Nocturnal Blood Pressure Variability Research Articles

Effect of azilsartan versus candesartan on nocturnal blood pressure variation in Japanese patients with essential hypertension

Background. Abnormal variations in night-time hypertension such as “non-dipping” type (< 10% decrease in nocturnal systolic blood pressure [SBP] from daytime SBP) are a risk factor for cardiovascular events independent of 24-h BP. Methods. As part of a randomized, double-blind study of azilsartan (20–40 mg once daily) and candesartan (8–12 mg once daily) in Japanese patients with essential hypertension, an exploratory analysis was performed using ambulatory BP monitoring (ABPM) at baseline and Week 14. Effects of study drugs on nocturnal BP variations according to patients’ nocturnal SBP dipping status were evaluated. Results. ABPM data were available for 273 patients treated with azilsartan and 275 with candesartan. In the dipping group (≥ 10% decrease from daytime SBP), azilsartan produced a greater reduction from baseline in daytime than in night-time SBP (− 14.1 and − 10.9 mmHg, respectively), and the change in daytime SBP was significantly greater with azilsartan than with candesartan (p = 0.0077). In the non-dipping group, azilsartan produced a greater reduction from baseline in night-time than in daytime SBP (− 20.2 and − 9.9 mmHg, respectively), and reductions in both night-time SBP (p = 0.02) and daytime SBP (p = 0.0042) were significantly greater with azilsartan than with candesartan. Conclusions. Once-daily azilsartan improved non-dipping night-time SBP to a greater extent than candesartan in Japanese patients with grade I–II essential hypertension.

Diabetic cardiovascular autonomic neuropathy: clinical implications

Diabetic cardiovascular autonomic neuropathy (DCAN), the impairment of the autonomic balance of the cardiovascular system in the setting of diabetes mellitus (DM), is frequently observed in both Type 1 and 2 DM, has detrimental effects on the quality of life and portends increased mortality. Clinical manifestations include: resting heart rate disorders, exercise intolerance, intraoperative cardiovascular lability, orthostatic alterations in heart rate and blood pressure, QT-interval prolongation, abnormal diurnal and nocturnal blood pressure variation, silent myocardial ischemia and diabetic cardiomyopathy. Clinical tests for autonomic nervous system evaluation, heart rate variability analysis, autonomic innervation imaging techniques, microneurography and baroreflex analysis are the main diagnostic tools for DCAN detection. Aldose reductase inhibitors and antioxidants may be helpful in DCAN therapy, but a regular, more generalized and multifactorial approach should be adopted with inclusion of lifestyle modifications, strict glycemic control and treatment of concomitant traditional cardiovascular risk factors, in order to achieve the best therapeutic results. In the present review, the authors provide aspects of DCAN pathophysiology, clinical presentation, diagnosis and an algorithm regarding the evaluation and management of DCAN in DM patients.

Obstructive sleep apnea syndrome increases serum angiotensin II and incidence of non-dipping circadian blood pressure in patients with essential hypertension

Obstructive sleep apnea syndrome (OSAS) is closely associated with hypertension. Activity of angiotensin II (Ang II) and non-dipping nocturnal blood pressure (BP) variability are implicated in hypertension-related target organ damage. We examined the correlation between OSAS with serum Ang II levels and evaluated the risk of non-dipping BP variability in 180 patients with essential hypertension (EHT). Eligible patients were divided into three subgroups based on their apnea–hypopnea index (AHI) evaluated by polysomnography. EHT alone, EHT with mild OSAS, and EHT with moderate/severe OSAS. Ambulatory BP monitoring was used to calculate mean BP over 24 h, as well as diurnal and nocturnal BP variability. Serum Ang II was determined with enzyme-linked immunosorbent assay. EHT patients with OSAS had significantly higher systolic BP calculated either over 24 h, or by diurnal or nocturnal monitoring (P < 0.05). More EHT patients with OSAS showed non-dipping BP profiles than did EHT patients alone (P < 0.05). The number of patients with non-dipping BP increased with increasing OSAS severity. Surgical treatment alleviated OSAS and reduced AHI (P < 0.05). Preoperative serum Ang II in EHT patients with OSAS was significantly higher than that in those without OSAS (P < 0.05), and showed a rising trend with OSAS severity (P < 0.05). Postoperative serum Ang II, BP and the incidence of non-dipping BP were reduced by surgery to levels lower than preoperative values in patients with OSAS. We therefore conclude that OSAS leads to increased serum Ang II and increased risk of non-dipping BP in patients with EHT.

ENDOTHELIAL DYSFUNCTION AND BLOOD PRESSURE VARIABILITY IN NORMOTENSIVE ADOLESCENTS: PP.6.244

Objective: To study the blood pressure (BP) variability (BPV) in normotensive adolescents with endothelial dysfunction (ED). Methods: It was conducted a prospective and transversal study, including 134 subjects (age: 15 ± 1.6 years), males (n = 63) and females (n = 71), normotensives, and free of cardiovascular disease. All subjects underwent 24-h ambulatory BP monitoring and endothelium-dependent flow-mediated dilation (FMD) in the brachial artery by high resolution ultrsonography. The systolic and diastolic BPV for 24-hour, day and night were expressed as the standard deviation of the obtained values. The presence of ED was defined as FMD less or equal to 10%. The variance ratio test (F-test) was applied to compare the BPV between the ED and normal endothelial function (NEF). Results: The ED prevalence was 23.9% (n = 32) in all adolescents, 53.1% (n = 17) in males and 46.9% (n = 15) in females (P:NS). Adolescents with ED showed significant higher nocturnal systolic and diastolic BPV than those with NEF, these values were (systolic BPV/diastolic BPV): 11.25/9.81 mmHg for ED and 10.22/8.50 mmHg for NEF (P < 0.01). The analysis by gender showed higher nocturnal BPV in males with ED than males with NEF (11.84/11.11 mmHg and 9.92/8.59 mmHg, respectively; P < 0.01), but the females did not show any significant differences. On the other hand, within the ED group, 24-h, diurnal and nocturnal systolic BPV was higher in males than females (11.09, 10.61, and 11.84 mmHg, and. 10.19, 9.97 and 9.17 mmHg, respectively; P < 0.01). Conclusions: There is a high ED prevalence in adolescents. In this age group, only nocturnal BPV is associated with the presence of ED. According to this study, the gender male with ED has abnormal systolic BPV levels. These conditions, ED and higher nocturnal BPV, are extremely important because from the early age the subjects could be in cardiovascular risk even they should be considered as healthy.

Relationship between nocturnal blood pressure variation and silent cerebral infarction in Chinese hypertensive patients

Background To investigate the relationship between nocturnal blood pressure (BP) variation and silent cerebral infarction (SCI) in hypertensive patients. Methods We retrospectively collected demographic, clinical, and laboratory data from 188 Chinese hypertensive patients (111 with SCI, 77 with non-SCI) and analyzed nocturnal BP variation in the SCI and non-SCI patients. Multiple logistic regression was used for analysis. Results We found that both single and multiple SCI were more common in nondipping patients than dipping patients. In further analysis comparing the SCI group with the non-SCI group, we found that carotid artery plaques and duration of hypertension were independent risk factors of SCI ( p < 0.05). The nocturnal BP fall ( r = −10.614, p = 0.000) was also found to be negatively correlated with SCI in our study. In addition, the prevalence of nondipping was not different between the users of three different classes of antihypertensive drugs. Conclusion Our ambulatory blood pressure monitoring study suggested that nondipping was associated with both single and multiple SCI. Abnormal circadian blood pressure rhythm, a parameter in evaluating injury of brain blood vessels, might be a risk factor of SCI.

Prognostic Value of Nocturnal Blood Pressure Reduction in Resistant Hypertension

The prognostic value of nocturnal blood pressure (BP) reduction in resistant hypertension (RH) is unknown. The objective of this prospective study was to evaluate its importance as a predictor of cardiovascular morbidity and mortality. At baseline, 556 patients with RH underwent clinical and laboratory examinations and 24-hour ambulatory BP monitoring. The primary end points were a composite of fatal or nonfatal cardiovascular events, all-cause mortality, and cardiovascular mortality. Multiple Cox regression was used to assess associations between the nocturnal BP reduction and the subsequent end points. After a mean follow-up of 4.8 years (range, 1-103 months), 109 patients (19.6%) reached the composite end point, with 70 all-cause and 46 cardiovascular deaths. A nondipping pattern was present in 360 patients (65.0%). After adjustment for age, sex, body mass index, diabetes, smoking status, physical inactivity, dyslipidemia, previous cardiovascular disease, number of antihypertensive drugs in use, and office and 24-hour ambulatory BP readings, the nondipping pattern was an independent predictor of the composite end point (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.12-2.71) and of cardiovascular mortality (HR, 2.31; 95% CI, 1.09-4.92). In subgroup analysis, the reduced (HR, 1.71; 95% CI, 1.03-2.83) and reverted (HR, 1.89; 95% CI, 1.04-3.43) dipping patterns were predictive of total cardiovascular events. The effect of the nondipping pattern on cardiovascular prognosis was stronger in younger patients and in those with true RH. The nocturnal BP variability patterns provide valuable prognostic information for stratification of cardiovascular morbidity and mortality risk in patients with RH, above and beyond other traditional cardiovascular risk factors and mean ambulatory BP levels.

A Possible Relationship of Nocturnal Blood Pressure Variability with Coronary Artery Disease in Diabetic Nephropathy

Evidence suggests a relationship between short-term blood pressure (BP) variability and cardiovascular target-organ damage. Although a blunted nocturnal decrease in BP and reduced heart rate variability have been shown to be associated with cardiovascular morbidity in diabetic patients, little information is available on short-term BP variability. In this study, short-term BP variability was assessed in 36 subjects with type 2 diabetes and overt nephropathy who underwent ambulatory BP monitoring, and the factors that correlated with short-term BP variability were examined. The incidence of coronary artery disease (CAD) was significantly greater in the patients with increased 24-h systolic BP variability (67% versus 11%; p < 0.0005), while that of cerebrovascular disease was not significantly affected (61% versus 50%). Multiple stepwise regression analysis revealed that serum cholesterol (cholesterol) and plasma norepinephrine (p-NE) were significant and independent contributors to nighttime systolic BP variability (partial R2 = 0.490, p < 0.001; partial R2 = 0.470, p < 0.001) and demonstrated that body mass index and p-NE were primary determinants of nighttime diastolic BP variability (partial R2 = 0.539, p < 0.0005; partial R2 = 0.304, p < 0.05). Diabetic nephropathy patients with CAD had significantly increased daytime systolic (17.8 mmHg versus 13.1 mmHg, p < 0.0005), nighttime systolic (17.4 mmHg versus 10.5 mmHg, p < 0.0001), and nighttime diastolic (10.4 mmHg versus 7.2 mmHg, p < 0.05) BP variability. Furthermore, logistic regression analysis demonstrated that nighttime systolic BP variability was an independent risk factor for CAD (odds ratio 3.13 [95% CI 1.02–9.61]; p < 0.05). The increase in nighttime BP variability is associated with a proportional sympathetic activation in diabetic nephropathy. Elevated short-term BP variability combined with relative sympathetic prevalence during the night might represent an important risk factor for cardiovascular events in the diabetic population.

Diurnal blood pressure pattern in patients with primary aldosteronism

The aim of the study was to evaluate diurnal blood pressure (BP) profiles in patients with primary aldosteronism and to compare them to those in subjects with essential hypertension. The effects of specific therapy on the circadian BP profiles have been studied. Sixty-four patients with primary aldosteronism were included in the study. Thirty of them revealed an aldosterone-producing adenoma (APA) and 34 had idiopathic hyperaldosteronism (IHA) due to bilateral adrenal hyperplasia. We did not find any significant differences in ambulatory BP monitoring (ABPM) between patients with APA and IHA. However, the circadian BP variation in the patients with primary hyperaldosteronism due to APA was preserved, while the patients with IHA showed lower nocturnal decline in comparison with patients with essential hypertension. There was a significant decline in office and ambulatory BP levels after treatment in the patients with both APA and IHA. The awake-sleep BP difference in patients with APA remained unchanged after surgical treatment, while in patients with IHA the night-time systolic and diastolic BP decline was significantly higher after spironolactone treatment. Primary hyperaldosteronism due to APA was associated with normal circadian BP variability and the surgical treatment led to highly significant decline in all BP parameters but had no influence on the extent of nocturnal BP variation. Spironolactone therapy restored normal nocturnal BP decline in patients with IHA. Reduction of night-time BP decline in patients with IHA is more likely to be related to the duration of the disease rather than to the aldosterone levels.

Ambulatory Blood Pressure in Patients with Mesangial Proliferative Glomerulonephritis

Twenty-four-hour ambulatory blood pressure was measured in seven normotensive and 10 hypertensive patients with biopsy proven mesangial proliferative glomerulonephritis (MPG). In normotensive patients, the nocturnal blood pressure variation was seen with a nightly drop in blood pressure while in hypertensive patients with MPG, 24-h blood pressure level was increased both at day- and night-time, but a nocturnal change in blood pressure was also observed in these patients. The pattern of blood pressure variation was not, however, different from the normotensive patients. None of the hypertensive patients with MPG was a so-called non-dipper, showing the same level of blood pressure both at day- and night-time. The hypertensive patients had a rapid increase in blood pressure in the early morning hours from 06.00 to 09.00 h, followed by a relatively abrupt decrease in blood pressure in the evening hours. The patients with high blood pressure were treated with antihypertensive drugs; all patients started with captopril 25 mg once a day, later increasing to twice daily. If the correction of the high blood pressure was not achieved with this drug, amlodipine 5 or 10 mg was added with or without furosemide. Most of the patients needed more than one drug. In all patients, a normal 24-h ambulatory blood pressure could be obtained. The lack of nightly non-dippers in the present hypertensive patients may be explained by a relatively short history of renal disease and the presence of normal or moderately reduced glomerular filtration rate. The abrupt rise in blood pressure during the early morning hours may be due to activation of the renin-angiotensin or sympathetic nervous system in the hypertensive patients with MPG.

Abnormal nocturnal blood pressure fall in normotensive adolescents with insulin-dependent diabetes is ameliorated following glycemic improvement.

Lack of the physiological nocturnal fall in blood pressure (BP) has been found in diabetics and it seems to be related to the presence of diabetic complications. The present study examined the changes in the nocturnal BP pattern of 8 normotensive insulin-dependent diabetic adolescents without nephropathy following improvement in glycemic control induced by an 8-day program of adequate diet and exercise. The same number of age- and sex-matched control subjects were studied. During the first and eighth nights of the program, BP was obtained by ambulatory BP monitoring. After a 10-min rest, 3 BP and heart rate (HR) recordings were taken and the mean values were considered to represent their awake values. The monitor was programmed to cuff insufflation every 20 min from 10:00 p.m. to 7:00 a.m. The glycemic control of diabetics improved since glycemia (212.0 +/- 91.5 to 140.2 +/- 69.1 mg/dl, P < 0.03), urine glucose (12.7 +/- 11.8 to 8.6 +/- 6.4 g/24 h, P = 0.08) and insulin dose (31.1 +/- 7.7 to 16.1 +/- 9.7 U/day, P < 0.01) were reduced on the last day. The mean BP of control subjects markedly decreased during the sleeping hours of night 1 (92.3 +/- 6.4 to 78.1 +/- 5.0 mmHg, P < 0.001) and night 8 (87.3 +/- 6.7 to 76.9 +/- 3.6 mmHg, P < 0.001). Diabetic patients showed a slight decrease in mean BP during the first night. However, the fall in BP during the nocturnal period increased significantly on the eighth night. The average awake-sleep BP variation was significantly higher at the end of the study (4.2 vs 10.3%, P < 0.05) and this ratio turned out to be similar to that found in the control group (10.3 vs 16.3%). HR variation also increased on the eighth night in the diabetics. Following the metabolic improvement obtained at the end of the period, the nocturnal BP variation of diabetics was close to the normal pattern. We suggest that amelioration of glycemic control may influence the awake-sleep BP and HR differences. This effect may be due at least in part to an attenuated insulin stimulation of sympathetic activity.

Determinants of circadian blood pressure rhythm and blood pressure variability in obstructive sleep apnoea.

The prevalence of hypertension in patients with obstructive sleep apnoea (OSA) is high and blood pressure profile is characterized by nocturnal blood pressure (BP) elevation and increased nocturnal BP variability. Ambulatory 24-hour-blood pressure monitoring (ABPM) is a valid, non-invasive method to describe circadian BP variation. Circadian BP profile and nocturnal BP variability were related to OSA severity (apnoea-hypopnoea index, mean low O2), age and body mass index (BMI) in 73 patients with OSA. Prevalence of hypertension was 75%, and in 59% BMI was greater than 30 kg m-2. A nocturnal decline of at least 10% from daytime mean BP values (night/day BP ratio <0.9; dipper) was found in only 25% of hypertensive patients and 39% of normotensive patients. Comparison between dippers and non-dippers showed significant differences in apnoea severity (apnoea-hypopnoea index 32 + 19 vs. 50 + 23/h, P < 0.01; mean low O2 84.5 + 4 vs. 80.2 + 5.8%, P < 0.01) but not for age and BMI. In multiple regression analyses with age, body mass index, apnoea-hypopnoea index and mean low O2 as independent and BP ratios and BP variability as dependent variables, sleep apnoea severity was the only independent predictor for circadian BP rhythm and nocturnal BP variability. The results presented here suggest that independent of age and obesity the severity of sleep apnoea is an important determinant of circadian BP variation and nocturnal BP variability.

The Relation between Sleep Apnea and Intra-Arterially Measured Blood Pressure in Hyperternsive Patients with Sleep Apnea Syndrome.

The relationship between sleep apnea and blood pressure was examined in 7 patients with sleep apnea syndrome (SAS). In addition, whether or not SAS is a risk factor for cerebrovascular disease was assessed. Polysomnography, including measurements of arterial O2 saturation (SaO2), was performed in 7 patients during a 3-day hospitalization period; direct intra-arterial blood pressure was continuously recorded. The blood pressure data were analyzed at the beginning of apnea, the beginning of fall in SaO2, the end of apnea, the time of maximum blood pressure, and the time of SaO2 recovery. Analysis was also carried out for 30s at 30-min intervals to assess nocturnal blood pressure variability. Two urine specimens, one accumulated from 9 a.m. to 9 p.m. and the other from 9 p.m. to 9 a.m., were collected. The pattern of blood pressure changes did not reveal the nocturnal decrease observed in normal subjects. A transient elevation of blood pressure was observed at the end of each apneic period; the mean increase in blood pressure was 28.0mmHg in systole and 16.4mmHg in diastole, and the maximum increase in systolic blood pressure was over 100mmHg. There was no significant difference between diurnal and nocturnal concentrations of urinary catecholamines, suggesting that the sympathetic activity of patients with SAS is not decreased at night. Furthermore, the transient but considerable elevation of blood pressure observed at the end of each apneic period suggests that SAS may potentially trigger cerebrovascular disease. (Hypertens Res 1993;16: 209-213)

38 Diurnal and nocturnal blood pressure variation in type I diabetics

s: Xth journees de I'Hypertension Arterielle Annual Scientific Meeting of the French Society of Hypertension,Section of the French Society of Cardiology Pairs, France: PDF Only