Is There a Role for the Incretin System in Blood Pressure Regulation?

Incretin-based therapies are now well established for diabetes management and are among the frontline agents for control of hyperglycemia. In addition to their antihyperglycemic effects, evidence is emerging on the role of these agents on blood pressure regulation, cardioprotective and renoprotective properties. Because of the pleiotropic nature of these affects, these agents could offer significant benefits with regards to the cardiorenal metabolic complications that are part of the diabetes and obesity epidemic in the United States and worldwide. We review the various known mechanisms or pathways by which incretin based therapy exerts its regulation of blood pressure with emphasis on novel mechanisms such as inflammation/immunomodulation and oxidative stress.     

Risers and Extreme‐Dippers of Nocturnal Blood Pressure in Hypertension: Antihypertensive Strategy for Nocturnal Blood Pressure

There is increasing evidence that disruption of diurnal blood pressure (BP) variation is a risk factor for hypertensive target organ damage and cardiovascular events. Especially, the risers (extreme non‐dippers), who exhibit a nocturnal BP increase compared with daytime BP, have the worst cardiovascular prognosis, both for stroke and cardiac events. On the other hand, extreme‐dippers (with marked nocturnal BP falls) are at risk for non‐fatal ischemic stroke and silent myocardial ischemia, particularly extreme‐dippers complicated with atherosclerotic arterial stenosis and excessive BP reduction due to antihypertensive medication. Extreme‐dipping status of nocturnal BP is closely associated with excessive morning BP surge and orthostatic hypertension. Hypertensive patients who have these conditions and exhibit marked BP variations are likely to have silent cerebral infarct and to be at high‐risk with regard to future stroke. Individualized antihypertensive medication targeting disrupted diurnal BP variation might thus be beneficial for such high‐risk hypertensive patients.     

Dietary Factors and Blood Pressure of Tibetan Population in Lhasa

随机抽取拉萨市４９～５４岁年龄组藏族居民１０８人，测定血压、体重指数，收集２４ｈ尿标本，测尿中钠、钾、钙、镁、尿素氮及氨基酸，采血测定总胆固醇、各型脂肪酸及电解质等指标，探讨拉萨藏族人群的饮食因素与血压水平的关系。研究设计及方法按ＣＡＲＤＩＡＣ研究方案实施，生化指标由ＣＡＲＤＩＡＣ中心统一分析。结果显示。收缩压、舒张压、高血压患病率、尿钠及钠／钾比等变量均升高；尿钙、镁、牛磺酸、１－甲基组氨酸等变量均降低。尿镁、３－甲基组氨酸、总胆固醇等分别与收缩压及舒张压呈显著负相关；血清豆蔻酸与收缩压及舒张压呈显著正相关。上述诸因子进入多元回归方程，提示拉萨藏族人群饮食中的多种营养素摄取失调与血压水平及高血压患病率均高可能有一定的关系。     

Relationship of Hypertension,Blood Pressure,and Blood Pressure Control With White Matter Abnormalities in the Women’s Health Initiative Memory Study (WHIMS)—MRI Trial

J Clin Hypertens (Greenwich). 2010;12:203–212. ^©2010 Wiley Periodicals, Inc. This paper evaluates the relationship of blood pressure (BP) levels at Women’s Health Initiative (WHI) baseline, treatment of hypertension, and white matter abnormalities among women in conjugated equine estrogen (CEE) and medroxyprogesterone acetate and CEE-alone arms. The WHI Memory Study—Magnetic Resonance Imaging (WHIMS-MRI) trial scanned 1424 participants. BP levels at baseline were significantly positively related to abnormal white matter lesion (WML) volumes. Participants treated for hypertension but who had BP ≥140/90 mm Hg had the greatest amount of WML volumes. Women with untreated BP ≥140/90 mm Hg had intermediate WML volumes. Abnormal WML volumes were related to hypertension in most areas of the brain and were greater in the frontal lobe than in the occipital, parietal, or temporal lobes. Level of BP at baseline was strongly related to amount of WML volumes. The results of the study reinforce the relationship of hypertension and BP control and white matter abnormalities in the brain. The evidence to date supports tight control of BP levels, especially beginning at younger and middle age as a possible and perhaps only way to prevent dementia.     

Blood Pressure Measurement: Sitting and Standing?

Prior to discussing some thoughts about positional changes in blood pressure, I'd like to comment on the me- asurement of blood pressure.It is rare for a medical student, a resident-in-training, a cardiovascular fellow-in-training, or even a practicing or academic cardiologist to take the patient's blood pressure. I would even go so far as to say that it is uncommon for a registered nurse to measure blood pressure. Copyright (c) 2008 Wiley Periodicals, Inc.     

Ambulatory or Home Measurement of Blood Pressure?

Ambulatory blood pressure monitoring (ABPM) and home blood pressure (HBPM) monitoring have been shown to be superior to conventional measurement of blood pressure in terms of reproducibility, relationship to the impact of high blood pressure on target organs, and the prediction of cardiovascular events. Nevertheless, these 2 techniques have yet to find their place in the diagnosis of hypertension and during evaluation of the efficacy of antihypertensive treatment. Although these 2 methods do not give identical results in approximately 20% of cases, their diagnostic performance and prognostic value are quite comparable. Although ABPM remains a valuable tool in clinical research, its utilization in routine clinical practice is limited by cost and availability. HBPM is increasingly employed for informed and well-managed patients, and it can help to improve control of the patient's blood pressure. Physicians involved in the management of hypertensive patients should be aware of its value in order to assist patients in their care.     

Which Measurement of Blood Pressure Is More Associated With Albuminuria in Patients With Type 2 Diabetes: Central Blood Pressure or Peripheral Blood Pressure?

The aim of this study was to investigate whether central systolic blood pressure (SBP) was associated with albuminuria, defined as urinary albumin excretion (UAE) ≥30 mg/g creatinine, and, if so, whether the relationship of central SBP with albuminuria was stronger than that of peripheral SBP in patients with type 2 diabetes. The authors performed a cross‐sectional study in 294 outpatients with type 2 diabetes. The relationship between peripheral SBP or central SBP and UAE using regression analysis was evaluated, and the odds ratios of peripheral SBP or central SBP were calculated to identify albuminuria using logistic regression model. Moreover, the area under the receiver operating characteristic curve (AUC) of central SBP was compared with that of peripheral SBP to identify albuminuria. Multiple regression analysis demonstrated that peripheral SBP (β=0.255, P<.0001) or central SBP (r=0.227, P<.0001) was associated with UAE. Multiple logistic regression analysis demonstrated that peripheral SBP (odds ratio, 1.029; 95% confidence interval, 1.016–1.043) or central SBP (odds ratio, 1.022; 95% confidence interval, 1.011–1.034) was associated with an increased odds of albuminuria. In addition, AUC of peripheral SBP was significantly greater than that of central SBP to identify albuminuria (P=0.035). Peripheral SBP is superior to central SBP in identifying albuminuria, although both peripheral and central SBP are associated with UAE in patients with type 2 diabetes.     

Effect of Functional Bread Rich in Potassium, γ-Aminobutyric Acid and Angiotensin-Converting Enzyme Inhibitors on Blood Pressure,Glucose Metabolism and Endothelial Function: A Double-blind Randomized Crossover Clinical Trial

Because it has been suggested that food rich in γ-aminobutyric acid (GABA) or angiotensin-converting enzyme inhibitor (ACEI) peptides have beneficial effects on blood pressure (BP) and other cardiovascular risk factors, we tested the effects of low-sodium bread, but rich in potassium, GABA, and ACEI peptides on 24-hour BP, glucose metabolism, and endothelial function.A randomized, double-blind, crossover trial was conducted in 30 patients with pre or mild-to-moderate hypertension, comparing three 4-week nutritional interventions separated by 2-week washout periods. Patients were randomly assigned to consume 120 g/day of 1 of the 3 types of bread for each nutritional intervention: conventional wheat bread (CB), low-sodium wheat bread enriched in potassium (LSB), and low-sodium wheat bread rich in potassium, GABA, and ACEI peptides (LSB + G). For each period, 24-hour BP measurements, in vivo endothelial function, and biochemical samples were obtained.After LSB + G consumption, 24-hour ambulatory BP underwent a nonsignificant greater reduction than after the consumption of CB and LSB (0.26 mm Hg in systolic BP and −0.63 mm Hg in diastolic BP for CB; −0.71 mm Hg in systolic BP and −1.08 mm Hg in diastolic BP for LSB; and −0.75 mm Hg in systolic BP and −2.12 mm Hg in diastolic BP for LSB + G, respectively). Diastolic BP at rest decreased significantly during the LSB + G intervention, although there were no significant differences in changes between interventions. There were no significant differences between interventions in terms of changes in in vivo endothelial function, glucose metabolism, and peripheral inflammatory parameters.Compared with the consumption of CB or LSB, no greater beneficial effects on 24-hour BP, endothelial function, or glucose metabolism were demonstrated after the consumption of LSB + G in a population with pre or mild-to-moderate hypertension. Further studies are warranted to clarify the effect of GABA on BP, preferably using a specific design for noninferiority trials and ambulatory BP monitoring as a measure of BP.This study was registered at Current Controlled Trials as ISRCTN31436822     

Blood Pressure Levels and Stroke: J-curve Phenomenon?

The blood pressure J-curve discussion has been ongoing for more than 30 years, yet there are still questions in need of definitive answers. On one hand, existing antihypertensive therapy studies provide strong evidence for J-curve-shaped relationships between both diastolic and systolic blood pressure and primary outcomes in the general hypertensive patient population, as well as in high-risk populations, including subjects with coronary artery disease, diabetes mellitus, left ventricular hypertrophy, and the elderly. On the other hand, we have very limited data on the relationship between systolic and diastolic blood pressure and stroke prevention. Moreover, it seems that this outcome is more a case of “the lower the better.” Further large, well-designed studies are necessary in order to clarify this issue, especially as existing available studies are observational, and randomized trials either did not have or lost statistical power and were thus inconclusive.     

The Effect of Measuring Ambulatory Blood Pressure on Nighttime Sleep and Daytime Activity—Implications for Dipping

Background and objectives: Ambulatory blood pressure (BP) monitoring is commonly used to assess the circadian pattern of BP. Circadian BP pattern is influenced by physical activity and sleep cycle. The effect of BP monitoring itself on the level of physical activity and sleep remains unknown. If BP monitoring affects these parameters, then monitoring itself may influence the circadian BP pattern.Design, setting, participants, & measurements: To assess the effect of ambulatory BP monitoring on sleep duration, sleep efficiency, and daytime activity, we measured physical activity using wrist actigraphy in 103 veterans with chronic kidney disease. After 6 to 7 days of continuous activity monitoring, participants underwent ambulatory BP monitoring with simultaneous actigraphy. The above experiment was repeated after 1 mo.Results: Among the top tertile of patients (most sleep), when wearing ambulatory BP patients spent less time in bed at night (−92 min, P < 0.0001), were less asleep during those hours (−98 min, P < 0.0001), and had reduced sleep efficiency (82% versus 77%, −5% P = 0.02). On the day of ambulatory BP monitoring, patients were more sedentary during waking hours (+27 minutes, P = 0.002). During ambulatory BP monitoring, waking after sleep onset more than median was associated with greater odds for nondipping (odds ratio 10.5, P = 0.008).Conclusions: Ambulatory BP monitoring is associated with disturbed sleep and reduced physical activity, characteristics that influence dipping. Ambulatory BP monitoring may itself induce nondipping and may thus mitigate the prognostic significance of the dipping phenomenon.Blood pressure (BP) in healthy people follows a circadian pattern that is influenced by the level of activity during the day and depth of sleep at night (1). Sleeping systolic BP, which should at least be 10% lower than awake systolic BP, is often measured by 24-hour ambulatory BP monitoring. This fall in BP during sleep—dipping—is a determinant of prognosis (2). Nondipping occurs in a variety of conditions and diseases, such as in patients with chronic kidney disease (CKD), sleep apnea, volume overload, nocturia, and those with sympathetic activation (3); nondipping is associated with left ventricular hypertrophy (4) and increased cardiovascular risk (5).Davies et al. (6) have reported that sensory stimulation as may occur during cuff inflation may cause cortical arousal, disturb sleep, and raise BP—a phenomenon they characterized in the sleep laboratory among six normal volunteers. However, it remains unknown to what extent ambulatory BP recording can impair nighttime sleep and whether it can also affect daytime activity.The purpose of this study was to assess the effect of ambulatory BP monitoring on sleep duration, sleep efficiency, and daytime activity. We hypothesized that ambulatory BP monitoring will reduce sleep efficiency and reduce daytime activity. Further, we hypothesized that those patients who have the maximal sleep disturbance will have the least dipping at night. If so, it would suggest that ambulatory BP monitoring may induce nondipping per se. These findings would have implications for assessing the independent prognostic value of dipping.     

Ambulatory Blood Pressure Monitoring in Children and Adolescents: Coming of Age?

Over the last years, ambulatory blood pressure monitoring has been introduced into the pediatric population, contributing to a significant increase in the bulk of knowledge of crucial clinically relevant issues. Guidelines have established the currently known conditions where ambulatory blood pressure monitoring is useful and where it will provide additional information in children and adolescents. How common and important the intra-individual differences are within clinical and ambulatory blood pressure is the keystone to the use of ambulatory blood pressure monitoring as a diagnostic tool. By using not only office, but also ambulatory blood pressure, four possible situations arise. Two of these have values in agreement for normotension or hypertension. Two have values that are discrepant. The latter two are known as white coat and masked hypertension. The relationship with hypertension-induced organ damage, the prognostic value and the assessment of treatment goals are key issues of ambulatory blood pressure monitoring. In children, the accurate identification of hypertension at the earliest possible age would, therefore, give health-care providers the opportunity to initiate preventive measures, thereby reducing the chance of developing end-organ damage and its attendant morbidity and mortality.     

Metabolic and Blood Pressure Effects of 6α-Methylprednisolone in the Conscious Sheep

Methylprednlsolone has been reported to be produce hypertension in the rat but to have no effect on blood pressure in the dog. In this study, methylprednlsolone infused to conscious sheep for up to 10 days at either 20 μg/kg/hr or 100 μg/kg/hr, failed to induce a hypertensive response. Metabolic effects characteristic of glucocorticoid activity, such as increased water intake and urine volume, were observed in all animals. No consistent decrease in plasma potassium concentration was observed with either rate of infusion, indicating a lack of in-vivo mlneralocortlcoid activity. In the conscious sheep, like the dog, methylprednlsolone exhibits only glucocorticoid activity and does not increase blood pressure.