Diurnal Blood Pressure Changes Research Articles

PS-B09-7: NON-DIPPER BLOOD PRESSURE CAUSED BY INTERMITTENT HYPOXIA AND ITS POSSIBLE MECHANISM IN THE KIDNEY

Background: Non-dipper, less than 10% decrease of blood pressure in nighttime than daytime, is one of the strongest risk factor of cardiovascular diseases among hypertensive disorders. High prevalence of non-dipper among patients of sleep-apnea syndrome suggests intermittent hypoxia in nighttime as the mechanism of non-dipper, although it is still to be revealed. Purpose: To identify the mechanism of non-dipper caused by intermittent hypoxia in nighttime. Method: C57Bl/6-background male mice were kept under 8AM-8PM of light and 8PM-8AM dark cycle in closed air-conditioned system which could decrease the O2 level from 21% room air to 5% every 3 minutes. Mice were divided into two groups, normoxia (NX) or intermittent hypoxia (IH), and were kept for two weeks under room air thoroughly or under the IH only during 8 AM to 5 PM respectively. The mice were euthanized at 12PM and kidneys were obtained. Blood pressure (BP) of left carotid artery was recorded by radio-telemetry during the latter one week. To evaluate diurnal change in BP, BPs of 8AM-5PM (inactive) and 5PM-8AM (active) were compared in each of NX and IH mice. Kidney lysate was fractionated by ultracentrifuge to obtain membrane fraction of protein. Result: BP of NX mice in the active phase was significantly higher than the inactive phase, although such diurnal change was not observed in IH mice, demonstrating a development of non-dipper pattern by IH. In the kidney lysates, membrane protein expression levels of phosphorylated-Na+-Cl- cotransporter (NCC) and Na + -K+-Cl- cotransporter 2 (NKCC2) were significantly increased in IH mice compared to NX mice, but those of full-length and cleaved form of ENaCα were not changed. Transcriptional expression levels of Sgk1, Gilz, Per1/2 and Cry1/2 were significantly increased and those of Bmal1 and Clock were decreased in IH mice compared to those of NX mice. Conclusion: These data suggest that defect in molecular clock of the kidney and sodium reabsorption augmented by NCC and/or NKCC2 in the kidney contributes to the development of non-dipper.

Diurnal changes in blood pressure and heart rate in children with narcolepsy with cataplexy.

The hypocretin neurons in the lateral hypothalamus are connected not only to brain alertness systems but also to brainstem nuclei that regulate blood pressure and heart rate. The premise is that regulation of blood pressure and heart rate is altered and affected by methylphenidate, a stimulant drug in children with narcolepsy with cataplexy. The changes in 24-hr ambulatory systolic and diastolic blood pressure and heart rate were compared among pre-treated narcolepsy with cataplexy patients (40 males, 10 females), with mean age 10.4 ± 3.5 years (M ± SD, range 5-17 years) with values from 100 archival age-sex-body mass index matched controls. Patients had a lower diurnal systolic blood pressure (-6.5 mmHg; p=0.000) but higher heart rate (+11.0bpm; p=0.000), particularly evident in the waketime, while diastolic blood pressure was comparable. With methylphenidate (18 mg sustained release at 08:00 hours), patients with narcolepsy with cataplexy had higher systolic blood pressure (+4.6 mmHg, p=0.015), diastolic blood pressure (+3.3 mmHg, p=0.005) and heart rate (+7.1bpm, p=0.028) during wake time, but nighttime cardiovascular values were unchanged from pre-treated values; amplitude variation in cardiovascular values was unchanged over 24 hr. In conclusion, children with narcolepsy with cataplexy had downregulation blood pressure profile but a higher heart rate, and lesser non-dipping profiles. Daytime methylphenidate treatment increases only waketime blood pressure and further elevated heart rate values.

Prediction of atrial fibrillation in patients with hypertension: A comprehensive comparison of office and ambulatory blood pressure measurements.

Hypertension is associated with the development of atrial fibrillation (AF). Evidence has shown that reverse dipping pattern, an abnormal increase of night‐time blood pressure (BP) comparing to daytime BP, is associated with cardiovascular events. However, the relationship between diurnal changes in BP and AF has not been sufficiently explored. This paper aims to cross‐sectionally explore the relationship between AF and ambulatory BP parameters, especially reverse dippers to the others, and further longitudinally analyze how BP patterns are associated to the risk of developing new‐onset AF. Between February 2012 and March 2021, five out of 412 patients were identified of AF at baseline; four were reverse dippers (3.7%) and one was from the others (.3%). Cross‐sectionally, the multivariate logistic regression analysis showed that reverse dippers were significantly more likely to have AF (odds ratio: 12.39, p = .030). After excluding patients with baseline AF, during the mean follow‐up of 4.6 ± 3.0 years, seven patients developed AF. Longitudinally, the multivariate Cox regression analysis revealed that 24‐h systolic BP (hazard ratio per 10 mmHg: 2.12, p = .015), night‐time systolic BP (hazard ratio per 10 mmHg: 2.27, p = .002), and presentation of reverse dipping (hazard ratio: 5.25, p = .042) were independently associated with new‐onset AF. None of the office BP measurements were associated with new‐onset AF. While ambulatory BP measurements were better predictors for the incidence of AF, careful management is necessary for reverse dippers as they are at high risk of developing AF.

Do diurnal changes in blood pressure affect myocardial work indices?

Do diurnal changes in blood pressure affect myocardial work indices?

Alcohol suppresses cardiovascular diurnal variations in male normotensive rats: Role of reduced PER2 expression and CYP2E1 hyperactivity in the heart.

The molecular mechanism of the adverse effects of ethanol on diurnal cardiovascular regulation remains unknown. In separate studies, the cardiac circadian rhythm protein period-2 (PER2) confers cardioprotection and, in other organs, PER2 interaction with the ethanol-metabolizing enzyme CYP2E1 underlies, via heme oxygenase-1 (HO-1) upregulation, tissue injury/dysfunction. Here, we hypothesized that suppressed PER2 expression and elevated CYP2E1/HO-1 levels in the heart underlie the disrupted diurnal cardiovascular rhythm/function in alcohol-fed normotensive rats. In ethanol-fed (5%, w/v; 8 weeks) or isocaloric liquid diet-fed male rats, diurnal changes in blood pressure (BP), heart rate (HR), HR vagal variability index, root mean square of successive beat-to-beat differences in beat-interval duration (rMSSD), and cardiac function were measured by radiotelemetry and echocardiography followed by exvivo molecular studies. Radiotelemetry findings showed ethanol-evoked reductions in BP (during the dark cycle), rMSSD (during both cycles), and in diurnal differences in BP and rMSSD. Echocardiography findings revealed significant (p<0.05) reductions in ejection fraction and fractional shortening (weeks 4-6) in the absence of cardiac remodeling (collagen content). Hearts of ethanol-fed rats exhibited higher (p<0.05) CYP2E1 activity (50%) and HO-1 expression (63%), along with reduction (p<0.05) in PER2 levels (29%), compared with the hearts of isocaloric diet-fed control rats. Our novel findings implicate upregulations of CYP2E1/HO-1 and downregulation of the circadian rhythm cardioprotective protein PER2, in the heart, in the chronic deleterious diurnal cardiovascular effects of alcohol in male rats.

Diurnal changes in central blood pressure and pulse pressure amplification in patients with obstructive sleep apnoea

Study objectivesRecent evidence suggests that compared to peripheral blood pressure (BP), central BP may be more strongly associated with target organ damage and cardiovascular morbidity and mortality. Technological advances now allow the ambulatory measurement of peripheral and central BP over 24 ​h. For the first time, we set out to characterise the diurnal profile of central BP and pulse pressure amplification (PPA) in patients with obstructive sleep apnoea (OSA). MethodsIn this observational study, patients with moderate to severe OSA underwent 24 ​h central and peripheral BP testing before and after at least 4 weeks of CPAP therapy. Concurrent actigraphy was performed to confirm sleep and wake times. Results36 patients were screened, 31 had successful testing (mean (SD) age 45 ​± ​10 years, AHI 58 ​± ​27 events/hr, Office BP 136/89 ​± ​10.7/9.5 ​mmHg, 32% on anti-hypertensives, 77% dippers), 21 completed testing post CPAP. Central systolic and diastolic BP followed the same nocturnal dipping profile as peripheral BP, however the peripheral pulse pressure (PP) narrowed in sleep (−3.2 ​mmHg, p ​< ​0.001), whereas the central PP remained unchanged (0.124 ​mmHg, NS), causing a significant reduction in PPA overnight (−10.7%, p ​< ​0.001). The magnitude of dip in central systolic pressure was less than peripheral systolic pressure (by 2.3 ​mmHg, p ​< ​0.001). After treatment with CPAP, the PPA reduction overnight was attenuated (by −3.3%, p ​= ​0.004). ConclusionsIn moderate to severe OSA, central BP and PPA reduce overnight during sleep. Further randomised controlled studies are needed to quantify the differential effects of CPAP and anti-hypertensives on central versus peripheral BP.

Diurnal blood pressure changes.

The definition of diurnal blood pressure changes varies widely, which can be confusing. Short-term blood pressure variability during a 24-h period and the dipping status of diurnal blood pressure can be captured by ambulatory blood pressure monitoring, and these metrics are reported to have prognostic significance for cardiovascular complications. Morning blood pressure surge also indicates this risk, but its effect may be limited to populations with specific conditions. Meanwhile, the combined use of conventional office blood pressure and out-of-office blood pressure allows us to identify people with white-coat and masked hypertension. Current home devices can measure nocturnal blood pressure during sleep more conveniently than ambulatory monitoring; however, we should pay attention to blood pressure measurement conditions regardless of whether they are in a home, ambulatory, or office setting. The relatively poor reproducibility of diurnal blood pressure changes, including the nocturnal fall of blood pressure, is another underestimated issue to be addressed. Although information on diurnal blood pressure changes is expected to be used more effectively in the future, we should also keep in mind that blood pressure levels have remained central to the primary and secondary prevention of blood pressure-related cardiovascular diseases in clinical practice.

Bmal1 in Perivascular Adipose Tissue Regulates Resting-Phase Blood Pressure Through Transcriptional Regulation of Angiotensinogen.

The perivascular adipose tissue (PVAT) surrounding vessels constitutes a distinct functional integral layer of the vasculature required to preserve vascular tone under physiological conditions. However, there is little information on the relationship between PVAT and blood pressure regulation, including its potential contributions to circadian blood pressure variation. Using unique brown adipocyte-specific aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) and angiotensinogen knockout mice, we determined the vasoactivity of homogenized PVAT in aortic rings and how brown adipocyte peripheral expression of Bmal1 and angiotensinogen in PVAT regulates the amplitude of diurnal change in blood pressure in mice. We uncovered a peripheral clock in PVAT and demonstrated that loss of Bmal1 in PVAT reduces blood pressure in mice during the resting phase, leading to a superdipper phenotype. PVAT extracts from wild-type mice significantly induced contractility of isolated aortic rings in vitro in an endothelium-independent manner. This property was impaired in PVAT from brown adipocyte-selective Bmal1-deficient (BA-Bmal1-KO) mice. The PVAT contractile properties were mediated by local angiotensin II, operating through angiotensin II type 1 receptor-dependent signaling in the isolated vessels and linked to PVAT circadian regulation of angiotensinogen. Indeed, angiotensinogen mRNA and angiotensin II levels in PVAT of BA-Bmal1-KO mice were significantly reduced. Systemic infusion of angiotensin II, in turn, reduced Bmal1 expression in PVAT while eliminating the hypotensive phenotype during the resting phase in BA-Bmal1-KO mice. Angiotensinogen, highly expressed in PVAT, shows circadian expression in PVAT, and selective deletion of angiotensinogen in brown adipocytes recapitulates the phenotype of selective deletion of Bmal1 in brown adipocytes. Furthermore, angiotensinogen is a transcriptional target of Bmal1 in PVAT. These data indicate that local Bmal1 in PVAT regulates angiotensinogen expression and the ensuing increase in angiotensin II, which acts on smooth muscle cells in the vessel walls to regulate vasoactivity and blood pressure in a circadian fashion during the resting phase. These findings will contribute to a better understanding of the cardiovascular complications of circadian disorders, alterations in the circadian dipping phenotype, and cross-talk between systemic and peripheral regulation of blood pressure.

Relationship between diurnal blood pressure and renal histopathological changes in white coat hypertension.

Multiple epidemiological studies have clearly demonstrated the macrovascular risks associated with white coat hypertension (WCH) or sustained hypertension (SH). In patients with WCH, there is no literature available on renal histopathological changes and that on blood pressure pattern and native kidney outcome is scant. We aimed to clarify the relationship between blood pressure variables and pathological features of kidney biopsies in living kidney donors with WCH. This cross-sectional study included living kidney donors with WCH (n = 10) and SH (n = 10), and 20 healthy kidney donors with similar demographic features (control group). Kidney allograft biopsy samples were obtained during transplantation and chronic glomerular, vascular and tubulointertitial changes were semiquantitatively scored according to the Banff classification. The mean age of the 20 hypertensive subjects (Group 1) and controls (Group 2) was 59.3 ± 8.5 versus 59.6 ± 7.6 years and almost half were female. There was no difference in renal function parameters between the groups; however, kidney histopathology in Group 1 was worse than Group 2 with a chronicity index of 2.80 ± 1.67 versus 1.75 ± 1.16 (p = 0.02). There was no difference between histopathological scores of patients with WCH or SH (chronicity index: 2.60 ± 1.43 vs. 2.70 ± 1.70, p = 0.88). Night-to-day mean arterial pressure (MAP) ratio was significantly associated with chronicity index in patients with WCH. Moreover, WCH patients with non-dipper hypertensive pattern had a worse chronicity index. Significant histopathological alterations in the kidney were observed in patients with WCH and SH, and were accentuated in WCH patients with non-dipper blood pressure pattern.

PS 05-30 CIRCADIAN BLOOD PRESSURE PATTERN, EPICARDIAL FAT THICKNESS AND LEFT ATRIAL FUNCTION

Objective: Epicardial adipose tissue reflects visceral adiposity and inflammation which can contribute to the fibrotic remodeling of the atrial myocardium. We aimed to investigate the relationship of echocardiographic epicardial fat thickness (EFT) and left atrial (LA) deformation parameter with diurnal blood pressure (BP) changes in patients with recently diagnosed essential hypertension. Design and method: This cross-sectional study included 511 recently diagnosed hypertensive patients, who underwent echocardiography and 24-hours ambulatory BP monitoring. EFT was measured with echocardiography, and global LA strain was obtained by two-dimensional speckle imaging with automated software. The patients were classified as non-dippers if their daytime ambulatory systolic and diastolic blood pressure did not decrease by at least 10% during the night. Results: The mean EFT, LA volume index as well as left ventricular (LV) filling pressure (E/Ea) were significantly higher in hypertensive patients, especially in non-dippers (all p < 0.001), whereas global LA strain was significantly lowest in non-dippers (normotensives; 23.2 ± 2.0% vs. dippers = 19.0 ± 3.3% vs. non-dippers = 17.4 ± 3.0%, P < 0.001). Moreover, LA strain was significantly associated with LV filling pressure (r = −0.422, p < 0.001), EFT (r = −0.187, p < 0.001), and 24 hour mean BP variability (r = −0.184, p < 0.001). Conclusions: Non-dipper hypertensive patients were associated with increased EFT and impaired LA deformation. This indicates that these subjects may be more prone to atrial rhythm disturbances.

Epicardial Fat Thickness and Neutrophil to Lymphocyte Ratio are Increased in Non-Dipper Hypertensive Patients.

BackgroundIn this study, we aimed to investigate the relationship between echocardiographic epicardial fat thickness (EFT), neutrophil to lymphocyte ratio (NLR; an important inflammatory marker), and diurnal blood pressure (BP) changes in patients with recently diagnosed essential hypertension.MethodsA total of 647 patients underwent echocardiography and 24 hours of ambulatory BP monitoring. EFT was measured by echocardiography, while NLR was measured by dividing the neutrophil count by the lymphocyte count. Patients were categorized into three groups according to BP pattern: the normotensive group, the dipper group, and the non-dipper group.ResultsThe mean EFT was highest in the non-dipper group (non-dipper group, 7.3 ± 3.0 mm; dipper group, 6.1 ± 2.0 mm; control group, 5.6 ± 2.0 mm; p < 0.001). NLR was also highest in the non-dipper group (non-dipper, 2.75 ± 2.81; dipper, 2.01 ± 1.32; control, 1.92 ± 1.11; p < 0.001). EFT was significantly correlated with age (r = 0.160, p < 0.001) and NLR (r = 0.353, p < 0.001). Furthermore, an EFT ≥ 7.0 mm was associated with the non-dipper BP pattern with 51.3% sensitivity and 71.6% specificity [95% confidence interval (CI) = 0.56–0.65, p < 0.001]. In a multivariate analysis, EFT [adjusted odds ratio (OR) = 3.99, 95% CI = 1.22–13.10, p = 0.022] and NLR (OR = 1.34, 95% CI = 1.05–1.71, p = 0.018) were independent parameters that distinguished a non-dipper pattern after adjustment for cardiovascular risk factors.ConclusionEFT and NLR are independently associated with impaired diurnal BP profiles in hypertensive individuals. EFT (as measured by echocardiography) and NLR appear to be helpful in stratifying cardiometabolic risk.

Prospective analysis of the association of ambulatory blood pressure characteristics with incident chronic kidney disease.

Ambulatory blood pressure measurement allows quantification of diurnal changes in blood pressure. While decreased nocturnal blood pressure dipping and elevated morning blood pressure surge are associated with an increased risk of cardiovascular events, the utility of ambulatory blood pressure measurements to predict renal events is unclear. African Americans, in addition to having an increased risk of chronic kidney disease (CKD), also have an increased prevalence of hypertension. Thus, we selected an African American population to study the association of ambulatory blood pressure parameters with incidence of CKD. Prospective cohort study of 603 participants with normal renal function enrolled in the Jackson Heart Study who underwent baseline 24-h ambulatory blood pressure monitoring between 2000 and 2004, with median follow-up of 8.1 years. We analyzed the association of nocturnal dipping and morning surge with both incident CKD [estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m] and annual rate of eGFR decline. In additional analyses, we examined the relation of nocturnal, daytime, white-coat, and masked hypertension with CKD incidence. We found that 10% higher nocturnal dipping was significantly associated with a decreased risk of incident CKD [odds ratio (OR) 0.55, 95% confidence interval (CI) 0.32-0.96] and a 0.4 ml/min per 1.73 m slower annual decline in eGFR. Morning surge was not associated with the incidence of CKD. Additional analyses revealed that isolated nocturnal hypertension and mean asleep SBP were associated with a nonsignificantly higher risk of CKD (OR 2.34, 95% CI 0.90-6.08) and (OR 1.31, 95% CI 0.99-1.72), respectively, in fully adjusted models. Loss of nocturnal blood pressure dipping, but not morning blood pressure surge, may promote the decline in GFR and increase the risk for development of CKD in high-risk individuals.

Recent advances in circadian rhythms in cardiovascular system.

Growing evidence shows that intrinsic circadian clocks are tightly related to cardiovascular functions. The diurnal changes in blood pressure and heart rate are well known circadian rhythms. Endothelial function, platelet aggregation and thrombus formation exhibit circadian changes as well. The onset of many cardiovascular diseases (CVDs) or events, such as myocardial infarction, stroke, arrhythmia, and sudden cardiac death, also exhibits temporal trends. Furthermore, there is strong evidence from animal models and epidemiological studies showing that disruption of circadian rhythms is a significant risk factor for many CVDs, and the intervention of CVDs may have a time dependent effect. In this mini review, we summarized recent advances in our understanding of the relationship between circadian rhythm and cardiovascular physiology and diseases including blood pressure regulation and myocardial infarction.

Association of circadian genes with diurnal blood pressure changes and non-dipper essential hypertension: a genetic association with young-onset hypertension.

Recent studies have suggested that circadian genes have important roles in maintaining the circadian rhythm of the cardiovascular system. However, the associations between diurnal BP changes and circadian genes remain undetermined. We conducted a genetic association study of young-onset hypertension, in which 24-h ambulatory blood pressure (BP) monitoring was performed. A total of 23 tag single-nucleotide polymorphisms (SNPs) on 11 genes involved in circadian rhythms were genotyped for correlations with diurnal BP variation phenotypes. A permutation test was used to correct for multiple testing. Five tag SNPs within five loci, including rs3888170 in NPAS2, rs6431590 in PER2, rs1410225 in RORββ, rs3816358 in BMAL1 and rs10519096 in RORα, were significantly associated with the non-dipper phenotype in 372 young hypertensive patients. A genetic risk score was generated by counting the risk alleles and effects for each individual. Genotyping was performed in an additional independent set of 619 young-onset hypertensive subjects. Altogether, non-dippers had a higher weighted genetic risk score than dippers (1.67±0.56 vs. 1.54±0.55, P<0.001), and the additive genetic risk score also indicated a graded association with decreased diurnal BP changes (P=0.006), as well as a non-dipper phenotype (P=0.031). After multivariable logistic analysis, only the circadian genetic risk score (odds ratio (OR), 1550; 95% confidence interval (CI), 1.225-1.961, P<0.001) and the use of β-blockers (OR, 1.519; 95% CI, 1.164-1.982, P=0.003) were independently associated with the presence of non-dippers among subjects with young-onset hypertension. Genetic variants in circadian genes were associated with the diurnal phenotype of hypertension, suggesting a genetic association with diurnal BP changes in essential hypertension.

Disturbed circadian rhythm of the intrarenal renin-angiotensin system: relevant to nocturnal hypertension and renal damage.

The intrarenal renin-angiotensin system (RAS) plays an important role in the development of hypertension and renal damage. Disruption of diurnal blood pressure (BP) variation is an additional risk factor for renal damage. However, little is known regarding whether intrarenal RAS circadian rhythm exists or if it influences the disruption of diurnal BP and renal damage. We investigated the circadian rhythm of urinary angiotensinogen (U-AGT) that reflects intrarenal RAS activity in 14 individuals without chronic kidney disease (CKD) and 36 CKD patients classified according to circadian BP rhythms. BP values were higher during the daytime than during the nighttime in both individuals without CKD and CKD patients. U-AGT levels were not different between the daytime and nighttime in individuals without CKD, but were significantly higher in the daytime in CKD patients (log U-AGT/creatinine: daytime, 2.39 ± 0.99; nighttime, 2.24 ± 1.06; p = 0.001). Furthermore, in CKD patients showing a riser pattern of circadian BP, U-AGT levels did not decrease during the nighttime compared with those in the daytime (log U-AGT/creatinine: daytime, 2.51 ± 0.65; nighttime, 2.52 ± 0.71; p = 0.78). Circadian fluctuation of albuminuria and proteinuria occurred parallel to that of the U-AGT levels. U-AGT levels were significantly and positively correlated with the levels of BP and circadian fluctuation of U-AGT was correlated with diurnal BP changes. These data suggest that the circadian rhythm of intrarenal RAS activation may lead to renal damage and hypertension, which are associated with diurnal BP variation.

Relationships between diurnal changes in blood pressure and catecholamines among Filipino‐American and European‐American women

Studies show that diurnal blood pressure (BP) sensitivity to epinephrine (EPI) in African-American women is significantly greater than that of European-American (EA) women. Few if any studies have examined diurnal catecholamine-BP relationships in women of other ethnic groups. The purpose of this study was to compare the effects of diurnal changes in EPI and norepinephrine (NE) on the diurnal changes in BP between Filipino-American (FA) and EA women. The subjects included 31 FA and 27 EA nurses and nurses aides and eight FA and 19 EA hotel workers from Hawaii who wore an ambulatory BP monitor and collected timed urine specimens (4 h at work, approx.4 h at home and approx. 8 h overnight) for assay of EPI and NE. Proportional changes in systolic and diastolic BP from sleep to work and sleep to home were examined using ANCOVA models including fixed effect-covariate interactions, with ethnicity as a fixed factor, and BMI and the appropriate proportional change in EPI or NE as covariates. The results show that there was no association between changes in EPI and BP, either overall or by ethnic group; however, overall changes in diastolic BP from sleep to work tended to be smaller among the FAs (P < 0.06). There was also an interactive effect of NE and ethnic group on diastolic BP such that among FAs, as diastolic BP increased, the corresponding NE change decreased (P < 0.039). The relationships between diurnal BP and catecholamine variations differ by ethnicity. Further research is needed to better understand the mechanisms behind the differences and to evaluate whether this vascular tonic relationship has been the focus of natural selective processes.

Short-term blood pressure variability in relation to outcome in the International Database of Ambulatory blood pressure in relation to Cardiovascular Outcome (IDACO)

Ambulatory blood pressure monitoring not only provides information on the blood pressure level, but on the diurnal changes in blood pressure as well. The present review summarizes the main fi ndings of the International Database on Ambulatory blood pressure in relation to Cardiovascular Outcome (IDACO) with regard to risk stratifi cation based on short-term blood pressure variability. An exaggerated morning surge, exceeding the 90th percentile of the population, is an independent risk factor for mortality and cardiovascular and cardiac events. Conversely, a sleep-through or pre-awakening morning surge less than 20 mm Hg in systolic blood pressure is probably not associated with an increased risk of death or cardiovascular events. Blood pressure variability represented by the average of the daytime and nighttime SD weighted for the duration of the daytime and nighttime interval (SDdn) and by average real variability (ARV24) predicted outcome, but only improved the prediction of the composite cardiovascular events by 0.1%. Overall, results of analyses using the IDACO support the concept that short-term blood pressure variability adds to risk stratifi cation, but 24-hour ambulatoryblood pressure level is the most valuable predictor for use in clinical practice.

Usefulness of the resistive index in renal Doppler ultrasonography as an indicator of vascular damage in patients with risks of atherosclerosis

Chronic kidney disease (CKD) is caused by various risk factors of cardiovascular disease (CVD). The estimated glomerular filtration rate (eGFR) is commonly used for the evaluation of the renal function in patients with CKD; however, it is difficult to assess the pathogenesis of CKD and predict the renal prognosis accurately using only eGFR. The resistive index (RI) in renal Doppler ultrasonography (RDU) is thought to be a good indicator of renal vascular resistance caused by atherosclerosis. In the present study, we investigated whether RI could be used to evaluate the pathogenesis of renal damage and predict the renal prognosis and investigated the correlation between RI and blood pressure (BP) fluctuations in patients with or without hypertension. The total study population included 194 patients (mean age: 66.2 years), who underwent RDU in our hospital ward between February 2009 and July 2010. We investigated the correlation between RI and multiple clinical parameters, including ambulatory blood pressure monitoring (ABPM). RI significantly correlated with age, eGFR, diastolic BP, pulse pressure and level of albuminuria. Patients with diabetes mellitus (DM) showed a significantly higher RI than patients without DM, although their eGFR was similar; thus, DM might accelerate renal vascular damage and RI could detect earlier changes of vascular damage proceeding the time eGFR is reduced. Regarding ABPM, patients with a larger morning surge [systolic blood pressure (SBP) in the early morning--lowest SBP during sleep] showed a significantly higher RI. The present study indicated that RI might be very useful for the evaluation of very early renal damage more effectively than eGFR and that diurnal BP change might be partly due to the progression of atherosclerotic change in the kidney evaluated by RI.

Blood pressure variability in relation to outcome in the International Database of Ambulatory blood pressure in relation to Cardiovascular Outcome

Ambulatory blood pressure (BP) monitoring provides information not only on the BP level but also on the diurnal changes in BP. In the present review, we summarized the main findings of the International Database on Ambulatory BP in relation to Cardiovascular Outcome (IDACO) with regard to risk stratification based on BP variability. The predictive accuracy of daytime and nighttime BP and the night-to-day BP ratio depended on the disease outcome under study and treatment status, and differed for fatal outcomes compared with the composite of fatal and nonfatal diseases. An exaggerated morning surge, exceeding the 90th percentile of the population, is an independent risk factor for mortality and cardiovascular and cardiac events. Conversely, a sleep-trough or preawakening morning surge in systolic BP below 20 mm Hg is probably not associated with an increased risk of death or cardiovascular events. BP variability as captured by the average of the daytime and nighttime s.d. weighted for the duration of the daytime and nighttime interval (s.d.(dn)) and the average real variability (ARV(24)) predicted the outcome, but improved the prediction of the composite of all cardiovascular events by only 0.1%. In conclusion, the IDACO observations support the concept that BP variability adds to risk stratification, but above all highlight that 24-h ambulatory BP level remains the main predictor to be considered in clinical practice.

Glucose and Non-glucose Predictors of Future Onset of Type 2 Diabetes in Newly Diagnosed Essential Hypertensives

Baseline fasting plasma glucose (FPG) level predicts the onset of type 2 diabetes mellitus (DM). Other predictors have been less investigated. This study aimed to investigate non-glucose predictors together with FPG for future onset of type 2 DM in fresh essential hypertensives. Consecutive nondiabetic patients with newly diagnosed essential hypertension were prospectively evaluated for diurnal blood pressure (BP) change by ambulatory BP monitoring, vascular endothelial function by plethysmography, and biomarkers by blood biochemistry. They were then given guideline-based treatment and followed-up regularly for more than 5 years. During a mean follow-up period of 5.9 years, 6 of the 106 study patients developed DM. Baseline FPG, alanine aminotransferase (ALT) level, and day-night difference in diastolic BP were related to future onset of DM. FPG > 5.8 mmol/L (p = 0.034) and ALT > 31 U/L (p = 0.048) independently and day-night difference in diastolic BP < or = 2.9% potentially predicted new-onset DM (p = 0.089). Simultaneously having at least 2 of the indicators mentioned above at baseline is predictive of new-onset DM. Parameters of reactive hyperemia by plethysmography were not relevant. In addition to FPG, baseline serum ALT level independently and diurnal diastolic BP changes potentially predicted future onset of type 2 DM in newly diagnosed hypertensives. Both glucose and non-glucose indicators could be examined together for early risk stratification of future DM.