Alcohol and premature death in Estonian men: a study of forensic autopsies using novel biomarkers and proxy informants

Abstract

BackgroundAlcohol makes an important contribution to premature mortality in many countries in Eastern Europe, including Estonia. However, the full extent of its impact, and the mechanisms underlying it, are challenging issues to research. We describe the design and initial findings of a study aimed at investigating the association of alcohol with mortality in a large series of forensic autopsies of working-age men in Estonia.Methods1299 male deaths aged 25-54 years were subject to forensic autopsy in 2008-2009. The routine autopsy protocol was augmented by a more systematic inspection of organs, drug testing, assay of liver enzymes and novel biomarkers of alcohol consumption (EtG, EtS and PEth), together with proxy interviews with next of kin for deaths among men who lived in or close to a major town.Results595 augmented autopsies were performed. Of these, 66% were from external causes (26% suicide, 25% poisoning). 17% were attributed to circulatory system diseases and 7% to alcoholic liver disease. Blood alcohol concentrations (BAC) of ≥ 0.2 mg/g were found for 55% of deaths. Interviews were conducted with proxy informants for 61% of the subjects who had resided in towns. Of these, 28% were reported in the previous year to have been daily or almost daily drinkers and 10% had drunk non-beverage alcohols. Blood ethanol and the liver enzyme GGT were only associated with daily drinking. However, the novel biomarkers showed a more graded response with recent consumption. In contrast, the liver enzymes AST and ALT were largely uninformative because of post-mortem changes. The presence of extremely high PEth concentrations in some samples also suggested post-mortem formation.ConclusionWe have shown the feasibility of deploying an extended research protocol within the setting of routine forensic autopsies that offer scope to deepen our understanding of the alcohol-related burden of premature mortality. The most unique feature of the study is the information on a wide range of informative alcohol biomarkers, several of which have not been used previously in this sort of post-mortem research study. We have demonstrated, for the first time, the epidemiological value and validity of these novel alcohol biomarkers in post-mortem samples.

A systematic review of the epidemiology of unrecorded alcohol consumption and the chemical composition of unrecorded alcohol

“…It may be that people who consumed surrogate alcohol consumed more ethanol than those people who consumed beverage alcohol (i.e. more heavy drinking occasions resulting in a higher average consumption) (for the relationship between heavy drinking and surrogate consumption, see ), or that people who drank surrogate alcohol did so in a more detrimental pattern of irregular heavy drinking (for definitions see ; for the relationship between surrogate drinking in Russia and detrimental drinking patterns see ). Both regular and irregular heavy drinking have been linked to higher mortality and burden of disease .…”

Prevalence of alcohol‐related pathologies at autopsy: E stonian F orensic S tudy of A lcohol and P remature D eath

“…Thus, although at autopsy the ethanol concentration is used commonly to determine whether acute intoxication is implicated as a cause of death, it is not informative about whether a death might be attributable to long-term harmful drinking. We have shown previously that at post-mortem GGT and EtG were the markers related most strongly to proxy-reported frequency of drinking [16]. Recently Rainio et al have shown that measuring vitreous humour EtG by immunoassay is a useful forensic tool for screening for ante-mortem alcohol use [25].…”

“…The circumstances in which a forensic autopsy is performed in Estonia have been described previously 16. According to data from the Estonian Forensic Science Institute, about 90% of forensic autopsy cases are tested for alcohol and 35–40% of these have a blood ethanol concentration exceeding 0.5 mg/g.…”

Glycated haemoglobin (HbA1c) for postmortem diagnosis of diabetes

“…The “other alcohol” group contains surrogate non-beverage alcohols (ethanol-containing liquids not intended for consumption), which are drunk particularly among men in Estonia [ 36 , 37 ]. In a previous study of association of alcohol with the mortality of Estonian men aged 25–54 years, alcohol was found in blood in concentrations ≥ 0.2 mg/g in 55% cases of death [ 38 ]. Results of that study of men also showed evidence of alcohol-induced pathologies in 75% of cases, and 32% had pathologies in two or more organs [ 39 ].…”

“…In the study by Ringmets et al. [ 38 ] it was stated that liver enzymes, used widely to detect liver damage in living subjects, have a limited postmortem value. AST and ALT are increased by haemolysis and hypoxia and so are subject to differences in the process of dying.…”