Ingrid Bayer Kristensen

Nationwide study of sudden cardiac death in persons aged 1–35 years

AIMS The aim of this investigation was to study the incidence of sudden cardiac death (SCD) in persons aged 1-35 years in a nationwide setting (5.38 million people) by systematic evaluation of all deaths. METHODS AND RESULTS All deaths in persons aged 1-35 years in Denmark in 2000-06 were included. Death certificates were read independently by two physicians. The National Patient Registry was used to retrieve information on prior medical history. All autopsy reports were read and the cause of death was revised based on autopsy findings. We identified 625 cases of sudden unexpected death (10% of all deaths), of which 156 (25%) were not autopsied. Of the 469 autopsied cases, 314 (67%) were SCD. The most common cardiac cause of death was ischaemic heart disease (13%); 29% of autopsied sudden unexpected death cases were unexplained. In 45% of SCD cases, the death was witnessed; 34% died during sleep; 89% were out-of-hospital deaths. Highest possible incidence rate of SCD in the young was 2.8 per 100 000 person-years including non-autopsied cases of sudden unexpected death. Excluding those, the incidence rate declined to 1.9 per 100 000 person-years. CONCLUSIONS A total of 7% of all deaths in the young can be attributed to SCD, when including non-autopsied cases (autopsy ratio 75%). The incidence rate of SCD in the young of 2.8 per 100 000 person-years is higher than previously reported.

Incidence and etiology of sports-related sudden cardiac death in Denmark—Implications for preparticipation screening

BACKGROUND Studies on incidences of sports-related sudden cardiac death (SrSCD) are few and data are needed for the discussion of preparticipation screening for cardiac disease. OBJECTIVE We sought to chart the incidence and etiology of SrSCD in the young in Denmark (population 5.4 million) and to compare this to the incidence of sudden cardiac death (SCD) in the background population. METHODS All 5,662 death certificates for decedents in the period 2000 to 2006 in the age group 12 to 35 years in Denmark were read independently by 2 physicians to identify cases of SCD. Information from autopsy reports, selected hospital records, and multiple registries was used to identify cases of SCD and SrSCD. SrSCD was defined as SCD occurring during or within 1 hour after exercise in a competitive athlete. The size of the athlete population was estimated from national survey data. RESULTS Fifteen (range 0 to 5 per year) cases of SrSCD were found, 8 of which had antecedent symptoms. The incidence rate was 1.21 (95% confidence interval [CI]: 0.68 to 2.00) per 100,000 athlete person-years. The most common autopsy findings were arrhythmogenic right ventricular cardiomyopathy (n = 4), sudden unexplained death (n = 4), and coronary artery disease (n = 2). The incidence of SCD in the general population age 12 to 35 was 3.76 (95% CI: 3.42 to 4.14) per 100,000 person-years. CONCLUSION In Denmark, SrSCD is a rare occurrence and the incidence rate is lower than that of SCD in the general population. This may imply a low value of preparticipation screening of athletes in Denmark.

Artery-Related Differences in Atherosclerosis Expression Implications for Atherogenesis and Dynamics in Intima-Media Thickness

Background and Purpose— Information about the expression of atherosclerosis in different arteries is important. The impact of cardiovascular risk factors is artery-related, and the assessment of arterial structure and function in peripheral arteries are increasingly used as surrogate markers for coronary atherosclerosis and the risk of developing heart attack. Methods— In an autopsy study, we analyzed the coronary, carotid and superficial femoral arteries from 100 individuals (70 men; 20 to 82 years of age) of which 27 died from coronary atherosclerosis. Microscopic sections (n=4756) were analyzed blindly using a modification of the histological classification endorsed by the American Heart Association (AHA). Results— We found distinct artery-dependent patterns of atherosclerosis with a high prevalence of foam cell lesions and lipid core plaques in the carotid arteries. The femoral arteries were least affected by atherosclerosis, foam cell lesions were rare, and the development of advanced atherosclerosis was strongly age-dependent and dominated by fibrous plaques. Plaques were most common in the left anterior descending coronary artery and the carotid bifurcation. In coronary (versus noncoronary) death, lipid core plaques were more prevalent in all arteries. Conclusions— The initiation, speed of development, and phenotypic expression of atherosclerotic plaques are artery-related. Foam cell lesions are frequent in the carotid arteries, probably explaining the dynamics in carotid intima-media thickness. Atherosclerosis develops slowly in femoral arteries, and severe atherosclerosis is dominated by fibrous plaques. The higher prevalence of lipid core plaques in all arteries in coronary death indicates a systemically more vulnerable expression of atherosclerosis in these individuals.

Wall shear stress and early atherosclerotic lesions in the abdominal aorta in young adults

OBJECTIVES To study the correlation between wall shear stress and early atherosclerotic lesions in the abdominal aorta. DESIGN Blinded histomorphometric studies. Comparison with in vitro data. MATERIALS Abdominal aortic haemodynamics were simulated in a realistic pulsatile flow model. Abdominal aortas from 10 young adults with no signs of atherosclerotic disease were obtained during autopsy. METHODS Quantitative wall shear stresses were measured at rest and exercise in one suprarenal and two infrarenal positions using laser Doppler anemometry. Intimal thickening indices were measured blindly at the corresponding locations using histomorphometric methods, and compared to wall shear stress variables using linear regression analysis. RESULTS Intimal thickness index increased significantly with age. Intimal thickness index was significantly lower in the suprarenal than the infrarenal aorta, and higher at the distal posterior vessel wall compared to the anterior wall. Intimal thickness index correlated significantly with mean, minimum and oscillating wall shear stresses measured at rest. CONCLUSION Intimal thickness in the undiseased abdominal aorta correlated significantly with mean, minimum and oscillating wall shear stresses at rest measured in a pulsatile flow model. No correlations were found with maximum shear stress parameters. Exercise changed the local wall shear stresses away from the characteristics associated with intimal thickness index.

Plaque in superficial femoral arteries indicates generalized atherosclerosis and vulnerability to coronary death: An autopsy study

OBJECTIVES Risk factors for atherosclerosis have limited ability to identify persons at high risk of coronary heart disease. Assessment of subclinical atherosclerosis in peripheral arteries might improve this limitation. We studied the relationship between atherosclerotic plaques in peripheral arteries, coronary plaques, and coronary death. METHODS Predefined segments from the left anterior descending coronary artery, the right coronary artery, bilateral carotid, and superficial femoral arteries (SFA) were obtained from 100 autopsies (20-82 years, 30 females, 27 coronary deaths). Based on microscopic examination of 4756 sections, the extension of atherosclerosis (plaque burden) and the largest plaque area in each segment were quantified. RESULTS Plaque burden in all arteries increased with age and was larger in coronary death (P < .05). SFA plaques occurred later than coronary and carotid plaques. When SFA plaque had developed, coronary plaque was also present. SFA plaque (odds ratio, 95% confidence interval: 7.07 [2.40-20.81]), but not carotid plaque, was significantly associated with coronary death, also after age and gender adjustment (21.25 [5.02-89.97]). The area under the receiver operating characteristic curves for the identification of coronary death individuals was 0.72 (95% confidence interval: 0.62-0.83) for coronary plaque, and 0.80 (0.72-0.89) for SFA plaque (age and gender adjusted). CONCLUSIONS Atherosclerosis develops slower in SFA compared with coronary and carotid arteries. In persons with plaque in the SFA, plaque is always present in the coronary arteries. In younger persons, the presence of SFA plaque indicates a generalized susceptibility to atherosclerosis and vulnerability to coronary death.

The prevalence of mutations in KCNQ1, KCNH2, and SCN5A in an unselected national cohort of young sudden unexplained death cases.

Introduction: Sudden unexplained death account for one‐third of all sudden natural deaths in the young (1–35 years). Hitherto, the prevalence of genopositive cases has primarily been based on deceased persons referred for postmortem genetic testing. These deaths potentially may represent the worst of cases, thus possibly overestimating the prevalence of potentially disease causing mutations in the 3 major long‐QT syndrome (LQTS) genes in the general population. We therefore wanted to investigate the prevalence of mutations in an unselected population of sudden unexplained deaths in a nationwide setting.

Effects of temperature and histopathologic preparation on the size and morphology of atherosclerotic carotid arteries as imaged by MRI.

Using magnetic resonance imaging the effects of temperature, formalin fixation, and decalcification on the size and morphology of atherosclerotic arteries were evaluated. Ten ex vivo carotid arteries were scanned fresh at body and room temperature and formalin‐fixed and decalcified at room temperature. Different spin‐echo pulse sequences were used and absolute T2 values calculated. During processing for histopathology, the contrast between the arterial layers increased. From body to room temperature there were significant increases in size (4%–7%), T2 of media (60→ 68 msec), and fibrous plaque component (95→ 110 msec). Formalin fixation caused significant increases in size (2%–3%) and media T2 (68→ 74 msec). Decalcification caused significant shrinkage (2%–5%) and decrease in T2 of media (74→ 53 msec) and fibrous plaque component (118→ 76 msec). Thus temperature and preparation have profound effects on contrast, size, and T2 of atherosclerotic arteries. Ex vivo experiments should be performed on fresh specimens at body temperature. J. Magn. Reson. Imaging 1999;10:876–885.

DNA level, tumor thickness, and stereological estimates of nuclear volume in stage I cutaneous malignant melanomas : a comparative study with analysis of prognostic impact

The mutual relation and prognostic value of three quantitative variables were investigated in a retrospective series of 56 stage I cutaneous malignant melanomas. Unbiased stereological estimates of nuclear volume, nuclear nu v were obtained along with measurements of melanoma thickness. The DNA index (DI) was determined by flow cytometry in adjacent sections from the same paraffin-embedded specimens. The correlation between tumor thickness and nuclear nu v was only moderate (r = .60). Euploid lesions had a smaller nuclear nu v than aneuploid tumors (2p = .01), but with considerable overlap. No significant association between tumor thickness and DI could be demonstrated. Single-factor analysis showed prognostic value of nuclear nu v and tumor thickness (2p = .0007 and 2p = .03, respectively), whereas DI was without prognostic impact (2p = .54). When analyzing the three parameters in a Cox model, nuclear nu v was the only independent, prognostically significant variable. Physical, three-dimensional nuclear volume is not solely a reflection of nuclear DNA content, and may represent a valuable, quantitative prognostic indicator in cutaneous malignant melanomas.

Sudden death caused by thrombosed coronary artery aneurysm Two unusual cases of Kawasaki disease

SummaryKawasaki disease primarily affects children below 5 years of age, and fatal coronary complications usually occur within 6–12 months following the acute illness. We report 2unusual fatal cases of thrombosed coronary artery aneurysms. The first case was an 11-year-old boy, who died suddenly 2 months after the acute illness. He had a classical clinical picture, but was misdiagnosed. The second case was a 29-year-old man without history of recent febrile episodes or cardiac symptoms. Bothsubjects fulfilled the stage 4 criteria of Kawasaki disease (healing stage) with extensive old myocardial damage. The cases illustrate the great variation in the clinical picture of Kawasaki disease. Teenagers can also be affected, and extensive myocardial damage may be asymptomatic formany years.ZusammenfassungDie Kawasaki-Krankheit betrifft primär Kinder im Lebensalter unter 5 Jahren, und akute koronare Komplikationen entstehen normalerweise innerhalb von 6–12 Monaten nach der akuten Erkrankung. Wir berichten über 2 ungewöhnliche Fälle von thrombosierten Koronar-Aneurysmen. Im ersten Fall handelte es sich um einen 11jährigen Jungen, welcher plötzlich 2 Monate nach der akuten Erkrankung verstarb. Er hatte ein klassisches klinisches Bild, aber dieses wurde fehldiagnostiziert. Der zweite Fall war ein 29 Jahre alter Mann ohne Anamnese, mit rezenten fieberhaften Episoden oder kardialen Symptomen. Beide Personen erfüllten die Kriterien des Stadiums 4 der Kawasaki-Krankheit (Heilungsstadium) mit ausgeprägten alten myokardialen Schäden. Die Fälle zeigen, daß eine große Variation im klinischen Bild der Kawasaki-Krankheit existiert. Auch Teenager können betroffen sein, und ausgeprägte myokardiale Schäden können für viele Jahre asymptomatisch sein.

An association study of suicide and candidate genes in the serotonergic system.

INTRODUCTION Strong evidence demonstrates a genetic susceptibility to suicidal behaviour and a relationship between suicide and mental disorders. The aim of this study was to test for association between suicide and five selected genetic variants, which had shown association with suicide in other populations. METHOD We performed a nationwide case-control study on all suicide cases sent for autopsy in Denmark between the years 2000 and 2007. The study comprised 572 cases and 1049 controls and is one of the largest genetic studies in completed suicide to date. The analysed markers were located within the Serotonin Transporter (SLC6A4), Monoamine Oxidase-A (MAOA) and the Tryptophan Hydroxylase I and II (TPH1 and TPH2) genes. RESULTS None of the genetic markers within SLC6A4, MAOA, TPH1 and TPH2 were significantly associated with completed suicide or suicide method in the basic association tests. Exploratory interaction test showed that the minor allele of rs1800532 in TPH1 has a protective effect for males younger than 35 years and females older than 50 years, whereas for the oldest male subjects, it tended to be a risk factor. We also observed a significant interaction between age-group and the 5-HTTLPR genotype (with and without rs25531) in SLC6A4. The long allele or high expression allele tends to have a protective effect in the middle age-group. LIMITATION We only analysed a limited number of genetic variants. CONCLUSION None of the analysed variants are strong risk factors. To reveal a better understanding of the genes involved in suicide, we suggest future studies should include both genetic and non-genetic factors.