Gender differences and health status in old and very old patients.

OBJECTIVES: To examine gender differences according to health status, social support, and DRG reimbursement in a population of elderly patients admitted to a hospital geriatric ward in Italy and also to examine the patterns of these differences across old age strata. DESIGN: Observational study PARTICIPANTS: A total of 2171 patients, 70 years and older (females = 1088), consecutively admitted for acute care to a geriatric ward in a general hospital during a 30-month period were included. Patients were stratified into 3 age groups: 70 to 79 (n = 1038, females = 521), 80 to 89 (n = 948, females = 476), and 90+ (n = 185, females = 91). MEASUREMENTS: Demographics, main reason for hospitalization, Charlson Index, APACHE II score, APACHE II-APS subscore, serum albumin, number of currently administered drugs, cognitive status, depression, functional status, length of stay, Diagnoses Related Group (DRG) weight, in-hospital, and 3-month mortality were recorded. Differences were evaluated according to gender across old age strata. RESULTS: In the group of 70- to 79-year-old patients, significant differences were found regarding number of comorbidities, biological and clinical markers of clinical severity (ie, serum albumin, APS, delirium), and functional status on admission (ie, the greater impairment was found in male patients, with a higher in-hospital and 3-month mortality). Moreover, females had less social support and more often live alone. DRG weight parallels clinical complexity, whereas length of stay is comparable. Gender differences were less evident in the 80-89 year-old patients and almost absent in those 90+. CONCLUSIONS: Data indicate that on hospital admission gender differences are significant in young old patients, but not in old and very old, suggesting a poor survivorship of males with increasing age.

Functional trajectories during hospitalization: a prognostic sign for elderly patients.

BACKGROUND: Clinicians have used measurements of pathological conditions and functional status to capture the heterogeneity of older individuals for prognostic purposes. However, the literature pays low attention to physical functional changes. METHODS: A retrospective cohort study to investigate the association between functional changes during hospitalization and 3-month mortality. A total of 1,119 acutely ill elderly patients admitted to four beds arranged like a high-dependency area in a geriatric unit (mean age 80.6 +/- 7.8 years) were subdivided into four groups according to degree of functional decline at admission in comparison with the premorbid level and ability or inability to regain function at discharge: with moderate loss, able to regain (group a) and unable to regain function (group b); and with severe loss, able to regain (group c) and unable to regain function (group d) during hospitalization. Age, gender, cognitive and functional status (basic activities of daily living -[BADL]), serum albumin, Acute Physiology Score, Acute Physiology and Chronic Health Evaluation II score, comorbid conditions, number of drugs, and length of stay were collected. RESULTS: Total 3-month mortality was 17.9%. Mortality rate was 10.7%, 17.6%, 14.5%, and 36.7% in groups a, b, c, and d, respectively. In three different multivariate Cox models including BADLs before admission, at admission, and at discharge, inability to regain function during hospitalization was an independent factor associated with 3-month mortality. CONCLUSIONS: In acutely ill elderly patients, lack of function regain during hospitalization is associated with higher mortality rate at 3 months, compared with those capable to regain the baseline functional status.

Hyperglycemia as a predictor of in-hospital mortality in elderly patients without diabetes mellitus admitted to a sub-intensive care unit.

OBJECTIVES: To investigate the association between hyperglycemia and in-hospital and 45-day mortality in acutely ill elderly patients. DESIGN: Retrospective cohort. SETTING: Hospital medical patients admitted to a sub-intensive care unit (sub-ICU) for elderly patients, which is a level of care between ordinary wards and intensive care. PARTICIPANTS: One thousand two hundred twenty-nine patients (mean age 79.6+/-8.4) admitted to the sub-ICU from January 2003 to January 2006. Forty patients with acute myocardial infarction and 34 patients with extreme fasting glucose values (<60 or >500 mg/dL) were excluded. Eight hundred twenty-two patients without a history of diabetes mellitus (DM) and 333 patients with a diagnosis of DM were selected and subdivided into three categories according to serum fasting blood glucose: 60 to 126 mg/dL (Group A), 127 to 180 mg/dL (Group B), and 181 to 500 mg/dL (Group C). MEASUREMENTS: Age, sex, mental and functional status, Acute Physiology Score, comorbid conditions, serum albumin, serum cholesterol, fasting serum glucose, and length of stay. In-hospital mortality was the primary outcome, and 45-day mortality was the secondary outcome. RESULTS: Total in-hospital mortality was 14.5%. In patients with and without DM, mortality was 8.8% and 11.3%, respectively, in Group A; 13.6% and 17.3% in Group B, and 12.6% and 34.3% in Group C. After controlling for confounders, newly recognized hyperglycemia (>181 mg/dL) was independently associated with in-hospital mortality (adjusted odds ratio=2.7, 95% confidence interval=1.6-4.8). Forty-five-day mortality in newly recognized hyperglycemic patients was 17.5%, 25.7%, and 42% in Groups A, B, and C, respectively, whereas it was 21.2% in patients with DM. CONCLUSION: In elderly patients, newly recognized hyperglycemia was associated with a higher mortality rate than in those with a prior history of DM. These data suggest that further randomized clinical trials are needed to assess the efficacy and the risk of a target glucose of greater than 180 mg/dL.

ACTH-secreting pituitary adenoma within an ovarian teratoma.

The differential diagnosis of Cushing's syndrome is one of the most difficult tasks in medicine, and it is especially problematic in cases with "occult" ectopic ACTH syndrome. We describe the case of a 26-year-old woman who was found to suffer from ectopic ACTH syndrome due to pituitary microadenoma, localized within a mature ovarian teratoma. Cushing's syndrome caused by ovarian neoplasia is unusual, but when it occurs, it is most often due to excessive cortisol production by the ovary. Only rarely has ectopic ACTH syndrome in association with an ovarian tumor been described.

Effects of olmesartan and enalapril at low or high doses on cardiac, renal and vascular interstitial matrix in spontaneously hypertensive rats.

We have evaluated the effects of different doses of an angiotensin-converting enzyme (ACE) inhibitor, enalapril (ENA) and of an angiotensin II type 1 receptor blocker olmesartan (OLM), on extracellular matrix of the heart, kidney, aorta and mesenteric artery of spontaneously hypertensive rats (SHR). Forty SHR and eight Wistar-Kyoto controls (WKY) were included in the study. Eight SHR were treated with high-dose OLM 15 mg/kg per day, eight with high-dose ENA 25 mg/kg per day, eight with low-dose OLM 1 mg/kg per day and eight with low-dose ENA (2 mg/kg per day). Eight SHR and eight WKY were kept untreated as controls. Treatment was from age 4 to 12 weeks. Systolic blood pressure (SBP) was measured non-invasively every week. The left ventricular weight to body weight (RLVM) was measured, and the cardiac, aortic and glomerular interstitial collagen content was evaluated using Sirius red staining and image analysis. Mesenteric small arteries were dissected and mounted on a micromyograph, and the media:lumen ratio (M/L) was calculated. Collagen subtypes were evaluated by polarized light microscopy. The SHR treated with high-dose OLM or ENA showed a normalization of SBP. The RLVM was significantly increased in untreated SHR compared with untreated WKY, whereas significantly lower values were observed in the groups of SHR treated with high-dose OLM or ENA. A significant increase in cardiac and glomerular collagen content was observed in untreated SHR. Both high- or low-dose OLM and ENA normalized collagen content in the heart and the kidney. Both high-dose OLM and high-dose ENA normalized M/L ratio; however, OLM proved to be more effective than ENA in normalizing collagen pattern. In fact, aortic collagen content was normalized by both high-dose and low-dose OLM, but only by high-dose ENA. In conclusion, both OLM and ENA were significantly and equally effective in the prevention of cardiac and renal damage in SHR, whereas OLM was more effective than ENA in terms of effects on vascular extracellular matrix.

Effect of treatment with candesartan or enalapril on subcutaneous small artery structure in hypertensive patients with noninsulin-dependent diabetes mellitus.

Structural alterations of subcutaneous small resistance arteries are associated with a worse clinical prognosis in hypertension and noninsulin-dependent diabetes mellitus (NIDDM). However, no data are presently available about the effects of antihypertensive therapy on vascular structure in hypertensive patients with NIDDM. Therefore, we have investigated the effect of an angiotensin-converting enzyme inhibitor, enalapril, and a highly selective angiotensin receptor blocker, candesartan cilexetil, on indices of subcutaneous small resistance artery structure in 15 patients with mild hypertension and NIDDM. Eight patients were treated with candesartan (8 to 16 mg per day) and 7 with enalapril (10 to 20 mg per day) for 1 year. Each patient underwent a biopsy of the subcutaneous fat from the gluteal region at baseline and after 1 year of treatment. Small arteries were dissected and mounted on a micromyograph and the media-to-internal lumen ratio was evaluated; moreover, endothelium-dependent vasodilation to acetylcholine was assessed. A similar blood pressure-lowering effect and a similar reduction of the media-to-lumen ratio of small arteries was observed with the 2 drugs. Vascular collagen content was reduced and metalloproteinase-9 was increased by candesartan, but not by enalapril. Changes of circulating indices of collagen turnover and circulating matrix metalloproteinase paralleled those of vascular collagen. The 2 drugs equally improved endothelial function. In conclusion, antihypertensive treatment with drugs that inhibit the renin-angiotensin-aldosterone system activity is able to correct, at least in part, alterations in small resistance artery structure in hypertensive patients with NIDDM. Candesartan may be more effective than enalapril in reducing collagen content in the vasculature.

Effects of candesartan cilexetil and enalapril on inflammatory markers of atherosclerosis in hypertensive patients with non-insulin-dependent diabetes mellitus.

OBJECTIVE: Circulating adhesion molecules may have a prognostic significance as markers of endothelial damage. Drugs which inhibit the renin-angiotensin system may be effective in reducing circulating or tissue adhesion molecules, albeit data available are scarce. The aim of the study was to investigate the effects of an angiotensin-converting enzyme (ACE) inhibitor, enalapril and a highly selective angiotensin receptor blocker, candesartan cilexetil, on circulating adhesion molecules in a large sample of patients with non-insulin-dependent diabetes mellitus (NIDDM). The study was comparative, multicenter, randomized and double blind, with two parallel groups. PATIENTS AND METHODS: NIDDM patients with a diagnosis of mild (grade 1) essential hypertension were included in the study, at the end of a 2-week placebo run-in period. The primary end-point of the study was to evaluate changes of intercellular adhesion molecule-1 (ICAM-1) plasma levels during treatment. The secondary end-points were: changes in vascular cells adhesion molecule-1 (VCAM-1), von Willebrand factor (vWF), fibrinogen and plasminogen activator inhibitor-1 (PAI-1) circulating levels and of urinary albumin excretion rate (AER) as well; 129 patients were randomized: 66 in the candesartan group and 63 in the enalapril group, 118 of them completed the scheduled 24-week treatment period. RESULTS: Candesartan and enalapril equally reduced circulating level of ICAM-1 and exerted comparable effects on changes of other adhesion molecules and coagulation factors. A similar blood pressure-lowering effect was observed with the two drugs (candesartan: from 148/90 +/- 11/8 to 132/82 +/- 12/7 mmHg, P < 0.01, enalapril: from 148/91 +/- 12/8 to 131/85 +/- 14/6 mmHg, P < 0.01). Candesartan was more effective than enalapril in the reduction of albuminuria (P < 0.05 between treatments), although urinary protein excretion can be considered normal in the majority of patients. The two drugs were comparable in terms of adverse events reported. CONCLUSION: Candesartan and enalapril showed similar effects on blood pressure and on circulating adhesion molecules. In this study urinary protein excretion was reduced more by candesartan.

Bradykinin and matrix metalloproteinases are involved the structural alterations of rat small resistance arteries with inhibition of ACE and NEP.

BACKGROUND AND AIM: Increased vascular resistance is a hallmark of hypertension and involves structural alterations, which may entail smooth muscle cell hypertrophy or hyperplasia, or qualitative or quantitative changes in extracellular matrix (ECM) proteins. Since the renin-angiotensin-aldosterone system modulates these changes, we investigated the effects of 8 weeks of treatment with an angiotensin-converting enzyme (ACE) inhibitor, ramipril (RAM), or a dual ACE and neutral endopeptidase (NEP) inhibitor, MDL-100240 (MDL), on mesenteric small artery structure and ECM proteins in mRen2-transgenic rats (TGRs), an animal model of hypertension with severe cardiovascular damage. MATERIALS AND METHODS: Thirty-five 5-week-old rats were included in the study: six TGRs received RAM; five TGRs RAM + the bradykinin receptor inhibitor, icatibant; six TGRs, MDL; and five TGRs MDL + icatibant, while eight TGRs and five normotensive Sprague-Dawley controls were kept untreated. Mesenteric small arteries were dissected and mounted on a micromyograph. The media-to-lumen ratio (M/L) was then calculated. Vascular metalloproteinase (MMP) content was evaluated by zymography. RESULTS: In untreated TGRs severe hypertension was associated with inward eutrophic remodelling of small arteries. Both RAM and MDL prevented the increase in blood pressure and M/L and decreased MMPs. Icatibant blunted the effect of MDL on BP, M/L and MMPs. CONCLUSIONS: Changes in collagenase activity induced by ramipril and MDL are associated with prevention of small artery structural alterations in TGRs. Furthermore, MDL-induced enhancement of bradykinin could play a role in both the prevention of vascular structural alterations and in the stimulation of MMPs.

Acromegalic patients show the presence of hypertrophic remodeling of subcutaneous small resistance arteries.

Structural alterations of small resistance arteries in patients with essential hypertension (EH) are mostly characterized by inward eutrophic remodeling. However, we have observed the presence of hypertrophic remodeling in patients with renovascular hypertension, as well as in patients with noninsulin-dependent diabetes mellitus, suggesting a relevant effect of humoral growth factors on vascular structure. Growth hormone may stimulate in vitro proliferation of vascular smooth muscle cells. However, no data are presently available about small artery structure in acromegalic patients. Therefore, we have investigated the structure of subcutaneous small arteries in 12 normotensive (NT) subjects, in 12 EH subjects, and in 9 acromegalic patients (APs). All subjects underwent biopsy of the subcutaneous fat; then, small resistance arteries were dissected and mounted on a micromyograph. The normalized internal diameter, media thickness, media-to-lumen ratio, the media cross-sectional area together with remodeling, and growth indices were calculated. Demographic variables were similar in the three groups, except for blood pressure. The media-to-lumen ratio was significantly greater in EH and AP, compared with NT. No difference was observed between EH and AP. The media cross-sectional area was significantly greater in AP compared with EH and with NT. The calculation of remodeling and growth index suggests the presence of eutrophic remodeling in EH (growth index 0%) and of hypertrophic remodeling in AP (growth index 40%). In conclusion, our data suggest the presence of hypertrophic remodeling of subcutaneous small resistance arteries of AP, probably as a consequence of growth-stimulator properties of IGF-1.

Adrenergic mechanisms and remodeling of subcutaneous small resistance arteries in humans.

BACKGROUND: Vascular structural alterations in small resistance arteries of patients with essential hypertension (EH) are mostly characterized by inward eutrophic remodeling. In fact, no difference in the smooth muscle cell volume (CV) between normotensive subjects (NT) and essential hypertensive patients was observed. However, experimental models of hypertension with chronic infusion of agonists of adrenergic receptors were characterized by the presence of smooth muscle cell hypertrophy or hyperplasia. Recently, we have observed the presence of vascular smooth muscle cell hypertrophy in patients with renovascular hypertension. OBJECTIVE: The aim of the study to investigate the structural characteristics of subcutaneous small resistance arteries of NT, of EH, and of patients with phaeochromocytoma (Phaeo). PATIENTS AND METHODS: Thirty Phaeo, 30 NT and 30 EH were included in the study. A biopsy of subcutaneous fat was taken from all subjects. Small resistance arteries (relaxed diameter 160-280 microm) were dissected and mounted on a micromyograph and the media : lumen ratio was calculated. In nine Phaeo, nine NT and 13 EH the cell volume was measured by an unbiased stereological principle, the 'disector' method. RESULTS No difference in smooth muscle cell volume was observed between groups. However, inward remodeling in Phaeo was less marked than in EH, although the increase in media : lumen ratio was similar compared with NT. However, the lack of changes in media cross-sectional area, compared with NT, suggest that there has been little hypertrophy, the changes observed thus being eutrophic. CONCLUSIONS: Our data show, based on a reasonably large sample, that a pronounced activation of the adrenergic system is not associated with vascular smooth muscle cell hypertrophy or hyperplasia in humans. It is therefore possible that adrenergic mechanisms may have a relevant role in the development of eutrophic remodeling in small vessels.

Effects of losartan and enalapril at different doses on cardiac and renal interstitial matrix in spontaneously hypertensive rats.

We have evaluated the effects of an ACE inhibitor, enalapril (ENA) and of an angiotensin II receptor blocker, losartan (LOS), administered either at hypotensive or non-hypotensive dosage, on the cardiac and renal structure of spontaneously hypertensive rats (SHR). Forty-eight rats were included in the study: eight SHR were treated with low-dose (ld, 1 mg/kg/day) ENA; eight with low-dose (ld, 0.5 mg/kg/day) LOS; eight with high-dose (hd, 25 mg/kg/day) ENA; eight with high-dose (hd, 15 mg/kg/day) LOS; while eight Wistar-Kyoto (WKY) and eight SHR were kept untreated (unt). Treatment was given from the 4th to the 12th week of age. Systolic blood pressure (SBP) was measured non-invasively every week. The left ventricular weight to body weight (RLVM) and the left + right kidney weight (RKW) to body weight was measured, and the cardiac and glomerular interstitial collagen content was evaluated using sirius red staining and image analysis. In addition, cardiac metalloproteinases activity (43 kDa MMP, MMP-2, and MMP-9) was evaluated by zymography. A significant reduction in RLVM was observed in SHR given ENA hd or LOS hd. Cardiac collagen was significantly reduced in SHR ENA hd and SHR LOS hd as well as in SHR LOS ld, but not in SHR ENA ld. The 43 kDa MMP collagenase activity was greater in WKY unt compared with SHR unt, being normalized only in SHR ENA hd. The gelatinase activity of MMP-9 showed a trend similar to 43 kDa MMP, but differences between SHR and WKY unt were only of borderline statistical significance. No difference among groups was observed in MMP-2 activity. No significant differences in RKW was observed between groups. However, the collagen content in the glomerular perivascular space was significantly reduced in all treated groups, including those given ld, compared with SHR unt. In conclusion, LOS and ENA showed a similar preventive effect on the increase of RLVM in SHR, but, at least in part, different effects on the extracellular matrix in different organs, being cardiac collagen less sensitive to low dose (ld) ACE inhibition.