AbstractHigher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.

Background and Aims: Achieve data reduction by employing cluster analyses of measurements of variables of vascular status. Additionally, to evaluate an vascular status score (VSS) based on the vascular variables. Associations between cluster subgroups, and markers of cardiovascular risk were examined to identify risk factors related to an unfavorable vascular status.

Summary A child, 2 years with the ‘hypercalprotectinaemia with hyperzincaemia’ clinical syndrome, presented with atypical symptoms and signs, notably persistent fever of approximately 38°C, thrombocythaemia of > 700 × 109/l and a predominance of persistent intestinal symptoms. In an effort to find a cure by identifying the dysregulated pathways we analysed whole-genome mRNA expression by the Affymetrix HG U133 Plus 2·0 array in blood on three occasions 3–5 months apart. Major up-regulation was demonstrated for the Janus kinase/signal transducer and activators of transcription (JAK/STAT) pathway including, in particular, CD177, S100A8, S100A9 and S100A12, accounting for the thrombocytosis; a large number of interleukins, their receptors and activators, accounting for the febrile apathic state; and the high mobility group box 1 (HMBG1) gene, possibly accounting for part of the intestinal symptoms. These results show that gene expression array technology may assist the clinician in the diagnostic work-up of individual patients with suspected syndromal states of unknown origin, and the expression data can guide the selection of optimal treatment directed at the identified target pathways.

Folic acid supplements are commonly used by infertile women which leads to a positive folate status. However, the effect of folic acid supplements on pregnancy outcome in women with unexplained infertility has not been well investigated. This study evaluated folic acid supplement use and folate status in women with unexplained infertility in relation to IVF pregnancy outcome. In addition, use of folic acid supplements and folate status were compared between women with unexplained infertility and fertile, nonpregnant control women. Women with unexplained infertility used significantly more folic acid supplements and had higher median total folic acid intake from supplements compared with fertile control women (both P < 0.001). Women with unexplained infertility also had significantly higher median plasma folate and lower median plasma homocysteine concentrations than fertile women (both P < 0.001), but folic acid supplementation or folate status were not related to pregnancy outcome in women with unexplained infertility. In conclusion, folic acid supplementation or good folate status did not have a positive effect on pregnancy outcome following infertility treatment in women with unexplained infertility. Folate is one of the B vitamins which has been suggested to be related to infertility. Folic acid is an artificial form of folate which is commonly used in dietary supplements. Folic acid supplementation has been shown to increase folate concentrations and decrease concentrations of the amino acid homocysteine in the blood. Folic acid supplementation is commonly used by infertile women, but the effect on pregnancy outcome in women with a diagnosis of unexplained infertility has not been thoroughly investigated. In the present study, folic acid supplement use and folate status (concentrations of folate and homocysteine) in women with unexplained infertility were evaluated in relation to pregnancy outcome. In addition, the use of folic acid supplements and folate status were compared between women with unexplained infertility and fertile control women. Our results showed that women with unexplained infertility used considerably more folic acid supplements and had higher total folic acid intake from supplements compared with fertile control women. Women with unexplained infertility had better blood folate and homocysteine concentrations than fertile women, but folic acid supplementation or folate status were not related to pregnancy outcome following the infertility treatment. In conclusion, high folic acid intake or good folate status did not increase the possibility of a birth of a healthy baby after infertility treatment in women with unexplained infertility.

Patients suffering from critical limb ischemia (CLI) have poor wound healing in the ankle and foot areas. Secondary wound infections are frequent and often treated with prolonged courses of antibiotics.

Objectives: Short relative telomere length (RTL) is associated with vascular ageing, inflammation and cardiovascular risk factors. Previous studies have reported an association between abdominal aortic aneurysm and short RTL. The presence of atherosclerosis among patients with aneurysm disease may, however, be a confounder. The aim was to explore the associations between short RTL and aneurysm disease, by comparing patients with isolated popliteal artery aneurysms with those having multiple aneurysms.Design and patients: DNA was retrieved from 183 patients with popliteal artery aneurysm (PAA). They were all examined with ultrasound at the time of blood-sampling, and had a total of 423 aneurysms (range 1-7, mean 2.3/patient).Methods: TL was measured with Real-Time PCR, RTL was calculated by comparing with three reference populations.Results: Patients with bilateral PAAs had a mean RTL of 0.985 vs. 1.038 with unilateral PAAs (P=0.326). Patients with abdominal aortic aneurysm had RTL 1.035, vs. 0.999 without (P=0.513). No difference was seen with or without femoral or iliac aneurysms. Fifty-six patients with isolated PAA at surgery and at re-examination had RTL 0.974, vs. 1.033 who had >1 aneurysm (P=0.308). RTL was not associated with the number of aneurysms at re-examination (P=0.727, one-way ANOVA). There was a trend towards shorter RTL among active smokers (0.93 vs. 1.04, P=0.066).Conclusions: No association between short RTL and multiple aneurysm disease was found. The previously reported association between AAA and short RTL may be secondary to cardiovascular risk factors, rather than by aneurysm disease. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

IntroductionMessenger RNA (mRNA) changes in the small intestine in response to acute mesenteric ischaemia (AMI) could offer novel diagnostic possibilities, but have not been described. The aim was to characterize the mRNA response to experimental AMI.Materials and methodsTwelve pigs underwent catheterisation of the superior mesenteric artery with injection of polivinylalcohol embolisation particles or sodium chloride. Laparotomy and intestinal tissue sampling were performed. Microarray analysis was performed using the GeneChip® whole porcine genome array.ResultsSeven down-regulated cellular pathways were associated with protein, lipid and carbohydrate metabolism. Seventeen up-regulated pathways were associated with inflammatory and immunological activity, regulation of extracellular matrix and decreased cellular proliferation. Thrombospondin (THS), monocyte chemoattractant protein 1(MCP-1) and gap junction alpha 1(GJA-1) were consistently up-regulated in all embolised pigs. Genes encoding earlier proposed biomarkers for AMI were up-regulated, such as lactate dehydrogenase and creatine kinase, or down-regulated, such as intestinal fatty acid binding protein and glutathione S-transferase.ConclusionThis study describes the intestinal tissue response on a gene expression level to AMI. THS, MCP-1 and GJA-1 were consistently up-regulated by ischaemia, whereas earlier proposed biomarkers for AMI were not. Gene expression may not be directly linked to the use of the corresponding proteins as potential clinical biomarkers.

AIMS:Oral anticoagulation (OAC), predominantly with warfarin, is an effective treatment to prevent thromboembolic events. Serious bleeding is a frequent and feared treatment complication. In this longitudinal cohort study of OAC-treated patients, we aimed to evaluate the relationship between von Willebrand factor (VWF) levels and risk of bleeding complications, cardiovascular mortality and all-cause mortality. METHODS AND RESULTS:A total of 719 patients receiving warfarin treatment were observed for a mean duration of 4.2 years. All bleeding complications causing hospitalization were registered and classified into clinically relevant bleeding (CRB) and major bleeding. Ischaemic stroke, peripheral arterial embolism, myocardial infarction, and death were also recorded. We identified 113 cases of CRB and 73 of major bleeding. In total, 161 deaths occurred during follow-up with cardiovascular disease identified as the cause of death in 110 patients. Patients in the highest tertile of VWF had a significantly increased risk of bleeding complications: hazard ratio (HR) 2.53 (95% CI 1.41-4.56) for major bleeding and HR 2.19 (95% CI 1.38-3.48) for CRB. VWF, expressed either in tertiles or as a continuous variable, showed a significant association with cardiovascular mortality (HR 1.68, 95% CI 1.40-2.01) and all-cause mortality (HR 1.77, 95% CI 1.52-2.05). In multivariate Cox regression analysis, the findings remained significant after adjusting for age, high-sensitivity C-reactive protein and creatinine. CONCLUSIONS:Patients with high levels of VWF had an increased risk of bleeding complications, cardiovascular mortality and all-cause mortality during OAC treatment. Our findings imply that the use of VWF as a risk marker for thromboembolic events is complicated by the association of VWF with bleeding complications.

There is growing evidence that folate status and variation in folate-metabolizing genes are involved in female reproductive functions. This study evaluated the influence of maternal blood folate, vitamin B(12), homocysteine and 10 folate pathway gene variants on IVF outcome. Also, the prevalence of these polymorphisms was compared in 439 female IVF patients and 225 fertile controls. MTHFR 677 CT heterozygotes had a higher proportion of good-quality embryos and an increased chance of pregnancy. MTHFR 1793 GA heterozygosity was associated with a lower percentage of previously failed IVF treatments. Heterozygosity for FOLR1 1816 C/delC and 1841 G/A was associated with a raised risk of pregnancy loss. The CTH 1208 GT genotype was associated with an increased chance of pregnancy and a smaller number of previously failed IVF cycles and the genotype frequency was lower in IVF patients with three or more previously failed IVF treatments compared with fertile controls. SLC19A1 80 GA heterozygotes had a decreased number of previously failed IVF treatments and were more prevalent among fertile controls. In conclusion, polymorphisms in folate-metabolizing genes may affect ovarian stimulation and pregnancy outcome of IVF, and heterozygous individuals, rather than the wild-type homozygotes, appeared to have more favourable outcomes.

When developing a genotyping assay by Pyrosequencing(trade mark) technology for the RFC1 (SLC19A1) c.80G>A polymorphism (rs1051266), unequal peak heights in the pyrograms were observed, probably due to unequal amplification of the mutated and wild-type alleles. This rarely occurring problem could potentially render assignment of heterozygous genotypes uncertain. When the PCR conditions were studied, it was found that substitution of the dGTP nucleotide in the master mix by dGTP and dITP in proportion 1:1 largely overcame this problem. Heat denaturation of the DNA at 95 degrees C before PCR also counteracted the problem. A combination of these two modifications of the standard pyrosequencing PCR protocol gave the best results. We conclude that, with these modifications, the RFC1 c.80G>A SNP can be reliably assayed by pyrosequencing.

Objective. Intestinal ischaemia is a life-threatening condition with high mortality, and the lack of accurate and readily available diagnostic methods often results in delay in diagnosis and treatment. The aim of this study was to investigate the accuracy of different plasma biomarkers in diagnosing intestinal ischaemia. Material and methods. Prospective inclusion of patients older than 50 years with acute abdomen admitted to hospital in Karlskrona, Sweden, between 2001 and 2003. Venous blood was sampled prior to any surgery and within 24 h from onset of pain. D-lactate, alpha glutathione S-transferase, intestinal fatty acid binding protein, creatine kinase B, isoenzymes of lactate dehydrogenase (LD) and alkaline liver phosphatase (ALP) were analysed. D-dimer was analysed using four different commercially available test kits. Results. In-hospital mortalities among patients with (n=10) and without (n=61) intestinal ischaemia were 40 % and 3 %, respectively (p=0.003). D-dimer was associated with intestinal ischaemia (p=0.001) independently of which assay was used. No patient presenting with a normal D-dimer had intestinal ischaemia. D-dimer > 0.9 mg/L had a specificity, sensitivity and accuracy of 82 %, 60 % and 79 %, respectively. Total LD, isoenzymes of LD 1-4 and liver isoenzyme of ALP (ALP liver) were significantly higher in patients with intestinal ischaemia, and accuracies for LD 2 (cut-off 2.3 mu kat/L) and ALP liver (cut-off 0.7 mu kat/L) were 69 % and 66 %, respectively. Conclusions. D-dimer may be used as an exclusion test for intestinal ischaemia, but lacks specificity. The other plasma biomarkers studied had insufficient accuracy for this group of patients. Further studies are needed.

The 776C > G polymorphism of the Transcobalamin II gene is located in a GC-rich region and TaqMan real-time polymerase chain reaction (PCR) does not yield satisfactory genotyping results. We therefore hypothesized that a method based on DNA sequencing would be needed for this single nucleotide polymorphism (SNP) analysis; Pyrosequencing technology was tested for this purpose. A Pyrosequencing protocol was developed, optimized and applied to a sample of 389 Swedish senior citizens. The three genotypes CC, CG, and GG consistently yielded typical programs that were readily distinguishable from each other. The prevalence of the mutated allele in the studied Swedish population was q=0.445. It is concluded that the TC II 776C > G polymorphism can be reliably genotyped by Pyrosequencing technology.

We have previously reported two novel mutations in the 5'-untranslated region (UTR) of the gene for folate receptor-alpha (FOLR1). In our search for additional mutations, 92 patient samples with elevated levels of homocysteine were screened by single-strand conformation polymorphism (SSCP) between nt - 425 and - 782, and - 712 and - 1110. Between nt - 425 and - 782 we did not find any mutations. Between nt - 712 and - 1110 there were three novel mutations. One subject had two mutations very close to each other, c. - 856C > T and c. - 921T > C. Two subjects had a c. - 1043G) A mutation. To get an idea of the prevalence of FOLR1 mutations in an unselected population, we also screened 692 healthy school children for mutations. In this cohort, between nt - 188 and + 272 we discovered one novel mutation, a single nucleotide substitution, c. - 18C > T, in addition to five children with the 25-bp deletion mutation previously described by us. Thus, so far we have discovered six novel mutations in the 5'-UTR region of the gene for folate receptor-alpha. We genotyped all 17 subjects with a FOLR1 mutation for the methylenetetrahydrofolate reductase ( MTHFR) 677C > T polymorphism, and developed new single-nucleotide polymorphism (SNP) genotyping protocols for MTHFR 1298A > C and 1793G > A utilising Pyrosequencing (TM) technology. None of the 17 subjects had the 677TT genotype, which ruled out this as a cause of elevated homocysteine levels, which was observed in some of the subjects. Further studies of mutations in the 5'-UTR of FOLR1, and in particular of their interplay with folate intake status, are warranted.

Objectives: The present paper focuses oil preanalytical aspects of tissue factor (TF) and vascular endothelial growth factor (VEGF) mRNA quantification: the choice of blood collection tubes and defining the time frame allowed before processing the sample.Design and methods: Blood was collected from healthy volunteers in K-3 EDTA tubes, CPT (TM), endotoxin-free EndoTube (TM) tubes and in PAXgene (TM) tubes. Total RNA concentration was determined by absorbance readings at 260 nm with a GeneQuantII UV spectrophotometer. RNA quantity and quality were also determined by the Lab oil a Chip technique (Agilent 2100 Bioanalyzer). Real-time RT-PCR assays were performed by the TaqMan technology.Results: The more expensive PAXgene and CPT tubes and the Endo tubes did not give superior results from those obtained in inexpensive routine K3 EDTA tubes. The PAXgene tubes preserved high molecular mass rRNA better than the other tubes.Conclusion: Both the PAXgene (TM) system and routine EDTA tubes are suitable for clinical purposes aimed at quantitation of mRNA for TF and VEGF. PAXgene (TM) yielded rRNA that was less degraded but had lower mRNA per mu g extracted RNA. A time frame tip to 24 h until sample processing is acceptable for TF and VEGF mRNA. (c) 2006 Published by The Canadian Society of Clinical Chemists.

Background. There is a shortage of reference values for cardiovascular risk factors such as serum lipids, glucose and insulin related to biological, social and lifestyle factors for Swedish children and adolescents. Such values are needed for planning and evaluation of public health activities, and for clinical use. Design and Methods. Data for this cross-sectional, school-based study were collected during a school year (September to May). A random sample of 1137 girls and boys aged 9 and 15 years from two locations in central Sweden participated in the study, and blood samples were taken from 969 of them. Methods. Fasting serum blood samples were analysed for triglycerides, total cholesterol, high-density lipoprotein cholesterol, glucose and insulin. Physical examination included measurement of height, weight and pubertal status. Questionnaires provided family background data. Total physical activity was measured by accelerometer registration. Results. Serum levels differed significantly between age and gender groups and were correlated to pubertal status. Neither genetic nor socio-economic background nor smoking status influenced the serum levels. Insulin levels were elevated in subjects with a body mass index in the highest decentile, compared with the levels in the rest of the subjects. The insulin levels were inversely associated with total physical activity, and physical activity varied with season. Conclusions. Pubertal status (biological age) should to be considered in the interpretation of serum values in schoolchildren rather than chronological age. The interpretation of insulin values should include both body mass index and physical activity level, and perhaps also season. Previously described regional differences in serum lipid levels in Swedish adults seem to be present also in children.

Objectives. To define risk factors associated with the development of abdominal aortic aneurysm (AAA) in a population-based case-control study.Material and Methods. Thirty-five patients found to have AAA at screening were compared with 140 age- and sex-matched controls. Three distinct comparisons were made. Current risk factors in both cohorts were compared. Because data were also available for both cohorts from a study conducted 12 years previously, a historical comparison was made between risk factors identified at the time of this initial evaluation. A longitudinal comparison was made between historical and current risk factors.Results. Elevated low-density-lipoprotein cholesterol, total cholesterol, and triglyceride levels 12 years before AAA screening were associated with current AAA with an odds ratio (OR) of 2.3 (95% confidence interval [Cl], 1.2 to 4.4); OF, 1.9 (95% CI, 1.3 to 2.8); and OR, 1.9 (95% CI,1.2 to 3.1)/mmol/L, respectively. Current variables assessed at AAA screening that were associated with AAA were: A history of atherosclerotic disease, OF, 3.8 (95% CI, 1.7 to 8.5); having a first-degree relative with AAA, OR, 4.4 (95% CI, 1.5 to 13.0); current smoking, OF, 5.2 (95% CI, 1.6 to 16.8); high-density-lipoprotein cholesterol level, OR, 0.1 (95% CI, 0.02 to 0.7)/mmol/L; and high-sensitivity C-reactive protein (hsCRP) level, OF, 1.1 (95% CI, 1.01 to 1.2)/mg/L. Hypertension and diabetes were not associated with AAA. A significant increase of hsCRP over time (12 years) was observed in AAA patients (P = .039) but not among controls. The variables of a history of atherosclerosis, smoking, and family history of AAA appear to interact synergistically to increase the prevalence of AAA (P < .001).Conclusion: Among traditional risk factors for atherosclerosis, some were associated with AAA and others were not, indicating complex and partly different causes. Inflammation and heredity appear to be important factors in the development of AAA.

BACKGROUND:Unstable coronary artery disease (CAD) is a multi-factorial disease involving thrombotic and inflammatory processes. Short-term low molecular weight (LMW) heparin treatment reduces coagulation activity and clinical events. We investigated the influence of prolonged treatment on coagulation, fibrinolysis and inflammation. METHODS AND RESULTS:Serial blood samples were obtained from 555 of 2,267 unstable CAD patients in the FRISC II study. Patients were treated with the LMW heparin dalteparin 120 IU kg(-1) s.c. twice daily for 5-7 days and randomized to placebo (n=285) or gender and weight-adjusted doses of dalteparin (5,000 or 7,500 IU) twice daily (n=270) for 3 months. Dalteparin persistently depressed coagulation activity with, when compared with placebo, lower median levels of factor VIIa (63 IU mL(-1) vs. 84 IU mL(-1)), prothrombin fragment 1 + 2 (0.86 nmol L(-1) vs. 1.09 nmol L(-1)) and D-dimer (21 microg L(-1) vs. 43 microug L(-1)) after 3 months, all P<0.01. Reactivation of coagulation activity was observed after cessation of both short-term and prolonged dalteparin treatment. Higher levels of tPA/PAI-1 complex (11.7 microg L(-1) vs. 6.5 microg L(-1), P<0.001) and von Willebrand factor (162% vs. 136%, P<0.001) were found during prolonged dalteparin treatment. Interleukin-6, C-reactive protein and fibrinogen levels were unaffected by dalteparin treatment. CONCLUSIONS:Three months dalteparin treatment resulted in a sustained and pronounced reduction of coagulation activity, which corresponds to the observed reduction in death and myocardial infarction during the initial 6 weeks in the FRISC II study. The persistently elevated levels of tPA/PAI-1 complex and von Willebrand factor might reflect effects on platelets and endothelial cells and thus contribute to the gradually decreased efficacy by prolonged dalteparin treatment in unstable CAD.

The aim was to define the most suitable specimen collection tubes for measurements of soluble Thrombomodulin (sTM), von Willebrand factor (vWF), and tPA/PAI-1 complex concentrations, and in particular whether the strongly acidic citrate additive in Stabilyte plasma would give significantly improved long-term stability of any of these analytes. We measured these analytes in paired specimens from 34 subjects, sampled 8-11 years before analysis, in serum, EDTA plasma, citrated plasma, and acidified citrated plasma (Stabilyte). Results were evaluated by regression analysis and Bland-Altman plots. All associations were linear across a wide assay range. Soluble TM was found to be highly unstable in serum as well as in EDTA plasma and to some extent even in ordinary citrate plasma: acidified citrate plasma is necessary to preserve sTM immunoreactivity in long-term storage. For hsCRP the slopes were not significantly different from that predicted by the dilution effect (0.83-0.86) of the citrate additive and there was no appreciable intercept. vWF values were comparable in citrate and acidified citrate plasma but serum and EDTA plasma samples yielded lower than expected results. For tPA/PAI-1 complex, Stabilyte tubes gave systematically lower results than the other tubes, with serum and EDTA plasma scoring the highest values, suggesting that in vitro increase in complex levels takes places upon blood collection and/or storage. We conclude that Stabilyte plasma is the specimen collection tube of choice for biobank projects aiming to measure fibrinolytic factors as well as several other analytes in the clotting system, such as soluble thrombomodulin and von Willebrand factor, in addition to the inflammatory marker hs-CRP. Indeed, using acidified Stabilyte plasma as the single medium would substantially simplify sampling for many epidemiological studies.

Background The summarized importance of haemostatic and metabolic variables (insulin, lipids including lipoprotein (a) [Lp(a)] and leptin) in predicting first myocardial infarction, as well as possible interactions among these variables, have not been reported.Design A prospective case-control study nested within the Northern Sweden Health and Disease Cohort.Methods Sixty-two men diagnosed with a first myocardial infarction were sex- and age-matched with 124 controls. Conditional logistic regression was conducted including established risk factors, plasma levels of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) mass concentration, von Willebrand factor, insulin, proinsulin, specific insulin, apolipoprotein A-I (apo A-I), Lp(a), and leptin. Interaction analysis was also performed for tPA, apo A-I, Lp(a), leptin and proinsulin.Results Smoking, low plasma levels of apo A-I and high plasma levels of cholesterol, Lp(a), tPA, PAI-1, proinsulin and leptin were associated with myocardial infarction in univariate conditional logistic regression analysis. High tPA [odds ratio (OR), 21.3; 95% confidence interval (CI) 2.04-222] and Lp(a) (OR, 7.21; 95% CI, 1.31-39.8) and low apo A-I (OR, 0.15; 95% CI, 0.02-0.93) remained significant risk determinants in multivariate analysis with smoking habits, body mass index, hypertension, cholesterol, and diabetes included as covariates. There were non-significant synergic interactions between high Lp(a) and leptin and tPA, respectively, and between high Lp(a) and low apo A-I.Conclusion Plasma levels of tPA, Lp(a), and apo A-I are independently associated with subsequent development of a first myocardial infarction in men. (C) 2004 The European Society of Cardiology.

OBJECTIVE:Elevated cortisol levels are associated with confusion and poor outcome after stroke. Dehydroepiandrosterone sulphate (DS), the most abundant adrenal androgen may act as an anti-glucocorticoid. An altered regulation of these steroids may affect numerous brain functions, including neuronal survival. The purpose of this study was to investigate serum cortisol and DS levels and the cortisol/DS ratio early after stroke and relate our findings to the presence of disorientation and mortality. DESIGN:Patients with acute ischaemic stroke (n = 88, 56 men and 32 women) admitted to a stroke unit were investigated with repeated clinical assessments and scores for degree of confusion, extent of paresis and level of functioning. Serum cortisol (C) and DS were measured on day 1 and/or day 4. Data for 28-day and 1-year mortality are presented. A control group of 65 age-matched healthy individuals was used. Multivariate analyses of mortality rates in the different tertiles or sixtiles of serum cortisol were performed with logistic regression, adjusting for age, sex, diabetes and level of consciousness. RESULTS:There was no difference in serum cortisol levels on day 1 for stroke patients when compared with control group values. Initial cortisol levels were significantly higher in the patients with acute disorientation versus orientated patients (P < 0.05). Cortisol levels on day 1 were an independent predictor of 28-day mortality, and patients with low cortisol levels (<270 nmol L(-1)) and increased levels (>550 nmol L(-1)) both had an increased 1-year mortality. DS levels on day 1 were significantly elevated in stroke patients. CONCLUSION:Hypercortisolism is associated with cognitive dysfunction early after ischaemic stroke. High and low circulating cortisol levels are associated with increased mortality after stroke. DS levels were not associated with clinical outcome.