This is the first study to demonstrate that a diminished nocturnal decline in blood pressure is a risk factor for cardiovascular mortality, independent of the overall blood pressure load during a 24-h period, in the general population.

Abstract-There is continuing controversy over whether the pattern of circadian blood pressure (BP) variation that includes a nocturnal decline in BP and a morning pressor surge has prognostic significance for stroke risk. In this study, we followed the incidence of stroke in 1430 subjects aged Ն40 years in Ohasama, Japan, for an average of 10.4 years. The association between stroke risk and the pattern of circadian BP variation was analyzed with a Cox proportional hazards model after adjustment for possible confounding factors. There was no significant association between total stroke risk and the nocturnal decline in BP (percentage decline from diurnal level) or between total stroke risk and the morning pressor surge. The cerebral infarction risk was significantly higher in subjects with a Ͻ10% nocturnal decline in BP as compared with subjects who had a Ն10% nocturnal decline in BP (Pϭ0.04). The morning pressor surge was not associated with a risk of cerebral infarction. On the other hand, an increased risk of cerebral hemorrhage was observed in subjects with a large morning pressor surge (Ն25 mm Hg; Pϭ0.04). Intracerebral hemorrhage was also observed more frequently in extreme dippers (those with a Ն20% nocturnal decline in BP) than dippers (those with a 10% to 19% decline; Pϭ0.02). A disturbed nocturnal decline in BP is associated with cerebral infarction, whereas a large morning pressor surge and a large nocturnal decline in BP, which are analogous to a large diurnal increase in BP, are both associated with cerebral hemorrhage.

Abstract-Day-by-day blood pressure and heart rate variability defined as within-subject SDs of home measurements can be calculated from long-term self-measurement. We investigated the prognostic value of day-by-day variability in 2455 Ohasama, Japan, residents (baseline age: 35 to 96 years; 60.4% women). Home blood pressure and heart rate were measured once every morning for 26 days (median). A total of 462 deaths occurred over a median of 11.9 years, composing 168 cardiovascular deaths (stroke: nϭ83; cardiac: nϭ85) and 294 noncardiovascular deaths. Using Cox regression, we computed hazard ratios while adjusting for baseline characteristics, including blood pressure and heart rate level, sex, age, obesity, current smoking and drinking habits, history of cardiovascular disease, diabetes mellitus, hyperlipidemia, and treatment with antihypertensive drugs. An increase in systolic blood pressure variability of ϩ1 between-subject SD was associated with increased hazard ratios for cardiovascular (1.27; Pϭ0.002) and stroke mortality (1.41; Pϭ0.0009) but not for cardiac mortality (1.13; Pϭ0.26). Conversely, heart rate variability was associated with cardiovascular (1.24; Pϭ0.002) and cardiac mortality (1.30; Pϭ0.003) but not stroke mortality (1.17; Pϭ0.12). Similar findings were observed for diastolic blood pressure variability. Additional adjustment of heart rate variability for systolic blood pressure variability and vice versa produced confirmatory results. Coefficient of variation, defined as within-subject SD divided by level of blood pressure or heart rate, displayed similar prognostic value. In conclusion, day-by-day blood pressure variability and heart rate variability by self-measurement at home make up a simple method of providing useful clinical information for assessing cardiovascular risk. Key Words: epidemiology Ⅲ cerebrovascular disease/stroke Ⅲ population science Ⅲ risk factors Ⅲ blood pressure measurement/monitoring H ome blood pressure measurement is reportedly more reliable than conventional blood pressure measurement, because this approach avoids both observer and regression dilution biases and eliminates the white coat effect. 1 Home blood pressure measurement offers more prognostic significance than office blood pressure 2 and is more indicative of target organ damage. 3 The clinical significance of home blood pressure measurement is primarily produced by multiple measurements of blood pressure. 2 These multiple measurements also provide information on day-by-day blood pressure variability under relatively controlled conditions. 4 Previous studies of ambulatory blood pressure monitoring have highlighted that circadian variation 5 and short-term blood pressure variability 6 can predict cardiovascular events above and beyond traditional risk factors. However, no studies have investigated associations between home blood pressure variability and cardiovascular events. We hypothesized that day-by-day blood pressure variability derived from self-measurement at home would provide further insights into pro...

In this study, the quantitative fluctuation of cytoplasmic lipid droplets (LD) and cryotolerance were investigated in bovine embryos derived from in vitro-matured (IVM) and in vitro-fertilized (IVF) oocytes developed in different culture systems using serum-free or serum-containing media. The serum-free cultures were grown using IVMD101 medium in conjunction with bovine cumulus/granulosa cell (BCGC) cocultures or IVD101 medium without BCGC cocultures, and the serum-containing cultures were grown in the presence of BCGC cocultures using HPM199 medium supplemented with 5% calf serum (HPM199 + CS). Large numbers of sudanophilic LD were present in the cytoplasm of bovine embryos from 2-cell to hatched blastocyst stages, and the number and size differed between the embryos cultured in serum-free and serum-supplemented media. In the embryos cultured in HPM199 + CS, large (2-6 microm in diameter) sudanophilic LD increased significantly from the morula to the blastocyst stages. Throughout the embryonic development, the embryos developed in serum-free cultures with and without BCGC cocultures had numerous sudanophilic LD, but most of these droplets were small (<2 microm in diameter) and large LD were less numerous than those embryos cultured in HPM199 + CS. Giant LD (>6 microm in diameter) were frequently observed in morulae and blastocysts (including early blastocysts) developed in HPM199 + CS. Electron microscopic observations demonstrated that large LD were abundant in the cytoplasm of trophoblast and embryonic (inner cell mass) cells of blastocysts cultured in HPM199 + CS. These large LD were identified as osmophilic LD, an indication that these lipid inclusions contained a significant proportion of unsaturated lipids. Many elongated mitochondria were found in embryos developed in IVMD101 and IVD101 at the morula and early blastocyst stages, whereas many of the mitochondria in the morulae developed in HPM199 + CS were of an immature form such as spherical or ovoid shape. The survival and hatching rates of embryos (morulae, early blastocysts, and blastocysts) produced in serum-free media (both IVMD101 and IVD101) after post-thaw culture were superior to those of embryos produced in serum-containing medium. These results showed that bovine embryos cultured in serum-containing medium abnormally accumulated cytoplasmic lipids into their cytoplasm and the excess accumulation of cytoplasmic LD in embryos may affect the cryotolerance of embryos.

Abstract-The objective of this study was to elucidate the long-term prognostic significance of ambulatory blood pressure.Ambulatory and casual blood pressure values were obtained from 1332 subjects (872 women and 460 men) aged Ն40 years from the general population of a rural Japanese community. Survival was then followed for 14 370 patient years and analyzed by a Cox hazard model adjusted for possible confounding factors. There were 72 cardiovascular deaths during the 10.8-year follow-up. The relationship between 24-hour systolic blood pressure and the cardiovascular mortality risk was U-shaped in the first 5 years, then changed to J-shaped over the rest of the 10.8-year follow-up. After censoring the first 2 years of data, the risk flattened until it again increased for the fifth quintile of 24-hour systolic blood pressure for the 10.8-year follow-up period. For 24-hour diastolic blood pressure, the J-shaped relationship remained unchanged, regardless of follow-up duration and censoring. Ambulatory systolic blood pressure values consistently showed stronger predictive power for cardiovascular mortality risk than did casual systolic blood pressure in the 10.8-year follow-up data, whereas such relationships became more marked after censoring the first 2 years. When nighttime and daytime systolic blood pressure values were simultaneously included in the same Cox model, only nighttime blood pressure significantly predicted the cardiovascular mortality risk for the 10.8-year follow-up data. We conclude that the relationship between ambulatory systolic blood pressure and cardiovascular mortality is not U-shaped or J-shaped, and that nighttime blood pressure has better prognostic value than daytime blood pressure. Key Words: blood pressure monitoring, ambulatory Ⅲ cardiovascular diseases Ⅲ prospective studies A mbulatory blood pressure (BP) has been used widely to diagnose and evaluate hypertension and to monitor treatment in the clinical setting. 1,2 Moreover, ambulatory BP is known to provide more reproducible information than does casual BP for individual patients with hypertension, 3,4 and is more strongly correlated with target-organ damage than casual BP in hypertensive subjects. Furthermore, the international guidelines for hypertension have emphasized the usefulness of ambulatory BP. 5,6 However, in contrast to the plethora of evidence about casual BP, there is still a lack of data that address the long-term prognostic significance of ambulatory BP. Few longitudinal studies, after Ն10 years, have so far examined the relationship between 24-hour BP and prognosis. Since 1987, we have been conducting a prospective cohort study to investigate the relationship between ambulatory BP and survival in the general population of Ohasama, Japan (the Ohasama Study). [7][8][9] In a previous report, we presented the results from a 5.1-year follow-up period. 8 The objective of the present study was to determine the prognostic significance of ambulatory BP for cardiovascular mortality risk based on a longer follow-up period, o...

There was no threshold for the number of home blood pressure measurements within the range of 1-14 measurements for increasing the predictive power of stroke risk, suggesting that as many measurements as possible, preferably more than 14 measurements, is recommended for better prediction of stroke risk. It should be emphasized that home blood pressure has a stronger predictive power than does conventional blood pressure, even for a lower number of measurements.

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Conventional BP measurements may not identify some individuals at high or low risk, but these people may be identifiable by the use of ambulatory BP.