Nocturnal Blood Pressure Decrease Research Articles

Autonomic nervous system activity is independently associated with the risk of shift in the non-dipper blood pressure pattern

An insufficient decrease in nocturnal blood pressure (BP) is a known factor in cardiovascular mortality. We aimed to determine whether autonomic nervous system (ANS) activity and its change over 2 years were associated with a shift to non-dipper status, independently of initial BP, in a general elderly population. From participants in the PROOF study, 600 subjects untreated for hypertension were selected (age at baseline: 65 years, men: 41.5%). Dipper/non-dipper status was defined using repeated measures of 24-h ambulatory BP at baseline and 2 years later. ANS activity was evaluated on the basis of 24-h heart rate variability at both examinations. Among the 454 dipper subjects at baseline, 26.2% became non-dippers. Multivariate analysis showed that a +1 between-subject s.d. increase in the very low frequency at baseline was associated with a decreased odds ratio for the shift to non-dipper status 2 years later (OR=0.61 [0.41-0.91], P=0.02). The within-subject change between the two measurements of day and night systolic BP and day diastolic BP also contributed significantly to the risk of shift to non-dipper status. Our results suggest that impaired ANS activity precedes an insufficient decrease in nocturnal BP independent of hypertension status.

THE BEDTIME DOSING OF BARNIDIPINE HYDROCHLORIDE RESTORES CIRCADIAN RHYTHM IN NONDIPPER HYPERTENSIVE PATIENTS: PP.33.303

Nondipper pattern (blunted or absent nocturnal decrease of blood pressure) is associated with increased cerebral, cardiovascular and renal events. Therefore, the normalization of blood pressure (BP) circadian rhythm is an important goal of antihypertensive treatment. Aim of this study was the evaluation of the effect of a bedtime administration of the calcium channel blocker (CCB) barnidipine hydrochloride on blood pressure dipping status of treated hypertensive subjects. Patients were selected according to the presence of a nighttime fall in systolic BP < 10% of daytime systolic BP on a previous ambulatory BP monitoring (ABPM). The reproducibility of non-dipping status was confirmed through a second 24-h ABP monitoring in 48 patients (mean age 59 ± 16 years, 20 females), whose treatment did no include a CCB. On top of the previous stable treatment regimen, a bedtime (10.00–11.00 pm) 10 mg dosing of barnidipine was added to all subjects. At study entry, mean daytime ABP was 135/83 ± 7/8 mmHg, while mean nighttime was ABP 131/82 ± 7/7 mmHg. After 12 weeks of add-on treatment with barnidipine a 24-h ABPM was repeated. At study end, mean daytime ABP resulted slightly reduced (126/79 ± 7/6, −9/4 mmHg), while mean nighttime ABP decreased in overt fashion (115/74 ± 6/6, −16/8 mmHg). The decrease in systolic and diastolic mean ABP induced by barnidipine bedtime administration resulted statistically significant (daytime systolic p < 0.05, daytime diastolic p < 0.05; nigttime systolic p < 0.025, nighttime diastolic p < 0.025; Student's t test for paired data; two-sided p, α level p < 0.05). Among the 48 nondipper patients 27 (56%) of them showed complete normalization of circadian rhythm. Add-on treatment with barnidipine resulted generally well tolerated. Two patients developed mild symptomatic diurnal hypotension and 4 individuals presented mild leg oedema. In conclusion, in treated hypertensive patients presenting nondipper pattern, bedtime dosing of the CCB barnidipine (added to previous stable treatment regimen) significantly reduced nighttime systolic and diastolic mean ABP and, in 56% of the subjects restored the previously altered circadian rhythm.

ADMINISTRATION TIME OF HIGH-DOSE VALSARTAN IN NON DIPPER HYPERTENSIVE PATIENTS: PP.33.306

Previous results with angiotensin II receptor blockers have shown their efficacy in reducing blood pressure (BP) throughout the 24 hours, independently of the administration time. However, the intake of these ARBs at night increased the diurnal/nocturnal ratio of BP. That is the reason why in this study we have analysed the chronotherapeutic efficacy of high-dose Valsartan in non dipper hypertensive patients. 45 patients (24 women) aged 62.3 ± 11.4 years-old with non-treated essential hypertension confirmed by ambulatory BP monitoring (ABPM) and with a non dipper circadian pattern were studied. After clinical and biological assessment, patients were assigned to two treatment groups according to the administration time of Valsartan 320 mg/day: on awakening (AWA) or at bedtime (BED). ABPM was performed (Spacelabs 90207 device), before and after 3 months of treatment and both the antihypertensive efficacy and the changes in the circadian pattern of BP were compared. After 3 months of treatment, there was a significant decrease in 24h-BP and diurnal BP (p < 0,001), similar in both groups, with proved antihypertensive efficacy throughout the 24 hours (decrease in 24h-SBP/DBP: 16.6/10 mmHg on AWA, 18.8/11.6 mmHg at BED; decrease diurnal SBP/DBP: 16.6/10.2 mmHg on AWA, 17.1/10.4 mmHg at BED). However, there were a higher nocturnal BP decrease in patients taking Valsartan 320 mg at bedtime (decrease in nocturnal SBP/DBP: 15.5/9,7 mmHg on AWA; 24.3/15.5 mmHg at BED; p < 0.001). Diurnal/nocturnal ratio of BP showed no change with Valsartan AWA (−0.4/+0.1%) but it increased in a significant way with Valsartan BED (+6.3/+7.4; p < 0.001) so 69.9% of the patients changed to a dipper circadian pattern. Administration of Valsartan 320 mg/day in non dipper hypertensive patients shows an excellent antihypertensive efficacy independently of the administration time. Nevertheless, when the medication is taken at bedtime, there is a higher decrease of nocturnal BP together with an increase in the diurnal/nocturnal ratio of BP which, in many cases, restores to normal the altered circadian pattern of these patients.

Antihypertensive Chronotherapie Chronopathologie renaler Hochdruckformen

Die Chronopathologie der Hypertonie beschreibt die verschiedenen Phänomene der Normabweichung im zeitlichen Verlauf der Blutdruckregulation, ihre Charakteristika, die Ursachen, die diagnostische und prognostische Bedeutung sowie die therapeutischen Konsequenzen. Bei der renalen Hypertonie sind der nächtliche Blutdruck und der Tag-Nacht-Rhythmus von besonderem Interesse. Daher sind die chronopharmakologischen Aspekte der antihypertensiven Therapie, also die Berücksichtigung von Pharmakokinetik und -dynamik in Abhängigkeit von der Tageszeit, der Applikation und der Wirkdauer der Substanzen, von großer klinischer Bedeutung bei Patienten mit renalen Hochdruckformen. Insbesondere eine nächtliche Blutdrucksenkung und die Wiederherstellung eines normalen zirkadianen Rhythmus sind wichtige Therapieziele bei Risikopatienten mit unzureichender Nachtabsenkung („non-dipper“) oder einer Inversion des Blutdruckrhythmus („inverted dipper“). Andererseits verbietet sich eine abendliche Dosierung bei Patienten mit spontan ausgeprägter nächtlicher Blutdruckabsenkung („super dipper“), um nächtliche Ischämien zu vermeiden. Dies gilt insbesondere für ältere Patienten und für Patienten mit kardiovaskulären Erkrankungen. Bei diesen Patienten sind eine individuelle Steuerung der antihypertensiven Medikation und eine Anpassung der Dosierungsintervalle nur mittels ambulanter Blutdrucklangzeitmessung möglich. Dieses Vorgehen beschreibt die antihypertensive Chronotherapie.

Melatonin for nondippers with coronary artery disease: assessment of blood pressure profile and heart rate variability

The aim of this study was to assess the effects of 5 mg melatonin before sleep in patients with coronary artery disease (CAD) and with an abnormal circadian pattern of blood pressure (BP) on changes in circadian BP profile and heart rate variability (HRV). Sixty patients with CAD, nondippers aged 48-80 years (male 75%), were included. In addition to previous treatment, they were randomly allocated to melatonin or placebo. After 90 days, a second 24-h BP monitoring was carried out. Each patient had two sessions (before randomization and at the end of study) of 24-h ECG monitoring to assess the changes in HRV. Inclusion of melatonin led to BP pattern normalization in 35% of patients in the melatonin group and in 15% of controls (P=0.609). This effect was reached not only by a decrease in nighttime BP, but also by an increase in daytime BP (significant in the melatonin group). A nonoptimal effect for BP profile was observed in 12.5% of patients: extreme- or reverse dippers. In patients with conversion from nondippers to dippers (responders), an increase in standard deviation of normal-to-normal intervals between initial and final HRV analyses was observed. Nonresponders represented an increase in the mean circadian heart rate. To avoid nonoptimal effects, the inclusion of melatonin in pharmacotherapy of patients with CAD should be based on monitoring of circadian BP profile, before and during treatment. As melatonin caused not only a nocturnal decrease in BP but also a daytime increase, it should not be recommended in patients with 'high normal' values of BP because of the danger of induction of arterial hypertension.

Association Between White-Coat Effect and Blunted Dipping of Nocturnal Blood Pressure

In this study, we assessed whether the white-coat effect (difference between office and daytime blood pressure (BP)) is associated with nondipping (absence of BP decrease at night). Data were available in 371 individuals of African descent from 74 families selected from a population-based hypertension register in the Seychelles Islands and in 295 Caucasian individuals randomly selected from a population-based study in Switzerland. We used standard multiple linear regression in the Swiss data and generalized estimating equations to account for familial correlations in the Seychelles data. The prevalence of systolic and diastolic nondipping (<10% nocturnal BP decrease) and white-coat hypertension (WCH) was respectively 51, 46, and 4% in blacks and 33, 37, and 7% in whites. When white coat effect and nocturnal dipping were taken as continuous variables (mm Hg), systolic (SBP) and diastolic BP (DBP) dipping were associated inversely and independently with white-coat effect (P < 0.05) in both populations. Analogously, the difference between office and daytime heart rate was inversely associated with the difference between daytime and night-time heart rate in the two populations. These results did not change after adjustment for potential confounders. The white-coat effect is associated with BP nondipping. The similar associations between office-daytime values and daytime-night-time values for both BP and heart rate suggest that the sympathetic nervous system might play a role. Our findings also further stress the interest, for clinicians, of assessing the presence of a white-coat effect as a means to further identify patients at increased cardiovascular risk and guide treatment accordingly.

A blunted decrease in nocturnal blood pressure is independently associated with increased aortic stiffness in patients with resistant hypertension

Increased arterial stiffness may be causally related to resistant hypertension. Our objective was to investigate the variables, particularly those derived from ambulatory blood pressure (BP) monitoring (ABPM), associated with increased aortic stiffness in resistant hypertensives. In a cross-sectional study, 600 resistant hypertensive patients without peripheral arterial disease were evaluated. Arterial stiffness was assessed by aortic pulse wave velocity (PWV), and was considered increased if >12 m s(-1). Statistical analyses included multiple linear and logistic regressions to assess the independent correlates of increased aortic stiffness. One hundred and sixty-eight patients (28%) had aortic PWV >12 m s(-1). Patients with increased PWV were older and had a higher prevalence of cardiovascular risk factors than did those patients with low PWV. On ABPM, patients with elevated PWV had higher daytime and night time systolic BP (SBP) and pulse pressures (PP), less nocturnal decrease in SBP and a higher prevalence of non-dipping pattern. On multiple linear regression, the independently associated variables with aortic PWV were age (P<0.001), 24-h PP (P<0.001), high-density lipoprotein (HDL)-cholesterol (P<0.001), microalbuminuria (P<0.001), fasting glycemia (P=0.001) and a decrease in nocturnal SBP (P=0.002). Multivariate logistic regression confirmed these results, with the non-dipping patients having a 72% higher likelihood of presenting with increased aortic stiffness (95% confidence interval: 1.12-2.65, P=0.013). This association was observed in both the reduced and reverted dipping patterns, but not in the extreme dipping pattern. In conclusion, a blunted nocturnal decrease in BP is independently associated with increased aortic stiffness in resistant hypertensive patients. Other independent correlates are older age, diabetes, microalbuminuria, low HDL-cholesterol and a widened 24-h PP.

The relation between serotonin levels and insufficient blood pressure decrease during night-time in hypertensive patients

Aim. The serotonin levels in thrombocytes are decreased in hypertensive patients. The aim of our study was to investigate the relationship between serotonin levels and insufficient nocturnal blood pressure (BP) decrease (non-dipper) in hypertensive patients.Patients and methods. Fifty-six hypertensive patients and 27 healthy control subjects were included in the study. Of the hypertensive patients, 28 were classified as dippers and 28 as non-dippers based on nocturnal BP drops of >10 mmHg and <10 mmHg, respectively. Thrombocyte serotonin levels, serum uric acid, and C-reactive protein (CRP), and urinary albumin/creatinine ratios were analysed. Thrombocyte serotonin levels were measured using an enzyme immunoassay.Results. The thrombocyte serotonin level was 378.9 ± 69.5 ng/109 platelet in the non-dipper group, 424.7 ± 58.6 ng/109 platelet in the dipper group, and 518.1 ± 35.9 ng/109 platelet in the control group. Serotonin levels in the non-dipper group were significantly lower than in the dipper group. Serotonin levels negatively correlated with blood pressure (r = −0.6, p<0.001). CRP concentration in the non-dipper group was higher than in the dipper (4.8 ± 1.4 vs 3.6 ± 1.6, p<0.01) and control (2.4 ± 0.9, p<0.001) groups, and microalbuminuria was significantly higher in the non-dipper group compared with dipper (24.9 ± 8.6 vs 13.4 ± 8.8, p<0.001) and control (9.6 ± 4.8, p<0.001) groups. Serotonin level was negatively correlated with microalbuminuria (p<0.001, r = −0.3), uric acid (p<0.01, r = −0.3), and CRP (p<0.01, r = −0.35).Conclusion. In non-dipper hypertensive patients, thrombocyte serotonin levels were significantly lower than in dipper and control groups. Serotonin levels may be related to insufficient nocturnal blood pressure decrease in hypertensive patients.

Nighttime Blood Pressure and Nocturnal Dipping Are Associated With Daytime Urinary Sodium Excretion in African Subjects

Blood pressure (BP) follows a circadian rhythm, with 10% to 15% lower values during nighttime than during daytime. The absence of a nocturnal BP decrease (dipping) is associated with target organ damage, but the determinants of dipping are poorly understood. We assessed whether the nighttime BP and the dipping are associated with the circadian pattern of sodium excretion. Ambulatory BP and daytime and nighttime urinary electrolyte excretion were measured simultaneously in 325 individuals of African descent from 73 families. When divided into sex-specific tertiles of day:night ratios of urinary sodium excretion rate, subjects in tertile 1 (with the lowest ratio) were 6.5 years older and had a 9.8-mm Hg higher nighttime systolic BP (SBP) and a 23% lower SBP dipping (expressed in percentage of day value) compared with subjects in tertile 3 (P for trend <0.01). After adjustment for age, the SBP difference across tertiles decreased to 5.4 mm Hg (P=0.002), and the SBP dipping difference decreased to 17% (P=0.05). A similar trend across tertiles was found with diastolic BP. In multivariate analyses, daytime urinary sodium and potassium concentrations were independently associated with nighttime SBP and SBP dipping (P<0.05 for each). These data, based on a large number of subjects, suggest that the capacity to excrete sodium during daytime is a significant determinant of nocturnal BP and dipping. This observation may help us to understand the pathophysiology and clinical consequences of nighttime BP and to develop therapeutic strategies to normalize the dipping profile in hypertensive patients.

Ambulatory Blood Pressure and Heart Rate in Hypertensives with Renal Failure: Comparison between Diabetic Nephropathy and Non-Diabetic Glomerulopathy

The purpose of this study was to examine a possible difference in the 24-h blood pressure (BP) profile between hypertensives with diabetic nephropathy (DN) and those with non-diabetic glomerulopathy (non-DN). We measured 24-h ambulatory BP in 34 type 2 DN and 34 non-DN patients who were hospitalized for the educational program in our hospital. There were no significant differences in 24-h and daytime systolic BP between DN (143 vs. 136 mmHg, NS for 24-h systolic BP) and non-DN (143 vs. 138 mmHg, NS for daytime systolic BP). Although both groups disclosed blunted nocturnal decrease in BP and were classified as “non-dipper” type, DN patients had a significantly higher nighttime systolic BP than patients with non-DN (142 vs. 132 mmHg, p = 0.0217). BP and heart rate (HR) variabilities were also estimated, and patients with DN showed a reduced nighttime HR variability than those with non-DN (4.8 vs. 6.6 beats/min, p = 0.0115). DN patients had an increase in urinary protein excretion (3.0 vs. 1.4 g/day, p = 0.0095) and a decrease in serum albumin concentration (3.1 vs. 3.7 mg/dl, p < 0.0001). Furthermore, urinary protein excretion was significantly correlated with nighttime systolic BP (r = 0.480, p = 0.0031) but not with nighttime HR variability. Taken together, these results demonstrate that the circadian rhythms of BP and HR are affected by underlying diseases and suggest that an elevated nighttime BP level may contribute to the enhanced urinary protein excretion in hypertensives with DN.

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.

Ethnic Differences in Sleep Quality Accompany Ethnic Differences in Night-time Blood Pressure Dipping

African Americans exhibit a smaller nocturnal decrease in blood pressure (BP) than whites, and there are also reports of poorer sleep quality among African Americans. We examined the contribution of sleep quality to ethnic differences in BP dipping in African American and white male and female college students. We hypothesized that African Americans would exhibit blunted nocturnal BP dipping compared to whites, which would be partly accounted for by poorer sleep quality among African Americans. Forty-three African American and 46 white college students aged 18 to 25 years completed an ambulatory BP protocol that included wrist actigraphy, which was used in conjunction with participant self-reports of sleep times for analyses of sleep quality. Although daytime and night-time BP did not differ according to ethnicity, African Americans had a smaller dip in systolic BP (P < .01), and African American women had a smaller dip in diastolic BP than whites (P < .01). Whites were more likely to be classified as a dipper (71%) than African Americans (41%) (P < .01). African Americans, compared to whites, spent less time in bed, were asleep for a shorter period of time, took longer to fall asleep, exhibited poorer sleep efficiency, and were awakened a higher percentage of the time by the inflation of the BP cuff (F > or = 4.85, P < .05). However, sleep quality did not appear to contribute to ethnic differences in diastolic BP dipping. Sleep quality accompanied ethnic differences in systolic and diastolic BP dipping, but did not account for these differences.

QT interval prolongation in association with impaired circadian variation of blood pressure and heart rate in adolescents with Type 1 diabetes

The aim of our study was to assess diurnal blood pressure (BP) and heart rate variability and their possible relationship to the duration of the QT interval in adolescents with Type 1 diabetes. In 48 normotensive, normoalbuminuric diabetic adolescents, with a mean (+/- sd) age of 17.3 (+/- 4.1) years and a mean (+/- sd) diabetes duration of 8.5 (+/- 3.3) years, 24-h ambulatory BP was recorded. In addition, 24-h heart rate (HR) monitoring was performed and QT and corrected QT (QTc) intervals were estimated as indices of autonomic function. The patients were divided into two groups according to the absence of a decrease (non-dippers) or the presence of a decrease (dippers) in nocturnal diastolic BP (DBP). In comparison with the dippers, the non-dippers showed reduced mean 24-h HR (79.6 vs. 84.0 beats/min, P = 0.05) and reduced mean daytime HR (81.3 vs. 86.0 beats/min, P = 0.05). The QT interval was prolonged in the non-dippers (366.3 vs. 347.5 ms, P = 0.015), and end systolic (28.7 vs. 25.9 mm, P = 0.004) and end diastolic left ventricular diameters (47.8 vs. 45.5 mm, P = 0.037) were greater. In stepwise multiple regression, HR variables were the most important factors affecting DBP ratio or the duration of the QT interval. In conclusion, normotensive diabetic adolescents with impaired nocturnal BP reduction also have impaired autonomic function tests, in association with prolonged QT interval and increased left ventricular diameters. These findings suggest that diabetic adolescents who have the 'non-dipper' phenomenon may need close follow-up for the possible development of vascular complications, such as cardiac arrhythmias and left-ventricular hypertrophy.

Obesity Is the Major Determinant of the Abnormalities in Blood Pressure Found in Young Women with the Polycystic Ovary Syndrome

Obesity and insulin resistance predispose patients with the polycystic ovary syndrome (PCOS) to abnormalities in blood pressure regulation. Our objective was to evaluate the impact of obesity on the blood pressure profiles of PCOS patients. PATIENTS, SETTING, AND DESIGN: Thirty-six PCOS patients and 20 healthy women participated in a case-control study at an academic hospital. We conducted ambulatory blood pressure monitoring and office blood pressure determinations. Hypertension (defined as increased office blood pressure confirmed by ambulatory blood pressure monitoring or by masked hypertension) was present in 12 PCOS patients and eight controls (P = 0.618). No differences between patients and controls were found in office and ambulatory blood pressure monitoring values and heart rate, yet the nocturnal decrease in mean blood pressure was smaller in patients (P = 0.038). Obese women (13 patients and eight controls) had increased frequencies of office hypertension (29% compared with 3% in lean plus overweight women, P = 0.005), increased diastolic (P = 0.009) and mean (P = 0.015) office blood pressure values, and increased heart rate values during the daytime (P = 0.038), nighttime (P = 0.002), and 24-h (P = 0.009) periods, independently of having PCOS or not. The frequency of a nocturnal nondipper pattern was 62% in obese PCOS patients, compared with 26% in lean plus overweight PCOS patients (P = 0.036) and 25% in obese and in lean plus overweight controls. Abnormalities in the regulation of blood pressure are common in young women with PCOS, yet, with the exception of the nondipper pattern, these abnormalities result from the frequent association of this syndrome with obesity.

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.

Enhanced Plasma Soluble CD40 Ligand Levels in Essential Hypertensive Patients With Blunted Nocturnal Blood Pressure Decrease

Hypertensives with a blunted nocturnal blood pressure (BP) decrease have increased risk of developing atherosclerotic disease. Soluble CD40 ligand (sCD40L) is involved in the pathogenesis of risk factor-related vascular damage. Therefore, we evaluated the relationship between circulating sCD40L levels, circadian BP profile, and early carotid atherosclerosis in essential hypertensives. Plasma sCD40L concentrations were assessed in two groups of 25 never-treated hypertensives, without additional cardiovascular risk factors, differentiated on the basis of a nocturnal decrease of BP either of >10% (dippers) or <10% (nondippers) of daytime values, and in 25 matched normotensives. Carotid intima-media thickness (IMT) was also measured in all participants. Plasma sCD40L concentrations were higher in nondippers (4.9 +/- 1.2 ng/mL) than in dippers (3.7 +/- 0.7, P = .0005) and controls (1.6 +/- 0.6, P < .0001). These latter had lower sCD40L concentrations than dippers (P < .0001). The IMT was higher in both hypertensive groups than in normotensives (P < .0001). In the entire hypertensive population IMT directly correlated with circulating levels of sCD40L (r = 0.365, P = .01) and inversely correlated with nocturnal systolic BP decreases (r = -0.286, P = .043). In a multivariate regression analysis sCD40L was the main determinant of IMT (r(2) = 0.157, P = .004). Nondippers have enhanced plasma sCD40L levels, which may contribute to their increased susceptibility to develop vascular damage.

Reviewer Critique of “Enhanced Plasma Soluble CD40 Ligand Levels in Essential Hypertensive Patients With Blunted Nocturnal Blood Pressure Decrease”

Reviewer Critique of “Enhanced Plasma Soluble CD40 Ligand Levels in Essential Hypertensive Patients With Blunted Nocturnal Blood Pressure Decrease”

Benefits of Candesartan on Arterial and Renal Damage of Non-Diabetic Hypertensive Patients Treated with Calcium Channel Blockers

Background/Aim: Although long-term, intensive blood pressure (BP) control with calcium channel blockers (CCBs) reduced arterial stiffness and renal damage of hypertensive patients, combination therapy with antihypertensive drugs is frequently needed to maintain the intensive BP control. The present study was conducted to examine add-on benefits of candesartan therapy on hypertensive patients treated with CCBs for at least 12 months. Methods: Pulse wave velocity (PWV), urinary albumin excretion (UAE), intima-media thickness (IMT) of the carotid arteries, and 24-hour ambulatory BP were determined in 50 non-diabetic hypertensive patients treated with CCBs before and 12 months after the start of therapy with candesartan or placebo. Results: Candesartan significantly decreased clinic BP and tended to decrease ambulatory BP, but the decreases were similar to those in the placebo group except nocturnal BP decrease, which was significantly enhanced by candesartan. Add-on candesartan significantly decreased PWV and UAE compared to placebo, but IMT was unchanged with candesartan or placebo. The decrease in clinic BP or nocturnal BP decrease did not contribute to the improvement of PWV or UAE. Conclusion: Add-on candesartan functionally improved the stiffened arteries of hypertensive patients treated with CCBs by the end of 12 months of treatment independently of its effects on BPs.

What effect on blood pressure can we expect from continuous positive airway pressure treatment in obstructive sleep apnoea?

What effect on blood pressure can we expect from continuous positive airway pressure treatment in obstructive sleep apnoea?

Prolonged (48-Hour) Modest Hyperinsulinemia Decreases Nocturnal Heart Rate Variability and Attenuates the Nocturnal Decrease in Blood Pressure in Lean, Normotensive Humans

Heart rate variability (HRV), an index of cardiac vagal activity, is decreased in individuals with metabolic disease. The relationship between decreased HRV and metabolic disease is unclear. The objective of this study was to determine whether experimentally induced glucose intolerance decreases HRV in a circadian relevant manner in healthy individuals. This was a within-subject, randomized design study with subjects infused for 48 h with saline (50 ml/h) or 15% glucose (200 mg/m2.min). HRV was evaluated using time domain measurements taken over the 48-h period. Blood pressure and heart rate were monitored, and blood samples were taken. This study was performed at the General Clinical Research Center of the Hospital of the University of Pennsylvania. Sixteen healthy subjects (eight men and eight women; 18-30 yr old; mean body mass index, 21.7 +/- 1.6 kg/m2) were studied. After glucose infusion, mean plasma glucose was increased by 16.8% (P < 0.0001), and plasma insulin was increased by 99.4% (P < 0.0001) compared with after saline infusion. Significant decreases in homeostasis model assessment indicated a decrease in insulin sensitivity (saline, 0.52 + 0.13; glucose, 0.34 + 0.12; P < 0.0001). The nocturnal root mean square successive difference, an index of cardiac vagal activity, was significantly decreased (P < 0.01), and nocturnal HR (P < 0.001) and blood pressure were significantly elevated (saline, 107.4 +/- 2.7; glucose, 112.5 +/- 3.3 mm Hg; P < 0.05) compared with the saline control. The change in homeostasis model assessment due to glucose infusion was significantly correlated with the change in root mean square successive difference (r = 0.48; P < 0.01). Prolonged mild hyperinsulinemia disrupts the circadian rhythm of cardiac autonomic activity. Early changes in the neural control of cardiac activity may provide a potential mechanism mediating the pathophysiological link between impaired glucose tolerance and cardiovascular disease.