Diurnal Blood Pressure Variation Research Articles

Genes Influencing Circadian Differences in Blood Pressure in Hypertensive Mice

Essential hypertension is a common multifactorial heritable condition in which increased sympathetic outflow from the central nervous system is involved in the elevation in blood pressure (BP), as well as the exaggerated morning surge in BP that is a risk factor for myocardial infarction and stroke in hypertensive patients. The Schlager BPH/2J mouse is a genetic model of hypertension in which increased sympathetic outflow from the hypothalamus has an important etiological role in the elevation of BP. Schlager hypertensive mice exhibit a large variation in BP between the active and inactive periods of the day, and also show a morning surge in BP. To investigate the genes responsible for the circadian variation in BP in hypertension, hypothalamic tissue was collected from BPH/2J and normotensive BPN/3J mice at the ‘peak’ (n = 12) and ‘trough’ (n = 6) of diurnal BP. Using Affymetrix GeneChip® Mouse Gene 1.0 ST Arrays, validation by quantitative real-time PCR and a statistical method that adjusted for clock genes, we identified 212 hypothalamic genes whose expression differed between ‘peak’ and ‘trough’ BP in the hypertensive strain. These included genes with known roles in BP regulation, such as vasopressin, oxytocin and thyrotropin releasing hormone, as well as genes not recognized previously as regulators of BP, including chemokine (C-C motif) ligand 19, hypocretin and zinc finger and BTB domain containing 16. Gene ontology analysis showed an enrichment of terms for inflammatory response, mitochondrial proton-transporting ATP synthase complex, structural constituent of ribosome, amongst others. In conclusion, we have identified genes whose expression differs between the peak and trough of 24-hour circadian BP in BPH/2J mice, pointing to mechanisms responsible for diurnal variation in BP. The findings may assist in the elucidation of the mechanism for the morning surge in BP in essential hypertension.

Relation Between Circadian Rhythm of Blood Pressure and Serum Uric Acid and Body Mass Index

OBJECTIVE: The effect of uric acid and obesity on diurnal blood pressure variation in hypertensive patients is unknown. We aimed to investigate the specific relationship between uric acid, obesity and nocturnal dipping status essential hypertensive patients with normal renal function. MATEriAl and METhOdS: Two hundred sixty-nine patients with newly diagnosed essential hypertension or on antihypertensive treatment underwent 24-hour ambulatory blood pressure monitoring, biochemistry analysis and urine testing. rESulTS: Patients were classified as either dippers (108 patients, 40%) or nondippers (161 patients, 60%). Uric acid levels were higher in nondippers than in dippers (6.5 +/1.2 mg/dL vs. 5.5 +/1.1 mg/dL, p==0.001). In the same line, body mass index is significantly higher in nondippers compared to dippers (29.9±3.9 kg/m2 vs. 27.8±3.9kg/m2, p=0.01). CONCluSION: This study demonstrates that increased serum uric acid levels and body mass index are associated with nondipping blood pressure patterns in patients with essential hypertension. kEY wOrdS: Hypertension, Obesity, Uric acid, Blood pressure, Non-dipping doi: 10.5262/tndt.2011.2001.06

Orthostatic Hypertension

See related article, pp 167–173 Orthostatic hypertension (OHT) is beneath the radar of many health care professionals. In the clinic, it is generally both unexpected and counterintuitive. After recheck, it may sometimes regress toward the mean. However, at other times the OHT can be dramatic and persistent. Nevertheless, our knowledge about its causes and significance remains circumscribed. It is in many ways the last hemodynamic frontier. Recently, there has been increasing interest in OHT and its possible consequences on health. The spectrum of degree and clinical context of OHT is very broad.1 In some cases, it can be a dramatic physical manifestation of 50 mm Hg or more in a disorder such as baroreflex failure. In other situations, it may only be an incidental physical finding. OHT is usually defined as an increase in blood pressure with upright posture or tilt, but precise criteria have not been established. Furthermore, few studies have entailed direct measurement of blood pressure in people with OHT. Such measurements would more faithfully reflect intraarterial pressure and would avoid the introduction of potential artifacts. Sphygmomanometers can underestimate blood pressure when it is perturbed by pressor reflexes, such as those engaged by upright posture, or if it is increased by pressor agents. Therefore, the magnitude of the blood pressure increase after standing might be even larger than is generally reported in patients with OHT. OHT has been long recognized. Some of the most thoughtful early studies were conducted by David Streeten …

Comparison of Blood Pressure Control and Left Ventricular Hypertrophy in Patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) and Automated Peritoneal Dialysis (APD).

This study aimed to investigate the influence of different peritoneal dialysis regimens on blood pressure control, the diurnal pattern of blood pressure and left ventricular hypertrophy in patients on peritoneal dialysis. Forty-four patients undergoing peritoneal dialysis were enrolled into the study. Patients were treated with different regimens of peritoneal dialysis: 26 patients on continuous ambulatory peritoneal dialysis (CAPD) and 18 patients on automated peritoneal dialysis (APD). All patients performed 24-hour ambulatory blood pressure monitoring (ABPM) and echocardiography. Echocardiography was performed for measurement of cardiac parameters and calculation of left ventricular mass index (LVMI). There were no significant differences in average of systolic and diastolic blood pressure during 24-hour, daytime, and nighttime between CAPD and APD groups. There were no significant differences in diurnal variation of blood pressure, systolic and diastolic blood pressure load, and LVMI between CAPD and APD groups. LVMI was associated with 24 hour systolic blood pressure load (r = 0.311, P < 0.05) and daytime systolic blood pressure load (r = 0.360, P < 0.05). In conclusion, this study found that there is no difference in blood pressure control, diurnal variation of blood pressure and left ventricular hypertrophy between CAPD and APD patients. The different peritoneal dialysis regimens might not influence blood pressure control and diurnal variation of blood pressure in patients on peritoneal dialysis.

Benefits of once-daily therapies in the treatment of hypertension

In patients with hypertension, 24-hour blood pressure control is the major therapeutic goal. The number of daily doses is one characteristic of an antihypertensive agent that may affect the adequacy of 24-hour control. One measure of therapeutic coverage is the 24-hour trough-to-peak ratio, which determines the suitability of an agent for once-daily administration. The closer an agent is to a 100% trough-to-peak ratio, the more uniform the 24-hour coverage and therefore blood pressure control. High trough-to-peak ratio, long-acting antihypertensive medications lower blood pressure more gradually, which reduces the likelihood of adverse events attributable to abrupt drug action that occurs with shorter-acting agents. In hypertension, the natural diurnal variation of blood pressure may be altered, including elevated nighttime pressures. An optimal once-daily hypertension therapy would not only lower blood pressure but also normalize any blunted circadian variations in blood pressure. The benefits of once-daily agents with sustained therapeutic coverage may also be explained, in part, by increased patient adherence to simpler regimens as well as lower loss of blood pressure control during virtually inevitable intermittent noncompliance. Studies have demonstrated that once-daily antihypertensive agents have the highest adherence compared with twice-daily or multiple daily doses, including greater adherence to the prescribed timing of doses.

Diurnal blood pressure variation and related behavioral factors

Blood pressure (BP) varies according to many internal and external factors, and behavioral factors have an important role in diurnal BP variation. BP rises sharply on waking in the morning and falls during sleep at night, although it varies throughout the day and night. These changes in BP are closely related to mental and physical activities, and the sympathetic nervous system mainly contributes to the diurnal variation in BP. Other behavioral factors, such as food consumption and obesity, dietary intake of sodium, drinking and smoking habits, consumption of coffee and tea, and bathing, also affect the diurnal variation in BP. Alterations in diurnal BP variation due to behavioral factors are frequently seen in patients with hypertension and can be classified as morning hypertension, daytime hypertension and nighttime hypertension. Appropriate lifestyle modifications may normalize or improve both the level and rhythm of BP in these patients.

Diurnal blood pressure variation, risk categories and antihypertensive treatment

Ambulatory blood pressure (BP) monitoring is a useful tool aiding diagnostic and management decisions in patients with hypertension. Diurnal BP variation or circadian rhythm adds prognostic value to the absolute BP elevation. The Spanish ABPM Registry has collected information from >30 000 treated hypertensive patients attended by either primary care physicians or referral specialists. The analysis of BP diurnal variation has allowed the conclusion that nocturnal BP decline is related to the level of risk. Patients with blunted nocturnal dip frequently belong to high- or very high-risk categories and specifically are often older, obese, diabetics or with overt cardiovascular or renal disease. With respect to treatment, the non-dipper profile is more often observed in patients receiving several antihypertensive drug agents, but it does not correlate with the time of drug administration. Among patients receiving only one drug, non-dihydropyridine calcium channel blockers and alpha-blockers are associated with less nocturnal BP decline than other antihypertensive drug classes, even after adjusting for the level of risk.

Blood Pressure Variability

A series of articles1–4⇓⇓⇓ published recently in The Lancet and Lancet Neurology raise an interesting issue that has implications for both the clinical management of hypertension and future research in hypertension, particularly in the development and use of different classes of blood pressure (BP)–lowering drugs. These studies, which were led by Peter Rothwell at the John Radcliffe Hospital in Oxford, United Kingdom, suggest that, whereas there is undoubted and well-proven benefit in the current practice of reducing mean BP to prevent cardiovascular events, there may be additional benefit in also reducing BP variability (BPV), especially to prevent stroke. The studies suggest, moreover, that different classes of drugs are superior to others in reducing BPV (calcium channel blockers being best and the β-blocker atenolol being worst). However, these articles, by virtue of their sheer volume (≈50 pages of printed text and many pages of supplementary web appendix data), could overwhelm all but the most stoic readers, and misinterpretation of the data could lead to confusion and have an adverse effect on clinical practice. It is important, therefore, to assess the scientific reality and determine how attention to BPV might benefit patients with hypertension. In the first analysis, systolic BPV between visits and maximum BP reached in 4 cohorts of patients with previous transient ischemic attacks were strong predictors for subsequent stroke.1 In treated hypertensive patients in the Anglo-Scandinavian Cardiac Outcome Trial-Blood Pressure Lowering Arm systolic BPV between visits was also a strong predictor of stroke and coronary events independent of mean clinic or ambulatory BP measurement (ABPM). BPV on ABPM was a weaker predictor overall but was related to visit-to-visit variability. Traditional measures of variability, such as SD and coefficient of variation (CV), were used in these analyses, but one of the problems encountered in the …

Assessment of the relationship between N-terminal pro-BNP levels and ambulatory blood pressure monitoring data in hypertensive patients

Objective. To study the association between N-terminal pro-brain natriuretic peptide (N-proBNP) and diurnal blood pressure profi le in hypertensive patients. Methods and results. A total of 40 patients were included in the study. Peptide concentration increased with age, correlated positively with diurnal pulse blood pressure variability and its mean cumulative value over night period in hypertensive patients. In patients with high plasma concentrations of peptide its level positively correlates with pulse blood pressure value and its variability and mean cumulative value over day period. In this subgroup signifi cant positive correlation between N-proBNP levels and systolic blood pressure over day period was found.

The Relationship Between Dipping Profile in Blood Pressure and Neurologic Deficit in Early Acute Ischemic Stroke

Blood pressure (BP) in healthy individuals exhibits a diurnal variation, with a nighttime dip of 10%-20%. A persistently high nighttime BP is associated with increased cardiovascular morbidity. The effects of diurnal BP variations on the neurologic deficit in acute stroke at presentation and in the first few weeks poststroke are unclear. We hypothesized that persistently elevated BP results in poor outcome. Patients with an acute ischemic stroke presenting within 48 hours of onset underwent 24-hour ambulatory monitoring of systolic, diastolic, and mean BP. There were a total of 35 patients (16 males; mean age, 74 ± 14 years). The percentage change between mean day and night BP classified patients into dippers (> 10% change), nondippers (0-10% change), or reverse-dippers (< 0% change). The Scandinavian Stroke Scale (SSS) and the National Institute of Health Stroke Scale (NIHSS) were assessed on admission, at week 1, and at week 3. The relationship between neurologic score and dipping classification was analyzed using analysis of variance and analysis of covariance, with age and baseline score as covariates. Based on both the SSS and NIHSS, the reverse-dippers had the lowest neurologic scores at baseline, week 1, and week 3, followed by the nondippers. The dippers performed the best in comparison. No significant differences in demographics and/or other BP characteristics among the groups that could account for these differences in outcome were noted. A reverse-dipping profile in diastolic BP was associated with poor neurologic state at baseline and weeks 1 and 3 compared with both dippers and nondippers.

Diurnal blood pressure variation and cardiovascular prognosis in a community-based study of Ohasama, Japan

The introduction of 24-h ambulatory blood pressure (BP) monitoring has enabled BP evaluations at specific times of the day. Associations between diurnal BP variation and cardiovascular prognosis have been investigated in the Ohasama study, which is an epidemiological survey of hypertension using ambulatory and home BP monitoring that has been ongoing since 1985 in the general population of Ohasama, a town located in northern Japan. A diminished nocturnal decline in systolic BP was associated with a greater common carotid intima-media thickness as well as a higher risk of cardiovascular morbidity and mortality, especially the risk for cerebral infarction. The consumption of large amounts of alcohol was associated with a higher morning pressor surge. A large nocturnal decline in BP and a large morning pressor surge were both associated with a risk of cerebral hemorrhage. Ambulatory BP monitoring provides not only static, but also dynamic information about BP that should be considered to ensure effective management of hypertension and cardiovascular diseases.

From pioneering to implementing automated blood pressure measurement in clinical practice: Thomas Pickering's legacy

Thomas G. Pickering spent most of his scientific career in carrying out research on clinical hypertension and blood pressure (BP) measurement. In our review of Pickering's seminal work, we first focused on white-coat hypertension and masked hypertension, two terms that he had introduced. Next, we highlighted the early publications of Pickering on diurnal BP variability and on the clinical application of self-measured BP. Pickering's work inspired many investigators worldwide and constituted a solid basis for further research. Pickering's original ideas led to algorithms for risk stratification involving white-coat hypertension and masked hypertension, diurnal BP variability, and self-measured BP. Recent studies validated Pickering's observations in terms of cardiovascular outcome and bridged the path from concept to application in clinical practice.

Differential sympathetic activation and blunted cardiovascular diurnal rhythms in a mouse model of hypertrophic cardiomyopathy

Mutations in the sarcomeric protein α‐tropomyosin (αTM) cause hypertrophic cardiomyopathy (HCM) in humans and mice. We recently reported that mice with HCM, induced by cardiac‐targeted transgenic expression of mutated αTM (Glu180Gly), exhibit myocyte disarray, cardiac fibrosis, left ventricular (LV) dysfunction, and decreased baroreflex sensitivity [Hypertension 2009]. In this study, we tested the hypothesis that sympathetic activity is increased and diurnal variations in heart rate (HR) and blood pressure (BP) are blunted in HCM mice. Cardiac function, BP, HR, locomotor activity and electrocardiograms were measured by echocardiography and telemetry, respectively, in 12–15wk old wild‐type (WT) and HCM mice (n=4, per group). LV ejection fraction and mean BP were significantly reduced in HCM mice. Diurnal changes (night‐day) in BP and HR were markedly attenuated in HCM, despite preserved diurnal changes in locomotor activity (Table). Interestingly, cardiac sympathetic tone (HR response to β‐blocker propranolol) was markedly increased in HCM mice, while vasomotor sympathetic tone (BP response to ganglionic blocker chlorisondamine) was reduced (Table). Furthermore, extensive thrombus in enlarged atria and cardiac arrhythmias were observed in HCM mice. *P&lt;0.05, HCM vs. WT mice WT HCM Diurnal BP (ΔmmHg) 23±3 10±2 * Diurnal HR (Δbpm) 76±11 30±14 * Diurnal Activity (Δcounts/min) 3.9±0.9 6.3±0.8 Cardiac Sympathetic Tone (Δbpm ) −109±12 −200±9 * Vasomotor Sympathetic Tone (ΔmmHg) −60±2 −31±4 * We conclude that cardiovascular diurnal rhythms are blunted and cardiac sympathetic activity is increased in HCM mice. We speculate that altered activity of cardiac afferents innervating the pathologic heart may trigger decreased vasomotor and increased cardiac sympathetic tone and arrhythmias in HCM.

Psychosocial determinants of hypertension: laboratory and field models

Tom Pickering had a profound influence on the study of biobehavioral factors in the development, diagnosis, and misdiagnosis of hypertension. His contributions influenced several avenues of research, including ecological momentary assessments of the sources and causes of diurnal blood pressure variation, the evaluation and impact of job strain on blood pressure and cardiovascular disease, and the role of blood pressure reactivity and recovery to acute stress in hypertension development. This overview approaches these topics by examining the seminal role of the work by Tom et al. in the current understanding of how biobehavioral factors contribute to hypertension.

Diurnal blood pressure variation and sympathetic activity

Blood pressure changes occurring over a 24-h period are under behavioral, humoral and reflex regulation. The sympathetic nervous system modulates blood pressure variation by affecting cardiac output and peripheral vascular resistance. This paper reviews evidence for the relationship between adrenergic neural drive and blood pressure as measured by direct and indirect approaches. This paper also reviews the sympathetic activity associated with increased 'in-office' and 'out-of-office' blood pressure, that is, the white-coat and the masked-hypertensive states. Finally, this paper examines altered neuroadrenergic influences on nocturnal blood pressure reduction and blood pressure variability.

Hypertension and Dementia

Although hypertension is well known as a cause of vascular dementia (VaD), recent findings highlight the role of hypertension in the pathogenesis of Alzheimer's disease (AD) as well as mild cognitive impairment (MCI). Recent studies have shown that disruption of diurnal blood pressure (BP) variation is closely associated with cognitive impairment via injury of the small cerebral arteries indicating that long-standing hypertension constitutes a risk of brain matter atrophy or white matter lesions (WMLs). In several clinical trials, BP-lowering with antihypertensive agents was suggested to reduce the risk of dementia or cognitive decline. This review paper focuses on the role of hypertension as a risk factor for cognitive impairment, and summarizes current knowledge on the relationships between ambulatory BP monitoring (ABPM) and cognitive impairment. Finally, an overview of the impact of antihypertensive therapy on dementia prevention is provided.

Flash Pulmonary Edema

Flash pulmonary edema (FPE) is a general clinical term used to describe a particularly dramatic form of acute decompensated heart failure. Well-established risk factors for heart failure such as hypertension, coronary ischemia, valvular heart disease, and diastolic dysfunction are associated with acute decompensated heart failure as well as with FPE. However, endothelial dysfunction possibly secondary to an excessive activity of renin-angiotensin-aldosterone system, impaired nitric oxide synthesis, increased endothelin levels, and/or excessive circulating catecholamines may cause excessive pulmonary capillary permeability and facilitate FPE formation. Renal artery stenosis particularly when bilateral has been identified has a common cause of FPE. Lack of diurnal variation in blood pressure and a widened pulse pressure have been identified as risk factors for FPE. This review is an attempt to delineate clinical and pathopysiological mechanisms responsible for FPE and to distinguish pathophysiologic, clinical, and therapeutic aspects of FPE from those of acute decompensated heart failure.

Potential renovascular hypertension, space missions, and the role of magnesium

Space flight (SF) and dust inhalation in habitats cause hypertension whereas in SF (alone) there is no consistent hypertension but reduced diurnal blood pressure (BP) variation instead. Current pharmaceutical subcutaneous delivery systems are inadequate and there is impairment in the absorption, metabolism, excretion, and deterioration of some pharmaceuticals. Data obtained from the National Aeronautics and Space Administration through the Freedom of Information Act shows that Irwin returned from his 12-day Apollo 15 mission in 1971 and was administered a bicycle stress test. With just three minutes of exercise, his BP was >275/125 mm Hg (heart rate of only 130 beats per minute). There was no acute renal insult. Irwin's apparent spontaneous remission is suggested to be related to the increase of a protective vasodilator, and his atrial natriuretic peptide (ANP) reduced with SF because of reduced plasma volume. With invariable malabsorption and loss of bone/muscle storage sites, there are significant (P < 0.0001) reductions of magnesium (Mg) required for ANP synthesis and release. Reductions of Mg and ANP can trigger pronounced angiotensin (200%), endothelin, and catecholamine elevations (clearly shown in recent years) and vicious cycles between the latter and Mg deficits. There is proteinuria, elevated creatinine, and reduced renal concentrating ability with the potential for progressive inflammatory and oxidative stress-induced renal disease and hypertension with vicious cycles. After SF, animals show myocardial endothelial injuries and increased vascular resistance of extremities in humans. Even without dust, hypertension might eventually develop from renovascular hypertension during very long missions. Without sufficient endothelial protection from pharmaceuticals, a comprehensive gene research program should begin now.

Non-dipper is a determinant of inappropriately high LV mass in essential hypertension patients

Background Inappropriately high LV mass (iLVM) other than LV hypertrophy is also known to be related to the cardiovascular prognosis. But the underlying pathogenic mechanisms are not fully understood. Nocturnal blood pressure (BP) was hypothesized to be related to iLVM due to the potentially undetected pressure overload or diurnal blood pressure variation. Methods 255 hypertensive patients regardless of hypertension medications were analyzed whom both ambulatory blood pressure monitoring and echocardiographic LV data were available.

Ambulatory blood pressure monitoring in stroke survivors: Do we really control our patients?

Background We aim to evaluate prospectively the long-term changes of blood pressure (BP) in stroke survivors using ambulatory BP monitoring (ABPM) and compare them with the clinic conventional measurements. Methods We studied 101 patients who were admitted within 24 h after stroke onset. To study the circadian rhythm of BP a continuous BP monitor (Spacelab 90207) was used. After six and twelve months follow-up a new ABPM was undertaken. Data were analyzed using the SSPS 12.0. Results We studied 62 males and 39 females, mean age: 70.9 ± 10.7 years. We included 88 ischemic strokes and 13 hemorrhagic strokes. In the acute phase mean 24 h BPs were 136 ± 19/78.6 ± 11.4 mm Hg. The normal diurnal variation in BP was abolished in 88 (87.1%) patients. After six months, 74 patients were assessed. Mean office readings were 137.5 ± 23.8/76.4 ± 11.4 mm Hg, and high systolic BPs and diastolic BPs were found in 37% and 11% of the subjects respectively. ABPM revealed a mean BP of 118.5 ± 20.1/70.3 ± 8.6 ( p < 0.0001). In 57 (76.9%), the normal BP pattern remained abolished ( p < 0.001). After one year, 63 patients were assessed. Mean office readings were 130.8 ± 26.3/77.6 ± 9.3 mm Hg, and high systolic BPs and diastolic BPs were found in 23.8% and 10% of the subjects respectively. Mean 24 h BPs were 117 ± 12.5/69.7 ± 7.2 ( p < 0.001). The normal diurnal variation in BP was now abolished in 47 (74.6%) patients ( p < 0.001). Conclusion Survivors of stroke, both hypertensive and non-hypertensive patients, present a chronic disruption of circadian rhythm of BP. Conventional clinical recordings are an unreliable method of controlling these patients and ABPM should be routinely performed in this population.