Orthostatic hypotension predicts all-cause mortality and coronary events in middle-aged individuals (The Malmö Preventive Project)

Aims Orthostatic hypotension (OH) has been linked to increased mortality and incidence of cardiovascular disease in various risk groups, but determinants and consequences of OH in the general population are poorly studied. Methods and results Prospective data of the Swedish 'Malmö Preventive Project' (n = 33 346, 67.3% men, mean age 45.7 +/- 7.4 years, mean follow-up 22.7 +/- 6.0 years) were analysed. Orthostatic hypotension was found in 6.2% of study participants and was associated with age, female gender, hypertension, antihypertensive treatment, increased heart rate, diabetes, low BMI, and current smoking. In Cox regression analysis, individuals with OH had significantly increased all-cause mortality (in particular those aged less than 42 years) and coronary event (CE) risk. Mortality and CE risk were distinctly higher in those with systolic blood pressure (BP) fall >/=30 mmHg [hazard ratio (HR): 1.6, 95% CI 1.3-1.9, P /=15 mmHg (HR: 1.4, 95% CI 1.1-1.9, P = 0.024 and 1.7, 95% CI 1.1-2.5, P = 0.01). In addition, impaired diastolic BP response had relatively greater impact (per mmHg) on CE incidence than systolic reaction. Conclusion Orthostatic hypotension can be detected in approximately 6% of middle-aged individuals and is often associated with such comorbidities as hypertension or diabetes. Presence of OH increases mortality and CE risk, independently of traditional risk factors. Although both impaired systolic and diastolic responses predict adverse events, the diastolic impairment shows stronger association with coronary disease

Multidisciplinary intervention reducing readmissions in medical inpatients: a prospective, non-randomized study

Gustav Torisson,1 Lennart Minthon,1 Lars Stavenow,2 Elisabet Londos1 1Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, 2Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden Background: The purpose of this study was to examine whether a multidisciplinary intervention targeting drug-related problems, cognitive impairment, and discharge miscommunication could reduce readmissions in a general hospital population. Methods: This prospective, non-randomized intervention study was carried out at the department of general internal medicine at a tertiary university hospital. Two hundred medical inpatients living in the community and aged over 60 years were included. Ninety-nine patients received interventions and 101 received standard care. Control/intervention allocation was determined by geographic selection. Interventions consisted of a comprehensive medication review, improved discharge planning, post-discharge telephone follow-up, and liaison with the patient's general practitioner. The main outcome measures recorded were readmissions and hospital nights 12 months after discharge. Separate analyses were made for 12-month survivors and from an intention-to-treat perspective. Comparative analyses were made between groups as well as within groups over time. Results: After 12 months, survivors in the control group had 125 readmissions in total, compared with 58 in the intervention group (Mann–Whitney U test, P = 0.02). For hospital nights, the numbers were 1,228 and 492, respectively (P = 0.009). Yearly admissions had increased from the previous year in the control group from 77 to 125 (Wilcoxon signed-rank test, P = 0.002) and decreased from 75 to 58 in the intervention group (P = 0.25). From the intention-to-treat perspective, the same general pattern was observed but was not significant (1,827 versus 1,008 hospital nights, Mann–Whitney test, P = 0.054). Conclusion: A multidisciplinary approach, targeting several different areas, could substantially lower readmissions and hospital costs in a non-terminal general hospital population. Keywords: medical inpatients, hospital readmissions, intervention, drug-related problems, cognitive impairment, hospital discharg

Interactions between cultured bovine arterial endothelial and smooth muscle cells; further studies on the effects of injury and modification of the consequences of injury

The hypothesis that cells of the arterial wall might modify the consequences of arterial injury was tested. Bovine aortic endothelial cells (EC) or smooth muscle cells (SMC) were exposed to the two toxic stimuli 3,4-benzo(a)pyrene (BP) and dimethylsulfoxide-soluble particulate matter from cigarette smoke (DSP) or factors released from platelets. The modification of the injury caused by these substances on arterial cells was studied by using a conditioned medium from arterial cells or an EC-SMC co-culture model. Direct addition of BP or DSP to the EC or SMC cultures induced toxic effects on the cells. DSP caused a decreased release of prostacyclin by EC. Conditioned medium from EC and SMC modified these toxic effects, which resulted in a reduced cell death and a further decreased cell proliferation, while conditioned medium from SMC increased the release of prostacyclin by EC injured by DSP. In EC-SMC co-culture the same modifications were obtained. The modification of cell injury was not linked to cell proliferation but instead the results suggested that the effects were mediated by multiple substances released from arterial cells. It is concluded that interactions between different cells in the arterial wall, in the non-injured as well as in the injured state, could be modified by endogeneous substances. This might be of relevance for atherogenesis

Interactions between cultured bovine arterial endothelial and smooth muscle cells; studies on the release of prostacyclin by endothelial cells

The release of prostacyclin by endothelial cells (EC) in culture was studied after exposure to two toxic stimuli (UV light or dimethylsulfoxide-soluble smoke particles (DSP)) or to medium conditioned by smooth muscle cells (SMC), basically or after injury to the SMC. An activity stimulating the release of prostacyclin was found together with growth inhibiting activity from arterial SMC, but dissociated from growth stimulating activity. The prostacyclin stimulating activity was increased when SMC were exposed to UV light, while DSP caused a decrease. EC directly exposed to UV light or DSP generally released more prostacyclin than controls. One exception was very low concentrations of DSP. UV light induced a burst of release in contrast to DSP where a continuous release after a two hours lag period was seen. It is concluded that EC will increase the release of prostacyclin in response to injury but the release pattern will depend on the kind and doses of the stimulus. SMC release prostacyclin stimulating activity for EC, which can be modified by exposure to toxic stimuli. The results might have applications for atherogenesis

Interactions between cultured bovine arterial endothelial and smooth muscle cells; effects of modulated low density lipoproteins on cell proliferation and prostacyclin release

We exposed bovine aortic endothelial cells in culture to native LDL (n-LDL) and LDL modulated by dimethylsulfoxide (DMSO-LDL), dimethylsulfoxide-soluble particles from cigarette smoke (DSP-LDL) or Cu2+ (Cu(2+)-LDL) to explore the hypothesis that these LDL-forms might influence interactions between endothelial and smooth muscle cells. It was shown that 3H-thymidine incorporation into endothelial cells was decreased by DMSO-LDL, DSP-LDL and Cu(2+)-LDL compared to n-LDL, while it was higher by DSP-LDL compared to its control i.e. DMSO-LDL. These effects could be transferred by conditioned medium to smooth muscle cell cultures. DSP-LDL or Cu(2+)-LDL decreased total cellular protein of endothelial cells. Initial (15 min) prostacyclin release from endothelial cells was increased by all LDL preparations compared to medium without LDL, most pronounced for Cu(2+)-LDL. If n-LDL was control, only Cu(2+)-LDL significantly increased the release of prostacyclin during 15 min and during 24 h. The release of prostacyclin assayed after 24 h was depressed by DSP-LDL compared to DMSO-LDL. This study demonstrated that interactions between endothelial and smooth muscle cells could be influenced by LDL treated by dimethylsulfoxide-soluble particles from cigarette smoke or by Cu2+, and their effects were not similar. DSP-LDL, in contrast to Cu(2+)-LDL, significantly decreased the release of prostacyclin by endothelial cells after 24 h incubations and via endothelial cell conditioned medium stimulated smooth muscle cell proliferation judged by increased 3H-thymidine incorporation. The results might be of relevance for atherogenesis

Interactions between cultured bovine arterial endothelial and smooth muscle cells : effects of injury on the release of growth stimulating and growth inhibiting substances

Dimethylsulfoxide-soluble particles (DSP) from cigarette smoke and ultraviolet light caused a low degree (cell death less than 30%) and high degree (cell death 60-90%) injury to bovine arterial endothelial cells and smooth muscle cells in culture. Conditioned medium from low degree injured endothelial cells and smooth muscle cells generally inhibited DNA synthesis in new smooth muscle cells or endothelial cells while high degree injury increased DNA synthesis in new cells. Specifically, the growth stimulating activity from endothelial cells was decreased after low degree injury but increased after high degree. UV light released more growth stimulating substances from smooth muscle cells after both low and high degree injury. The release of growth inhibiting substances was dependent on both cell kind and degree of injury. In co-culture low and high degree DSP injury to endothelial cells inhibited smooth muscle cell proliferation, which was in contrast to the effect of conditioned medium from high degree injured endothelial cells. Conditioned medium from endothelial cells treated with LDL and glucose inhibited DNA synthesis in smooth muscle cells. It is concluded that injury to endothelial cells or smooth muscle cells will modify the release of growth inhibiting and growth stimulating activity and that this release will depend on cell kind as well as degree and kind of the injurious stimulus