Whether mean arterial pressure (MAP) and pulse pressure (PP), two indicators of cerebral perfusion, could guide the selection of anti-hypertensive strategies after acute ischaemic stroke remains uncertain. Our study was to explore the impact of early anti-hypertensive intervention on adverse clinical outcomes following ischaemic stroke stratified by the levels of MAP and PP based on the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS).

The trial randomised 4071 acute ischaemic stroke patients with elevated systolic blood pressure (SBP) to receive anti-hypertensive treatment (targeting a 10%-25% reduction in SBP during the 24 hours postrandomisation, reaching a BP level <140/90 mm Hg in 7 days, further keeping these levels throughout hospitalisation) or discontinue anti-hypertensive treatment during hospitalisation. The primary outcome was death or major disability at 14 days or hospital discharge. Study outcomes were analysed by comparing the BP-lowering intervention group and control group, stratified by tertiles of MAP or PP levels.

No significant difference was observed in the primary outcome between the intervention and control groups across all MAP (p=0.69 for homogeneity) and PP (p=0.78 for homogeneity) categories. The corresponding odds ratios (95% CIs) were 1.08 (0.85-1.36), 0.92 (0.74-1.15) and 1.00 (0.81-1.25) for participants with low, intermediate, and high MAP and were 0.99 (0.79-1.25), 1.06 (0.84-1.34) and 0.95 (0.77-1.18) for participants in PP subgroups, respectively. Furthermore, early anti-hypertensive intervention was not associated with secondary outcomes (including neurological deterioration, recurrent stroke, vascular events and all-cause mortality) by MAP and PP (all p>0.05).

Early anti-hypertensive therapy neither decreased nor increased the odds of major disability, mortality, recurrent stroke or vascular events in patients with acute ischaemic stroke regardless of different MAP and PP levels.

ClinicalTrials.gov identifier: NCT01840072.

Blood pressure has been shown to change by outdoor temperature, but whether intra- and inter-day temperature variability (TV) will bring higher effect on BP is not clear. Based on a prospective cohort study, the mixed effect model was selected to estimate the relationship between TV (daily temperature variability (DTV) and hourly temperature variability (HTV)) and BP (systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP)) after adjusting for confounding variables. We found that there was a positive linear correlation between TV and BP. The results of DTV and HTV were basically consistent, but the effect estimates of HTV seemed to be larger. Gender, age, BMI, education level and BP status may modify the relationship between TV and BP. The effect of TV on BP was greater in non-heating season than in heating season. Our work contributes to a further macro mechanism evidence for the TV-CVDs association.

Cardiorespiratory fitness (CRF) prompts antiatherogenic adaptations in vascular function and structure. However, there is an extraordinary interindividual variability in response to a standard dose of exercise, wherein a substantial number of adults with intellectual and developmental disabilities (IDD) do not improve CRF. We (1) evaluated the effects of 12-month of moderate-intensity continuous training (MICT) on CRF and arterial stiffness and (2) tested whether an additional 3-month of high-intensity interval training (HIIT) would add to improvements in CRF responsiveness and arterial stiffness.

Fifteen adults with mild-to-moderate IDD (male adults = 9, 30.1 ± 7.5 years old) met 3 days per week for 30 min MICT for 12 months, after which the incidence of CRF responsiveness was calculated (≥5.0% change in absolute peak VO₂ ). Thereafter, responders and non-responders started HIIT for 3 months with identical daily training load/frequency. Peak VO₂ , local and regional indices of arterial stiffness were assessed prior to and after each period.

Sixty per cent of the participants were non-responders following MICT, but the incidence dropped to 20% following HIIT (P = 0.03). Absolute peak VO₂ values reached significant difference from pre-intervention (+0.38 ± 0.08 L min^-1 , P = 0.001) only when HIIT was added. Lower limb pulse wave velocity (PWV) decreased following MICT (-0.8 ± 1.1 m s^-1 , P = 0.049), whereas central PWV only decreased following HIIT (-0.8 ± 0.9 m s^-1 , P = 0.013).

Cardiorespiratory fitness responsiveness and reductions in PWV to a 12-month MICT period in adults with IDD improved following a period of HIIT programme inducing higher metabolic stress.

Tooth extraction is one of the most common causes of dental anxiety and pain, leading to the elevation of blood pressure (BP) and heart rate (HR). Such effects may be exaggerated and cause life-threatening accidents in patients with hypertension. Therefore, the pain and anxiety management of these patients is imperative. Virtual reality (VR) has been demonstrated to be a distraction method to relieve anxiety and pain in clinical operations. Thus, we hypothesized that VR can control the elevation of BP and HR in patients with hypertension. In this study, 96 eligible patients with controlled hypertension who needed tooth extraction were randomized to the VR or standard care group by stratified randomization of anxiety grade and gender. Their BP and HR were dynamically monitored. The corresponding systolic and diastolic BP and HR values were selected when systolic BP was at the highest point of the process. BP was converted into mean arterial pressure (MAP) for comparison per the following formula: MAP = (systolic BP + 2 × diastolic BP)/3. Statistical analyses were by intention to treat and conducted in SPSS. Nonparametric rank sum tests were used to compare the difference of ΔMAP and ΔHR between the VR and standard care groups. Multivariate linear regression was applied to evaluate the effect of VR on ΔMAP and ΔHR. The results showed that the VR technique significantly decreased the elevation of MAP (P < 0.001) and HR (P < 0.001), and this effect was found even after adjusting for baseline characteristics and additional surgical procedures (ΔMAP, P < 0.001, R² = 0.276; ΔHR, P < 0.001, R² = 0.152). VR did not increase the incidence of adverse events (P = 0.677). In conclusion, the VR technique was effective in controlling BP and HR within an acceptable range and can help manage BP and HR during tooth extraction for patients with hypertension (Chinese Clinical Trial Registry: ChiCTR2100042132).

The prognostic implication of isolated systolic hypertension (ISH), defined as SBP at least 140 mmHg and DBP less than 90 mmHg, among young-to-middle-aged adults remains controversial. We examined the association of ISH with cardiovascular disease (CVD) risk in adults aged 30-49 years.

In a prospective cohort of representative Japanese general populations from the NIPPON DATA80 (1980-2009), we studied 4776 participants (mean age, 39.4 years; 55.4% women) without clinical CVD or antihypertensive medication. Participants were classified as follows: normal blood pressure (BP) (SBP/DBP, <120/<80 mmHg), high-normal BP (120-129/<80 mmHg), elevated BP (130-139/80-89 mmHg), ISH, isolated diastolic hypertension (IDH) (<140/≥90 mmHg), and systolic--diastolic hypertension (SDH) (≥140/≥90 mmHg).

ISH was observed in 389 (8.1%) participants. During the 29-year follow-up, 115 participants died of CVD, 28 of coronary heart disease, and 49 of stroke. Cox proportional hazards models adjusted for demographics and CVD risk factors showed that participants with ISH had higher risk of CVD mortality than those with normal BP [hazard ratio (confidence interval), 4.10 (1.87-9.03)]. The magnitude of CVD mortality risk related to ISH was comparable with that related to IDH [3.38 (1.31-8.72)] and not as great as that related to SDH [5.41 (2.63-11.14)]. We found significant associations of ISH with coronary and stroke mortality. The association of ISH with CVD mortality was consistent across men and women and those aged 30-39 and 40-49 years.

ISH among young-to-middle-aged Japanese adults was independently associated with higher risk of CVD mortality later in life.

[Figure: see text].

The study aimed to analyze the association between hypertension control and subclinical cerebrovascular health using a comprehensive multimodal imaging approach.

The study included 200 hypertensive older males without previous cardiovascular diseases. Clinic blood pressure (BP) was measured using a standard approach. Cerebrovascular health was evaluated using magnetic resonance imaging in the following four aspects: Intracranial atherosclerosis as determined by vessel wall imaging; Vascular rarefaction (defined as less discernible vessels on angiography) was evaluated using a custom-developed technique. Cerebral blood flow (CBF) and white matter hyperintensity (WMH) were assessed using arterial spin-labeling imaging and fluid-attenuated inversion recovery imaging, respectively.

A total of 189 subjects had MRI scans. The mean age was 64.9 (± 7.2) years. For intracranial atherosclerosis, there was a significant association between uncontrolled hypertension and presence of intracranial plaque. When systolic and diastolic BP were analyzed separately, the association remained significant for both. For vascular rarefaction, uncontrolled hypertension was associated with less discernible vessel branches or shorter vessel length on angiography. Further analysis revealed that this is due to uncontrolled diastolic BP, but not uncontrolled systolic BP. There was an association between uncontrolled hypertension and reduced CBF, which was also mainly driven by uncontrolled diastolic BP. We also found that uncontrolled diastolic BP, but not uncontrolled systolic BP, was associated with increased WMH volume.

Uncontrolled hypertension was associated with subclinical cerebrovascular injury globally, with both small and medium-to-large arteries being affected.

• In this study, we leveraged the advantage of a series of cutting-edge MR imaging and analysis techniques and found uncontrolled hypertension is associated with subclinical globally compromised cerebrovascular health. • The detrimental consequences of uncontrolled BP affect not only the small vessels but also the medium-to-large arteries, and uncontrolled systolic and diastolic BP are both independently associated with certain types of cerebrovascular injury. • Our data suggest that cerebrovascular health is impaired globally in uncontrolled hypertension before the onset of stroke.

To investigate the associations between mean arterial pressure (MAP) and mortality in patients with peritoneal dialysis (PD).

A total of 1737 patients with terminal renal diseases under PD in the First Affiliated Hospital of Zhejiang University from 2008 to 2016 were enrolled. Patients were followed up for 33.0(19.3, 52.4) months. The mean arterial pressure over the first 3 months of PD therapy were calculated. All-cause death and cardiovascular death were assessed using Cox regression models adjusted for demographics, laboratory measurements, comorbid conditions and antihypertensive medications.

During the follow-up, 208 patients died, among which 95(45.7%) patients died of cardiovascular causes. Compared with patients with MAP >95-<120 mmHg, patients with MAP ≤ 95 mmHg were associated with significantly higher risk of all-cause death (HR=1.40,95%CI:1.01-1.93,P<0.05); patients with MAP ≥ 120 mmHg were associated with significantly higher risk of all-cause (HR=2.12,95%CI:1.32-3.40, P<0.01) and cardiovascular morality (HR=2.55, 95%CI:1.38-4.70, P<0.01). MAP presents a U-shaped association with all-cause mortality and a J-shaped association with cardiovascular mortality.

Both high MAP and low MAP are associated with higher risk of mortality in PD patients.

Mean arterial pressure (MAP) is the strongest predictor of stroke. The combination of clopidogrel and aspirin within 24 hours after onset has been suggested by the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) study to be superior to aspirin alone. However, it is not clear whether poststroke blood pressure has an influence on the efficacy and safety of dual antiplatelet treatment. We have performed a post hoc analysis from the CHANCE trial. Patients were stratified into three groups based on MAP levels. Among patients with MAP <102 mm Hg, there was no significant difference in stroke recurrence between the clopidogrel-aspirin group and the aspirin group (7.7% vs 7.5%; hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.73-1.45). However, compared to aspirin treatment, the clopidogrel-aspirin dual treatment was more effective at reducing the risk of stroke in patients with MAP ≥113 mm Hg (6.9% vs 12.3%, HR, 0.55; 95% CI, 0.39-0.78) or 102-113 mm Hg (9.5% vs 14.9%, HR, 0.62; 95% CI, 0.48-0.81). There was a significant interaction between MAP and antiplatelet therapy as it relates to stroke recurrence (P for interaction = 0.037), and a similar result was found for combined vascular events (P for interaction = 0.027). In conclusion, dual antiplatelet therapy may be more effective at reducing combined vascular events in patients with higher MAP after minor stroke or transient ischemic attack.

This study aims to develop and validate a stroke risk model incorporating pulse pressure (PP) as a potential risk factor. Recent evidence suggests that PP, defined as the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP), could be an incremental risk factor beyond SBP.

Electronic health records (EHRs) of hypertensive patients from a US integrated health delivery system were analyzed (January 2004 to May 2012). Patients with ≥ 1 PP reading and ≥ 6 months of observation prior to the first diagnosis of hypertension were randomly split into development (two-thirds of sample) and validation (one-third of sample) datasets. Stroke events were identified using ICD-9-CM 433.xx-436.xx. Cox proportional hazards models assessed time to first stroke event within 3 years of first hypertension diagnosis based on baseline risk factors, including PP, age, gender, diabetes, and cardiac comorbidities. The optimal model was selected using the least absolute shrinkage and selection operator (LASSO); performance was evaluated by the c-statistic.

Among 34,797 patients selected (mean age 59.3 years, 48% male), 4272 patients (12.3%) had a stroke. PP was higher among patients who developed stroke (mean [SD] PP, stroke: 02.0 [15.3] mmHg; non-stroke: 58.1 [14.0] mmHg, p < 0.001). The best performing risk model (c-statistic, development: 0.730; validation: 0.729) included PP (hazard ratio per mmHg increase: 1.0037, p < 0.001) as a significant risk factor.

This study was subject to limitations similar to other studies using EHRs. Only patient encounters occurring within the single healthcare network were captured in the data source. Though the model was tested internally, external validation (using a separate data source) would help assess the model's generalizability and calibration.

This stroke risk model shows that greater PP is a significant predictive factor for increased stroke risk, even in the presence of known risk factors. PP should be considered by practitioners along with established risk factors in stroke treatment strategies.

There have been no investigations concerning the association of each blood pressure (BP) reading with future cardiovascular disease (CVD) when multiple measurements are taken on one occasion. This community-based, prospective cohort study (n = 23 344, mean age = 62.4 years) investigated the associations between the BP obtained from the first and second of two consecutive measurements on one occasion and future cardiovascular events in men and women.

During the mean follow-up of 5.5 years, 624 CVD events were identified. On the Cox regression analysis of age- and BP-adjusted models, the increased CVD risk of a hypertensive first measurement (systolic BP ≥ 140 mmHg) was independent from the second measurement in men. Even in subjects without a hypertensive second measurement, the CVD risk of the hypertensive first measurement was increased in men. In women, despite a hypertensive first measurement, subjects with a systolic BP < 130 mmHg on the second measurement showed a significantly reduced risk for CVD compared with subjects who retained a hypertensive level during the two measurements.

An elevated BP on the first measurement should not be disregarded for CVD risk estimation in men, even if the second BP moves to the normal range. In women, elevated BP on the first measurement may have relatively less meaning for CVD prediction if the second BP shifts to a normal range.

White matter hyperintensities (WMH) are associated with hypertension. We examined interactions among blood pressure (BP), internal carotid artery (ICA) flow velocity parameters, and WMH. We obtained BP measurements from 694 community-dwelling subjects at mean ages 69.6 (±0.8) years and again at 72.6 (±0.7) years, plus brain MRI and ICA ultrasound at age 73±1 years. Diastolic and mean BP decreased and pulse pressure increased, but systolic BP did not change between 70 and 73 years. Multiple linear regression, corrected for vascular disease and risk factors, showed that WMH at the age of 73 years were associated with history of hypertension (β=0.13; P<0.001) and with BP at the age of 70 years (systolic β=0.08, mean β=0.09, diastolic β=0.08; all P<0.05); similar but attenuated associations were seen for BP at the age of 73 years. Lower diastolic BP and higher pulse pressure were associated with higher ICA pulsatility index at the age 73 years (diastolic BP age 70 years: standardized β=-0.24, P<0.001; pulse pressure age 70 years: β=0.19, P<0.001). WMH were associated with higher ICA pulsatility index (β=0.13; P=0.002) after adjusting for BP and correction for multiple testing. Therefore, falling diastolic BP and increased pulse pressure are associated with increased ICA pulsatility index, which in turn is associated with WMH. This suggests that hypertension and WMH may either associate indirectly because hypertension increases arterial stiffness that leads to WMH over time, or coassociate through advancing age and stiffer vessels, or both. Reducing vascular stiffness may reduce WMH progression and should be tested in randomized trials, in addition to testing antihypertensive therapy.

We conducted a genome-wide association study meta-analysis of mean arterial pressure and pulse pressure among 26,600 East Asian participants (stage 1) followed by replication study of up to 28,783 participants (stage 2). For novel loci, statistical significance was determined by a P<5.0×10(-8) in joint analysis of stage 1 and stage 2 data. For loci reported by the previous mean arterial and pulse pressure genome-wide association study meta-analysis in Europeans, evidence of transethnic replication was determined by consistency in effect direction and a Bonferroni-corrected P<1.4×10(-3). No novel loci were identified by the current study. Five independent mean arterial pressure variants demonstrated robust evidence for transethnic replication including rs17249754 at ATP2B1 (P=7.5×10(-15)), rs2681492 at ATP2B1 (P=3.4×10(-7)), rs11191593 at NT5C2 (1.1×10(-6)), rs3824755 at CYP17A1 (P=1.2×10(-6)), and rs13149993 at FGF5 (P=2.4×10(-4)). Two additional variants showed suggestive evidence of transethnic replication (consistency in effect direction and P<0.05), including rs319690 at MAP4 (P=0.014) and rs1173771 at NPR3 (P=0.018). For pulse pressure, robust evidence of replication was identified for 2 independent variants, including rs17249754 at ATP2B1 (P=1.2×10(-5)) and rs11191593 at NT5C2 (P=1.1×10(-3)), with suggestive evidence of replication among an additional 2 variants including rs3824755 at CYP17A1 (P=6.1×10(-3)) and rs2681492 at ATP2B1 (P=9.0×10(-3)). Replicated variants demonstrated consistency in effect sizes between East Asian and European samples, with effect size differences ranging from 0.03 to 0.24 mm Hg for mean arterial pressure and from 0.03 to 0.21 mm Hg for pulse pressure. In conclusion, we present the first evidence of transethnic replication of several mean arterial and pulse pressure loci in an East Asian population.

Conflicting results have been reported on whether the association between increments in systolic blood pressure (SBP) and cardiovascular disease differs between men and women. We performed a systematic review with meta-analysis to compare reliably sex-specific associations between SBP and cardiovascular risk.

PubMed MEDLINE was systematically searched for prospective population-based cohort studies published between January 1, 1966, and March 31, 2012. Studies were selected if they presented sex-specific estimates, with associated variability, of the relative risk for either ischemic heart disease or stroke according to SBP. The data were pooled using random effects models with inverse variance weighting, and estimates of the ratio of the relative risks per 10 mm Hg increment in SBP, comparing women with men, were derived.

Data from 124 prospective cohort studies, including information on 1197 472 individuals (44% women) and 26 176 stroke and 24 434 ischemic heart disease events, were included. Overall, there was no evidence to suggest a sex difference in the relationship between SBP and either the risk of stroke (pooled ratio of relative risks, 0.98 [95% confidence interval, 0.96; 1.01]; P=0.13) or ischemic heart disease (pooled ratio of relative risks, 1.00 [95% confidence interval, 0.97; 1.04]; P=0.85).

Elevated levels of SBP are a major risk factor for stroke and ischemic heart diseases in both women and men. This study unequivocally demonstrates the broadly similar impact of SBP increments on cardiovascular outcomes in both sexes.

High blood pressure is a significant risk factor for cardiovascular disease and mortality. Japan has traditionally had higher levels of measured blood pressure than many Western countries, and reducing levels of hypertension has been a major focus of Japanese health policy over recent decades. In the West, hypertension is strongly associated with sociodemographic and behavioral (smoking and body mass index, BMI) factors; studies of the association between sociodemographic factors and biological indicators have not been fully explored in the elderly population of Japan using nationally representative survey data.

To describe hypertension prevalence rates with increasing age and to examine the link between sociodemographic and behavioral factors (including age, gender, education, residence, smoking, and BMI) and measures of blood pressure and overall hypertension in the Japanese population aged ≥68 years.

Data were collected in 2006 during the fourth wave of the Nihon University Japanese Longitudinal Study of Aging, a nationally representative sample of those ≥68. The analytic sample includes 2,634 participants. Pulse pressure, systolic, diastolic, and mean blood pressure, as well as hypertension, were regressed on sociodemographic and behavioral factors.

There is no significant difference in the prevalence of overall hypertension by age for men and women from ages 68-69 to 90+. Higher BMI and older age were linked to higher blood pressure and higher chance of having hypertension. More years of education and being female were associated with a lower likelihood of measured hypertension. Smoking, rural residence, and living alone were not significantly associated with the outcome measures.

The increase in hypertension with higher BMI raises concerns about future health in Japan as BMI increases. The lack of a relationship between smoking and any measure of blood pressure or hypertension is an indicator that smoking may have different effects in Japan than in other countries. Because there is no effect of living alone on blood pressure, compliance with drug regimes may not be enhanced by living with others in Japan.

Neurologic decompression sickness (NDCS) can affect high-altitude pilots, causing variable central nervous system symptoms. Five recent severe episodes prompted further investigation.

We report the hyperintense white matter (HWM) lesion imaging findings in 50 U-2 pilot volunteers, and compare 12 U-2 pilots who experienced clinical NDCS to 38 U-2 pilots who did not. The imaging data were collected using a 3T magnetic resonance imaging scanner and high-resolution (1-mm isotropic) three-dimensional fluid-attenuated inversion recovery sequence. Whole-brain and regional lesion volume and number were compared between groups.

The NDCS group had significantly increased whole brain and insular volumes of HWM lesions. The intergroup difference in lesion numbers was not significant.

A clinical episode of NDCS was associated with a significant increase in HWM lesion volume, especially in the insula. We postulate this to be due to hypobaric exposure rather than hypoxia since all pilots were maintained on 100% oxygen throughout the flight. Further studies will be necessary to better understand the pathophysiology underlying these lesions.

This study investigates age-related shifts in the relative importance of systolic (SBP) and diastolic (DBP) blood pressures as predictors of stroke and whether these relations are influenced by other cardiovascular risk factors. Using 34 European cohorts from the MOnica, Risk, Genetics, Archiving, and Monograph (MORGAM) Project with baseline between 1982 and 1997, 68 551 subjects aged 19 to 78 years, without cardiovascular disease and not receiving antihypertensive treatment, were included. During a mean of 13.2 years of follow-up, stroke incidence was 2.8%. Stroke risk was analyzed using hazard ratios per 10-mm Hg/5-mm Hg increase in SBP/DBP by multivariate-adjusted Cox regressions, including SBP and DBP simultaneously. Because of nonlinearity, DBP was analyzed separately for DBP ≥ 71 mm Hg and DBP <71 mm Hg. Stroke risk was associated positively with SBP and DBP ≥ 71 mm Hg (SBP/DBP ≥ 71 mm Hg; hazard ratios: 1.15/1.06 [95% CI: 1.12-1.18/1.03-1.09]) and negatively with DBP <71 mm Hg (0.88[0.79-0.98]). The hazard ratio for DBP decreased with age (P<0.001) and was not influenced by other cardiovascular risk factors. Taking into account the age × DBP interaction, both SBP and DBP ≥ 71 mm Hg were significantly associated with stroke risk until age 62 years, but in subjects older than 46 years the superiority of SBP for stroke risk exceeded that of DBP ≥ 71 mm Hg and remained significant until age 78 years. DBP <71 mm Hg became significant at age 50 years with an inverse relation to stroke risk. In Europeans, stroke risk should be assessed by both SBP and DBP until age 62 years with increased focus on SBP from age 47 years. From age 62 years, emphasis should be on SBP without neglecting the potential harm of very low DBP.

This study was designed to determine if fractional systolic/diastolic pressures act as predictors of the extent of coronary artery disease.

A total of 545 consecutive patients (305 men, 240 women, with mean age 54.2 years) were involved in the study. The patients were diagnosed with coronary and non-coronary artery disease confirmed by angiography.

353 patients were confirmed to have coronary artery disease, with 134 cases involving one vessel, 101 two vessels and 118 three vessels. There were significant differences between brachial and ascending aortic systolic blood pressures, fractional systolic blood pressures and fractional diastolic blood pressures in the patients with coronary artery disease compared with patients with non-coronary artery disease. Blood pressure measured in the brachial artery was higher than the pressure measured in the ascending artery. Ascending aortic fractional systolic/diastolic pressures were associated with coronary Gensini score, and were significantly related to the number of diseased vessels.

Fractional systolic and diastolic pressures in the ascending aorta were strong predictive factors for the extent of coronary artery disease. Central pressures measured invasively in the ascending aorta were more predictive than peripheral pressures for the evaluation of coronary artery disease.

Arterial stiffness is a stroke risk factor. The home arterial stiffness index (HASI) can be calculated from self-measured blood pressure using the same formula as the calculation of ambulatory arterial stiffness index (AASI).

In 2,377 inhabitants (baseline age, 35-96 years) without a history of stroke, home blood pressure was measured once every morning for 26 days (median). HASI was defined as 1 minus the regression slope of diastolic over systolic on home blood pressure in individual subjects. The standardized hazard ratio (HR) of HASI was computed for cerebral infarction, while adjusting for sex, age, body mass index, pulse pressure, mean arterial pressure, heart rate, day-by-day variability of systolic blood pressure, smoking and drinking habits, serum total cholesterol, diabetes mellitus, and antihypertensive treatment.

A total of 191 (8.0%) cerebral infarctions and 75 (3.2%) hemorrhagic strokes occurred over a median of 13.8 years. Mean ± s.d. of HASI was 0.60 ± 0.23 units. An increase in HASI of 1 s.d. was associated with an increased HR for cerebral infarction in all subjects (1.19, P = 0.034), men (1.37, P = 0.002), and normotensive subjects (1.46, P = 0.006), but not in women or hypertensive patients (P > 0.56). For hemorrhagic stroke, HASI was not prognostic.

HASI predicted cerebral infarction independent of pulse pressure and other risk factors in men and normotensive subjects. One important role of home blood pressure measurement is early recognition of onset of hypertension in normotensive subjects who are at risk of developing hypertension. HASI provides additional benefits for such subjects.

Blood pressure (BP) screening is important to identify those at risk of cardiovascular disease, but there has been little data on the appropriate interval of screening. We aimed to evaluate the optimal interval and the best measure for BP re-screening by estimating the long-term, true change variance ('signal') and short-term, within-person variance ('noise'). Study design was a cohort study from 2005 to 2008. Target population was Japanese healthy adults not taking antihypertensive medication at baseline, in a teaching hospital. We measured annually the systolic BP (SBP) and the diastolic BP (DBP), and calculated the pulse pressure (PP) and the mean arterial pressure (MAP). A total of 15,055 individuals (51% male) with a mean age of 49 years had annual check-ups. Short-term coefficient of variation was lowest for MAP at 5.2%, followed by SBP (5.7%) and DBP (5.8%), and highest for PP (12%). After 3 years, the 'signal' of true BP changes of only SBP and MAP equaled the 'noise' of BP measurement; however, it was larger for those with higher initial BPs. SBP or MAP appears to be a better screening measure. The optimal interval should be 3 years or more, with SBP<130 mm Hg and 2 years for those with SBP ≥ 130 mm Hg.

Although pulse pressure has been recognized a risk factor for coronary heart disease in both middle-aged and elderly, and for stroke in the elderly, the contribution of pulse pressure to the risk of stroke among the middle-aged is uncertain.

A total of 33 372 participants (11 684 men and 21 688 women aged 40-69 years) living in communities, free of prior diagnosis of cardiovascular disease and cancer, completed health check-up examination. They were followed from 1990-1992 to the end of 2004 in the Japan public health center-based prospective study on cancer and cardiovascular disease. After 422 864 person-years of follow-up, 1081 incident strokes (559 men and 522 women) were documented.

Pulse pressure was positively associated with risk of stroke as was systolic and diastolic blood pressures. The multivariable hazard ratio of total stroke associated with a 1-SD increment (13.2 mmHg) of pulse pressure was 1.14 (1.05-1.24). The excess risk was observed for the stratum of systolic blood pressure below 140 mmHg, but not of higher systolic blood pressure levels after adjustment for diastolic blood pressure and other potential confounding factors; the multivariable hazard ratio of stroke associated with a 1-SD increment of pulse pressure was 1.32 (1.07-1.64) among persons with normal systolic blood pressure levels.

Pulse pressure is a risk factor for stroke among normotensive individuals with systolic blood pressure below 140 mmHg, which suggests that pulse pressure may be useful to predict the risk of stroke among middle-aged nonsystolic hypertensive patients.

Japan is one of the countries with the longest longevity in the world, and it was accomplished by a drastic decline in stroke mortality from 1960's. The decline in stroke mortality would be largely explained by a population-wide decreasing trend in blood pressure (BP) level, because higher BP has been the strongest risk factor of stroke; about 20% of total deaths can be explained by higher BP above optimal in Japan. Decreasing trend in BP occurred both in men and women in all age-groups, which cannot be fully explained by the widespread use of anti-hypertensive agents. The most probable reason for the population-wide BP decline in Japan would be a large decline in dietary salt intake after 1950's. However, other factors including obesity, high alcohol intake, and unfavorable dietary habits could increase BP level of Japanese again.

It is unclear which blood pressure (BP) components (that is, systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP) and mean arterial pressure (MAP)) are superior predictors of chronic kidney disease (CKD). Furthermore it is unclear whether the combination of SBP+DBP or PP+MAP is superior to any of these four individual BP components in predicting CKD. We enrolled 9928 Japanese men aged 40-55 years who had a normal estimated glomerular filtration rate (eGFR), no proteinuria and no history of cardiovascular disease and were not taking any antihypertensive medications at baseline. CKD was defined as an eGFR of <60 ml min(-1) per 1.73 m(2) using the modified diet in renal disease equation. ΔAkaike's information criterion (ΔAIC) was used to compare the BP components-added model to the model without them in a Cox proportional hazards model. During the 52 428 person-years of follow-up, there were 434 cases of CKD. Of all four BP components, the model including DBP- or MAP-alone had the highest values of ΔAIC (10.2 and 9.85, respectively). The PP-alone model had the lowest ΔAIC value (-1.48). The combination models including SBP+DBP (ΔAIC 8.42) or PP+MAP (8.42) were not superior to the models including DBP- or MAP-alone. These findings suggested that, of the four BP components, both DBP and MAP were the most useful predictors for subsequent incidence of CKD, but PP was not an important predictor. The combination model, including SBP+DBP or PP+MAP, was not superior to the models including DBP- or MAP-alone for predicting CKD.

We examined the risk of cardiovascular disease, stroke, ischaemic heart disease, and diabetes with the metabolic syndrome according to the new harmonised definition and its components using a national longitudinal data set from an Asian population.

Data of 9791 men and women aged 20+ from 1998 and 2001 Korea National Health and Nutrition Examination Surveys were individually linked to national hospitalisation and mortality data using unique personal identification numbers. During a 5.8-year follow-up through 2005, 288 incident cardiovascular events (184 strokes and 122 cases of ischaemic heart disease) and 85 new diabetes cases have been detected.

Men and women with the metabolic syndrome had 48%, 39%, 64%, and 127% greater risks of cardiovascular disease, stroke, ischaemic heart disease, and diabetes, respectively, than those without the metabolic syndrome. The increased risks of cardiovascular disease, ischaemic heart disease, and diabetes remained significant after adjusting for health behaviours, bio-clinical factors, family history, and socio-demographic factors. Analysis results on population attributable risks showed that about a quarter of total diabetes occurrence and more than 10% of cardiovascular disease was attributable to the metabolic syndrome. The number of metabolic syndrome components was linearly associated with risks of outcomes. High blood pressure was significantly associated with all four outcomes while hypertriglyceridemia and hyperglycemia were also important for ischaemic heart disease and diabetes, respectively.

Reduction of metabolic risk factors is necessary in South Korea to lower the burden of associated diseases, especially ever-increasing ischaemic heart disease and diabetes.

The relationship between pulse pressure (PP) and stroke has been described in populations outside Japan. Here, we investigated the relationship between PP and stroke incidence in Japan.

Study subjects were 11,097 people (4315 men and 6782 women) in 12 rural areas of Japan enrolled in the Jichi Medical School Cohort Study, a population-based prospective study. The subjects were divided into quintiles of PP. Baseline data were obtained by questionnaire and health checkups between April 1992 and July 1995, and the incidence of all strokes and stroke subtypes was monitored.

A total of 412 strokes were observed during a mean follow-up period of 10.7 years. After adjusting for age, smoking status, drinking status, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, body mass index and diabetes mellitus, hazard ratios [HRs] in the second to fifth quintiles of PP for all strokes were 1.06 (95% confidence interval [CI] 0.69-1.64), 1.53 (CI 1.02-2.28), 2.02 (CI 1.38-2.96) and 2.22 (CI 1.53-3.20) compared with the first quintile using Cox's proportional hazard model, respectively.

Our findings suggest high PP is at an increased risk of stroke.

The volume of T2-hyperintense white matter (HWM) is an important neuroimaging marker of cerebral integrity with a demonstrated high heritability. Pathophysiology studies have shown that the regional, ependymal, and subcortical HWM lesions are associated with elevated arterial pulse pressure and arterial blood pressure (BP), respectively. We performed bivariate, whole-genome linkage analyses for HWM volumes and BP measurements to identify chromosomal regions that contribute jointly to both traits in a population of healthy Mexican Americans. Our aims were to localize novel quantitative trait loci acting pleiotropically on these phenotypes and to replicate previous genetic findings on whole brain HWM volume and BP measurements.

BP measurements and volumes of whole-brain (WB), subcortical, and ependymal HWM lesions, measured from high-resolution (1 mm(3)) 3-dimensional fluid-attenuated inversion recovery images, served as focal quantitative phenotypes. Data were collected from 357 (218 females; mean age=47.9±13.2 years) members of large extended families who participated in the San Antonio Family Heart Study.

Bivariate genomewide linkage analyses localized a significant quantitative trait locus influencing WB and regional (ependymal) HWM volumes and pulse pressure and systolic BP to chromosomal location 1q24 between markers D1S196 and D1S1619. Several other chromosomal regions (1q42, 10q24-q26, and 15q26) exhibited suggestive linkages. The results of the post hoc analyses that excluded 55 subjects taking antihypertensive medication showed no substantive differences from the results obtained in the full cohort.

This study confirms several previously observed quantitative trait loci influencing BP and cerebral integrity and identifies a novel significant quantitative trait locus at chromosome 1q24. The genetic results strongly support a role for pleiotropically acting genes jointly influencing BP and cerebral white matter integrity.

The cerebral volume of T2-hyperintense white matter (HWM) is an important neuroimaging marker of cerebral integrity. Pathophysiology studies identified that subcortical and ependymal HWM are produced by 2 different mechanisms but shared a common risk factor: high arterial pulse pressure. Recent studies have demonstrated high heritability of the whole-brain HMW volume and reported significant and suggestive evidence of genetic linkage. We performed heritability and whole-genome linkage analysis to replicate previous reported findings and to study shared genetic variance, and possible overlap for specific loci, between subcortical and ependymal HWM volumes in a population of healthy Mexican Americans.

The volumes of subcortical and ependymal HWM regions were measured from high-resolution (1 mm(3)), 3-dimensional fluid-attenuated inversion recovery images acquired for 459 (283 females, 176 males) active participants in the San Antonio Family Heart Study. Subjects ranged in age from 19 to 85 years of age (47.9+/-13.5 years) and were part of 49 families (9.4+/-8.5 individuals per family).

The volumes of whole-brain, subcortical, and ependymal HWM were highly heritable (h(2)=0.72, 0.66, and 0.73, respectively). The subcortical and ependymal HWM volumes shared 21% of genetic variability indicating significant pleiotropy. Genomewide linkage analysis showed only a suggestive bivariate linkage for subcortical and ependymal HWM volumes (log of odds=2.12) on chromosome 1 at 288 cM.

We replicated previous findings of high heritability for the whole-brain HWM volume. We also showed that subcortical and ependymal volume shared a significant portion of genetic variability and the bivarate linkage analysis produced a suggestive linkage near the locus previously identified in a study of whole-brain HWM volume and arterial pulse pressure.

Information has been sparse on the comparison of 4 blood pressure (BP) indexes (systolic BP [SBP], diastolic BP, pulse pressure, and mean BP [MBP]) in relation to long-term incidence of stroke and myocardial infarction, particularly in middle-aged and older Asians.

The Japan Arteriosclerosis Longitudinal Study Group conducted a meta-analysis of 16 cohort studies in Japan. A total of 48,224 men and women 40 to 89 years of age participated at baseline, and 1231 stroke events and 220 myocardial infarction events occurred during an average 8.4-year follow-up. Multivariate-adjusted hazard ratios with a 1-SD higher value for each BP index were determined by Poisson regression. Analyses were also done in 4 age-sex groups. All 4 BP indexes were significantly related to all stroke risk. Stroke risk was most strongly related to MBP and SBP in both sexes and most weakly related to pulse pressure. Both stroke subtypes, ischemic and hemorrhagic, were most strongly related to MBP and SBP in both sexes. In addition, in men and women 70 to 89 years of age, MBP or SBP showed the strongest relation to all stroke risk. Myocardial infarction risk was most strongly related to SBP or MBP in both sexes. For any end points in any age-sex groups, pulse pressure was not the strongest predictor.

The long-term incident risk of stroke and myocardial infarction associated with high BP in East Asian populations should be assessed mainly on the basis of SBP. MBP also may be an important predictor, but pulse pressure is a less important predictor for cardiovascular disease risk.

To evaluate the effect of age and other risk factors for atherosclerosis on arterial blood velocity, carotid arteries in 179 healthy individuals ranging from 21 to 102 years old were examined using color Doppler ultrasonography. Velocity in common and internal carotid arteries decreased consecutively from young adults to very elderly people except for peak internal carotid artery velocity. Peak common carotid artery velocity in the elderly (> or = 65 years old) people was inversely associated with age and diastolic blood pressure and directly associated with pulse pressure. Minimum velocity of common carotid artery was inversely correlated with age and diastolic blood pressure in the elderly people. In elderly group, peak internal carotid artery velocity correlated only with serum high-density lipoprotein cholesterol. Minimum internal carotid artery velocity correlated inversely with systolic blood pressure in adults and diastolic blood pressure in elderly people. Blood velocity in the very elderly population approaches the critical level for thrombogenesis.

Information has been sparse on the comparison of pulse pressure (PP) and mean arterial pressure (MAP) in relation to ischemic stroke among patients with uncontrolled hypertension. The present study examined the relation among PP, MAP, and ischemic stroke in uncontrolled hypertensive subjects in China.

A total of 6104 uncontrolled hypertensive subjects aged > or = 35 years were screened with a stratified cluster multistage sampling scheme in Fuxin county of Liaoning province of China, of which 317 had ischemic stroke.

After multivariable adjustment for age, gender, and other confounders, individuals with the highest quartile of PP and MAP had ORs for ischemic stroke of 1.479 (95% CI: 1.027 to 2.130) and 2.000 (95% CI: 1.373 to 2.914) with the lowest quartile as the reference. Adjusted ORs for ischemic stroke were 1.306 for MAP and 1.118 for PP with an increment of 1 SD, respectively. Ischemic stroke prediction of PP was annihilated when PP and MAP were entered in a single model. In patients aged < 65 years, on a continuous scale using receive operating characteristics curve, ischemic stroke was predicted by PP (P=0.001) and MAP (P<0.001). The area under the curve of PP (0.570, 95% CI: 0.531 to 0.609) differed from the area under the curve of MAP (0.633, 95% CI: 0.597 to 0.669; P<0.05). Among patients aged > or = 65 years, presence of ischemic stroke was only predicted by MAP.

PP and MAP were both associated with ischemic stroke. Ischemic stroke prediction of PP depended on MAP. On a continuous scale, MAP better predicted ischemic stroke than PP did in diagnostic accuracy.

Hypertension is a major risk for stroke; a linear or J-shaped relationship between blood pressure (BP) and stroke have been reported. The authors examined the relationship between systolic and diastolic BP and risk of stroke in the general population in Japan. The study included 11,097 men and women who were divided into quintiles by systolic BP and diastolic BP in each sex. Follow-up duration was 10.7 years. In men, risks of second to fifth quintiles of systolic BP for all stroke were 1.5 (95% confidence interval [CI], 0.7-3.0), 2.2 (CI, 1.2-4.2), 3.0 (CI, 1.7-5.5), and 4.2 (CI, 2.4-7.6) compared with a reference of the first quintile using Cox's proportional hazard model, respectively. In women, risk of second to fifth quintiles of systolic BP for all stroke were 1.2 (95% CI, 0.6-2.4), 1.5 (CI, 0.8-2.9), 2.2(CI, 1.2-4.1), and 3.1 (CI, 1.7-5.6), respectively. Systolic BP and diastolic BP were related to stroke incidence linearly in the general Japanese population. Systolic BP was slightly more predictive of the risk of stroke than diastolic BP.

Ambulatory arterial stiffness index (AASI) and pulse pressure (PP) are indexes of arterial stiffness and can be computed from 24-hour blood pressure recordings. We investigated the prognostic value of AASI and PP in relation to fatal outcomes.

In 1542 Ohasama residents (baseline age, 40 to 93 years; 63.4% women), we applied Cox regression to relate mortality to AASI and PP while adjusting for sex, age, BMI, 24-hour MAP, smoking and drinking habits, diabetes mellitus, and a history of cardiovascular disease.

During 13.3 years (median), 126 cardiovascular and 63 stroke deaths occurred. The sex- and age-standardized incidence rates of cardiovascular and stroke mortality across quartiles were U-shaped for AASI and J-shaped for PP. Across quartiles, the multivariate-adjusted hazard ratios for cardiovascular and stroke death significantly deviated from those in the whole population in a U-shaped fashion for AASI, whereas for PP, none of the HRs departed from the overall risk. The hazard ratios for cardiovascular mortality across ascending AASI quartiles were 1.40 (P=0.04), 0.82 (P=0.25), 0.64 (P=0.01), and 1.35 (P=0.03). Additional adjustment of AASI for PP and sensitivity analyses by sex, excluding patients on antihypertensive treatment or with a history of cardiovascular disease, or censoring deaths occurring within 2 years of enrollment, produced confirmatory results.

In a Japanese population, AASI predicted cardiovascular and stroke mortality over and beyond PP and other risk factors, whereas in adjusted analyses, PP did not carry any prognostic information.

The ambulatory arterial stiffness index (AASI) can be computed from individual 24-h blood pressure recordings.

We investigated the prognostic value of AASI and 24-h pulse pressure in a random sample of 1829 Danes, aged 40-70 years. We adjusted for sex, age, body mass index, mean arterial pressure, smoking, diabetes, ratio of total to high-density lipoprotein cholesterol, and history of cardiovascular disease with Cox regression.

Over a median follow-up of 9.4 years, incidences of fatal and nonfatal endpoints were 40 for stroke, 150 for coronary heart disease, and 212 for cardiovascular events. In fully adjusted models, the hazard ratios associated with 1 SD increase (0.14 U) in the AASI were 1.62 (95% confidence interval, 1.14-2.28; P = 0.007) for stroke, 0.96 (0.80-1.14; P = 0.62) for coronary heart disease, and 1.06 (0.91-1.23; P = 0.49) for cardiovascular events. None of these ratios reached significance for pulse pressure (P > 0.47). The AASI still predicted stroke after excluding individuals with previous cardiovascular disease or after adjustment for systolic and/or diastolic blood pressure instead of mean arterial pressure.

In a randomly recruited European population, the AASI was a strong predictor of stroke, beyond traditional cardiovascular risk factors, including the mean arterial pressure and pulse pressure.

We investigated the association between stroke and blood pressure (BP) indices (systolic BP [SBP], diastolic BP [DBP], mean BP [MBP], and pulse pressure [PP]) determined by ambulatory BP monitoring. The predictive power for stroke of these indices was compared in the general Japanese population. We obtained ambulatory BP data in 1271 subjects (40% men) aged > or = 40 (mean: 61) years. During a mean follow-up of 11 years, 113 strokes were observed. The multivariate adjusted relative hazard and likelihood ratio for a 1-SD increase for each BP index was determined by Cox proportional hazard regression. Comparison of the likelihood ratio between Cox models including 2 indices and those including 1 index indicated that PP was significantly less informative than other indices (P<0.01 when adding MBP, SBP, or DBP to the PP model; P>0.09 when adding PP to the model including another index). However, after removing age from covariates, PP became more informative than DBP and MBP (P<0.0001 when adding PP to the MBP or DBP model, whereas SBP was more informative than PP even after removing age; P<0.05 when adding SBP to the PP model). In conclusion, PP was the weakest predictor of stroke. Exclusion of age from covariates increased the predictive power of PP, suggesting that the stroke risk associated with PP reflected the risk of aging per se.

An open-label, multicentre study was conducted to evaluate the antihypertensive efficacy of a 4-week course of losartan 50 mg plus hydrochlorothiazide 12.5 mg in Asian patients with essential hypertension whose blood pressure had previously been treated with but not controlled by valsartan 80 mg.

A total of 237 eligible patients with mean trough sitting diastolic blood pressure (SiDBP) 95-115 mmHg and a mean trough sitting systolic blood pressure (SiSBP) < 190 mmHg entered the baseline period of treatment with valsartan 80 mg/day for 4 weeks. Those (n = 165) whose SiDBP remained > 90 mmHg and who were not excluded for other reasons were then switched to a single-tablet formulation of losartan 50 mg/hydrochlorothiazide 12.5 mg combination once daily for a further 4 weeks.

Mean SiDBP (study primary endpoint) at the end of combination therapy was reduced to 86.9 mmHg from 95.2 mmHg. SiSBP (study secondary endpoint) was reduced to 132.6 mmHg from 140.7 mmHg. Mean reductions after switching from valsartan 80 mg to losartan 50 mg/hydrochlorothiazide 12.5 mg were thus 8.3 and 8.1 mmHg for SiDBP and SiSBP, respectively (p < or = 0.001 for both outcomes). The goal of SiDBP < or = 90 mmHg was attained in 72% of the patients previously not controlled to the same level by valsartan 80 mg/day. Combination therapy with losartan 50 mg/hydrochlorothiazide 12.5 mg was generally well tolerated. Mean compliance with the losartan 50 mg/hydrochlorothiazide 12.5 mg combination was > 99%.

These results demonstrate that in Asian patients who do not reach the goal of mean trough SiDBP < or = 90 mmHg with valsartan monotherapy at 80 mg once-daily, switching to a single-tablet combination of losartan 50 mg/hydrochlorothiazide 12.5 mg once-daily is well tolerated, provides effective control of blood pressure and is an excellent choice to achieve blood pressure reduction goals.

To quantify the effects of hormone-replacement therapy (HRT) on components of the metabolic syndrome in postmenopausal women.

Comprehensive searches of electronic databases were performed from April 1966 to October 2004. We included randomized controlled trials that were of at least 8 weeks duration and evaluated the effect of HRT on metabolic, inflammatory or thrombotic components. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Subgroup analysis evaluated the effects for transdermal and oral treatment and for diabetic and non-diabetic women.

Pooled results of 107 trials showed that HRT reduced abdominal fat [-6.8% (CI, -11.8 to -1.9%)], HOMA-IR [-12.9% (CI, -17.1 to -8.6%)] and new-onset diabetes [relative risk 0.7 (CI, 0.6-0.9)] in women without diabetes. In women with diabetes, HRT reduced fasting glucose [-11.5% (CI, -18.0 to -5.1%)] and HOMA-IR [-35.8% (CI, -51.7 to -19.8%)]. HRT also reduced low-density lipoprotein/high-density lipoprotein cholesterol ratio [-15.7% (CI, -18.0 to -13.5%)], lipoprotein(a) [Lp(a)] [-25.0% [CI, -32.9 to -17.1%)], mean blood pressure [-1.7% (CI, -2.9 to -0.5%)], E-selectin [-17.3% (CI, -22.4 to -12.1%)], fibrinogen [-5.5% (CI, -7.8 to -3.2%)] and plasminogen activator inhibitor-1 [-25.1% (CI, -33.6 to -15.5%)]. Oral agents produced larger beneficial effects than transdermal agents, but increased C-reactive protein (CRP) [37.6% (CI, 17.4-61.3%)] and decreased protein S [-8.6% CI, -13.1 to -4.1%)], while transdermal agents had no effect.

HRT reduces abdominal obesity, insulin resistance, new-onset diabetes, lipids, blood pressure, adhesion molecules and procoagulant factors in women without diabetes and reduced insulin resistance and fasting glucose in women with diabetes. Oral agents adversely affected CRP and protein S, while transdermal agents had no effects.

To clarify the relationship between mortality due to cardiovascular diseases (CVD) and systolic blood pressure (SBP) and diastolic blood pressure (DBP) in young and elderly Japanese men in the absence of antihypertensive treatments.

A 19-year cohort study using the 1980 National Survey of Cardiovascular Diseases and the identification of the underlying causes of death using national vital statistics data.

In 1999, a 19-year follow-up study was conducted among participants randomly selected from the Japanese population for the 1980 National Survey of Cardiovascular Diseases. Among the male participants that were not receiving antihypertensive treatment, information was obtained for about 91.3% of the subjects (n = 3779). Age-adjusted mortality rates using the person-year method were calculated to compare the relationships of SBP and DBP levels with CVD mortality for different age groups (aged 30-64, 65-74, and 75 years or more).

The total number of observed person-years was 64 598 and the number of CVD-related deaths after 19 years was 253. Both SBP and DBP levels were significantly and linearly related to CVD mortality in the age groups 30-64 years (P < 0.001 and P = 0.01, respectively) and 65-74 years (P < 0.001 and P = 0.03, respectively). In the group of participants that were at least 75 years old, however, no significant increase in the relative risk of CVD was observed with increasing DBP levels (P = 0.156), whereas the relative risk of CVD increased significantly with increasing SBP levels (P = 0.038). Multivariate analysis adjusting for major risk factors confirmed these relationships. Standardized hazard ratios (95% confidence intervals) of SBP were 1.53 (1.19-1.96) for 30-64 year olds, 1.70 (1.31-2.20) for 64-74 year olds, and 1.23 (1.03-1.47) for participants 75 years old or more, whereas those of DBP were 1.52 (1.12-2.06), 1.60 (1.21-2.10), and 1.10 (0.94-1.28), respectively.

These data show that elevated SBP is an independent risk factor for CVD mortality for Japanese men of all ages, whereas elevated DBP is not an independent risk factor for CVD mortality for elderly men.

Our purpose was to investigate leukoaraïosis (LA) using three-dimensional MR imaging combined with advanced image-processing technology to attempt to group signal abnormalities according to their etiology. Coronal T2-weighted fast fluid-attenuated inversion-recovery (FLAIR) sequences and three-dimensional T1-weighted fast spoiled gradient recalled echo sequences were used to examine cerebral white matter changes in 75 elderly people with memory complaint but no dementia. They were otherwise healthy, community-dwelling subjects. Three subtypes of LA were defined on the basis of their shape, geography and extent: the so-called subependymal/subpial LA, perivascular LA and "bands" along long white matter tracts. Subependymal changes were directly contiguous with ventricular spaces. They showed features of "water hammer" lesions with ventricular systematisation and a more frequent location around the frontal horns than around the bodies (P=.0008). The use of cerebrospinal fluid (CSF) contiguity criterion allowed a classification of splenial changes in the subpial group. Conversely, posterior periventricular lesions in the centrum ovale as well as irregular and extensive periventricular lesions were not directly contiguous with CSF spaces. The so-called perivascular changes showed features of small-vessel-associated disease; they surrounded linear CSF-like signals that followed the direction of perforating vessels. Distribution of these perivascular changes appeared heterogeneous (P ranging from .04 to 5.10(-16)). These findings suggest that subependymal/subpial LA and subcortical LA may be separate manifestations of a single underlying pulse-wave encephalopathy.