Trine Madsen

C-reactive protein, dietary n-3 fatty acids, and the extent of coronary artery disease

The acute-phase reactant C-reactive protein (CRP) has emerged as an independent risk factor for coronary artery disease. Experimental and clinical studies provide evidence of anti-inflammatory effects of n-3 polyunsaturated fatty acids (PUFA) derived from fish. We have studied the effect of marine n-3 PUFA on CRP levels in 269 patients referred for coronary angiography because of clinical suspicion of coronary artery disease. All patients filled out a food questionnaire regarding fish intake. The n-3 PUFA content of granulocyte membranes was determined and the concentration of CRP in serum was measured using a highly sensitive assay. The results were related to angiographic findings. CRP was significantly higher in patients with significant coronary stenoses than in those with no significant angiographic changes (p <0.001), but the CRP levels were not associated with the number of diseased vessels. Subjects with CRP levels in the lower quartile had a significantly higher content of docosahexaenoic acid (DHA) in granulocytes than subjects with CRP levels in the upper quartile (p = 0.02), and in a multivariate linear regression analysis, DHA was independently correlated to CRP (R(2) = 0.179; p = 0.003). The inverse correlation between CRP and DHA may reflect an anti-inflammatory effect of DHA in patients with stable coronary artery disease and suggest a novel mechanism by which fish consumption may decrease the risk of coronary artery disease.

The effect of dietary n-3 fatty acids on serum concentrations of C-reactive protein: a dose-response study.

C-reactive protein (CRP) is a sensitive marker for low-grade inflammation. Long-chain n-3 polyunsaturated fatty acids (PUFA) have anti-inflammatory effects. The objective of the present study was to investigate the effect on serum levels of CRP of n-3 PUFA at two different doses. We also investigated correlations between CRP and the cellular contents of PUFA. Sixty healthy volunteers (twenty-five women and thirty-five men) were randomly assigned to three treatment groups in a double-blind design. The subjects received a supplement of either 6.6 g n-3 PUFA/d, 2.0 g n-3 PUFA/d or placebo (olive oil) for 12 weeks. CRP was measured using a highly sensitive assay. The median serum CRP concentration was 0.78 mg/l. No significant correlations were found between CRP and the content of n-3 PUFA in granulocytes or platelets. Subjects receiving n-3 PUFA had a significant (P<0.01) increase in the cellular contents of 20 : 5n-3, 22 : 5n-3 and 22 : 6n-3, with the largest increase occurring in the group receiving 6.6 g PUFA/d. A significant (P<0.01) decrease in cellular content of 18 : 2n-6 and 20 : 4n-6 was observed simultaneously. Serum CRP concentrations, however, were unaffected by the PUFA-containing supplements. The present study shows that dietary supplementation with PUFA-containing supplements has no effect on serum concentrations of CRP, measured with a highly sensitive assay, in healthy subjects.

Heart rate variability and n-3 polyunsaturated fatty acids in patients with diabetes mellitus

Abstract. Hagstrup Christensen J, Aarup Skou H, Madsen T, Tørring I, Berg Schmidt E (Aalborg Hospital, Aalborg; and Hjørring/Brønderslev Hospital, Hjørring, Denmark). Heart rate variability and n‐3 polyunsaturated fatty acids in patients with diabetes mellitus. J Intern Med 2001; 249: 545–552.

Predictors of Psychiatric Inpatient Suicide: A National Prospective Register-Based Study

OBJECTIVE To study the incidence and risk factors of psychiatric inpatient suicide within a national cohort representing all psychiatric hospital admissions. METHOD This national prospective register-based study followed all psychiatric hospital admissions in Denmark from the date of patient admission until patient discharge or inpatient suicide over a 10-year study period from 1997 through 2006. By using survival analysis techniques, this study was the first to take the inpatient time at risk into account in the estimation of the suicide rate and the predictors of suicide among hospital-admitted psychiatric patients. RESULTS Among 126,382 psychiatric inpatients aged 14 years or older, 279 suicides occurred. The risk of inpatient suicide was high: 860 suicides per 100,000 inpatient years. Of those individuals who completed suicide, 50% died within 18 days of admission. The inpatient suicide rate significantly decreased, about 6% each year (HR = 0.94; 95% CI, 0.90-0.99), over this 10-year period. Several significant predictors of suicide were found, including the following: Patients with a bachelors degree had a significantly higher hazard ratio (HR) of suicide compared with those with a primary school education (HR = 0.41; 95% CI, 0.29-0.60) or those with vocational training (HR = 0.54; 95% CI, 0.39-0.77). Having a personality disorder as a secondary diagnosis (all psychiatric diagnoses were made according to ICD-10) raised the risk of suicide (HR = 1.60; 95% CI, 1.01-2.53), as did having recent contact (within the last year) with a private psychologist (HR = 1.85; 95% CI, 1.05-3.28). Recent suicide attempt before admission to the hospital was associated with the highest risk of inpatient suicide (HR = 4.99; 95% CI, 3.57-6.96). CONCLUSIONS This study demonstrated a high risk of psychiatric inpatient suicide in Denmark of 860 per 100,000 inpatient years and also revealed several significant predictors of psychiatric inpatient suicide. Furthermore, the inpatient suicide rate decreased from 1997 through 2006 in Denmark.

Latent trajectories of trauma symptoms and resilience: the 3-year longitudinal prospective USPER study of Danish veterans deployed in Afghanistan.

OBJECTIVE To identify trajectories of posttraumatic stress disorder (PTSD) symptoms from before to 2.5 years after deployment and to assess risk factors for symptom fluctuations and late-onset PTSD. METHOD 743 soldiers deployed to Afghanistan in 2009 were assessed for PTSD symptoms using the PTSD Checklist (PCL) at 6 occasions from predeployment to 2.5 years postdeployment (study sample = 561). Predeployment vulnerabilities and deployment and postdeployment stressors were also assessed. RESULTS Six trajectories were identified: a resilient trajectory with low symptom levels across all assessments (78.1%) and 5 trajectories showing symptom fluctuations. These included a trajectory of late onset (5.7%), independently predicted by earlier emotional problems (OR = 5.59; 95% CI, 1.57-19.89) and predeployment and postdeployment traumas (OR = 1.10; 95% CI, 1.04-1.17 and OR = 1.13; 95% CI, 1.00-1.26). Two trajectories of symptom fluctuations in the low-to-moderate range (7.5% and 4.1%); a trajectory of symptom relief during deployment, but with a drastic increase at the final assessments (2.0%); and a trajectory with mild symptom increase during deployment followed by relief at return (2.7%) were also found. Symptom fluctuation was predicted independently by predeployment risk factors (depression [OR = 1.27; 95% CI, 1.16-1.39], neuroticism [OR = 1.10; 95% CI, 1.00-1.21], and earlier traumas [OR = 1.09; 95% CI, 1.03-1.16]) and deployment-related stressors (danger/injury exposure [OR = 1.20; 95% CI, 1.04-1.40]), but not by postdeployment stressors. DISCUSSION The results confirm earlier findings of stress response heterogeneity following military deployment and highlight the impact of predeployment, perideployment, and postdeployment risk factors in predicting PTSD symptomatology and late-onset PTSD symptoms.

Marine n-3 Polyunsaturated Fatty Acids in Patients With End-stage Renal Failure and in Subjects Without Kidney Disease: A Comparative Study

OBJECTIVE Patients with end-stage renal disease treated with chronic hemodialysis (HD) are reported to have low levels of marine n-3 polyunsaturated fatty acids (PUFA) in plasma and cell membranes compared with healthy subjects. The aim of this study was to investigate whether n-3 PUFA levels in plasma and cells are lower in HD patients as compared with subjects without kidney disease. RESEARCH DESIGN A comparative study was carried out. SETTING This study was carried out at the Departments of Nephrology and Cardiology, Aalborg Hospital, Aarhus University Hospital, Denmark. PARTICIPANTS This study consisted of 2 study populations comprising HD patients and 5 study populations comprising subjects without kidney disease. INTERVENTION The fatty acid distribution in plasma phospholipids and platelet phospholipids was measured using gas chromatography. MAIN OUTCOME MEASURE Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) levels in plasma or serum phospholipids and platelet phospholipids in HD patients were compared with n-3 PUFA levels in subjects without kidney disease. RESULTS EPA and DHA were lower and AA/EPA was higher in plasma/serum phospholipids in HD patients than in subjects without kidney disease. Similarly, higher AA and AA/EPA and lower EPA and DHA levels were found in platelet phospholipids of HD patients. Adjustment for gender, age, and habitual intake of fish and fish oil supplements did not change these results. CONCLUSION HD patients have lower n-3 PUFA levels in plasma and cells compared with subjects without kidney disease.

Low-dose fish oil supplementation increases serum adiponectin without affecting inflammatory markers in overweight subjects

Obesity is associated with an increased risk of cardiovascular disease, whereas long-chain n-3 polyunsaturated fatty acids (PUFAs) from fish may have cardioprotective and anti-inflammatory effects. This study aimed to investigate the hypothesis that acute and short-term supplementation with a low dose of marine n-3 PUFA exerts an anti-inflammatory effect in overweight subjects. In a double-blind, placebo-controlled trial with 2 parallel groups, 50 overweight subjects were randomized to receive daily supplementation with 2 capsules containing either 2 g of fish oil (1.1 g marine n-3 PUFA) or 2 g of olive oil. Blood samples and adipose tissue biopsies were collected at baseline, after 1 day (acute effect), and after 6 weeks (short-term effect) of supplementation. No significant effects were seen after supplementation for 1 day, but after 6 weeks, subjects receiving fish oil had a significant increase in the n-3 PUFA content of granulocytes and adipose tissue (P < .01). Serum adiponectin levels were increased by 0.55 μg/mL (95% confidence interval, 0.02-1.08) in the fish oil group compared with the control group (P = .04) after 6 weeks of supplementation. Levels of interleukin 6 were inversely correlated to the marine n-3 PUFA content of granulocytes and adipose tissue at baseline (excluding α-linolenic acid). In conclusion, daily supplementation with 1.1 g of marine n-3 PUFA significantly increased serum adiponectin, but the effect was small, and no overall anti-inflammatory effect of the supplement could be demonstrated.

Marine n-3 fatty acids: basic features and background.

There is some evidence from epidemiology that intake of n-3 polyunsaturated fatty acids (PUFA) from seafood may protect against coronary artery disease (CAD). This hypothesis is further supported from animal data showing a beneficial effect of n-3 PUFA on thrombosis and atherosclerosis in animals fed fish oils in most, but not all, studies. There are several mechanisms by which an increased intake of marine n-3 PUFA may protect against CAD; the most universal finding is a reduction of plasma triglycerides. It is puzzling, however, that a very low amount of n-3 PUFA, with no known beneficial biochemical effects, seems to be cardioprotective. It has therefore been of paramount interest to perform clinical trials. Such evidence and trials are discussed in later chapters, and the results have been very encouraging.

Suicidal behavior and mortality in first-episode psychosis.

Abstract Suicide is a serious public health problem, with more than 800,000 deaths taking place worldwide each year. Mental disorders are associated with increased risk of suicide. In schizophrenia and other psychotic disorders, the lifetime risk of suicide death is estimated to be 5.6%. The risk is particularly high during the first year of the initial contact with mental health services, being almost twice as high as in the later course of the illness. The most consistently reported risk factor for suicide among people with psychotic disorders is a history of attempted suicide and depression. Suicide risk in psychosis in Denmark decreased over time, most likely because of improved quality of inpatient and outpatient services. There is a high proportion of young people with first-episode psychosis who attempted suicide before their first contact with mental health services. This finding suggests that the mortality rates associated with psychotic disorders may be underreported because of suicide deaths taking place before first treatment contact. However, currently, no data exist to confirm or refute this hypothesis. Attempted suicide can be an early warning sign of later psychotic disorder. Data from different studies indicate that the risk of suicide attempt during the first year of treatment is as high as 10%. The most important risk factors for attempted suicide after the first contact are young age, female sex, suicidal plans, and a history of suicide attempt. Early intervention services are helpful in first-episode psychosis, and staff members should, in collaboration with the patients, monitor the risk of suicide and develop and revise crisis plans.

Diagnostic Accuracy of the Posttraumatic Stress Disorder Checklist–Civilian Version in a Representative Military Sample

This study aimed to assess the diagnostic accuracy of the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C; Weathers, Litz, Herman, Huska, & Keane, 1993) and to establish the most accurate cutoff for prevalence estimation of posttraumatic stress disorder (PTSD) in a representative military sample compared to a clinical interview. Danish soldiers (N = 415; 94.4% male, mean age 26.6 years) were assessed with the PCL-C and the Structured Clinical Interview for the DSM-IV (SCID; First, Spitzer, Gibbon, & Williams, 2002) 2.5 years after their return from deployment to Afghanistan. Diagnostic accuracy of the PCL-C was assessed through receiver operating characteristic curve analysis. The PCL-C displayed high overall accuracy (area under the curve = .95, confidence interval [.92, .98]) and performed well (sensitivity > .70 and specificity ≥ .90), with cutoff scores ranging from 37 to 44. When including sensitivity values a little below .70 (.69), the PCL-C performed well for cutoff levels up to 53. Prevalence of PTSD varied considerably with the application of different cutoff values and scoring methods. Our results show that the PCL-C is a relevant and valid tool for screening for probable PTSD in active military samples. However, it is of great importance that cutoff scores be chosen based on the sample and the purpose of the particular study or screening.