Martin Christensen

Preeclampsia and cardiovascular disease risk assessment – Do arterial stiffness and atherosclerosis uncover increased risk ten years after delivery?

OBJECTIVES Epidemiological studies associate preeclampsia with increased risk of premature cardiovascular disease (CVD) later in life. This study aims to make a comprehensive CVD risk assessment comparing women with previous preeclamptic pregnancies to women with previous normotensive pregnancies 10years after index pregnancy. STUDY DESIGN A nested, matched, observational cohort study. MAIN OUTCOME MEASURES Markers of arterial stiffness, aortic pulse wave velocity (aPWV) and augmentation index (AIx-75), and markers of atherosclerosis, carotid intima-media thickness (cIMT) and carotid plaque presence. Traditional CVD risk factors and 10-year and 30-year Framingham CVD risk scores were also assessed. RESULTS Women were included from April 2014 to October 2014 at a tertiary referral hospital in Denmark. Twenty-one exposed women with a history of preeclampsia and 21 unexposed with a history of normotensive pregnancies were included. Ten years after delivery, significantly more exposed women suffered from hypertension and received antihypertensive treatment and significantly more fulfilled the hypertension-definition at screening. Previously preeclamptic women also tended to have more unfavorable CVD risk estimates. The Framingham risk scores seemed to extend the unfavorable CVD risk. The exposed women tended to have a higher aPWV compared to unexposed women, (P=0.057). No differences were shown in the other examined arteriosclerotic or atherosclerotic variables. CONCLUSIONS Ten years after delivery, we found increased risk of hypertension and trend toward unfavorable CVD risk profile in 40-year-old previously preeclamptic women. However, arterial stiffness and atherosclerosis did not uncover any additional CVD risk information at this time point.

Drug-induced bilateral ischemic infarction in an amphetamine addict

A 33-year old Caucasian male amphetamine addict died at an intensive care unit due to bilateral cerebral infarction complicated by multi-organ failure. Two days prior to admission he had taken several illegally bought pills, allegedly amphetamine and methamphetamine. A friend had told the police that after taking the drugs he had remained unconscious for 2 days at her home. Eventually she suspected that something was wrong and had called for help. He was admitted to the intensive care unit where he remained in a comatose state. A CT-scan performed upon admission showed extensive infarction of both cerebral hemispheres (Figs. 1, 2). During admission he was examined by a neurologist and declared decorticate. Eventually he developed multi-organ failure and died 19 days after hospital admission. The forensic autopsy and histological study of the deceased was performed at the Department of Forensic Pathology, University of Aarhus. The brain and spinal cord were examined by a neuropathologist. The autopsy revealed symmetrical necrosis of the white matter of both cerebral hemispheres, spanning the entire length of the brain from the frontal to the occipital lobes (Figs. 3, 4); furthermore there was necrosis of the left hemisphere of the cerebellum. Histological studies confirmed extensive necrosis of the cerebral tissue, with demyelination, and infiltration by macrophages (Figs. 5, 6). There was severe edema of the brain but minimal hemorrhage and no inflammation. Further histological studies revealed steatosis of the liver, non-specific ischemic changes of the kidneys and bronchopneumonia. Toxicological studies of blood samples taken at the time of admission were performed at the Department of Forensic Toxicology of University of Aarhus, Denmark. The toxicological methods used were qualitative screening for illegal and prescriptive drugs by chromatographic analysis with UV-detection (HPLC–DAD) and mass spectrometric detection (GC–MS). Qualitative screening for illegal drugs and opioids was performed by immunological methods (EMIT/CEDIA—Enzyme Multiplied Immunoassay Technique/Cloned Enzyme Donor Immunoassays). Confirmation and quantification of detected substances were performed by LC-MSMS (amphetamine, met-amphetamine, fentanyl, codeine) and GC–MS (methadone). Alcohol was analyzed by headspace GC-FID on two different chromatographic columns with different polarity. The toxicological analysis showed traces of fentanyl (0.002 mg/kg), codeine (0.024 mg/kg), methadone (0.12 mg/kg), methamphetamine (\0.01 mg/kg) and amphetamine (0.04 mg/kg); there was no detectable alcohol. The interpretation of the toxicological results, performed by a clinical chemist, showed that the concentration of amphetamine in the blood sample taken on admission 2 days after amphetamine and methamphetamine intake was below toxic levels. However, the peak-concentration of amphetamine and methamphetamine was assumed to have been higher. Due to great inter-individual variation in metabolism of drugs the determination of peak-concentration after drug intake is very uncertain. The concentration of methadone and codeine was below the level of toxicity. M. R. Christensen (&) I. Lesnikova I. Rosendal J. Banner Department of Forensic Medicine, University of Aarhus, Brendstrupgardsvej 100, 8200 Aarhus N, Denmark e-mail: mrchristensen81@gmail.com

Preeclampsia and later cardiovascular disease – What do national guidelines recommend?

Preeclamptic women have an increased risk of hypertension and cardiovascular disease (CVD) later in life. The aim was to compare the latest clinical recommendations on post-preeclamptic prevention of hypertension and CVD published by eight National Associations of Gynecologists and Obstetricians. Definitions of preeclampsia differ internationally. Recommendations on when, how and who to screen to reduce post-preeclamptic CVD risk also show substantial variation. The diverging preeclampsia definitions make CVD prevention strategies difficult to compare. The variations in clinical recommendations are in line with the lacking evidence of cost-efficient follow-up strategies and stress the need for further research to optimize prevention strategies.

Early gestational age at preeclampsia onset is associated with subclinical atherosclerosis 12 years after delivery

Women with a history of preeclampsia have increased risk of cardiovascular disease later in life. However, it is unclear whether early gestational age at preeclampsia onset is associated with higher cardiovascular disease risk. This study aimed to test the association between gestational age at preeclampsia onset (including the early‐onset/late‐onset preeclampsia distinction) and subclinical atherosclerosis and arterial stiffness in age‐matched women 12 years after index pregnancy.

Elevated levels of 8-oxoGuo and 8-oxodG in individuals with severe mental illness – An autopsy-based study

Abstract Elevated systemic oxidative stress levels of 8‐oxoGuo and 8‐oxodG have been reported in individuals with severe mental illness (SMI). As no previous studies have addressed the link between local levels of 8‐oxoGuo and 8‐oxodG in the central nervous system (CNS), measured in cerebrospinal fluid (CSF), and urinary systemic levels, we employed autopsy‐based material to elucidate this aspect. Additionally, we investigated the impact of 8‐oxoGuo and 8‐oxodG levels on the prevalence of somatic co‐morbidities. Based on post mortem samples from deceased individuals with SMI (N = 107), we found significantly elevated urinary levels of both 8‐oxoGuo and 8‐oxodG compared to mentally healthy living controls. While we found an association between urinary and CSF 8‐oxodG levels (r = 0.50, P < 0.001), a similar correlation was not evident for 8‐oxoGuo (r = 0.15, P = 0.16). Additionally, the two r‐values were significantly different (P < 0.001). Neither marker in urine or CSF was associated with obesity‐related variables, metabolic syndrome or type 2 diabetes. The post mortem interval did not affect the results, but the agonal phase seemingly introduced bias. This study provided novel insights into the cellular oxidative stress levels in individuals with SMI. We demonstrated that increased oxidative stress locally and systemically is correlated and is a clear phenomenon in SMI. Although post mortem measurements contain some weaknesses, our study indicates DNA as the main site of oxidative stress modifications in the CNS in SMI. This may provide novel opportunities for treatment modalities. Additionally, our study demonstrated the applicability of post mortem material investigating systemic and local 8‐oxoGuo and 8‐oxodG levels. Graphical abstract Figure. No caption available. HighlightsMentally ill have elevated markers of oxidative stress compared to mentally healthy.8‐oxodG levels in cerebrospinal fluid correlates with ditto levels in urine.DNA may be the main target for oxidative stress damage in the brain in mental illness.8‐oxoGuo and 8‐oxodG appear stable post mortem in urine and cerebrospinal fluid.Agonal phase might increase levels of oxidative stress.