Carotid Flow Augmentation, Arterial Aging, and Cerebral White Matter Hyperintensities.

Objective- Aortic stiffness and pressure wave reflection are associated with age-related cerebral microvascular disease, but the underlying mechanism remains obscure. We hypothesized that cerebral (carotid) flow alterations potentially mediate these associations. Approach and Results- Doppler waveforms were recorded in 286 patients with hypertension to measure the carotid flow augmentation index (FAIx) as the late/early-systolic velocity amplitude ratio. Tonometric waveforms were recorded to estimate the aortic pressure AIx (PAIx), aortic compliance, and carotid-femoral and carotid-radial pulse wave velocities. Additionally, white matter hyperintensities on brain magnetic resonance imaging were evaluated using the Fazekas scale. With increasing age, the carotid late systolic velocity increased, whereas the early systolic velocity decreased, although the aortic augmented pressure increased in parallel with the incident wave height ( P<0.001). Both FAIx and PAIx increased with age, but the age-dependent curves were upwardly concave and convex, respectively. FAIx increased exponentially with increasing PAIx ( r=0.71). Compared with PAIx, FAIx was more closely ( P≤0.001) correlated with the aortic pulse wave velocity, aortic compliance, and elastic/muscular pulse wave velocity ratio. FAIx was associated with white matter hyperintensities scores independently of confounders including age, sex, diabetes mellitus, hypercholesterolemia, and aortic pulse wave velocity ( P=0.01), and was more predictive of white matter hyperintensities presence than PAIx. Conclusions- Carotid FAIx had closer associations with age, aortic stiffness, and cerebral white matter hyperintensities than aortic PAIx. These results indicate that carotid flow augmentation (enhanced by aortic stiffening and pressure wave reflection from the lower body) causes microcerebrovascular injury potentially through increasing cerebral flow pulsations, but this detrimental effect is greater than that estimated from PAIx.

Low frequency of cervicocranial artery involvement in Japanese with renal artery fibromuscular dysplasia compared with that of Caucasians.

BACKGROUND: Fibromuscular dysplasia (FMD), which usually affects the renal artery, also affects the carotid, vertebral, and intracranial arteries. Previous studies have shown a high prevalence of concomitant renal artery and cervicocranial lesions in FMD patients. However, the analyzed subjects were mostly Caucasians in Western countries. METHOD: We performed a retrospective analysis to examine the prevalence of cervicocranial vascular lesions in Japanese FMD patients with renal artery involvement at a single institution. The presence of cervicocranial lesions was evaluated by Doppler echography and magnetic resonance angiography. We compared this prevalence with that reported in the literature. RESULT: Thirty-one Japanese FMD patients with renal artery lesions were studied. The mean age was 30 ± 12 years, 71% were women, and 16% were smokers; all patients were Asians and had hypertension. Multifocal, tubular, and unifocal types of renal lesions were found in 52, 35, and 13% of patients, respectively. Bilateral renal lesions were found in 13% of patients. None of the patients had a cervical vascular lesion associated with FMD. Only two patients (8%) had a lesion in the intracranial artery, of which one was a known case of moyamoya disease. CONCLUSION: These findings suggest that cervical artery involvement and intracranial artery involvement are not common in renal FMD patients in Japan, which is in contrast to the data reported for Caucasian patients in Western countries. Ethnic differences could influence the occurrence of cervicocranial lesions. A study with a larger sample size should be performed to validate these findings.

Central hemodynamics and target organ damage in hypertension.

Recent advances in technology have enabled the noninvasive evaluation of pulsatile hemodynamics in the central aorta; namely, central pressure and flow measurements. The central blood pressure represents the true load imposed on the heart, kidney and brain, and the central blood flow influences the local flow into these vital organs. An elevation of the central blood pressure has a direct, adverse impact on the target organ and, thus, the cardiovascular prognosis in patients with hypertension. A decrease in the central blood flow can cause organ dysfunction and failure. The central pressure and flow dynamics were conventionally regarded as unidirectional from the heart to the periphery. However, current evidence suggests that it should be recognized as a bidirectional interplay between the central and peripheral arteries. Specifically, the pressure pulse wave is not only transmitted forward to the periphery but also reflected backward to the central aorta. The flow pulse wave is also composed of the forward and reverse components. Aortic stiffening and arteriolar remodeling due to hypertension not only augment the central pressure by increasing the wave reflection but also may alter the central bidirectional flow, inducing hemodynamic damage/dysfunction in susceptible organs. Therefore, central hemodynamic monitoring has the potential to provide a diagnostic and therapeutic basis for preventing systemic target organ damage and for offering personalized therapy suitable for the arterial properties in each patient with hypertension. This brief review will summarize hypothetical mechanisms for the association between the central hemodynamics and hypertensive organ damage in the heart, kidney and brain.

Inverse association between obesity and aortic pressure augmentation is attenuated in women: the Wakuya study.

OBJECTIVE: Pressure wave reflection predicts cardiovascular events in the general population. Obesity is negatively associated with pressure wave reflection. Muscular arterial diameter (responsible for pressure wave reflection) increases with obesity, and obesity-dependent dilation of muscular arteries is attenuated in women compared with men. We investigated the sex differences in the cross-sectional relationship between obesity and pressure wave reflection in a general population cohort. METHODS: Tonometric pressure waveforms were recorded in 928 adults (mean age, 56 ±â€Š10 years) to estimate the aortic augmentation index. The BMI was calculated using height and body weight, and waist circumference was recorded at the umbilical level. RESULTS: Aortic augmentation index was significantly higher in women than in men. Indices of obesity (BMI and waist circumference) were negatively correlated with the aortic augmentation index in both men and women, even after adjusting for mean arterial pressure (both P  < 0.001). Sex and BMI had no synergistic effect on the aortic augmentation index. However, when waist circumference was substituted for BMI, sex and waist circumference had a reciprocal influence on decreasing the aortic augmentation index independent of age, mean arterial pressure, diabetes, and hyperlipidemia (interaction, P  = 0.045). CONCLUSION: The negative correlation between overweight/obesity and aortic pressure augmentation from peripheral wave reflection is inhibited in women more than in men. Sex differences in aortic pressure augmentation are greater in individuals with central (abdominal) obesity than in those with general obesity.

Being overweight worsens the relationship between urinary sodium excretion and albuminuria: the Wakuya study.

BACKGROUND/OBJECTIVES: (Micro)albuminuria (a manifestation of renal microvascular damage) is an independent predictor of mortality risk, even when the urinary albumin/creatinine ratio is ≥ 10 mg/g in the general population. Excessive sodium intake and obesity are strong predictors of cardiovascular disease. However, the effect of obesity on the relationship between sodium intake and albuminuria is not fully understood. SUBJECTS/METHODS: The purpose of the present study was to investigate the cross-sectional relationships among dietary sodium intake, obesity, and albuminuria in a general population cohort. Subjects were 928 apparently healthy adults. Body mass index was calculated using the height and body weight. Urinary sodium/creatinine and albumin/creatinine ratios were measured in spot urine samples. Estimated 24-h urinary sodium/creatinine ratio (e24UNa/Cr) was assessed using age, height, body weight, and spot urinary sodium/creatinine ratio. RESULTS: Both the body mass index and e24UNa/Cr positively correlated with the urinary albumin/creatinine ratio (both, P < 0.001), and had a synergistic effect on increasing urinary albumin/creatinine ratio independent of age, sex, mean arterial pressure, and diabetes (interaction P = 0.04). When subjects were divided into 6 groups according to the tertiles of e24UNa/Cr and body mass index < (normal-weight) or ≥ 25 (overweight), the prevalence rate of urinary albumin/creatinine ratio ≥ 10 mg/g increased with rising e24UNa/Cr and being overweight (P < 0.001). CONCLUSION: An increase in body mass index increases the positive association between urinary sodium excretion and (micro)albuminuria in the general population. Excess sodium intake may strengthen cardiovascular risk by increasing (micro)albuminuria, particularly in overweight individuals.

Central-to-peripheral stiffness gradients determine diastolic pressure and flow fluctuation waveforms: time domain analysis of femoral artery pulse.

OBJECTIVE: Blood pressure fluctuates during diastole to create a dicrotic wave but the mechanistic origin remains poorly understood. We sought to investigate the characteristics and determinants of diastolic pressure and flow fluctuations with a focus on stiffness gradients between the central aorta and peripheral arteries. METHODS: Using applanation tonometry and duplex ultrasound, pulse waveforms were recorded on the femoral artery in 592 patients (age: 55 ±â€Š14 years) to estimate the diastolic pressure fluctuation as a residual wave against the mono-exponential decay and the diastolic flow fluctuation as a bidirectional (forward and reverse) velocity wave. The radial, carotid, and dorsalis pedis pressures were also recorded to measure the peripheral/aortic pulse pressure (PP) and pulse wave velocity (PWV) ratios. RESULTS: There were close resemblances between the femoral pressure and flow fluctuation waveforms. The pressure and flow fluctuations were mutually correlated in relative amplitude as indexed to the total pulse height (r = 0.63), and the former temporally followed the latter. In multivariate-adjusted models, higher peripheral/aortic PP and PWV ratios were independently associated with greater pressure and flow fluctuation indices (P < 0.001). Mediation analysis revealed that the associations of PP and PWV ratios with the pressure fluctuation index were largely mediated by the flow fluctuation index [indirect/total effect ratio: 57 (95% CI 42-80)% and 54 (30-100)%, respectively]. CONCLUSION: These results suggest that central-to-peripheral pulse amplification and stiffness gradients contribute to triphasic flow fluctuations and dicrotic pressure waves. Diminished or inverted stiffness gradients caused by aortic stiffening may thus reduce diastolic runoff leading to ischemic organ damage.

Aortic diastolic pressure decay explains sex-related differences in the subendocardial viability ratio: the Wakuya study.

OBJECTIVE: Coronary heart disease is the leading cause of mortality in women. Despite a higher risk of heart failure after the first myocardial infarction in women compared with men, the sex-specific mechanisms are unknown. We hypothesized that myocardial ischemia is attributable to sex-related diastolic alterations in the central hemodynamics. METHODS: We investigated the subendocardial viability ratio (myocardial oxygen supply/demand) and aortic diastolic pressure decay index in 962 apparently healthy adults (mean age, 56 ±â€Š10 years). Using noninvasive applanation tonometry, the subendocardial viability ratio, aortic diastolic pressure decay index, and aortic augmentation index were estimated in all participants. The aortic diastolic pressure decay index was quantified by fitting an exponential curve: P(t) = P0e-λt (λ, decay index; P0, end-systolic pressure; t, time from end-systole). RESULTS: Women showed a significantly higher aortic diastolic pressure decay index, even after adjusting for age, hypercholesterolemia, and diabetes, and a significantly lower subendocardial viability ratio than men (P < 0.001). Analysis demonstrated a mediating effect of the aortic decay index on the sex-related differences in the subendocardial viability ratio (71%), despite different effects of the augmentation index (5%). CONCLUSION: These results suggest that the predisposition of women to coronary heart disease is more likely attributable to impaired myocardial perfusion caused by accelerated aortic diastolic pressure decay, rather than increased myocardial load due to augmented aortic systolic pressure.

Albuminuria Intensifies the Link Between Urinary Sodium Excretion and Central Pulse Pressure in the General Population: The Wakuya Study.

BACKGROUND: Central pulse pressure (cPP) is responsible for the hemodynamics of vital organs, and monitoring this parameter is important for cardiovascular disease (CVD) prevention. Excess sodium intake and (micro)albuminuria (a manifestation of renal microvascular damage) are known to be strong predictors of CVD. We sought to investigate the cross-sectional relationships among dietary sodium intake, albuminuria, and cPP in a general population cohort. METHODS: The subjects were 933 apparently healthy adults (mean age, 56 ± 10 years). Radial pressure waveforms were recorded with applanation tonometry to estimate mean arterial pressure (MAP), cPP, forward and backward pressure amplitudes, and augmentation index. The urinary sodium/creatinine and albumin/creatinine ratios were measured in spot urine samples. RESULTS: Both the urinary sodium/creatinine and albumin/creatinine ratios were positively correlated with cPP, even after adjusting for MAP (P < 0.001). Moreover, both ratios had a synergistic influence on increasing the cPP independent of age, sex, estimated glomerular filtration rate, hyperlipidemia, and diabetes (interaction P = 0.04). A similar synergistic influence was found on the forward pressure amplitude, but not on the backward pressure amplitude or augmentation index. The overall results were not altered when the urinary albumin/creatinine ratio was replaced with the existence of chronic kidney disease (CKD). CONCLUSIONS: (Micro)albuminuria strengthens the positive association between urinary sodium excretion and cPP and systolic forward pressure. Excess sodium intake may magnify the cardiovascular risk by widening the aortic pulsatile pressure, particularly in the presence of concomitant CKD.

Concurrent analogous organ damage in the brain, eyes, and kidneys in malignant hypertension: reversible encephalopathy, serous retinal detachment, and proteinuria.

Malignant hypertension, a form of hypertensive emergency, causes acute damage in vital organs such as the brain, eyes, and kidneys. We aimed to examine the concurrency of acute hypertensive damage across the target organs to elucidate the underlying analogous pathophysiology. This single-center retrospective study evaluated the characteristics of organ damage, short-term clinical course, and interorgan relationships in patients with malignant hypertension treated between 2008 and 2019. Baseline characteristics of 20 patients who met our inclusion criteria were mean age 48 ± 13 years and blood pressure 222 ± 18/142 ± 16 mmHg; the median estimated glomerular filtration rate and urinary protein level were 49 mL/min/1.73 m2 (interquartile range [IQR] 27-79) and 1.9 g/g creatinine (IQR 0.2-4.0), respectively. Posterior reversible encephalopathy syndrome (PRES) was found in 60% of patients with major involvement and a wide variety of distribution patterns in the brainstem. In the fundus, serous retinal detachment was found in 60% of patients. Patients with PRES and serous retinal detachment showed higher levels of urinary protein than those without symptoms (P = 0.007 and 0.02, respectively), and proteinuria >1 g/g creatinine highly complicated both PRES and serous retinal detachment (91%). Matrix analysis also showed that the three symptoms were highly associated with each other. These results demonstrate the close relationship and concurrency of hypertensive acute organ damage in the brain, eyes, and kidneys. A common analogous mechanism, such as hyperperfusion-induced capillary leakage in each organ, implies an underlying pathophysiology of PRES, serous retinal detachment, and proteinuria.

Different role of wave reflection magnitude and timing on left ventricular mass reduction during antihypertensive treatment.

OBJECTIVE: Regression of left ventricular (LV) mass during antihypertensive treatment has been associated with reduction in aortic augmentation index, a composite measure of peripheral wave reflection. The aim of this study was to clarify which of the two reflection factors, that is magnitude or timing, plays the dominant role in this regression. METHODS: We evaluated the reflection magnitude (RM; the reflected-to-forward pressure wave amplitude ratio), the round-trip travel time of the pressure wave (a parameter for reflection timing), and the aortic pulse wave velocity (PWV) with echocardiographic LV mass in 61 hypertensive patients before and after 1-year standard medical treatment. RESULTS: Antihypertensive therapy significantly (P < 0.01) decreased brachial and aortic blood pressures and aortic PWV, reduced LV mass, and increased travel time. Neither increase in travel time nor decrease in PWV, however, was related to the reduction in LV mass. By contrast, treatment-induced change in RM was significantly correlated with change in LV mass; the correlation was particularly close in patients with LV hypertrophy (r = 0.61, P < 0.001). Only a marginal correlation was observed between the changes in RM and travel time. The association between RM decrease and LV mass reduction was independent of age, sex, changes in travel time and blood pressure, and use of renin-angiotensin system inhibitors (beta = 0.41, P = 0.001). CONCLUSION: Decreased wave RM contributes to LV mass regression more strongly than, and independently of, delayed reflection timing. Peripheral muscular arteries (from which reflection arises) appear to be more important therapeutic targets in regressing LV mass than central elastic arteries.

Cost-effectiveness of the introduction of home blood pressure measurement in patients with office hypertension.

OBJECTIVE: Cost-effectiveness of hypertension treatment is an important social and medical issue in Western as well as in Eastern countries, including Japan. Home blood pressure (HBP) measurements have a stronger predictive power for cardiovascular events than casual clinic blood pressure (CBP) measurements. Therefore, the introduction of HBP measurement for the diagnosis and treatment of hypertension should lead to a decrease in medical expenditure. This study presents calculations of the cost savings likely to take place when HBP is implemented for newly detected hypertensive subjects in Japan. DESIGN AND METHODS: We estimate the cost savings from the perspective of a Japanese healthcare system. To estimate the costs associated with changing from CBP to HBP measurement as the diagnostic tool, we constructed a simulation model using data from the Ohasama study. These calculations are based on current estimates for cost of treatment, prevalence of white-coat hypertension at baseline, and varying the incidence of new hypertension after the initial screening. RESULTS: When HBP measurement is not incorporated into the diagnostic process, the medical cost is estimated at US$10.89 million per 1000 subjects per 5 years. When HBP measurement is incorporated, the medical cost is estimated at US$9.33 million per 1000 subjects per 5 years. The reductions in medical costs vary from US$674,000 to US$2.51 million per 1000 subjects per 5 years for treatment of hypertension, when sensitivity analysis is performed. CONCLUSIONS: The introduction of HBP measurement for the treatment of hypertension is very useful for reducing medical costs.

Predictive value of ambulatory heart rate in the Japanese general population: the Ohasama study.

BACKGROUND: Resting heart rate can predict cardiovascular disease mortality or all-cause mortality. Because of the effect of the alert reaction, heart rates measured out-of-office should have better predictive power than those obtained at clinics. However, only a few studies have described the relationship between heart rate measured by ambulatory blood pressure monitoring devices and cardiovascular disease prediction. METHODS: We studied 1444 individuals from the Japanese general population who did not have a history of cardiovascular diseases including arrhythmia. We used multiple adjusted Cox proportional hazards to calculate the mortality risk of daytime heart rate, night-time heart rate, and the day-night heart rate dip ratio [day-night heart rate dip ratio = (daytime heart rate--night-time heart rate)/daytime heart rate x 100]. RESULTS: After 12 years of follow-up, 101, 195, and 296 participants died due to cardiovascular diseases, noncardiovascular diseases, and all causes, respectively. As shown by others, neither daytime nor night-time heart rate predicted cardiovascular disease mortality, whereas both predicted noncardiovascular disease mortality. The day-night heart rate dip ratio was significantly related to all-cause mortality. When night-time heart rate and day-night heart rate dip ratio were simultaneously included into the same Cox model, only night-time heart rate significantly and independently predicted all-cause mortality (relative hazard per 10 bpm increase = 1.29, 95% confidence interval, 1.07-1.54). CONCLUSION: Night-time heart rate value seems to have the most important predictor of all-cause mortality among ambulatory heart rate parameters in this population.

Increased expression of adrenomedullin 2/intermedin in rat hearts with congestive heart failure.

Adrenomedullin 2/intermedin (AM2/IMD) is a novel member of the calcitonin/calcitonin gene-related peptide family. To investigate the pathophysiological role of AM2/IMD in heart failure, we examined the expression of AM2/IMD, adrenomedullin (AM) and receptor complex components (calcitonin receptor-like receptor, three types of receptor activity-modifying proteins) by quantitative RT-PCR and immunohistochemistry in the hearts and kidneys of rats with congestive heart failure (CHF). Significantly increased levels of AM2/IMD mRNA were found in the atrium, right ventricle, non-infarcted part of the left ventricle and the infarcted part of the left ventricle of CHF rats, compared with sham operated rats (about 2.8-fold, 1.7-fold, 1.7-fold and 2.5-fold, respectively). Expression levels of mRNA encoding AM and the receptor complex components were also increased in the hearts of CHF rats. In a separate experiment, AM2/IMD mRNA levels in the heart did not differ between Wistar-Kyoto and spontaneously hypertensive rats. In both sham operated and CHF rats, the myocardium was diffusely immunostained with AM2/IMD. The fibrotic infarcted layer was not immunostained with AM2/IMD but was surrounded by positively immunostained myocardial layers. These findings suggest that the expression of AM2/IMD is enhanced in the failing heart, and AM2/IMD has a certain pathophysiological role in heart failure.

Association between wasted pressure effort and left ventricular hypertrophy in hypertension: influence of arterial wave reflection.

BACKGROUND: Wave reflection during the systole increases left ventricular (LV) pressure, tension-time index (TTI) and myocardial oxygen requirement. The purpose of this study was to extract that component of extra myocardial oxygen requirement that is due to early systolic wave reflection, define it as wasted effort (DeltaE(w)), and examine its relationship to LV hypertrophy (LVH). METHODS: Radial artery pressure waveforms were recorded using applanation tonometry and central aortic waveforms generated in 98 patients with untreated hypertension. Aortic augmentation index (AI(a)), wave reflection amplitude (i.e., aortic augmented pressure (AG)) and systolic duration (ED-Tr), ejection duration (ED) and round-trip travel time of the pressure wave (Tr) were calculated from the aortic waveform, and DeltaE(w) estimated as 2.09 AG (ED-Tr). Carotid-femoral pulse wave velocity (PWV(e)) was also measured and LV mass index (LVMI) determined by echocardiography. RESULTS: DeltaE(w) was significantly correlated with age, body height, and LVMI. Women had greater DeltaE(w) than men. The correlation between DeltaE(w) and LVMI was independent of age, gender and body height (P = 0.003). Patients with LVH (LVH (+) group) showed greater DeltaE(w) than patients without LVH (LVH (-) group) (P = 0.003), and this difference remained significant when adjusted for confounding factors. Also, AI(a) and AG were higher in the LVH (+) than in the LVH (-) group (both P < 0.01). In contrast, PWV(e) was not different between the groups, and Tr showed only a marginal difference (P = 0.07). CONCLUSIONS: DeltaE(w) appears to be directly and positively associated with LVH in untreated hypertensive patients. The amplitude and duration of the reflected wave, rather than its travel time, are probably responsible for this association.

Optimal cutoff point of waist circumference and use of home blood pressure as a definition of metabolic syndrome: the Ohasama study.

BACKGROUND: Self-measured blood pressure (BP) at home (HBP) has a stronger predictive power for cardiovascular mortality and morbidity than casual-screening BP (CBP). No studies have evaluated the clinical significance of self-measured HBP for diagnosing metabolic syndrome (MS). Eight scientific associations recently defined MS for the Japanese population. However, this definition remains controversial, especially with respect to the cutoff value of waist circumference (WC) being higher in women than in men. METHODS: The: participants of this population-based survey were the 395 residents (> or =35 years of age) of Ohasama, a rural Japanese community. They measured HBP and underwent the oral glucose tolerance test between the years 2000 and 2006. We calculated the optimal cutoff values of WC required to diagnose MS, and examined the association of HBP with metabolic risk-factor clustering using multivariate analyses. RESULTS: Receiver operation characteristic analysis indicated that the optimal WC cutoff values for identifying clusters of metabolic risk factors were 87 and 80 cm in men and women, respectively. Elevated HBP was significantly associated with the clustering of metabolic risk factors but CBP was not. CONCLUSION: The appropriate WC cutoff value in the current MS criteria for Japanese women would be 80 cm. We suggest that HBP would be useful when considering a diagnosis of MS. The association between MS determined using HBP and the prognosis of cardiovascular diseases (CVDs) requires further investigation.

Association of microalbuminuria with brachial-ankle pulse wave velocity: the Ohasama study.

BACKGROUND: Microalbuminuria is recognized as a marker of generalized vascular dysfunction. However, the associations between microalbuminuria and pulse wave velocity (PWV), carotid intima-media thickness (IMT), and ambulatory blood pressure (ABP), respectively, have not been investigated. METHODS: Brachial-ankle PWV (baPWV), IMT, and ABP were determined in 328 individuals (mean age, 65.7 +/- 6.4 years) from the general population of Ohasama, a rural Japanese community. The participants were assigned to groups with microalbuminuria and with normoalbuminuria, and their characteristics were compared. We also examined the association between microalbuminuria and baPWV, IMT, and ABP, respectively, using multivariate analyses. RESULTS: Seventy-nine participants (24%) with microalbuminuria had significantly higher baPWV (P < 0.001) and 24-h systolic BP (SBP) (P = 0.006) than those with normoalbuminuria, although 24-h pulse pressure and mean IMT did not significantly differ between the groups. Multiple logistic regression analyses showed that baPWV, but not 24-h ABP, was independently associated with microalbuminuria (P = 0.002) when adjusted for various confounding factors. After further adjustment for 24-h SBP, the association between baPWV and microalbuminuria remained significant (P = 0.012). The trend was significant even when daytime or nighttime SBP was used instead of 24-hour SBP in this model. CONCLUSIONS: Microalbuminuria appears to be associated with baPWV more closely than with IMT and ABP, and its association with baPWV is independent of ABP and other cardiovascular risk factors.

Proposal of a risk-stratification system for the Japanese population based on blood pressure levels: the Ohasama study.

The aim of the present study was to propose a risk-stratification system based on self-measurement of home blood pressure (HBP) as well as casual-screening BP (CBP) in relation to Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2004). For 4 weeks, the subjects measured their HBP while seated every morning within 1 h after awaking, after having rested for at least 2 min. The subjects included 2,368 Ohasama residents aged > or = 35 years, with no history of stroke. CBP was measured twice consecutively at baseline. Among all subjects, there were 174 incidences of stroke or transient ischemic attack (TIA) observed during 9.4 years (interquartile 7.0-12.4) of follow-up. The analysis revealed statistically significant linear increases in stroke or TIA risk in both the CBP-based and HBP-based classifications. The risk for high-normal blood pressure (BP) was not significantly high according to the CBP-based classification (relative hazard [RH] 1.52; 95% confidence interval [CI] 0.89-2.60), whereas it was significantly high by the HBP-based classification (RH 1.91; 95% CI 1.04-3.51). On the basis of the data in the absolute risk table, the risks of first stroke or TIA for the 4 groups in the CBP-based and HBP-based classifications were proposed. Stroke or TIA risk increased linearly with the increase in the stage of stratified risk, regardless of BP information (trend p < 0.0001). Risks for non-hypertensive individuals should be assessed in the next version of the Japanese BP guidelines. Furthermore, the importance of HBP should be emphasized in order to accurately evaluate BP risks for individuals.

Difference between home and office blood pressures among treated hypertensive patients from the Japan Home versus Office Blood Pressure Measurement Evaluation (J-HOME) study.

This study sought to clarify the factors associated with the magnitude of the difference between home and office blood pressures in treated hypertensive patients. Study subjects consisted of 3,308 essential hypertensive patients (mean age, 66 years; males, 44%) receiving antihypertensive treatment in primary care settings in Japan. Patients were classified into 3 groups (the home effect group, small difference group, and office effect group) according to tertiles of the magnitude of the office-home systolic blood pressure difference. Compared to the other two groups, the home effect group patients were significantly and independently older, were more often habitual drinkers, had a greater family history of cerebrovascular disease or personal history of ischemic heart disease, and were prescribed a greater number of antihypertensive drugs, non-amlodipine calcium channel blockers, and alpha-blockers as antihypertensive drugs. Compared to the other two groups, the office effect group patients were significantly and independently younger, included more females, less frequently had a family history of cerebrovascular disease or personal history of ischemic heart disease, and were less often prescribed alpha-blockers as antihypertensive drugs. The characteristics of home effect group patients and the factors negatively affecting the blood pressure difference were the same. Among treated hypertensive patients, compared to patients in the other groups, office effect group patients had a lower-risk profile, whereas home effect group patients had a higher-risk profile. These predictive factors might be useful clinically to help identify patients who may have a large difference between home and office blood pressures.

Increased gene expression of urotensin II-related peptide in the hearts of rats with congestive heart failure.

Urotensin II-related peptide (URP) is a novel endogenous ligand for urotensin II receptor (UT-R). To investigate the pathophysiological role of URP in heart failure, we examined URP, UII and UT-R expression in hearts and kidneys of rats with congestive heart failure due to coronary ligation by quantitative RT-PCR and immunocytochemistry. Significantly increased expression levels of URP mRNA were found in the atrium, the right ventricle and the infarcted part of left ventricle of heart failure rats, when compared with sham-operated rats (about 2.2-fold, 2.7-fold and 3.9-fold, respectively). Expression levels of UII mRNA in the heart were about 10% of URP mRNA, and were slightly increased only in the infarcted part of left ventricle of heart failure rats, when compared with sham-operated rats. The expression levels of UT-R mRNA were increased in the atrium of heart failure rats. There was no significant change of URP, UII and UT-R mRNA expression levels in the kidney between heart failure and sham-operated rats. The myocardium was diffusely immunostained with URP in both rats. The blood vessels in the heart were positively immunostained with URP in heart failure rats, but not in sham-operated rats, whereas they were positively immunostained with UT-R in both rats. These findings suggest that the expression of URP, UII and UT-R is enhanced in failing heart, and the UII/URP/UT-R system has important pathophysiological roles in the progression of heart failure.