Masashi Okuro

Deletion allele of the angiotensin-converting enzyme gene as a risk factor for pneumonia in elderly patients ☆

PURPOSE Aspiration due to an age-related reduction in cough is a major cause of pneumonia in elderly persons. Because the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene (ACE) has been associated with the cough reflex, we studied whether this genetic polymorphism was also associated with the risk of pneumonia. SUBJECTS AND METHODS We studied 1011 elderly inpatients (221 men and 790 women, mean [+/- SD] age of 82 +/- 7 years) in a long-term care hospital. The association between the ACE I/D polymorphism and the incidence of pneumonia (defined using specific criteria that included radiographic abnormalities) was assessed during an 8-month period that excluded the winter. Data were analyzed using proportional hazards models, with adjustment for age, sex, and other potential confounders. RESULTS During follow-up, 87 cases (9%) of pneumonia occurred, 38 of which were fatal. The ACE DD allele (vs. ID + II) was associated with an increased risk of pneumonia (relative risk [RR] = 2.9; 95% confidence interval [CI]: 1.7 to 4.8, P < 0.001) and fatal pneumonia [RR = 4.4; 95% CI: 2.1 to 9.0; P < 0.0001). CONCLUSIONS The ACE D allele is an independent risk factor for pneumonia in elderly persons.

Increased Plasma Levels of the Soluble Form of Fas Ligand in Patients With Acute Myocardial Infarction and Unstable Angina Pectoris

OBJECTIVES To examine whether the Fas/Fas ligand system is involved in the pathogenesis of acute myocardial infarction (AMI), we measured the levels of the soluble form of the Fas ligand (sFasL) in the plasma of patients with AMI and stable or unstable angina pectoris (AP). BACKGROUND The Fas ligand (FasL) is rapidly cleaved off by a metalloproteinase from the cell membrane to become a soluble form as a cytokine. Fas is expressed in most cells, including cardiomyocytes, whereas FasL is mainly expressed in inflammatory cells such as macrophages, which are greatly accumulated in unstable plaque. METHODS Thirty patients with AMI, 10 patients with unstable AP, 10 patients with stable AP and 30 control subjects were enrolled in the present study. RESULTS Plasma sFasL levels were significantly elevated on hospital admission in patients with AMI and unstable AP, compared with control subjects. Time-course studies revealed that plasma sFasL levels rapidly decreased within 3 h and then increased again after percutaneous transluminal coronary angioplasty in patients with AMI, but not in patients with stable AP. Importantly, the sFasL levels were higher in the coronary sinus than in the circulation. In addition, in vitro studies showed that the expression of FasL messenger ribonucleic acid was upregulated in mononuclear cells isolated from patients with AMI and that hypoxia stimulated the release of sFasL from isolated mononuclear cells. CONCLUSIONS This demonstration of elevated levels of sFasL in patients with AMI and unstable AP suggests that activation of the Fas/FasL system may play a pathogenic role in AMI and acute coronary syndromes.

Risk factors for pressure ulcers in bedridden elderly subjects: Importance of turning over in bed and serum albumin level

The purpose of the present paper was to determine clinical risk factors for the development of pressure ulcers in bedridden elderly inpatients.

Electromagnetic fields inhibit endothelin-1 production stimulated by thrombin in endothelial cells

Electromagnetic field (EMF) radiation has been found to induce arteriolar dilatation, but the mechanism of action remains largely unknown. This study investigated the effect of EMF radiation on the production of endothelin-1 (ET-1), a potent vasoconstrictor, by cultured endothelial cells. EMF radiation reduced ET-1 basal levels in human umbilical vein and microvascular endothelial cells, but failed to reduce ET-1 basal levels in bovine and human aortic endothelial cells. EMF radiation significantly inhibited thrombin-stimulated ET-1 production in all four endothelial cell types in a dose-dependent manner. EMF radiation significantly inhibited thrombin-induced endothelin-1 mRNA expression in all four cell types. The inhibitory effect of EMF radiation on ET-1 production was abolished by the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (10−3 mol/l). These results demonstrate that EMF radiation modulates ET-1 production in cultured vascular endothelial cells and the inhibitory effect of EMF radiation is, at least partly, mediated through a nitric oxide-related pathway.

Sleep Apnoea Syndrome as a Risk for Mortality in Elderly Inpatients

OBJECTIVE: The characteristics of sleep apnoea syndrome (SAS) in the elderly, including subtype classification and association with mortality, have not been fully elucidated. This study examined these factors in an elderly Japanese inpatient population. METHODS: Overnight polysomnography was used to diagnose and classify SAS in 145 elderly inpatients (mean ± age 81 ± 8 years). Clinical data, including brain computerized tomography findings, were recorded. The study population included nine inpatients with obstructive SAS, 12 with central SAS, 25 with mixed SAS and 99 controls (no SAS). RESULTS: Increased body mass index and grade of aortic arch calcification independently contributed to risk of all subtypes of SAS combined. There was an independent association between SAS and increased risk of mortality from all causes as well as from pneumonia and from cardiovascular disease. Only mixed SAS was independently and positively associated with increased risk of death from pneumonia. CONCLUSIONS: Obstructive, central and mixed SAS were associated with increased risk of cardiovascular-related and all-cause mortality. Mixed SAS was associated with an increase in mortality from pneumonia. There was no relationship between mortality and severity of SAS.

Association of severe hypertension with pneumonia in elderly patients with acute ischemic stroke

Pneumonia is one of the most frequent complications in elderly patients with acute ischemic stroke. Although severe hypertension is often observed in the early phase of acute stroke, there are few studies of acute hypertension as a factor influencing the incidence of stroke-associated pneumonia (SAP) in elderly subjects with acute ischemic stroke. To assess the association of acute phase blood-pressure elevation with the incidence of SAP, we compared 10 elderly patients with acute ischemic stroke complicated with severe hypertension (⩾200/120 mm Hg) with 43 patients with moderate hypertension (160–199/100–119 mm Hg), as well as with 65 control normotensive or mildly hypertensive (<160/100 mm Hg) controls on admission. Data were collected on known risk factors, type of ischemic stroke and underlying chronic conditions. The significance of differences in risk factors was analyzed using univariate and multivariate comparisons of 38 SAP cases and others, 8 SAP death cases and others, and 28 patients with poor outcome associated with in-hospital death or artificial feeding at discharge and others. After adjustment for potential confounding factors, the relative risk estimates for SAP, SAP death and poor outcome were 2.83 (95% confidence interval 1.14–7.05), 5.20 (1.01–26.8) and 6.84 (1.32–35.4), respectively, for severe hypertension relative to normotensive or mildly hypertensive controls. We conclude that severe hypertension on admission is an independent predictive factor for SAP in elderly patients with acute ischemic stroke.

Association between blood pressure and disability-free survival among community-dwelling elderly patients receiving antihypertensive treatment

A reduction of elevated blood pressure (BP) is an important treatment goal in elderly hypertensive patients. However, excessive reduction of systolic BP (SBP) and/or diastolic BP (DBP) might be harmful in such patients. We investigated whether this was the case with regard to risk of incident disability or death in community-dwelling elderly subjects. We analyzed 570 patients receiving antihypertensive treatment aged 65–94 years. The endpoint was the composite outcome of incident disability, defined as first certification of a support/care need or death. Relationships among each of the four classes of SBP or DBP and the risk of incident disability or death were estimated using the Cox proportional hazards model. Over four years, 77 (13.5%) incident disabilities or deaths occurred. After adjustment for age, sex and variables selected according to their univariate analysis P-value <0.20, the risk of events was significantly higher in subjects with baseline SBP<120 mm Hg (hazard ratio (HR)=2.81, P=0.023) and ⩾160 mm Hg (HR=4.32, P<0.001), compared with subjects with baseline SBP of 140–159 mm Hg, who showed the lowest incidence of events. This J-curve relationship was observed in very elderly patients (⩾75 years) but not in younger patients. Patients with SBP<120 mm Hg tended to have a higher risk of incident disability caused by cerebral events, and those with SBP⩾160 mm Hg had a higher risk of incident disability caused by falls/bone fractures. These observations indicate that excessive BP reduction could cause discontinuance of disability-free survival in community-dwelling elderly patients.

Association between hypertension status and the screening test for frailty in elderly community-dwelling Japanese

To clarify the possible association of frailty with hypertension prevalence, treatment and blood pressure (BP) control in the elderly, we conducted a screening survey of 1091 elderly community-dwelling subjects aged ⩾65 years, using data from public health check-ups and frailty was determined by a 25-item questionnaire, the Basic Checklist for Frailty (BCF). The significance of differences in the association of BCF categories or BCF items with each hypertension status was analyzed using multiple logistic regression analysis after adjusting for age, sex and possible confounding underlying chronic conditions. A total of 63% of subjects were hypertensive (BP⩾140/90 mm Hg), and of those, 85% were receiving antihypertensive treatment, and 56.0% of those receiving treatment had controlled BP (<140/90 mm Hg). BCF categories that showed an independent association with hypertension status were ‘impaired walking status’ and absence of ‘impaired nutritional status’ for prevalence of hypertension, ‘impaired instrumental activity of daily living status’ and ‘impaired nutritional status’ for untreated hypertension among hypertensives and ‘impaired oral function’ for BP-uncontrolled hypertension among treated hypertensives. In addition, BCF items that showed an independent association were ‘inability to walk for more than 15 min without rest’ and absence of ‘Body mass index (BMI) <18.5 kg m−2’ for prevalence of hypertension, ‘weight loss of more than 2–3 kg in the past 6 months’ for untreated hypertension, and ‘difficulty eating hard food’ for BP-uncontrolled hypertension. These observations indicate that assessment of these specified frailty categories and/or items may be useful for evaluating hypertension status in elderly community-dwelling subjects.

Association between human metapneumovirus seroprevalence and hypertension in elderly subjects in a long-term care facility

Recently, relations between hypertension and infections caused by several pathogens have been reported. However, few studies have examined the relationship between human metapneumovirus (hMPV) and hypertension in elderly inpatients. To assess the association between anti-hMPV-immunoglobulin G (IgG) titer and the prevalence of hypertension, we conducted a case–control study in a Japanese long-term care facility (LTCF). The participants included 84 hypertensive patients aged ⩾65 years, and 84 age- and sex-matched normotensive controls (38 males and 46 females in each group; cases, 79.9±8.4 (s.d.) years; controls, 80.1±8.3 years). Data on underling chronic clinical conditions were collected. Titers were measured using an immunofluorescence assay kit. The significance of risk factor differences was analyzed using univariate and multivariate comparisons of cases and controls. All serum samples were positive for hMPV, and IgG titers ranged from 40-fold to more than 5120-fold. There were no significant sex- or age-related differences in log2 (anti-hMPV-IgG titer/10) among the subjects. Compared with normotensive subjects, hypertensive patients presented significantly higher log2 (anti-hMPV-IgG titer/10) values (P<0.001). After adjustment with multiple logistic analysis, the odds ratio for log2 (anti-hMPV-IgG titer/10) was 1.42 (95% confidence interval 1.16–1.75, P=0.001) relative to normotensive subjects. In all subjects, stepwise multiple regression analysis revealed that both hypertension and a poor nutritional state independently contributed to increased log2 (anti-hMPV-IgG titer/10). These observations suggest that an increased anti-hMPV-IgG titer was closely related to hypertension in elderly subjects in a Japanese LTCF.

Association of angiotensin‐I converting enzyme DD genotype with influenza pneumonia in the elderly

Background: Although angiotensin‐I converting enzyme (ACE) is known to associate with cough reflex and inflammatory conditions, and both may participate in influenza pneumonia in the elderly, no study has been carried out on the association between influenza pneumonia and the insertion/deletion (I/D) polymorphism of the ACE gene (ACE).