Development and usefulness of a new questionnaire for assessing geriatric syndrome.

AIM: To assess the validity and reliability of a pre-visit questionnaire newly developed to identify geriatric conditions in older adults in an outpatient clinical setting. METHODS: A new self-administered questionnaire consisting of 17 items was distributed to 277 patients or their caregivers visiting a memory clinic. The questionnaire was designed to address common symptoms associated with an increasing age based on yes/no responses with symptom-oriented questions avoiding the use of 'jargon'. The patients also underwent comprehensive geriatric assessments (CGAs), as well as tests of the Barthel index, Lawton instrumental activities of daily living, mini-mental state examination (MMSE), geriatric depression scale and vitality index to assess construct validity in a factor analysis. The differences in the prevalence of symptoms between the patients and their caregivers were also assessed. RESULTS: The factor analysis detected eight components that included symptoms referring to gait disturbance, numbness, urinary incontinence, insomnia or body weight loss and were significantly correlated with the measurements of the CGA. Cronbach's alpha coefficient for the internal consistency of the questionnaire was 0.729. The caregivers tended to respond to the questionnaire for older patients (81.6±5.5 vs. 76±9.7 years of age for patients with caregivers as responders versus patients as responders respectively, p<0.001) and those with lower MMSE scores (19.4±5.8 vs. 24.8±4.2 points, p<0.001). A higher prevalence of falls and episodes of delusions was observed among the patients with caregivers as responders. CONCLUSIONS: These results demonstrate that the current questionnaire is a valid and reliable instrument for use in clinical practice and that obtaining collateral source information is essential for assessing significant geriatric symptoms. Such information also provides clinicians with a guide to conducting more detailed evaluations of geriatric conditions and aids in the diagnostic process in older patients with multidisciplinary complications.

Efficacy of combined use of three non-invasive atherosclerosis tests to predict vascular events in the elderly; carotid intima-media thickness, flow-mediated dilation of brachial artery and pulse wave velocity.

BACKGROUND: Intima-media thickness (IMT) of the carotid artery, flow-mediated dilation (FMD) of the brachial artery, and pulse wave velocity of the central artery (PWV) have been widely used to evaluate progression of atherosclerosis. Our previous work has revealed that IMT, FMD and PWV are related to each other, and the combination of these measurements was useful in identifying patients with atherosclerotic disease. The aim of the present study was to investigate whether combination of these measurements would predict future cardiovascular events better than each test alone. METHODS AND RESULTS: From November 2000 to March 2008, 274 consecutive elderly subjects (men/women; 114/160, mean age; 71 ± 12 years) were enrolled in this study. We measured IMT, FMD, and PWV in all of these subjects and followed them for a mean of 41 ± 28 months. During the follow-up period, vascular events occurred in 42 patients (15.3%). IMT (hazard ratio = 1.28 [95%CI, 1.09-1.50], p = 0.002 per 0.1 mm increase in mean IMT) and brachial-ankle (ba) PWV (hazard ratio = 1.06 [95%CI, 1.01-1.10], p = 0.015 per 1 m/s increase in baPWV) were independent predictors of future vascular events by Cox proportional hazard analysis, although FMD did not reach statistical significance (hazard ratio = 0.85 [95%CI, 0.72-1.01], p = 0.062 per 1% increase in %FMD). Importantly, the number of tests showing results in the worst tertile was a more powerful predictor (hazard ratio = 2.21 [95%CI, 1.42-3.43], p = 0.0004 for number of tests showing worst tertile) of future vascular events than either IMT, baPWV, or FMD alone. When both IMT and baPWV (with respective cut-off values of 0.98 mm and 19.1 m/s) were taken into consideration, the efficacy increased as compared with each test alone (odds ratio 4.9). CONCLUSION: These results indicate that IMT and baPWV, especially when combined, are useful in predicting future vascular events in elderly subjects.

Angiotensin converting enzyme inhibitor attenuates oxidative stress-induced endothelial cell apoptosis via p38 MAP kinase inhibition.

BACKGROUND: The effects of angiotensin converting enzyme (ACE) inhibitors on oxidative stress-induced apoptosis of endothelial cells and the intracellular signaling were investigated. METHODS: Cultured endothelial cells derived from a bovine carotid artery were treated with H2O2 or TNF-alpha to induce apoptosis. Apoptosis was evaluated by DNA fragmentation and cell viability, p38 MAP kinase activity by Western blotting, and oxidative stress by formation of 8-isoprostane. The effects of ACE inhibitors were examined by adding them into the medium throughout the experiments. RESULTS: Apoptosis was attenuated by ACE inhibitors, temocapril and captopril, in a dose-dependent manner (1-100 micromol/l). H2O2 (0.2 mmol/l for 1.5 h) or TNF-alpha (10 ng/ml for 72 h) treatment stimulated the activities of p38 MAP kinase. Temocapril and captopril decreased the activity of p38 MAP kinase as well as 8-isoprostane formation induced by H2O2. A p38 MAP kinase inhibitor, SB203580, partially inhibited the effect of temocapril on apoptosis. CONCLUSIONS: These results suggest that ACE inhibitors protect endothelial cells from oxidative stress-induced apoptosis, and that p38 MAP kinase plays a critical role in the process.

Impact of blood pressure variability on cardiovascular events in elderly patients with hypertension.

Blood pressure variability is one of the characteristic features of hypertension in the elderly. However, its clinical significance remains to be determined. We therefore examined the impact of blood pressure variability on the development of cardiovascular events in elderly hypertensive patients. A total of 106 consecutive hypertensive patients aged more than 60 years old (mean age, 73.9 +/- 8.1 years old; male, 54%), all of whom underwent 24-h ambulatory blood pressure monitoring, were followed up (median, 34 months; range, 3-60 months). During the follow-up period, 39 cardiovascular events were observed, including 14 cases of cerebral infarction and 7 cases of acute myocardial infarction. The coefficient of variation (CV) of 24-h systolic blood pressure (SBP) values was used as an index of blood pressure variability. The patients showed a mean CV value of 10.6%, and were divided into two groups according to this mean value as a cut-off point: a high CV group (n = 46) and a low CV group (n = 60). Although baseline clinical characteristics were similar in the two groups, Kaplan-Meier plots for event-free survival revealed that the rate of cardiovascular events was significantly higher in high CV group than in low CV group (p < 0.05). Cox's proportional hazards analysis showed that increased blood pressure variability (a high CV value of 24-h SBP) was an independent predictive variable for cardiovascular events. The CV value of daytime SBP and the SD value of both 24-h SBP and daytime SBP also had positive correlations with the onset of cardiovascular events. These results suggest that increased blood pressure variability may be an independent risk factor for cardiovascular events in elderly hypertensive patients.

Renin-angiotensin system modulates oxidative stress-induced endothelial cell apoptosis in rats.

The role of the renin-angiotensin system in oxidative stress-induced apoptosis of endothelial cells (ECs) was investigated using a rat model and cultured ECs. EC apoptosis was induced by 5-minute intra-arterial treatment of a rat carotid artery with 0.01 mmol/L H2O2 and was evaluated at 24 hours by chromatin staining of en face specimens with Hoechst 33342. Although activity of angiotensin-converting enzyme in arterial homogenates was not increased, administration of an angiotensin-converting enzyme inhibitor temocapril for 3 days before H2O2 treatment inhibited EC apoptosis, followed by reduced neointimal formation 2 weeks later. Also, an angiotensin II type 1 (AT1) receptor blocker (olmesartan) inhibited EC apoptosis, whereas angiotensin II administration accelerated apoptosis independently of blood pressure. Next, cultured ECs derived from a bovine carotid artery were treated with H2O2 to induce apoptosis, as evaluated by DNA fragmentation. Combination of angiotensin II and H2O2 dose-dependently increased EC apoptosis and 8-isoprostane formation, a marker of oxidative stress. Conversely, temocapril and olmesartan reduced apoptosis and 8-isoprostane formation induced by H2O2, suggesting that endogenous angiotensin II interacts with H2O2 to elevate oxidative stress levels and EC apoptosis. Neither an AT2 receptor blocker, PD123319, affected H2O2-induced apoptosis, nor a NO synthase inhibitor, NG-nitro-L-arginine methyl ester, influenced the effect of temocapril on apoptosis in cell culture experiments. These results suggest that AT1 receptor signaling augments EC apoptosis in the process of oxidative stress-induced vascular injury.

Reduced endothelial vasomotor function and enhanced neointimal formation after vascular injury in a rat model of blood pressure lability.

Increased short-term blood pressure variability is known to be associated with hypertensive target organ damage. Sinoaortic denervation (SAD) induces a marked increase in blood pressure lability without affecting the average blood pressure level. The aim of this study was to investigate the effects of blood pressure lability on endothelial vasomotor function and neointimal formation after balloon injury in SAD rats. Direct longterm measurement of mean arterial pressure showed no significant difference in the average of mean arterial pressure between the SAD group and sham-operated control group. In contrast, the standard deviation of mean arterial pressure, as an index of blood pressure lability, was 3-fold greater in SAD rats. To study endothelial function, isometric tension of aortic rings was measured 4 weeks after SAD or sham operation. Endothelium-dependent vasorelaxation induced by acetylcholine was significantly reduced in the SAD group (20% reduction at maximum relaxation). Endothelium-independent vasorelaxation induced by sodium nitroprusside was similar in each group. Acetylcholine-induced NO release from aortic rings was significantly reduced in the SAD group. Next, we examined neointimal formation in carotid arteries in SAD and sham-operated rats at 2 weeks after balloon injury. The neointimal-to-medial area ratio in the SAD group was 50% higher than that in the sham-operated group. The percentage of proliferating cell nuclear antigen-positive cells in the intima was significantly higher in the SAD group. These findings suggest that increased blood pressure lability, independently of average blood pressure level, impairs endothelial function by inhibiting NO production, enhances neointimal formation after balloon injury, and may thereby contribute to atherogenesis.