogenesis. Therefore, the effect of angiotensin-converting enzyme (ACE)-inhibitors on haemostasis is of interest. The therapeutic dose of perindopril was previously shown to reduce platelet aggregation. In the present study, selected parameters of haemostasis were investigated in 23 patients with first and second stage of non-treated essential hypertension. The measurements were carried out before therapy, after 1 week of placebo administration, and after 1 week and after 1 month of ACE-inhibitor perindopril therapy in a once-daily dose of 4 mg. Plasma prothrombin time, activated partial thromboplastin time, fibrinogen level, plasminogen and antithrombin III activities, protein C and free protein S antigens, total fibrinolytic activity as well as fibrin monomers and D-dimers were assayed. There were no significant changes in any haemostasis variables investigated following placebo administration or perindopril therapy. On the basis of this study, no unfavourable effects on haemostasis induced by this therapy were found. The platelet-inhibitory effect of perindopril, without any harmful effects on coagulation or fibrinolytic activity and coagulation inhibitors, is desirable in the new approach to hypertension treatment. These properties of perindopril may be important in terms of the beneficial role of anti-hypertensive drugs in cardiovascular morbidity.     

Oxidative stress in patients with essential hypertension: A comparison of dippers and non-dippers

BackgroundOxidative stress seems to play an important role in the pathophysiology of essential hypertension. We aimed to examine serum MDA, NO, 8-OHdG, ADMA, NT, CoQ10 and TAC as biomarkers of oxidative stress in dipper and non-dipper hypertensive patients.MethodsEighteen dipper hypertensives, 20 non-dipper hypertensives and 22 healthy control subjects were included in the study. Clinical assessment and ambulatory blood pressure monitoring were performed in patients. Serum MDA, TAC and NO levels were measured by using spectrophotometric methods. CoQ10 levels were measured by HPLC method. 8-OHdG, ADMA and NT were quantitated by ELISA methods.ResultsMDA levels were significantly higher in dipper and non-dipper groups compared to controls (p < 0.05 and p < 0.01, respectively). TAC levels were found at low level in patients dipper and non-dipper patients compared to control group (p < 0.01). Higher ADMA and NT levels but lower CoQ10 levels were found in non-dipper group compared to healthy controls (p < 0.01, p < 0.05, and p < 0.05, respectively). ADMA levels were found higher in non-dipper group than those of dipper group (p < 0.01).DiscussionIncreased ADMA, NT levels and decreased CoQ10 levels in non-dipper hypertensive patients might indicate more severe oxidative stres compared with dipper hypertensive patients, which plays an important role in the development of cardiovascular diseases. Increased MDA and reduced TAC levels might be considered as prospective prognostic markers of the development of cardiovascular diseases in dipper and non-dipper hypertensive patients.     

Frequency domain of heart rate and blood pressure variability in essential hypertensive patients during sleep: differences between dippers and non-dippers

METHODS: Autonomic nervous function was evaluated by means of power spectral analysis of heart rate and blood pressure variability in dipper (n = 10) and non-dipper (n = 9) essential hypertensive subjects during sleep. The non-dipper subjects were defined as those in whom the nocturnal decrease in blood pressure was < 10% of the daytime blood pressure. We measured beat-to-beat blood pressure by using a Finapres device and all stages of sleep by simultaneous polysomnographic recording during spontaneous nocturnal sleep. We analysed the pattern of changes in blood pressure for random periods of 4 min duration while the patient was awake and during all stages of sleep. For each period (waking, stages 2, 3 and 4 of sleep) a segment of 256 stationary data points was analysed. In the frequency domain, the spectral characteristics of the stationary segments were estimatred by fast Fourier transformation over three frequency bands: low frequency (0.025-0.07 Hz), mid-frequency (0.07-0.14 Hz) and high frequency (0.14-0.35 Hz). RESULTS: Pulse-interval power spectral analysis did not reveal any difference between dippers and non-dippers during waking. In dipper patients, the low-frequency pulse interval (LFPI) decreased during sleep whereas the high-frequency pulse interval increased; the mid-frequency systolic blood pressure and diastolic blood pressure (DBP) decreased significantly and the high-frequency DBP increased during sleep. In non-dipper patients, the LFPI increased from wakefulness to stages 2 and 3 of sleep and the high-frequency pulse interval decreased during sleep; the mid-frequency systolic blood pressure and DBP increased in stage 4 sleep and the high-frequency DBP decreased during sleep. CONCLUSIONS: These findings indicate that non-dipper hypertensive subjects are characterized by increased LFPI and mid-frequency blood pressure during sleep compared with dipper subjects. This alteration in the autonomic nervous function may explain the non-dipper phenomenon in essential hypertension.     

24-hour blood pressure behavior in patients with untreated and treated hypertension in comparison with normotensive patients

Blood pressure was continuously monitored over 24 h in 201 patients with mild to moderate essential hypertension using a noninvasive method. Measurements were made both before and after 6 months of antihypertensive treatment and the data were compared to results from 100 normotensive patients. The frequency with which blood pressure values above 140/90 mm Hg occurred during the 24-h period proved to be the most reliable parameter for distinguishing between hypertensive and normotensive profiles. The blood pressures of all patients could be normalized (less than 140/90 mm Hg) on single or combined drug therapy as assessed by casual measurement. However, significant differences were observed between the 24-h profiles of the treated patients and the control group. The mean 24-h blood pressure, the mean day and nighttime blood pressures, the mean hourly pressure, and the frequency of increased blood pressure values were all significantly higher in the patients on medication as compared to the normotensive controls. This would suggest that normotension, as defined by the control group, cannot be attained with antihypertensive medication. In conclusion, 24-h continuous blood pressure monitoring allows a better evaluation of blood pressure profiles and consequently, will be of greater value in assessing cardiovascular risk than occasional random measurements.     

Effect of losartan on nocturnal blood pressure in patients with stroke: comparison with angiotensin converting enzyme inhibitor

BACKGROUND: Treatment of nocturnal hypertension has been reported to be beneficial for primary and secondary prevention of stroke. We compared the effects of angiotensin II antagonist (losartan) and angiotensin converting enzyme inhibitor (quinapril) on nocturnal blood pressure (BP) and sympathetic nervous activity in patients with hypertension and stroke. METHODS: According to a prospective, randomized, cross-over design, 30 hypertensive patients with a previous history of stroke (25 hemorrhage, 5 infarction) were assigned randomly to receive losartan (50 mg) or quinapril (10 mg) once daily for 4 weeks. The patients were switched to the alternative regimen for an additional 4-week period. In the last week of each treatment, 24-h ambulatory BP monitoring was performed every 30 min, and 24-h urine was collected for the measurement of catecholamine. RESULTS: Neither systolic nor diastolic BP during daytime differed between losartan and quinapril treatments, but those during nighttime were lower with losartan treatment than with quinapril treatment. The nocturnal decreases in systolic and diastolic BP were both greater with losartan treatment than with quinapril treatment (systolic BP: 6.1% +/- 5.9% v 2.5% +/- 6.9%, diastolic BP: 6.4% +/- 6.5% v 3.3% +/- 7.8%, both P <.05). The nocturnal decrease in urinary norepinephrine excretion was greater with losartan treatment than with quinapril treatment (52.8% +/- 9.7% v 42.8% +/- 17.2%, P <.05). CONCLUSIONS: Losartan enhances the nocturnal decrease in ambulatory BP compared with that of quinapril in patients with a previous history of stroke presumably by way of the suppression of nocturnal sympathetic nervous activity.     

Effect of angiotensin-converting enzyme inhibitor on cardiopulmonary baroreflex sensitivity in patients with acute myocardial infarction

We evaluated the effect of angiotensin-converting enzyme inhibition (quinapril) on cardiopulmonary baroreflex sensitivity in 30 patients with uncomplicated myocardial infarction (quinapril group, 15 patients; placebo group, 15 patients) at 5 and 10 days after the onset of myocardial infarction. This study indicates that quinapril improved cardiopulmonary baroreflex and thus reduced sympathetic outflow in patients with acute myocardial infarction.     

24-hour blood pressure recording in patients with orthostatic hypotension

Continuous intra-arterial blood pressure measurement and electrocardiograms were obtained in two ambulatory patients with orthostatic hypotension due to autonomic dysfunction. Systolic and diastolic arterial pressure presented marked variations which took place mainly during the day and were related to several physical activities; however, marked falls in blood pressure were also observed during sleep and at the moment of arousal. A peak incidence of hypotensive events was found in the afternoon, mainly in the hours following the afternoon meal. Recording was repeated after 3 weeks of treatment with propranolol, 40 mg t.i.d. In patient 1, beta blockade drastically reduced the number and severity of hypotensive episodes, while propranolol failed to control blood pressure in patient 2, who experienced a higher number of hypotensive events during treatment. Findings of this study may be relevant to the management of patients with orthostatic hypotension and should contribute to a more accurate characterization of blood pressure profile in autonomic dysfunction.     

Can an angiotensin-converting enzyme inhibitor with a short half-life effectively lower blood pressure for 24 hours?

Twenty-four-hour noninvasive ambulatory blood pressure monitoring was used to study the antihypertensive effect of morning (8 AM) versus evening (10 PM) administration of the new angiotensin-converting enzyme inhibitor quinapril, 20 mg. Eighteen patients with mild to moderate hypertension were studied in a double-blind, crossover fashion after 2 weeks of placebo for 4 weeks of each of the two active treatments. The results show that 20 mg of quinapril given once daily is effective in lowering blood pressure levels throughout a 24-hour period. The 24-hour blood pressure profiles showed a more sustained antihypertensive effect with an evening dose of quinapril compared with a morning dose of quinapril; with the morning dose a smaller reduction in blood pressure was observed during nighttime hours. Evening administration seems preferable, because it produces a more sustained and stable 24-hour blood pressure control probably through a more favorable modulation of tissue angiotensin-converting enzyme inhibition or effect on the adrenergic-induced rise in blood pressure that occurs during early morning hours.     

老年人清晨血压与全天血压相关性探讨

目的：探讨老年人清晨血压与全天血压之间的关系。方法根据动态血压监测结果,从我院2015年9至10月接受动态血压监测的体检老年人中选取全天血压均值升高的高血压患者和全天血压均值正常者各44例,分别为高血压组（A 组）和正常对照组（B 组）。比较两组的清晨血压与全天血压均值,并分析清晨收缩压／舒张压均值与全天血压收缩压／舒张压均值之间是否存在相关性。结果A 组的清晨和全天血压均值都高于 B 组。两组的清晨收缩压／舒张压均值与全天收缩压／舒张压均值之间呈正相关关系,且差异有统计学意义（P ＜0．001）。结论老年人清晨血压能在一定程度上反映全天血压水平,建议在老年人中积极推行清晨血压管理。     

Ambulatory 24-hour blood pressure monitoring in patients with resistant hypertension

The aim of the study was to assess the usefulness of 24-hour blood pressure (BP) and heart rate (HR) monitoring in patients with "resistant" hypertension. 30 patients (44.1 +/- 9.9 years) with diastolic BP 100 mm Hg or more in spite of treatment with three or more antihypertensive drugs were studied. Ambulatory recording of BP and HR was performed by means of Del Mar Avionics monitoring system 9000. Mean recording time was 21.5 hours and mean number of measurements during one recording--56.7. Mean ambulatory systolic and diastolic BP values were significantly lower than mean value of three casual measurements (146.0 +/- 24.6 vs 171.5 +/- 21.2 mm Hg for systolic and 97.2 +/- 11.3 vs 110.4 +/- 7.5 mm Hg for diastolic BP p less than 0.01) In 14 (46.6%) systolic BP and in 10 patients (33.3%) diastolic BP were normal. The patients with normal and abnormal ambulatory BP recordings did not differ in regard to age and mean clinic BP levels. However, patients with abnormal ambulatory BP recordings were more often overweight and showed a greater frequency of left ventricular hypertrophy and family history of hypertension and its complications. The results of the study show that ambulatory BP monitoring may be of value in assessing the response to antihypertensive treatment in patients with so called resistant hypertension as judged on the basis of clinic pressure.     

Effect of alcohol abstinence on blood pressure: assessment by 24-hour ambulatory blood pressure monitoring

Several studies have shown that cessation of alcohol drinking reduces blood pressure (BP). However, attempts to reproduce these findings by ambulatory BP monitoring (ABPM) have shown inconsistent results. The aim of the present study was to assess the effect of 1 month of proven abstinence from alcohol on the 24-hour BP profile in heavy alcohol drinkers. Forty-two men who were heavy drinkers (>100 g of pure ethanol per day) were consecutively admitted to a general ward for voluntary alcohol detoxification. On the day of admission, they received a total dose of 2 g/kg of ethanol diluted in orange juice in 5 divided doses, and a 24-hour ABPM was performed. A new 24-hour BP monitoring in the same environmental conditions was performed after 1 month of proven alcohol abstinence while the subjects were receiving the same amount of fluid but without the addition of alcohol. After 1 month of proven alcohol abstinence, BP and heart rate (HR) significantly decreased. The reduction was 7.2 mm Hg for 24-hour systolic BP (SBP) (95% CI, 4.5 to 9.9), 6.6 mm Hg for 24-hour diastolic BP (DBP) (95% CI, 4.2 to 9.0), and 7.9 bpm for HR (95% CI, 5.1 to 10.7). The proportion of alcoholic patients considered hypertensive on the basis of 24-hour BP criteria (daytime SBP >/=135 mm Hg or daytime DBP >/=85 mm Hg) fell from 42% during alcohol drinking to 12% after 1 month of complete abstinence. Abstinence did not modify either the long-term BP variability, assessed by SD of 24-hour BP, or its circadian profile. We conclude that abstinence in heavy alcohol drinkers significantly reduces BP assessed by 24-hour ABPM and that this reduction is clinically relevant. These results show that heavy alcohol consumption has an important effect on BP, and thus cessation of alcohol consumption must be recommended as a priority for hypertensive alcohol drinkers.     

Pharmacogenetic interactions between angiotensin-converting enzyme inhibitor therapy and the angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure

OBJECTIVES: We evaluated the interaction of angiotensin-converting enzyme (ACE) inhibitor therapy with the effect of the ACE D/I polymorphism on heart failure survival. BACKGROUND: The ACE deletion allele, ACE-D, is associated with increased ACE activity. The utilization of ACE genotyping to predict the impact of ACE inhibitor dose has not been previously evaluated. METHODS: We prospectively studied 479 subjects with systolic dysfunction (left ventricular ejection fraction 0.25 +/- 0.08). Subjects were divided on the basis of ACE inhibitor therapy into low dose (50%, n = 201), or those receiving angiotensin receptor antagonists (n = 51). Patients were genotyped for the ACE D/I polymorphism, followed to the end point of death or cardiac transplantation, and transplant-free survival compared by genotype. RESULTS: The ACE-D allele was associated with an increased risk of events (p = 0.026). In analysis by ACE inhibitor dose, this effect was primarily in the low-dose group (1-year percent event-free survival: II/ID/DD = 86/77/71,2-year = 79/66/59, p = 0.032). In the standard-dose group, the impact was markedly diminished (1-year: II/ID/DD = 91/81/80, 2-year: 77/70/71, p = 0.64). The impact of beta-blockers and high dose ACE inhibitors was greatest in subjects with the ACE DD genotype (p = 0.001) and was less apparent with the II and ID genotypes (p = 0.38). CONCLUSIONS: Higher doses of ACE inhibitors diminished the impact of the ACE-D allele, and the benefits of beta-blockers and high-dose ACE inhibitors appeared maximal for DD patients. Determination of ACE genotype may help target therapy for patients with heart failure.     

Effect of continuous positive airway pressure therapy on 24-hour blood pressure in patients with obstructive sleep apnea syndrome

BACKGROUND: Patients with obstructive sleep apnea syndrome (OSAS) are subject to an increased cardiovascular morbidity including systemic hypertension. Little is known about the effects of treatment with nasal continuous positive airway pressure (CPAP) on systemic hypertension. METHODS: Automated ambulatory 24-h blood pressure (BP) monitoring was performed in 88 consecutive patients who were referred for evaluation of snoring or suspected OSAS. In addition, the long-term effects of CPAP therapy on 24-h BP were assessed. RESULTS: A total of 62 patients had OSAS and 26 habitual snoring. Patients with OSAS had significantly higher mean arterial BP values than snorers (102.7 +/- 10.7 v 94.0 +/- 10.2 mm Hg; P < .01). Multiple stepwise linear regression analysis disclosed that the degree of systemic hypertension was independently associated with the severity of OSAS as determined by the apnea/hypopnea index (R = 0.43; P < .001), but not with age, body mass index, or smoking habits. Of the 62 patients with OSAS, 52 were treated with CPAP and reevaluated after 9 months. The CPAP resulted in a significant decrease in mean arterial BP (from 103.7 +/- 10.4 to 99.1 +/- 10.8 mm Hg; P < .05). For those patients with systemic hypertension whose BP improved with CPAP therapy, 24-h mean pulse pressure at baseline (r = -0.36; P < .05) as well as average heart rate during the day (r = -0.35; P < .05) turned out as predictors. CONCLUSIONS: Obstructive sleep apnea syndrome contributes, at least in part, to the development of systemic hypertension, and CPAP may improve BP values in treated OSAS patients. Predictors of a beneficial CPAP effect on BP are a high heart rate and a high pulse pressure before treatment.     

Parkinson's disease and hypotension: 24-hour blood pressure recording in ambulant patients

Continuous intra-arterial blood pressure was recorded in 5 ambulatory patients with Parkinson's disease and in 5 control subjects. The 24-h mean systolic blood pressure was 135 +/- 7.6 mmHg in controls and 123.8 +/- 8.1 mmHg (p less than 0.01) in the parkinsonian group. Similarly, diastolic blood pressure was 89 +/- 8.1 mmHg in the control group while in the parkinsonian patients it was lower, 69.4 +/- 5.8 (p less than 0.01). Averages were also calculated for 8-h periods, the results of which indicate that both systolic and diastolic blood pressure were significantly lower in patients than in controls in all three 8-h periods of the day. We normalized the blood pressure curve to mealtimes and arousal times and did not observe any difference between parkinsonian patients and controls. This first study reporting continuous intra-arterial blood pressure measurements in ambulant parkinsonian patients demonstrates that blood pressure in such patients is lower than the mean for their age group. This finding may be of direct relevance in the management of idiopathic parkinsonism.     

Correlation of blood pressure readings from 6-hour intervals with the daytime period of 24-hour ambulatory blood pressure monitoring in pediatric patients

J Clin Hypertens (Greenwich). 2012; 14:396–400. ©2012 Wiley Periodicals, Inc.Shorter‐interval (6‐hour) ambulatory blood pressure monitoring (ABPM) has been shown to correlate well with 24‐hour ABPM in adults, but this has not been studied in children. The authors selected 131 patients aged 9 to 18 who underwent 24‐ABPM from 2000–2008. Six‐hour intervals beginning at different start times were compared with the daytime and 24‐hour period, with subset analysis for normotensive and hypertensive patients. Concordance correlation coefficients (CCCs) were used to assess for agreement. Among normotensive patients, the mean difference between daytime and 6‐hour intervals ranged from −0.1 mm Hg to 0.0 mm Hg for diastolic blood pressure (DBP) and −1.1 mm Hg to 0.6 mm Hg for systolic blood pressure (SBP) with CCCs of 0.88 to 0.93 for DBP and 0.93 to 0.96 for SBP. For hypertensive patients, mean difference ranged from −0.6 to 1.3 mm Hg for DBP and −0.8 to 1.1 mm Hg for SBP with CCCs of 0.89 to 0.98 for DBP and 0.86 to 0.95 for SBP. Shorter‐interval monitoring correlates significantly with full daytime monitoring in children, allowing for assessment of blood pressure with improved convenience.

Hypertension is one of the leading health care problems in the United States. The incidence of hypertension in children prior to the past decade was 1% to 3%. Recent reports confirm an increase in the average blood pressure (BP) in children with a prevalence of hypertension as high as 4.5% in school‐aged children. ¹ Currently, studies evaluating end organ structures demonstrate hypertension as a risk factor for development of left ventricular hypertrophy ² and carotid artery intimal‐medial thickness. ³ Clinic BP (CBP) is the standard for measuring BP in the office; however, ambulatory BP monitoring (ABPM) is becoming the preferred standard for evaluation of children with suspected hypertension. The indications for use of an ABPM device continue to grow and prompted the American Heart Association (AHA) in 2008 to publish a scientific statement providing guidelines on the use and the interpretation of ABPM in the pediatric population. ⁴ One indication for ABPM includes identifying children at greater risk for end organ damage. The ABPM results are a stronger predictor of hypertension‐associated target organ damage compared with CBP. ⁵ , ⁶ , ⁷ The 2008 AHA scientific statement outlines utilization of 24‐hour ABPM. Many families may find 24‐hour monitoring too burdensome or too costly. As such, one option is to order a shorter interval of monitoring. To date, nothing in the literature has provided evidence on the efficacy of shorter intervals of monitoring for the diagnosis of hypertension among children. Several studies have evaluated shorter intervals among the adult population. Ernst and colleagues ⁸ found that 6‐hour monitoring can approximate mean 24‐hour BP results; however, it does not provide information about circadian variations. Graves and colleagues ⁹ report 6‐hour monitoring as comparable to accurate office measurements without the limitations of poor reproducibility and observer bias. Two older studies ¹⁰ , ¹¹ concluded that 3 or 4 readings per hour during a shorter interval correlated with mean daytime pressures by 24‐hour ABPM.Given the option of 6‐hour ABPM at our institution and the recommendations for the use of 24‐hour monitoring, the evaluation of the concordance between the shorter and longer intervals could provide guidance for clinicians as well as increase power of future research studies on ABPM in children. The aim of this study was to determine whether mean and median systolic BP (SBP) and diastolic BP (DBP) from a 6‐hour daytime interval correlate with statistical significance with the mean and median daytime and 24‐hour SBP and DBP among pediatric patients who have undergone 24‐ABPM.