Alarming rise in infective endocarditis-related deaths among 25-44 year olds in the U.S.

In a recent study published in the Journal of The American Heart Association, researchers assess trends in infective endocarditis (IE)-associated deaths in the United States from 1999 to 2020.

Study: Trends in Infective Endocarditis Mortality in the United States: 1999 to 2020: A Cause for Alarm. Image Credit: SquareMotion /

What is IE?

IE is a severe heart disease with a high morbidity and death rate. Despite a rise in IE-associated hospital admissions in the U.S., in-hospital deaths have been declining globally. However, age-standardized mortality rates remain steady.

The U.S. is currently experiencing the largest opioid epidemic in history, with injection drug usage (IDU) being a significant consequence. The typical IE epidemiology in the U.S. has changed due to the opioid crisis, with younger, healthy individuals becoming more susceptible.

Studies on IE trends among U.S. adults are limited and typically only include hospital results. There is also limited information on the national-level implications of opioid surge on IE-associated mortality.

About the study

In the present nationwide cross‐sectional study, researchers examine national- and state-level trends in IE-associated mortality among U.S. residents 15 years of age and older. Mortality differences by age, race, sex, and geography among U.S. residents were also evaluated using data obtained from death certificates and associations of IE with substance use.

The U.S. Centers for Disease Control and Prevention’s Wide‐Ranging Online Data for Epidemiologic Research (CDC WONDER) multiple causes of death (MCOD) data were analyzed between 1999 and 2020. IE and substance use were identified from the International Classification of Diseases, tenth revision, and clinical modification (ICD-10-CM) codes.

The Vital Statistics Cooperative receives death certificate data from 57 vital statistics authorities in the U.S. The CDC National Center for Health Statistics (NCHCS) compiles the MCOD statistics.

National- and state-level crude death rates among individuals aged between 15-24, 25-34, 35-44, 45-54, 55-64, 65-74, 75-84 years, and 85 years and older were also obtained. Mortality rates with IE as the underlying cause of death (UCOD) and IE with substance usage disorders as comorbid conditions were compared between 1999-2006, 2007-2013, and 2013-2020. Age‐adjusted mortality rates (AAMR) trends were examined by log‐linear regression modeling, and the average annual percent change (AAPC) values were calculated.

Study findings

IE‐associated AAMRs in the U.S. were reduced from 26.2 for every one million individuals in 1999 to 22.4 for every one million in 2020. A statistically significant reduction in age-adjusted IE-associated AAMRs was observed between 1999 and 2020.

Between 1999 and 2004, there was a non-significant increase in AAMR, followed by significant decreases until 2020. Of all reported IE fatalities, 84 had immunodeficiencies, 10,803 were diabetic, and 9,911 had chronic renal disease.

Period cohort study findings showed that the relative risk was the least for individuals born around 1960 and increased for cohorts born after 1960, which led to a 2.3-point relative risk in the 1990 cohort. However, IE-associated crude deaths rose significantly among individuals aged between 25 and 34 years and those between 35 and 44 years of age, with AAPC values of 5.4 and 2.3, respectively.

IE-associated crude deaths remained stable among individuals aged between 45 and 54 years of age but significantly reduced among individuals 55 years of age and older. Kentucky, West Virginia, and Tennessee were associated with accelerated age‐adjusted death rates as compared to other U.S. states with predominantly reducing or static trends. Individuals between 25-34 and 35-44 years of age died at a higher rate, with IE and substance usage disorders reported as comorbidities.

State-level trends with IE and drug use as comorbidities were associated with the highest AAMR values for Kentucky, Tennessee, and West Virginia. IE-associated AAMRs reduced from 25 for every one million in 1999 to 20 for every one million in 2020 among women, yielding an AAPC value of one. Significant reductions in IE‐associated AAMRs were observed among males from 28 for every one million in 1999 to 26 for every one million in 2020, yielding an AAPC value of 0.6.

IE-associated AAMR significantly decreased among black and white individuals, in addition to Pacific Islander and Asian individuals. IE‐associated AAMR reduced among Hispanic individuals from 18 for every one million in 1999 to 12 for every one million individuals in 2020, thus yielding an AAPC value of 1.30. IE‐associated AAMR among non‐Hispanic individuals reduced from 27 for every one million in 1999 to 24 for every one million in 2020, yielding an AAPC value of 0.6.


While age-adjusted death rates for IE have decreased, there has been a significant increase in mortality among individuals between 25 and 44 years of age, particularly in states like Tennessee, West Virginia, and Kentucky.

The increases in IE-related mortality may be due to the opioid crisis, which has disproportionately affected young adults. Further research is needed to understand the causes of rising IE-related mortality and the impact of harm reduction initiatives on IE epidemiology.

Journal reference:
  • Chobufo, M. D., Atti, V., Vasudevan, A., et al. (2023). Trends in Infective Endocarditis Mortality in the United States: 1999 to 2020: A Cause for Alarm. Journal of the American Heart Association. DOI: doi:10.1161/JAHA.123.031589

Posted in: Men's Health News | Medical Research News | Medical Condition News | Women's Health News

Tags: Chronic, Endocarditis, Epidemiology, Heart, Heart Disease, Hospital, International Classification of Diseases, Mortality, Renal disease, Research

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Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.

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