Cardiometabolic diseases remain leading cause of excess American mortality

Between 1999 and 2022, the US had substantially higher death rates than other wealthy nations, largely due to cardiovascular disease, metabolic diseases (including diabetes), Alzheimer's disease and related dementias, and drug and alcohol complications. Policies are needed to address the underlying health, social, and economic conditions that increase Americans' risk of developing these diseases.

Despite having similar access to advanced medical technology, the United States has substantially higher death rates than other high-income countries (HICs), and the gap has been growing for decades. Cardiovascular diseases were the leading cause of excess US deaths, according to a new study led by researchers at Boston University School of Public Health (BUSPH). 

Published in JAMA Network Open, the study found that between 1999-2022, the annual number of excess US deaths-deaths that would not have occurred had the mortality rate in the US been the same as in other HICs-increased steadily through 2019 and then rose rapidly during the COVID-19 pandemic. By 2022, all-cause mortality rates in the US were 38 percent higher than in other HICs. An estimated 12.7 million US deaths could have been averted during this period if US mortality rates mirrored those of its peers. The authors refer to these excess US deaths as "missing Americans."

The study investigated the causes of these excess US deaths, and found that cardiovascular diseases, including heart disease, hypertension, and stroke, were the leading cause of excess mortality nearly every year of this period. Together, cardiovascular and metabolic diseases accounted for over half of all excess US deaths in 2022. Drug poisonings, alcohol-related diseases, and suicides emerged as another major cause of excess mortality during this period, particularly among men and people under 45 years old. Homicide and HIV/AIDS also had mortality rates many times higher in the US than in other HICs; however, these causes were responsible for only a small share of excess US deaths. 

The study builds upon previous findings by the researchers which showed that excess US deaths have increased since 1980 and continued to increase even after the COVID-19 pandemic. The new analysis is the first study to identify all leading causes responsible for these excess US deaths-what the authors refer to as a "population autopsy." Quantifying causes of the US mortality disadvantage can reveal opportunities for intervention, including policies to prevent these fatal conditions from occurring in the first place.

"In public health, we know that death certificates only list the most proximate cause of death and not the full causal chain. Differences in social factors between the US and other HICs can lead to differences in behavioral risk factors, which in turn can lead to higher risks of specific causes of death," says study lead and corresponding author Dr. Jacob Bor, associate professor of global health and epidemiology at BUSPH. "These findings pinpoint the issues that we should be focusing on if we want to address the US mortality disadvantage relative to peer countries."

For the study, Dr. Bor and colleagues from BUSPH, Harvard Medical School, and Hunter College at the City University of New York analyzed US excess deaths by sex, age, and year. They utilized cause-of-death data from the World Health Organization Mortality Database for all deaths occurring from 1999-20222 in the US and 17 other HICs, including Australia, Canada, France, Japan, and the United Kingdom. The team compared excess mortality among the countries used three metrics: excess deaths, which is the difference between reported deaths and deaths that would have occurred if the US had the mortality rate of other HICs; years of life lost, which is the years of potential life lost due to premature deaths; and mortality rate ratios, which compare the risk of different causes of death between the US and other countries. 

Among more than 63.5 million total deaths that occurred during this period, the US experienced an estimated 12,675,646 more excess deaths than would have occurred if their death rates were equal to other HICs. Despite declining between 1999-2009, cardiovascular diseases remained the leading cause of excess deaths during the entire study period, except for 2010, before rising sharply and continuously through 2022. Diabetes, kidney, and metabolic conditions also rose sharply from 2010-2022, following no significant increases from 1999-2009. In 2022, mental health and nervous system disorders such as Alzheimer's disease and other dementias were the leading cause of excess death among people 85 and older. Respiratory illnesses, transportation accidents, and homicides were also major causes of US excess deaths. COVID-19 was a leading cause of US excess deaths from 2020-2022, representing 1 in 5 US excess deaths in 2020 and 2021, and also coinciding with sharp increases in other diseases. 

Importantly, the study findings revealed stark differences in the burden of these causes of deaths, depending on whether they were viewed in absolute or relative terms. For example, in 2022, excess deaths from drug poisonings were 7.48 times higher in the US than in other countries, but only accounted for 10 percent of US excess deaths, while cardiovascular diseases were 1.63 times as high in the US than in other countries, but accounted for 40 percent of US excess deaths.

"In US population health research, examining the stagnation in US life expectancy that began in 2010 usually focuses on drug overdoses, alcohol-related deaths, and suicide, known as 'deaths of despair,'" say study senior author Dr. Andrew Stokes, associate professor of global health at BUSPH. "One dramatic finding from this study is that on an absolute scale, cardiometabolic diseases are key contributors to the increase in US death rates. If there was one thing we could address on a population scale, tackling cardiometabolic diseases would substantially reduce the US mortality gap with other wealthy nations."

Drug poisonings are still a critical component of the US excess death conversation, the researchers note, particularly in terms of years of life lost, as this measure focuses on premature deaths and captures the societal burden of losing young people. These deaths represented the fastest increase in excess US deaths, rising from a near-equivalent level with peer countries in 1999 to more than 130,000 excess deaths in 2022, with a particular rise in 2013 after fentanyl entered the US drug supply. These causes also contributed to excess deaths among people ages 45-65.

The US did outperform peer countries in a couple of categories, comprising fewer excess deaths in 2022 for cancers (excluding lung cancer) and influenza, which Dr. Stokes attributes partly to advancements within the US healthcare system. "We've come a long way with medical innovations to screen and treat cancers," he says.

The team says that more research is needed to understand the sharp rise in excess deaths after 2010, but that federal policy changes that address the root causes of these excess deaths with evidence-based interventions will help alleviate the current national mortality burden. 

"While new therapeutics such as GLP-1s could make a major dent in cardiometabolic mortality, our findings suggest that other policies should be considered too," says Dr. Bor. "Countries that have the same, or even worse, access to advanced medical technology perform far better on these metrics than the US. We need to identify the policies that other countries have implemented, and think about how we can emulate those policies in the US."