Alcohol Abuse Mortality Patterns Shift With Age

Nancy A. Melville

April 25, 2016

Alcohol use disorder is associated with a nearly sixfold increase in all-cause mortality across age groups, but the risks are linked to individual and familial predispositions in early adulthood and to the course of alcohol abuse in later years, new research shows.

"The effects of the predispositions were more prominent early in the life course and in the earlier years of AUD [alcohol use disorder]. The direct effect of AUD on mortality became progressively more important later in life and later in the course of alcohol use disorder," the authors, led by Kenneth S. Kendler, MD, of the Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, in Richmond, write.

"These results have clear implications for interventions that seek to reduce the substantially elevated rates of mortality in those with alcohol use disorder," the investigators add.

The study was published online April 20 in JAMA Psychiatry.

Direct Effect

It is well known that alcohol abuse is a general risk factor for increased mortality. However, the investigators sought to better understand whether the increased risk was linked more to individual characteristics, including heritable factors, or to alcohol use disorder itself.

For the study, the researchers evaluated a prospective Swedish population registry that included information on half-siblings, full siblings, and monozygotic twins who differed with respect to alcohol use disorder. The analysis included individuals born between 1940 and 1965. Participants were followed from January 1, 1973, to December 31, 2010.

Of 1,447,887 men and 1,373,149 women in the analysis, 131,895 men and 42,163 women were registered as having alcohol use disorder. The mean age of the participants was 39 years at the time of the documentation of alcohol use.

After adjustments for variables that included sex, educational status, and year of birth, alcohol use disorder was associated with a mortality hazard ratio of 5.83 (95% confidence interval, 5.76 - 5.90). However, the hazard ratio showed an inverted U-shaped curve in accordance with age.

In comparison with the general population, substantial familial confounding was observed in younger age groups, with a lower alcohol use disorder–associated mortality hazard ratio among differing close relatives than in the general population.

Familial confounding patterns decreased in middle to late adulthood, suggesting a direct effect of alcohol use disorder on increased mortality.

In the oldest age group (65-70 years), the mortality hazard ratios were similar across the population and for all relative pairs, suggesting that the excess mortality was largely a result of alcohol use disorder, the authors reported.

Limitations of the study include the fact that the prevalence of alcohol use disorder in the sample was significantly lower than has been estimated in other countries, including the United States and Norway, and the sample likely included heavy drinkers who may have never been registered as having alcohol use disorder.

The authors also noted that use of International Classification of Diseases (ICD) codes for specific causes of death could help in interpretation of the findings.

"An important future research question would be the degree to which an examination of these [ICD] codes can shed further light on the causal association between alcohol use disorder and premature mortality," they write.

Untangles Environmental, Genetic Factors

In an accompanying editorial, Andreas Heinz, MD, PhD, of the Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Germany, and colleagues note that the study offers important insights into the underlying factors that may contribute to alcohol-related mortality.

"The study by Kendler and coauthors disentangles the environmental and genetic risk factors that contribute to increased mortality among individuals with alcohol use disorders," they write.

They agreed that, with many comorbidities associated with alcohol use, such as tobacco use, specifics on causes of death could provide essential information.

"Exploration of International Classification of Diseases codes for causes of death may stimulate research in the widely understudied area of alcohol-related aggression, the role of comorbid drug consumption (eg, tobacco), and other environmental and social risk factors."

Such data could also shed light on behavioral factors, such as alcohol-induced violence, which may or may not have familial links.

"This is of particular interest because several adoption studies and 1 twin study showed that there was no genetic contribution to violent behavior except in combination with AUDs [alcohol use disorders]," the editorialists wrote.

"Therefore, further studies on specific causes of mortality associated with AUDs in early to middle adulthood and their association with risk taking and violent experiences are highly warranted."

The study received support from the National Institute of Alcohol Abuse and Alcoholism, the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare (Forte), and Region Skåne. The authors and editorialists have disclosed no relevant financial relationships.

JAMA Psychiatry. Published online April 20, 2016. Full text, Editorial

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