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Biomedical subjects

K Kario

Publications and source records attributed to K Kario.

At least 19 recordsLinked to original sources
PubMed2001

Factors associated with the occurrence and magnitude of earthquake-induced increases in blood pressure.

BACKGROUND: Blood pressure increases transiently after a major earthquake, but the characteristics and the mechanism of this increase are unknown. METHODS: The study involved 124 elderly hypertensive outpatients from two clinics near the epicenter of the Hanshin-Awaji earthquake (7.2 on the Richter scale) for whom ambulatory blood pressure monitoring and assessment of end-organ damage had been performed before the earthquake. RESULTS: During the 1 to 2 weeks after the earthquake, while major aftershocks persisted, mean (+/- SD) systolic blood pressure was 14 +/- 16 mm Hg greater and mean diastolic blood pressure was 6 +/- 10 mm Hg greater, but these values returned to baseline by 3 to 5 weeks after the earthquake. The earthquake-induced increase in blood pressure correlated significantly with the "white coat" effect ([clinic systolic blood pressure minus 24-hour systolic blood pressure] r = 0.34, P <0.001), body mass index (r = 0.28, P <0.001), and age (r = 0.24, P <0.01). The earthquake-induced blood pressure increase was prolonged in patients with microalbuminuria for at least 2 months after the earthquake, whereas it was less pronounced in patients who had been treated with an alpha-blocker and in patients with diabetes mellitus. CONCLUSIONS: These elderly patients with hypertension had a substantial increase in blood pressure after a major earthquake; the increase was usually transient, except in patients who had microalbuminuria. The correlation with white-coat hypertension suggests that both phenomena are related to sympathetic activation.

Aged↗
PubMed2001

Hyperinsulinemia and hemostatic abnormalities are associated with silent lacunar cerebral infarcts in elderly hypertensive subjects.

OBJECTIVES: We sought to study the association of the silent cerebral infarct (SCI), a predisposing condition of stroke, with hyperinsulinemia and hemostatic abnormalities in older hypertensive subjects. BACKGROUND: Hypertension is a powerful risk factor for stroke. However, the role of other risk factors for stroke in hypertensive subjects remains incompletely understood. METHODS: We performed brain magnetic resonance imaging and measured cardiovascular risk factors, by administering the 75-g oral glucose tolerance test and measuring plasma insulin and hemostatic variables, in 123 asymptomatic hypertensive subjects (mean age 69 years). RESULTS: At least one SCI was detected in 80 subjects (65%), and multiple SCIs were found in 48 subjects (39%). The presence of SCIs was associated with older age, higher levels of 24-h systolic blood pressure, 2-h insulin, thrombin-generation markers (prothrombin fragment 1+2 and thrombin-antithrombin complexes), plasminogen activator inhibitor-1 (PAI-1), D-dimer and von Willebrand factor (vWF), but not with plasmin-alpha2-plasmin complex (PIC) levels. The 2-h insulin area under the curve (AUC) was positively correlated with PAI-1 and vWF levels (p < 0.01), and the PAI-1 level was negatively correlated with the PIC level (p < 0.02). Multiple logistic regression analysis revealed that age and the 2-h insulin AUC were significantly associated with SCIs, particularly those located in the subcortical white matter, and hemostatic abnormalities were significantly associated with the presence of multiple SCIs, particularly those located in the basal ganglia. CONCLUSIONS: In older asymptomatic hypertensive subjects, hyperinsulinemia appears to be associated with lacunar-type SCIs, particularly those located in the subcortical white matter, and hemostatic abnormalities show an association with the presence of multiple SCIs, particularly those located in the basal ganglia.

Aged↗
PubMed2001

Interaction between monocytes and vascular endothelial cells induces adrenomedullin production.

Adrenomedullin (AM), a potent vasodilator peptide, has natriuretic effects, and its plasma concentration is elevated in cardiovascular diseases. In the present study, we investigated the induction of AM expression due to interactions between THP-1 cells (human monocytic cell line) and human umbilical cord vein endothelial cells (HUVECs). AM levels in the culture medium were measured by radioimmunoassay. The luciferase vector containing the 5'-flanking region of the human AM gene was transfected into either HUVECs or THP-1 cells. Addition of THP-1 cells to HUVECs for 48 h induced marked increases in AM levels, which were 16-fold higher than those of HUVECs alone. Luciferase vectors containing the 5'-flanking region of human AM gene (pLCF-1534) were transferred into THP-1 cells or HUVECs. Addition of THP-1 cells to pLCF-1534-transfected HUVECs induced an increase in luciferase activity in cell lysates, which was 5-fold higher than that of the transfected HUVECs alone. In contrast, the luciferase activity of lysates from pLCF-1534-transfected THP-1 cells was not affected by coculture with HUVECs. A separate coculture experiment revealed that direct contact of THP-1 cells and HUVECs contributed to enhanced AM production in the cocoulture. Co-incubation of the cell membrane fraction from THP-1 cells augmented AM production by HUVECs. Both anti-interleukin (IL)-1alpha antibody and IL-1 receptor antagonist significantly inhibited AM production in the cocultures. The cell-to-cell interaction between monocytes and HUVECs induces AM production by HUVECs, which may play an important role in the pathogenesis of vascular disorders.

Adrenomedullin↗
PubMed2001

High plasma homocyst(e)ine levels in elderly Japanese patients are associated with increased cardiovascular disease risk independently from markers of coagulation activation and endothelial cell damage.

Elevated plasma homocyst(e)ine is a risk factor for cardiovascular disease (CVD) in many populations, but the relationship between homocyst(e)ine and CVD in Japanese subjects has been unclear. It has been hypothesized that the link between homocyst(e)ine and CVD may be mediated in part by activation of coagulation and endothelial cell injury in the elderly Japanese subjects. To further evaluate this hypothesis, the present cross-sectional study was designed to assess the relationships among plasma homocyst(e)ine concentrations, risk of CVD, and markers of coagulation (fibrinogen, FVII, F1+2, FVIIa and FXIIa) and endothelial cell damage (vWF and thrombomodulin) in 146 elderly Japanese subjects (79 healthy controls and 67 patients with CVD). The geometric mean (range) of plasma homocyst(e)ine concentrations was 10.2 (3.2--33) micromol/l in 79 Japanese healthy elderly subjects. As expected, healthy female and male elderly subjects had homocyst(e)ine levels that were 2.5 and 5.3 micromol/; higher, respectively, compared to healthy young control subjects (n=62). Healthy young and elderly men had homocyst(e)ine levels that were 1.7 and 4.5 micromol/l higher, respectively, compared to values in women. This higher plasma homocyst(e)ine levels in the elderly subjects were negatively correlated with levels of folic acid, albumin and total cholesterol, but were not significantly related to markers of coagulation or endothelial cell-damage. The results of multiple logistic regression analyses suggested that high homocyst(e)ine levels were independently related to CVD risk. In addition, levels of FVIIa, and F1+2 were significantly higher in elderly Japanese patients with CVD compared to elderly subjects without CVD, but were unrelated to plasma homocyst(e)ine concentrations. In summary, elevated plasma concentrations of homocyst(e)ine, FVIIa, and F1+2 were associated with increased risk of CVD in elderly male and female Japanese subjects, but the association between homocyst(e)ine and CVD was unrelated to abnormalities in markers of coagulation and endothelial cell damage in this population.

Aged↗
PubMed2001

Silent and clinically overt stroke in older Japanese subjects with white-coat and sustained hypertension.

OBJECTIVES: We investigated whether white-coat hypertension is a risk factor for stroke in relation to silent cerebral infarct (SCI) in an older Japanese population. BACKGROUND: It remains uncertain whether white-coat hypertension in older subjects is a benign condition or is associated with an increased risk of stroke. METHODS: We studied the prognosis for stroke in 958 older Japanese subjects (147 normotensives [NT], 236 white-coat hypertensives [WCHT] and 575 sustained hypertensives [SHT]) in whom ambulatory blood pressure monitoring was performed in the absence of antihypertensive treatment. In 585 subjects (61%), we also assessed SCI using brain magnetic resonance imaging. RESULTS: Silent cerebral infarcts were found in 36% of NT (n = 70), 42% of WCHT (n = 154), and 53% of SHT (n = 361); multiple SCIs (the presence of > or =2 SCIs) were found in 24% of NT, 25% of WCHT and 39% of SHT. During a mean 42-month follow-up period, clinically overt strokes occurred in 62 subjects (NT: three [2.0%]; WCHT: five [2.1%]; SHT: 54 [9.4%]), with 14 fatal cases (NT: one [0.7%]; WCHT: 0 [0%]; SHT: 13 [2.3%]). A Cox regression analysis showed that age (p = 0.0001) and SHT (relative risk, [RR] [95% confidence interval, CI]: 4.3 [1.3-14.2], p = 0.018) were independent stroke predictors, whereas WCHT was not significant. When we added presence/absence of SCI at baseline into this model, the RR (95% CI) for SCI was 4.6 (2.0-10.5) (p = 0.003) and that of SHT was 5.5 (1.8-18.9) versus WCHT (p = 0.004) and 3.8 (0.88-16.7) versus NT (p = 0.07). CONCLUSIONS: In older subjects the incidence of stroke in WCHT is similar to that of NT and one-fourth the risk in SHT. Although SCI is a strong predictor of stroke, the difference in stroke prognosis between SHT and WCHT was independent of SCI. It is clinically important to distinguish WCHT from SHT even after assessment of target organ damage in the elderly.

Aged↗
PubMed2001

Lower standing systolic blood pressure as a predictor of falls in the elderly: a community-based prospective study.

OBJECTIVES: We investigated prospectively the relationships among falls, physical balance, and standing and supine blood pressure (BP) in elderly persons. BACKGROUND: Falls occur often and adversely affect the activities of daily living in the elderly; however, their relationship to BP has not been clarified thoroughly. METHODS: A total of 266 community-dwelling elderly persons age 65 years or over (123 men and 143 women, mean age of 76 years) were selected from among residents of Coop City, Bronx, New York. Balance was evaluated at baseline using computerized dynamic posturography (DPG). During a one-year follow-up, we collected information on subsequent falls on a monthly basis by postcard and telephone follow-up. RESULTS: One or more falls occurred in 60 subjects (22%) during the one-year follow-up. Women fell more frequently than men (28% vs. 16%, p < 0.03), and fallers were younger than nonfallers. Fallers (n = 60) had lower systolic BP (SBP) levels when compared with nonfallers (n = 206) (128 +/- 17 vs. 137 +/- 22 mm Hg for standing, p < 0.006; 137 +/- 16 vs. 144 +/- 22 mm Hg for lying, p < 0.02), whereas diastolic BP was not related to falls. Falls occurred 2.8 times more often in the lower BP subgroup (<140 mm Hg for standing SBP) than in the higher BP subgroup (> or =140 mm Hg, p < 0.0003), and gender-related differences were observed (p = 0.006): 3.4 times for women (p < 0.0001) versus 1.9 times for men (p = 0.30). Loss of balance, as detected by DPG, did not predict future falls and was also not associated with baseline BP levels. Multiple logistic regression analysis demonstrated that female gender (relative risk [RR] = 2.1, p = 0.02), history of falls (RR = 2.5, p = 0.008) and lower standing SBP level (RR = 0.78 for 10 mm Hg increase, p = 0.005) were independent predictors of falls during one year of follow-up. CONCLUSIONS: Lower standing SBP, even within normotensive ranges, was an independent predictor of falls in the community-dwelling elderly. Elderly women with a history of falls and with lower SBP levels should have more attention paid to the prevention of falls and related accidents.

Accidental Falls↗
PubMed2001

Different patterns of silent cerebral infarct in patients with coronary artery disease or hypertension.

The aim of the present study was to clarify the differences in the progression and the characteristics of silent cerebral infarcts (SCI) between patients with coronary artery disease (CAD) and hypertensive patients. Silent cerebral infarcts, a powerful prognostic indicator for stroke, are frequently found in patients with CAD and in hypertensives. However, the differences in the characteristics of SCI and related risk factors between CAD and hypertensive patients have not been thoroughly investigated. We evaluated the number of SCI and their distribution using brain magnetic resonance imaging (T1- and T2-weighted images) in 107 patients with CAD (validated by coronary angiography) and 101 hypertensive patients without history of clinical stroke. The prevalence of multiple SCI (three or more infarcts per person) in patients with CAD and with hypertension was significantly higher than in hypertensives without CAD (46% v 21%; P = .001), whereas that of patients with CAD without hypertension was intermediate (31%). The patients with multi- (two- or three-vessel) vessel diseases (VD) had a significantly higher prevalence of multiple SCI than the hypertensives and the no-stenosis or 1-VD group (68.1% in the 3-VD group, 52.0% in the 2-VD group, 26.8% in the 1-VD group, and 21.0% in the no-stenosis group). Multiple logistic regression analysis revealed that in the CAD group, the number of involved coronary arteries was an independent determinant of SCI (P < .005), whereas in the hypertensive group, age was an independent determinant of SCI (P < .005). When we investigated the distribution of SCI, in the CAD group, SCI in the deep perforator territory (the basal ganglia and the thalamus) were independently associated with the number of involved coronary arteries (P < .005), whereas SCI in the white matter were independently associated with age only (P < .005). In conclusion, SCI were more advanced in the patients with multivessel CAD than in the hypertensive patients, and were more common in patients with CAD and hypertension than in those without hypertension. Coronary atherosclerosis was independently and specifically associated with SCI located in the deep perferator territory but not of SCI located in the white matter. The CAD-atherosclerosis and hypertension may be independently involved in the pathologic process of SCI.

Arteriosclerosis↗
PubMed2001

Silent cerebral infarcts in basal ganglia are advanced in congenital protein C-deficient heterozygotes with hypertension.

Congenital protein C deficiency is now widely recognized as a genetic risk for venous thrombosis. However, it remains uncertain whether this condition also confers risk for arterial thrombosis. We evaluated the association of congenital protein C deficiency with hypertension and silent cerebrovascular disease using brain magnetic resonance imaging (MRI) (T1- and T2-weighted and proton density images) in a large family pedigree of protein C deficiency diagnosed by gene analysis, compared with 46 non-pedigree related control subjects with normal protein C levels (> or = 75%) who were selected from among 55 asymptomatic hypertensive subjects matched for age and cardiovascular risk factors. Of the 58 living subjects in this pedigree, we measured plasma protein C levels in 45 subjects, and found 2 cerebral infarctions in the 24 heterozygotic subjects, whereas there was no stroke in the 21 normal homozygotic subjects. We performed brain MRI in 14 asymptomatic hypertensive subjects without any cardiovascular disease and in two patients with cerebral infarction, and found 28 cerebral infarcts (two corresponded to the patients' neurologic deficits and 26 were silent). All were lacunar infarcts < 10 cm in size. A total of 25 silent lacunar infarcts were found in nine heterozygotic subjects, whereas only one was found in the seven normal homozygotic subjects (2.8 v 0.14 lacunes per person, P = .002). No advanced white matter hyperintense lesions in T2-weighted images were found in either group. The prevalence of silent lacunar infarcts in the heterozygotic subjects was also significantly higher than that in normal control subjects (1.0 per person, P = .01). Concerning the distribution of silent infarcts, the number of lacunes located in the basal ganglia was higher in the heterozygotic subjects (2.3 per person, P < .001) than in the seven normal homozygotic subjects (0.14 per person) or in the control group (0.28 per person), whereas the number of lacunes in the white matter was not different among the groups. In conclusion, congenital protein C deficiency may accelerate the progression of silent cerebral infarct formation in hypertension, particularly in the basal ganglia, and may be a potential risk for stroke or vascularly induced dementia.

Aged↗
PubMed2001

Effects of long-acting ACE inhibitor (temocapril) and long-acting Ca channel blocker (amlodipine) on 24-h ambulatory BP in elderly hypertensive patients.

In a prospective randomised cross-over study, we compared the effects of ACE inhibitor temocapril and calcium channel blocker (CCB) amlodipine on ambulatory blood pressure in 59 asymptomatic elderly hypertensive patients (mean age 69 years). This study was performed in a cross-over fashion after a 2-week placebo period and 4 to 8 weeks each of treatment with temocapril and amlodipine. Of those 59 hypertensive patients, three patients with side effects and 10 patients whose office BPs did not achieve the target BPs were excluded, and the remaining 46 were analysed in this study: they consisted of 30 dippers, with a night time reduction in systolic BP (SBP) > or = 10% and 16 non-dippers, with reduction by < 10%. At the baseline, there were no significant differences in the office, 24-h or daytime BPs between the two groups (dippers and non-dippers). Though the office BPs and daytime BPs were successfully controlled to the same levels with both treatments and in both dipping groups, the antihypertensive effects were stronger with the CCB than with the ACE inhibitor in the night time and morning, especially in non-dippers. We conclude that even though office BPs were controlled successfully to almost the same levels, there is a possibility that these long-acting drugs have differential antihypertensive effects on night time and morning BPs among hypertensive patients with different night time BP dipping statuses.

Aged↗
PubMed2001

Nocturnal non-dipping: what does it augur?

The non-dipping pattern of blood pressure (defined as a nocturnal fall of less than 10%) occurs in about 25% of hypertensives, with increased prevalence in certain sub-groups such as diabetics, African-Americans, and patients with renal disease. It almost certainly has multiple causes, including factors such as the levels of activity and arousal during both the day and the night, the depth and quality of sleep, and the activity of the sympathetic nervous system, among others. In patients with uncomplicated hypertension, the reproducibility is relatively low. There is evidence suggesting that the non-dipping pattern may have an adverse prognosis: thus, it appears to predict the progression of renal disease, to be associated with increased target-organ damage (in some studies), and also to predict increased cardiovascular morbidity. Antihypertensive drug treatment can normalize the non-dipping pattern, but the therapeutic consequences of this are unknown.

Black or African American↗
PubMed2001

Early morning surge in blood pressure.

Early-morning blood pressure is generally viewed as an important therapeutic target, for two reasons. First, for antihypertensive agents taken once daily in the morning, the timing of the trough plasma drug level, and thereby the lowest pharmacodynamic effect, often coincides with the early morning rise in blood pressure and heart rate. Evidence has been accumulated to suggest that blood pressure control throughout the 24 h period may be necessary to gain complete benefit from antihypertensive medication. In fact, in a longitudinal study, the regression of cardiac hypertrophy in patients with hypertension was more accurately predicted by treatment-induced changes in average 24 h ambulatory blood pressure than by clinic or home-monitored blood pressure readings. The other reason for the importance of morning blood pressure is that cardiovascular risk is heightened at this time of day. A morning surge in sympathetic activity alters haemodynamic forces and predisposes vulnerable coronary atherosclerotic plaques to rupture. At the same time as this risk of plaque rupture is greatest, circadian variations in haemostatic and fibrinolytic factors result in morning hypercoagulability and hypofibrinolysis, promoting the formation of intraluminal thrombi. We recently showed that, in older hypertensives, a greater morning blood pressure surge, mediated at least in part by an exaggerated alpha-sympathetic activity, is associated with more advanced silent cerebrovascular disease as well as a higher future incidence of stroke. The early morning surge in blood pressure could become a new therapeutic target for preventing target-organ damage and subsequent cardiovascular events in hypertension. Of greatest interest is the potential benefit of a chronotherapeutic approach, involving, for example, long-acting chronoformulations, which has not yet been extensively studied.

Blood Pressure↗
PubMed2001

Stroke prognosis and abnormal nocturnal blood pressure falls in older hypertensives.

It remains uncertain whether abnormal dipping patterns of nocturnal blood pressure influence the prognosis for stroke. We studied stroke events in 575 older Japanese patients with sustained hypertension determined by ambulatory blood pressure monitoring (without medication). They were subclassified by their nocturnal systolic blood pressure fall (97 extreme-dippers, with >/=20% nocturnal systolic blood pressure fall; 230 dippers, with >/=10% but <20% fall; 185 nondippers, with >/=0% but <10% fall; and 63 reverse-dippers, with <0% fall) and were followed prospectively for an average duration of 41 months. Baseline brain magnetic resonance imaging (MRI) disclosed that the percentages with multiple silent cerebral infarct were 53% in extreme-dippers, 29% in dippers, 41% in nondippers, and 49% in reverse-dippers. There was a J-shaped relationship between dipping status and stroke incidence (extreme-dippers, 12%; dippers, 6.1%; nondippers, 7.6%; and reverse-dippers, 22%), and this remained significant in a Cox regression analysis after controlling for age, gender, body mass index, 24-hour systolic blood pressure, and antihypertensive medication. Intracranial hemorrhage was more common in reverse-dippers (29% of strokes) than in other subgroups (7.7% of strokes, P=0.04). In the extreme-dipper group, 27% of strokes were ischemic strokes that occurred during sleep (versus 8.6% of strokes in the other 3 subgroups, P=0.11). In conclusion, in older Japanese hypertensive patients, extreme dipping of nocturnal blood pressure may be related to silent and clinical cerebral ischemia through hypoperfusion during sleep or an exaggerated morning rise of blood pressure, whereas reverse dipping may pose a risk for intracranial hemorrhage.

Aged↗
PubMed2001

Gender differences in associations of diurnal blood pressure variation, awake physical activity, and sleep quality with negative affect: the work site blood pressure study.

This study reports on the associations among depression, anxiety, awake physical activity, sleep quality (assessed by nocturnal physical activity), and diurnal blood pressure (BP) variation in a nonpsychiatric sample (The Work Site Blood Pressure Study). We conducted ambulatory BP (ABP) monitoring and actigraphy in 231 working men and women. Depression and anxiety were measured by the Brief Symptom Inventory. There were gender-specific associations between depression or anxiety and ABP parameters. In men, depression was associated positively with the sleep/awake systolic BP (SBP) ratio (r=0.24, P=0.006). After controlling for age, body mass index, and awake and sleep activity, depression remained significantly associated with the sleep/awake SBP ratio (r=0.25, P=0.005) and was also significantly related to sleep SBP (r=0.21, P=0.02). Anxiety, which was related to depression (r=0.73, P<0.0001), had a similar but slightly weaker pattern of associations with ABP and activity. These associations were not found in women, but there were associations of anxiety with awake SBP (r=0.24, P=0.01) and pulse rate (r=0.27, P=0.006). In conclusion, depression is associated with disrupted diurnal BP variation independent of ambulatory physical activity in working men, whereas anxiety is associated with awake SBP and pulse rate in women.

Adult↗
PubMed2001

Circadian variation of autonomic nervous activity in patients with multivessel coronary spasm.

The present study investigated whether the circadian rhythm of sympathovagal activity is related to the severity of coronary spasm or multivessel coronary spasm. Heart rate variability was examined in 22 consecutive patients with vasospastic angina provoked by intracoronary injection of acetylcholine, who had either multivessel spasm (Group M, n=11 ) or single vessel spasm (Group S, n= 11), in 20 subjects without coronary artery disease (Group C) and 20 patients with effort angina who had organic coronary artery stenosis (Group E). The frequency domain indices were analyzed, including low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-0.4Hz), the latter being an index of efferent parasympathetic activity, and the ratio (L/H) as an index of sympathovagal balance. The circadian variation of the parameters was analyzed by its pattern and was quantified by the difference of the mean values between daytime and nighttime. Although the HF power increased during nighttime in Groups C and S, this increase was attenuated in Groups E and M. The circadian variation of the L/H ratio (ie, a drop during nighttime) was smaller in the S and M groups than in Groups C and E. Accordingly, in Group M, the circadian variation of both sympathetic and parasympathetic nervous activity was attenuated, but in Group S, the variation of sympathetic nervous activity, but not parasympathetic nervous activity, was decreased. These data suggest that relatively enhanced sympathetic nervous activity at night may be involved in the mechanism underlying multivessel coronary spasm.

Acetylcholine↗