Higher Blood Pressure Variability Research Articles

White-Coat Hypertension and Risk of Stroke

The term “white-coat hypertension” (WCH; also commonly referred to as isolated office hypertension) describes the transient increase in blood pressure (BP), resulting from an alerting reaction and pressor response, observed in certain individuals when attending a clinic or doctors’ office.1 The diagnosis of WCH is usually ascribed when clinic BPs exceed 135/85 mmHg and average daytime BPs do not. WCH could be dismissed as a risk factor for stroke and other cardiovascular events, because the increase in BP is transient and may be idiosyncratic to the clinic setting.2 However, WCH may be a marker of stress reactivity per se, because surges in BP that occur in the doctor’s office are indicative of BP surges in other stressful scenarios.3 The article by Verdecchia et al featured in this edition of Hypertension 4 reports data from 6000 Italian, Japanese, and American adults. The purpose of the study was to explore the relationship between classically defined WCH and incident stroke during a median follow-up of 5.4 years. When compared with normotensive controls, a tendency for increased stroke incidence was observed in patients with WCH (unadjusted hazard ratio, 1.15). However, because the variance around the estimates of effect is large (95% confidence interval, 0.61 to 2.16), this association is not statistically significant, despite this study being the largest of its kind to date. By contrast, a statistically significantly association between ambulatory hypertension and stroke was observed (unadjusted hazard ratio, 2.01; 95% confidence interval, 1.31 to 3.08). The hypothesis that Verdecchia et al test is important because vessels in the brain may be particularly susceptible to transient elevations in BP. Furthermore, because WCH is highly prevalent,5 even a relatively small increase in stroke risk on an individual level could convey a high population-attributable risk. Although Verdecchia et al have demonstrated using …

Mechanisms of blood pressure variability-induced cardiac hypertrophy and dysfunction in mice with impaired baroreflex

Enhanced blood pressure variability contributes to left ventricular hypertrophy and end-organ damage, even in the absence of hypertension. We hypothesized that the greater number of high-blood pressure episodes associated with enhanced blood pressure variability causes cardiac hypertrophy and dysfunction by activation of mechanosensitive and autocrine pathways. Normotensive mice were subjected to sinoaortic baroreceptor denervation (SAD) or sham surgery. Twelve weeks later, blood pressure variability was doubled in SAD compared with sham-operated mice. Blood pressure did not differ. Cardiac hypertrophy was reflected in greater heart/body weight ratios, larger myocyte cross-sectional areas, and greater left ventricular collagen deposition. Furthermore, left ventricular atrial and brain natriuretic peptide mRNA expression was greater in SAD than in sham-operated mice. SAD had higher left ventricular end-diastolic pressures and lower myocardial contractility indexes, indicating cardiac dysfunction. Cardiac protein content of phosphorylated p125 focal adhesion kinase (p125 FAK) and phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) was greater in SAD than in sham-operated mice, indicating activation of mechanosensitive pathways of cardiac hypertrophy. Furthermore, enhanced cardiac renin and transforming growth factor-beta1 (TGFbeta1) protein content indicates activation of autocrine pathways of cardiac hypertrophy. Adrenal tyrosine hydroxylase protein content and the number of renin-positive glomeruli were not different, suggesting that sympathetic activation and the systemic renin-angiotensin system did not contribute to cardiac hypertrophy. In conclusion, more frequent blood pressure rises in subjects with high blood pressure variability activate mechanosensitive and autocrine pathways leading to cardiac hypertrophy and dysfunction even in the absence of hypertension.

Greater hypertrophy in right than left ventricles is associated with pulmonary vasculopathy in sinoaortic-denervated Wistar-Kyoto rats.

1. Biventricular hypertrophy has been described in a high blood pressure variability (BPV) model of sinoaortic-denervated (SAD) rats without systemic hypertension. To explore the possible involvement of the lung in SAD-induced right ventricular hypertrophy (RVH), we examined lung morphology, in addition to systemic haemodynamics and ventricle morphology, in Wistar-Kyoto rats 32 weeks after SAD. 2. In Wistar-Kyoto rats 32 weeks after SAD, there existed a substantial elevation in BPV, with no change in the average level of arterial pressure. Biventricular hypertrophy following SAD was characterized by a greater hypertrophy in right than left ventricles; both absolute and normalized right ventricular weights were significantly increased by 22 and 27%, respectively, and only normalized left ventricular weight was significantly increased by 12%. No infarcts were found in any ventricles examined. 3. In the lung, the most prominent change following SAD was pulmonary vasculopathy, including wall thickening, perivascular fibrosis and cell infiltration. In pulmonary arteries with an internal diameter of 70-130 microm, the external diameter, wall thickness and wall thickness to internal diameter ratio were increased in SAD compared with control rats. 4. There was no correlation between right and left ventricular weights. In contrast with BPV-correlated left ventricular weight, right ventricular weight was correlated with the wall thickness of the pulmonary artery, but not with BPV. 5. These findings suggest that greater RVH following SAD is associated with pulmonary vasculopathy, but is not secondary to the left ventricular problems or high BPV.

Effect of upper airway obstruction on blood pressure variability after stroke

Approx. 60% of acute stroke patients have periods of significant UAO (upper airway obstruction) and this is associated with a worse outcome. UAO is associated with repeated fluctuation in BP (blood pressure) and increased BP variability is also associated with a poor outcome in patients with acute stroke. UAO-induced changes in BP, at a time when regional cerebral perfusion is pressure-dependent in areas of critically ischaemic brain, could explain the detrimental effect of UAO on outcome in these patients. The aim of the present study was to examine the relationship between UAO and BP variability in patients with acute stroke. Twelve acute stroke patients and 12 age-, sex- and BMI (body mass index)-matched controls underwent a sleep study with non-invasive continuous monitoring of BP to assess the impact of UAO on BP control after stroke. Stroke patients had significantly more 15 mmHg dips in BP/h than the controls (51 compared with 6.7 respectively; P<0.004). Stroke patients also demonstrated significantly higher BP variability than the controls (26.8 compared with 14.4 mmHg; P<0.001). There were significantly more 15 mmHg dips in BP/h in stroke patients who had significant UAO than those who did not (85.7 compared with 29.5 respectively; P<0.032). Furthermore, stroke patients without UAO (RDI <10, where RDI is respiratory disturbance index) had significantly more 15 mmHg dips in BP/h than the controls (29.5 compared with 6.7 respectively; P<0.037). There was a positive correlation between the severity of UAO (RDI) and 15 mmHg dips in BP/h (r=0.574, P<0.005) in stroke patients. Our results suggest that UAO alone does not explain BP variation post-stroke, but it does play an important role, particularly in determining the severity of the BP fluctuation.

Aromatase-deficient (ArKO) mice have reduced blood pressure and baroreflex sensitivity.

Aromatase-deficient (ArKO) mice are deficient in estrogens due to deletion of the aromatase gene. We hypothesized that there may be changes in the cardiovascular system of ArKO mice because of evidence linking estrogens with improved cardiovascular outcomes and the induction of the glucocorticoid-metabolizing enzyme, 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2), gene in the kidney, which is important for the regulation of blood pressure (BP). BP and baroreflex sensitivity (BRS) in female conscious ArKO mice were compared with those in age- and weight-matched wild-type (WT) mice. Power spectral analysis was used to determine cardiovascular variability and BRS. Although systolic BP was similar in the two groups, diastolic and mean BPs were lower in the ArKO mice (-6.3 +/- 1.9 and -4.6 +/- 2.1 mm Hg, respectively). Heart rate (HR) was greater in the ArKO mice (+36 +/- 6 beats/min). The mean BP in WT mice was 105 mm Hg, and the HR was 481 beats/min. In the autonomic frequency range, BP variability was 74% greater, and HR variability was only 26% that in WT mice. The BRS of ArKO mice was 46% of the value observed in WT mice. 11betaHSD2 levels were unaltered in ArKO mice, except in the kidney, where they were only 10% of WT levels. Estradiol administration to ArKO mice restored renal 11betaHSD2 to WT levels. The results show that ArKO mice have lower diastolic BP, but increased BP variability, perhaps due to an impaired BRS. Thus, aromatase activity is critical for normal autonomic control of the heart and, hence, for reducing the deleterious effects of high BP variability.

Association between Altered Circadian Blood Pressure Profile and Cardiac End-Organ Damage in Patients with Renovascular Hypertension

Background: Patients with renovascular hypertension (RVH) have a higher degree of cardiovascular end-organ damage compared to patients with essential hypertension (EH). The precise mechanisms underlying this phenomenon, however, have not been fully elucidated. This study investigated the relationship between circadian blood pressure (BP) profile and cardiac involvement in patients with RVH and EH. Methods: Twenty patients with RVH and 20 with EH, matched for demographic characteristics, underwent simultaneous 24-hour ambulatory BP recording and Holter ECG monitoring. Also, each participant underwent echocardiographic assessment of left ventricular mass. Cardiac damage was defined as the presence of left ventricular hypertrophy, myocardial ischemia or arrhythmias. Results: Casual BP was similar in both groups, whereas 24-hour ambulatory BP values were higher in RVH than in EH patients; moreover, RVH patients had higher blood pressure variability and blunted nocturnal BP fall compared to those with EH. Left ventricular mass, as well as the prevalence of myocardial ischemia and the presence and severity of cardiac arrhythmias, were higher in RVH than in EH patients. Conclusions: Patients with RVH have altered circadian BP profile compared to those with EH. This abnormality might contribute to their increased prevalence of cardiac damage and might adversely affect the prognosis of these patients.

Comparative study of sinoaortic denervated rats and spontaneously hypertensive rats

Background Both hypertension and high blood pressure variability (BPV) are involved in cardiovascular damage. This comparative study was designed to explore the possible effects of both of these phenomena on the cardiovascular system. Methods The high BPV model of 16-week sinoaortic denervated (SAD) rats and the hypertension model of spontaneously hypertensive rats (SHR) were used for comparison at the same age of 26 weeks. The comparison was focus on hemodynamics, cardiovascular hypertrophy, and hemodynamic responses to ketanserin. Linear regression analysis was performed to study the role of hemodynamics in cardiovascular hypertrophy. Results In SHR, hypertension was accompanied by a moderately high BPV, whereas in SAD rats, substantially high BPV existed alone, without hypertension. Left ventricular hypertrophy was severe in SHR but was mild in SAD rats. Aortic hypertrophy was present in SAD rats but was absent in SHR. In SAD rats, the hypertrophy was correlated with BPV but not with blood pressure (BP) level. However, in SHR, hypertrophy was correlated with both BP and BPV level. The BP-lowering effect of ketanserin was comparable in both models, whereas its BPV-lowering effect was greater in SAD rats than in SHR. This hypersensitivity was associated with basal BPV level in SAD rats. Conclusions These results indicate that hypertension may be more important than high BPV in causing left ventricular hypertrophy, and that the aorta may be more sensitive to substantially high BPV.

Determinants of the White‐Coat Effect in Normotensives and Never‐Treated Mild Hypertensives

The prognostic significance of the white‐coat effect (WCE) is unclear. Knowledge of the predictors of the WCE may help illuminate the clinical significance of this phenomenon. The purpose of this study was to (i) compare characteristics of subjects demonstrating a WCE, those not demonstrating a WCE, and those demonstrating a reverse WCE and (ii) determine clinical features that may influence the size of the WCE. Forty‐one subjects with normotension or mild hypertension who had never been treated with antihypertensive medications were recruited for the study. All subjects underwent a battery of anthropometrical measurements and clinic blood pressure (BP) measurements. To calculate arterial compliance, impedance cardiography was used to measure resting stroke volume in each subject. All subjects performed a laboratory mental stress protocol to determine the size of the BP reactivity. Ambulatory blood pressure (ABP) profiles were studied in each subject with the use of an oscillometric ABP recorder. White‐coat effect was determined by subtracting the awake period of the ambulatory systolic blood pressure (SBP) from the clinical SBP. Subjects were grouped according to the size of their WCE. Those who showed a WCE of 5 mmHg and above were assigned to the WCE group; those who showed a WCE of between −5 and 5 mmHg were assigned to the no white coat effect (NWCE) group; those who exhibited a WCE of −5 mmHg and lower were assigned to the reverse white‐coat effect (RWCE) group. Subjects with a positive WCE had significantly higher body mass index (BMI) than those without a WCE and those with a RWCE. The WCE group had significantly higher clinic SBP and heart rate (HR) than the RWCE group. Arterial compliance was significantly lower in the WCE group as compared to the NWCE group and the RWCE group. The three groups had comparable ABP profiles. In terms of BP variability, the increase in SBP in response to mental stress did not differ among the three study groups nor did the 24‐hour and awake BP variability. For the sample as a whole, clinic HR and clinic‐ambulatory SBP difference were higher and arterial compliance were lower in women than in men. Furthermore, clinic SBP significantly correlated with the systolic WCE (r = 0.40, P = 0.009). When men and women were analyzed separately, the correlation between clinic SBP and the systolic WCE was significant in women (r = 0.63, P = 0.001) but not in men (P = 0.95). Multiple linear regression showed that sex (P = 0.013) and clinical SBP (P = 0.003) were the only two variables that significantly influenced the systolic WCE. These two variables together accounted for 29% of the variation in the systolic WCE. In conclusion sex and clinic BP are two major determinants of the WCE. The results of this study indicate that WCE is not related to higher stress reactivity or higher BP variability.

The importance of blood pressure variability in rat aortic and left ventricular hypertrophy produced by sinoaortic denervation.

The main objective was to examine the role of hemodynamics in rat aortic and left ventricular hypertrophy produced by sinoaortic denervation (SAD). Rats were examined at different times after SAD or sham operation (Sham). Hemodynamics were recorded continuously in conscious unrestrained rats. The time course of hemodynamic changes and cardiovascular hypertrophy was observed and linear regression analysis was performed to study the role of hemodynamics in SAD-induced aortic and left ventricular hypertrophy. Long-term mortality, water and food intake, and body weight were also determined after operation. High mortality (40%), dramatic reduction of water and food intake, and weight loss occurred within 1 week after SAD. Chronic SAD rats exhibited a marked increase in blood pressure variability (BPV), with no change in the average level of blood pressure (BP), as compared with the Sham control rats. Increased BPV was higher at 2 weeks (about threefold) than 16 weeks (about twofold) after SAD. Aortic hypertrophy existed in all three kinds of examined rats: 2-, 10- and 16-week SAD rats. Left ventricular hypertrophy was found only in 10- and 16-week SAD rats. Both aortic hypertrophy and left ventricular hypertrophy were significantly and positively correlated with BPV, but not with BP level. Persistent high BPV following SAD can lead to aortic and left ventricular hypertrophy. The aorta is more sensitive to increased BPV than the heart.

Mechanism of blood pressure and R-R variability: insights from ganglion blockade in humans.

Spontaneous blood pressure (BP) and R-R variability are used frequently as 'windows' into cardiovascular control mechanisms. However, the origin of these rhythmic fluctuations is not completely understood. In this study, with ganglion blockade, we evaluated the role of autonomic neural activity versus other 'non-neural' factors in the origin of BP and R-R variability in humans. Beat-to-beat BP, R-R interval and respiratory excursions were recorded in ten healthy subjects (aged 30 +/- 6 years) before and after ganglion blockade with trimethaphan. The spectral power of these variables was calculated in the very low (0.0078-0.05 Hz), low (0.05-0.15 Hz) and high (0.15-0.35 Hz) frequency ranges. The relationship between systolic BP and R-R variability was examined by cross-spectral analysis. After blockade, R-R variability was virtually abolished at all frequencies; however, respiration and high frequency BP variability remained unchanged. Very low and low frequency BP variability was reduced substantially by 84 and 69 %, respectively, but still persisted. Transfer function gain between systolic BP and R-R interval variability decreased by 92 and 88 % at low and high frequencies, respectively, while the phase changed from negative to positive values at the high frequencies. These data suggest that under supine resting conditions with spontaneous breathing: (1) R-R variability at all measured frequencies is predominantly controlled by autonomic neural activity; (2) BP variability at high frequencies (> 0.15 Hz) is mediated largely, if not exclusively, by mechanical effects of respiration on intrathoracic pressure and/or cardiac filling; (3) BP variability at very low and low frequencies (< 0.15 Hz) is probably mediated by both sympathetic nerve activity and intrinsic vasomotor rhythmicity; and (4) the dynamic relationship between BP and R-R variability as quantified by transfer function analysis is determined predominantly by autonomic neural activity rather than other, non-neural factors.

U-curve relationship between orthostatic blood pressure change and silent cerebrovascular disease in elderly hypertensives: orthostatic hypertension as a new cardiovascular risk factor.

The study investigated the clinical significance and mechanism of orthostatic blood pressure (BP) dysregulation in elderly hypertensive patients. Although orthostatic hypotension (OHYPO), often found in elderly hypertensive patients, has been recognized as a risk factor for syncope and cardiovascular disease, both the clinical significance and the mechanism of orthostatic hypertension (OHT) remain unclear. We performed a head-up tilting test and brain magnetic resonance imaging (MRI) in 241 elderly subjects with sustained hypertension as indicated by ambulatory BP monitoring. We classified the patients into an OHT group with orthostatic increase of systolic blood pressure (SBP) of >or=20 mm Hg (n = 26), an OHYPO group with orthostatic SBP decrease of >or=20 mm Hg (n = 23), and a normal group with neither of these two patterns (n = 192). Silent cerebral infarcts were more common in the OHT (3.4/person, p < 0.0001) and OHYPO groups (2.7/person, p = 0.04) than in the normal group (1.4/person). Morning SBP was higher in the OHT group than in the normal group (159 vs. 149 mm Hg, p = 0.007), while there were no significant differences of these ambulatory BPs between the two groups during other periods. The OHT (21 mm Hg, p < 0.0001) and OHYPO (20 mm Hg, p = 0.01) groups had higher BP variability (standard deviation of awake SBP) than the normal group (17 mm Hg). The associations between orthostatic BP change and silent cerebrovascular disease remained significant after controlling for confounders, including ambulatory BP. The orthostatic BP increase was selectively abolished by alpha-adrenergic blocking, indicating that alpha-adrenergic activity is the predominant pathophysiologic mechanism of OHT. Silent cerebrovascular disease is advanced in elderly hypertensives having OHT. Elderly hypertensives with OHT or OHYPO may have an elevated risk of developing hypertensive cerebrovascular disease.

Isolated systolic hypertension: cardiovascular risk and treatment benefits.

Pathogenetic factors: Age-related vascular and neurohumoral changes are important factors leading to the development of hypertension and particularly of ISH. Arterial compliance deteriorates because of structural and functional changes and increases is collagen, extracellular protein matrix, ground substance, elastin that occur with age. These changes create structural and mechanical alterations in the vessel intima and media. Calcium binds to the elastin, and undifferentiated muscle cells of the media proliferate and migrate through the elastic laminae to the intima. The proliferation of the connective tissue results in intimal thickening and fibrosis, increases the stiffness of the vessels with partial loss of contractility. Consequently, arterial compliance diminishes and the so called „windkessel function of the large arteries decreases. Pulse pressure and pulse wave velocity increase with an earlier reflection of pressure waves from the periphery, to a disproportionate increase in systolic blood pressure. Consequently, systolic blood pressure increases while diastolic blood pressure does not change or decreases particularly over the age of 60 (3, 4, 5).Cardiac output, stroke volume, intravascular volume, renal blood flow and plasma renin activity decrease, while left ventricular mass (prevalence of left ventricular hyperthrophy - LVH), circulating catecholamines, particularly noradrenaline, and total peripheral vascular resistance increase. Baroreceptor sensitivity to blood pressure changes also decreases causing a higher blood pressure variability.

Birth weight influences blood pressure values and variability in children and adolescents.

The objective of the present study was to assess the relationships between birth weight and the values and variability of ambulatory blood pressure. Six hundred thirty healthy children (369 girls) age 4 to 18 years (mean, 9.9 years) born at term after a normotensive pregnancy were included. The subjects were divided into 5 groups according to birth weight. For each subject, a 24-hour ambulatory blood pressure monitoring was performed according to the protocol designed. Average and variability (estimated as the standard deviation) of ambulatory blood pressure and heart rate were calculated separately for 24-hour, daytime, and nighttime periods. When values were adjusted for gender, current age, weight, and height, children with the lowest birth weights had the highest ambulatory blood pressure values and variability, whereas no differences in heart rate were observed. Multiple regression analysis showed that although current weight was the strongest predictor for 24-hour systolic blood pressure (P<0.001), there was also an independent and significant inverse relationship for birth weight (P<0.002) after controlling for gender, current age, and height. Likewise, birth weight was independently and inversely correlated with 24-hour systolic blood pressure variability (P<0.03). In conclusion, children who had lower birth weights tended to have not only the highest blood pressure values but also the highest blood pressure variability, independent of the increases in ambulatory blood pressure values. Knowing that high blood pressure variability is at least partially independent of blood pressure values, the importance of this variability on further blood pressure rises and/or on vascular damage later in life needs to be assessed in future studies.

The importance of 24-h blood pressure control

The primary goal of antihypertensive therapy is to restore blood pressure to normal levels and to prevent the complications associated with hypertension. In order to maximize these goals by improving patient compliance, clinical researchers have focused on developing antihypertensive agents that can be given once daily. These agents provide many advantages over multiple-dose daily therapies, but it should not be assumed that they are all equivalent in providing adequate blood pressure control over the full 24-h dosing interval. Ambulatory blood pressure monitoring has uncovered important differences in commonly used once-daily therapies and has provided additional insights into the cardiovascular risks associated with high blood pressure loads and blood pressure variability. In addition to ambulatory blood pressure monitoring data, the calculated trough:peak ratio provides useful information on an agent's ability to provide smooth and consistent blood pressure control. Using such assessments, it has been found that agents with a trough:peak ratio > or = 0.50 are better able to control blood pressure over the full 24h while maintaining natural circadian patterns. Ambulatory blood pressure monitoring studies assessing a recently introduced class of antihypertensive drugs, the angiotensin receptor blockers, have demonstrated 24-h efficacy with once-daily dosing, particularly with the newer agents.

Relationship between circadian blood pressure patterns and progression of early carotid atherosclerosis: A 3-year follow-up study.

Arterial hypertension is a major risk factor for cardiovascular damage. The results of several studies suggest that target organ damage is greater in hypertensive persons with high blood pressure variability. During 3.3 years of follow-up, we studied the relationship between circadian blood pressure changes and the progression of early carotid atherosclerosis in 286 patients aged >55 years. Blood pressure patterns were evaluated with a long-term blood pressure monitor, and the extent of atherosclerosis was measured as the intima-media wall thickness (IMT) of the common carotid artery. Patients were subdivided according to blood pressure variability. The progression of IMT was significantly greater in the patients with increased systolic blood pressure variability (0.11 mm/y [95% CI 0.09 to 0.14] versus 0.05 mm/y [0.03 to 0.08]; P:<0.005) even after adjustment for other risk factors. Multivariate regression analysis revealed the daytime systolic blood pressure variability to be the best predictor for the progression of IMT. Raised daytime systolic blood pressure variability (>15 mm Hg) is associated with an increased relative risk of the development of early atherosclerosis (3.9 [1.4 to 11.1]; P:<0.01) and of cardiovascular events (1.87 [1.08 to 3.20]; P:<0.01). The daytime systolic blood pressure variability is a strong predictor of early carotid atherosclerosis progression and is useful to define the risk-benefit ratio of therapeutic approaches.

Which Parameters of Beat-to-Beat Blood Pressure and Variability Best Predict Early Outcome After Acute Ischemic Stroke?

In hypertensive populations, increasing blood pressure (BP) levels and BP variability (BPV) are associated with a greater incidence of target organ damage. After stroke, elevated 24-hour BP levels predict a poor outcome, although it is uncertain whether shorter-length BP recordings assessing mean BP levels and BPV have a similar predictive role. The objectives of this study were to compare the different measures of beat-to-beat BP and BPV on outcome after acute ischemic stroke and assess whether these parameters were affected by stroke subtype. Ninety-two consecutive admissions with a CT-confirmed diagnosis of acute ischemic stroke were recruited, of whom 54 had cortical infarction, 29 subcortical, and 9 posterior circulation infarction. Casual and two 5-minute recordings of beat-to-beat BP (Finapres, Ohmeda) were made under standardized conditions within 72 hours of ictus, with mean BP levels taken as the average of this 10-minute recording and BPV as the standard deviation. Outcome was assessed at 30 days as dead/dependent or independent (Rankin </=2). The effects of BP, BPV, and stroke subtype on outcome were studied with the use of logistic regression. Stroke subjects were subsequently divided by BP quartiles and within each quartile into low- and high-variability groups; the influence of high BPV on outcome was also assessed. The odds ratio for death/dependency was significantly higher in cortical strokes compared with subcortical and posterior circulation strokes even after controlling for differences in BP and BPV (OR 4.19, P=0.002). Beat-to-beat systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP +/- SD) levels were higher in the dead/dependent group compared with the independent group (MAP 106+/-20.4 mm Hg vs 97+/-19.1 mm Hg, P<0.02), as was MAP variability: 6.1 (interquartile range 4.5 to 7.4 mm Hg) versus 4.9 (3.8 to 6.4 mm Hg, P=0.02). The odds ratio for a poor outcome was 1. 38 (P=0.014) for every 10-mm Hg increase in MAP and 1.32 (P=0.02) for every 1-mm Hg increase in MAP variability. Casual BP measurements had no prognostic significance. For the group as a whole when separated into BP quartiles, those with a high MAP and DBP but not SBP variability within each quartile had a worse prognosis compared with those with a low BPV. A poor outcome at 30 days after ischemic stroke was dependent on stroke subtype, beat-to-beat DBP, and MAP levels and variability. Important prognostic information can be readily obtained from a short period of noninvasive BP monitoring in the acute stroke patient. These findings have important implications, particularly regarding the use of hypotensive agents in the acute stroke period.

Lack of Association Between Blood Pressure Variability and Left Ventricular Mass in Essential Hypertension

Blood pressure (BP) variability could induce detrimental effects on left ventricular (LV) structure in hypertension. We investigated the association between short-term BP variability, assessed with 24-h noninvasive ambulatory BP monitoring, and LV mass at echocardiography in 1822 untreated subjects (953 men, 869 women) with essential hypertension (EH). The standard deviation (SD) of daytime and night-time systolic BP (SBP, r = 0.13/0.10; both P < .001), but not of diastolic BP, showed a weak correlation with LV mass. Because the SD of daytime SBP showed a direct association with average 24-h SBP (r = 0.27), subjects were ranked into quartiles of the distribution of 24-h SBP. For each quartile, the subjects with SD of daytime (and night-time) SBP below or above the median were classified at low or high BP variability. In both genders, subjects with high daytime SBP variability were older than those at low variability (both P < .01). Within each quartile, LV mass did not differ between the groups at low v those at high SBP variability. Overall, age-adjusted LV mass index was 115 and 115 g/m 2 in men at low and high daytime SBP variability ( P = .84), and 116 and 114 g/m 2 in men at low and high nighttime SBP variability ( P = .31). The corresponding values in women were 98 and 99 g/m 2 ( P = .53) and 98 and 99 g/m 2 ( P = .64). In conclusion, when the effects of age, gender, and average 24-h BP are taken into account, short-term BP variability assessed with noninvasive monitoring is unrelated to LV mass in subjects with EH.

Prognostic significance of blood pressure variability in essential hypertension

BACKGROUND: Blood pressure variability is a determinant of target organ damage in essential hypertension, but its independent prognostic significance has not yet been assessed in prospective studies of cardiovascular morbidity and mortality. OBJECTIVE: To assess the relationship between blood pressure variability, assessed non-invasively using 24 h ambulatory blood pressure monitoring and subsequent incidence of cardiovascular morbid events in persons with essential hypertension. DESIGN: Prospective observational study. PATIENTS AND METHODS: We followed for up to 8.6 years (mean 2.92) 1372 individuals with essential hypertension whose initial off-therapy diagnostic work-up included 24 h non-invasive ambulatory blood pressure monitoring. Those with a standard deviation of daytime or night-time blood pressure below or above the group mean were classified as having low or high blood pressure variability, respectively. One hundred and eighty-two participants underwent repeated ambulatory blood pressure monitoring and echocardiography during follow-up, 2.7 years later. RESULTS: Target organ damage score was greater in the participants with high variability of daytime (P = 0.004) and night-time (P = 0.011) systolic blood pressure than in those with low blood pressure variability. In those who underwent repeated echocardiography, for every quartile of baseline ambulatory blood pressure, left ventricular mass at follow-up was greater (all P < 0.05) in those with high baseline blood pressure variability than in those with low baseline variability. During follow-up there were 106 major cardiovascular morbid events. Event rate was 1.99 and 3.26 events per 100 patient-years, respectively, in participants with low and high variability of daytime systolic pressure and 1.98 and 3.38 events per 100 patient-years, respectively, in those with low and high variability of night-time systolic pressure (log-rank test: both P < 0.05). However, in a Cox multivariate analysis, the variability score for daytime and night-time systolic pressure failed to enter the model (age, diabetes mellitus, previous cardiovascular events and average night-time systolic pressure were independently associated with cardiovascular events). CONCLUSION: Increased blood pressure variability, assessed with non-invasive monitoring, is associated with a higher incidence of cardiovascular morbid complications of hypertension, but also with a higher blood pressure, older age and a higher prevalence of diabetes mellitus. Because of the relevant predictive effect of these associated factors, the adverse prognostic significance of increased blood pressure variability is no longer detectable in multivariate analysis.

Predictive Value of Blood Pressure Dipping and Swinging with Regard to Vascular Disease Risk

This prospective 6-year follow-up study of 176 patients treated with antihypertensive drugs investigates the extent to which an excessive circadian blood pressure (BP) amplitude (above the 90th percentile of gender- and age-matched peers) contributes to the risk of adverse vascular outcomes (coronary events, ischaemic stroke, renal failure and retinal bleeding). The results are compared with those based on the standard deviation (SD) of BP and a measure of ‘dipping’ (night-time vs daytime BP difference). A relative risk invariably larger than unity is found for ‘over-swingers’, that is for patients with an excessive circadian BP amplitude, and with one exception also for patients with an SD in the upper decile of the distribution. A classification of patients as dippers vs non-dippers does not detect any statistically significant difference in the incidence of adverse vascular outcomes in the sample investigated. A combination of ambulatory or manual BP monitoring and chronobiological data analysis and interpretation facilitates the diagnosis of an excessive circadian BP amplitude and can serve to guide the timing of treatment, not only for lowering BP but also to reduce BP variability — in particular, an excessive circadian amplitude. The latter condition, and an SD in the upper decile of the distribution, in this order, were associated with the largest increase in risk for ischaemic stroke and nephropathy. The excessive circadian BP amplitude constitutes an a priori no-win situation in the case of reliance upon conventional casual measurements, since in this condition, the BP is elevated only during part of the day. Thus, if casual BP measurements are taken when pressures are acceptable, the patient is likely to be left untreated, but would remain at a very high risk of developing vascular disease. Conversely, should the patient be examined when pressures are high, drugs may be prescribed that may lower the BP too much when given at the wrong time when, unknowingly, pressures are already spontaneously low and may barely suffice for perfusion. Since some antihypertensive drugs can reduce both BP and BP variability, further studies are required in order to examine whether treatment aimed at reducing an excessive circadian BP amplitude improves prognosis in subjects with high BP variability.

Cardiovascular effects of cigarette smoking.

The risk of cardiovascular morbidity and mortality is greatly affected by cigarette smoking. In order to study the pressor response to smoking, 10 normotensive and 10 mild or moderate essential-hypertensive smokers (> 20 cigarettes daily) were compared with 2 comparable groups of non-smokers. All subjects were asked to smoke 4 cigarettes during 1 h; blood pressure (BP) and heart rate (HR) were monitored beat-to-beat by a non-invasive device (Finapres Ohmeda) during the smoking period and during the immediately preceding non-smoking hour. Furthermore, all subjects underwent 24-hour ambulatory BP monitoring. In all groups, each cigarette induced a similar and statistically significant increase from baseline for both BP and HR. The recovery from the marked rise in BP and HR was very slow so that in the smoking hours BP and HR were persistently higher than in non-smoking hours; there were no statistically significant differences between the four groups. During 24-hour ambulatory monitoring both normo- and hypertensive smokers showed higher BP values and higher BP variability in comparison with the respective non-smokers' group. In conclusion, smoking habits were associated with a persistent increase in BP in each group we studied, possibly contributing to a smoking-related cardiovascular risk.