Clear public messages should warn of higher risk for obese COVID-19 patients, while more must be done to tackle the endemic issue of systemic racism in the U.S., researchers urged Tuesday, stressing that both obese and minority patients have fared worse in the American Heart Association’s (AHA) COVID-19 Cardiovascular Disease Registry.
These calls came at the AHA Scientific Sessions 2020 virtual conference and were based on findings reported in three new analyses of the registry for hospitalized COVID-19 patients. The results were presented by UT Southwestern Medical Center’s James De Lemos, MD, PhD.
Besides worse outcomes for patients in the two studies on body mass index (BMI) and race and ethnicity, De Lemos also presented the “surprising” results of a more general registry analysis showing that, overall, prevalent in-hospital cardiovascular complications were less common than expected.
The latest analyses cover data running from the registry’s inception on April 3 through July 31, for which clean data are available in approximately 9,000 patients. As of Nov. 9., the study includes 109 hospitals across 35 U.S. states, with more than 22,500 patient records – a number that is growing by around 1,000 records per week, De Lemos said on Tuesday.
The COVID-19 pandemic has driven severe outcomes in some patients, killing more than 1.3 million at the time of reporting on Tuesday, according to the World Health Organization. Although experts have been rushing to fill in the data blanks throughout 2020 on the novel coronavirus and its effects, it is believed that patients with cardiovascular disease and cardiovascular risk factors were likely at greater risk of severe outcomes.
Multiple cardiovascular and thrombotic complications have been reported among those hospitalized, authors of the overarching registry report noted.
The aim of the registry is to provide generalizable insights on patients hospitalized with the disease and to understand its impact on the heart. It was rapidly deployed, leveraging the existing AHA “Get With The Guidelines” (GWTG) platform.
Patient data cover detailed patient demographics, cardiovascular risk factors and existing prevalent cardiovascular disease, alongside other medical comorbidities. The researchers are also collecting “granular data” on over 200 data fields per patient, including deep information on laboratory tests and biomarkers, De Lemos said, as well as medication and comorbidities.
So far, 55 research proposals have been received for the registry, of which 21 are active.
The obesity findings came from the registry study on the association of BMI with death, mechanical ventilation and cardiovascular outcomes in COVID-19, led by Nicholas Hendren, MD.
The researchers compared distribution of BMI in the registry with an adjusted U.S. population sample from National Health and Nutrition Examination Survey (NHANES), finding that patients admitted to hospital with COVID-19 are notably more obese than that U.S. population.
In particular, there was a higher prevalence of Class III (severe) obesity, at 11% in the AHA registry compared to 7% in the general population as recorded by NHANES.
The differences were magnified among people younger than 50 years, an age group in which obesity is “dramatically over-represented in hospitalized COVID,” De Lemos said during a news conference announcing the results. He added that, in particular, the probability of BMI greater than 40 kg/ m2 in the AHA registry was double that of the overall population younger than 50.
There were “striking differences” in age between hospitalized patients of a normal weight and the severely obese, who were almost 20 years younger, he added.
The interaction between BMI and age can also clearly be seen for in-hospital death rates and mechanical ventilation (as a function of BMI), said De Lemos.
“The relationship is attenuated and not significant among middle-aged and older adults,” he said.
It is likely that threefactors could play a role in the increased risk for obese people, De Lemos said in a question-and-answer session with press:
- Concomitant obesity risk factors, including larger burden of diabetes, hypertension and other cardiovascular issues;
- Severely obese people are at a mechanical disadvantage when it comes to pulmonary morbidity; and
- The virus’s purported effects on the renin-angiotensin system, which is already dramatically upregulated for obesity.
The findings have important public health implications, as COVID-19 is “currently surging,” he said. This calls for “clear public health messaging for younger obese individuals who may have received the false message that they are at low risk for severe COVID infection,” he said.
In addition, severely obese individuals, including young people, should be considered at higher risk for infection and, therefore, could warrant prioritization for vaccination, De Lemos said.
Race and ethnicity
The data also highlighted the endemic national issue of systemic racism, with Black and Hispanic people making up the majority (58%) of hospitalized cases in the corresponding analyses of around 8,000 individuals.
In the study of racial and ethnic differences in presentation and outcomes for patients hospitalized with COVID-19, the investigators compared those enrolled in the AHA registry with census-tracked data from the hospitals where those patients were admitted.
The percentage of Black and Hispanic people hospitalized with COVID-19 in the AHA registry, 58%, is a much larger proportion than “in the communities where the hospitalizations occur,” De Lemos said.
Black and Hispanic patients admitted to the hospital were younger than white patients by 9 and 12 years, respectively, while the probability of patients being uninsured or self-payers was significantly higher than in white people (non-Hispanic white 2.5%, non-Hispanic Black 4.5%, Hispanic all races 12.8%). Obesity, diabetes and hypertension were more prevalent in Black and Hispanic people.
Black patients were also over-represented in the obesity study, in the group with Class III severe obesity, making up 40% of the total.
Nevertheless, once in the hospital, race and ethnicity were not independently associated with worse outcomes, although Black and Hispanic patients did clearly face disproportionate mortality and morbidity because of higher rates of hospitalization.
The figures show an issue with disparities in care “upstream of the hospitalization event,” De Lemos said.
During the Q&A session, he added that the findings raise the “hugely important question” of socioeconomic factors driving these disparities, including structural racism.
“Black and Hispanic individuals are more likely to be on the frontlines of essential worker workforces, with less access to COVID-19 testing and perhaps presenting at the hospital a little later in disease severity, even though they’re younger,” he said. These factors all intersect to create this “terrible situation … with regard to our failure in health equity.”
In the overall study analysis, researchers were surprised to find that in-hospital cardiovascular complications were “somewhat less common than we thought” at registry launch, De Lemos said.
Overall, in-hospital mortality across the survey was frequent, with 16.7% of patients dying in the hospital and a further 2.8% referred for hospice, although the overwhelming majority of these outcomes (72%) were caused by respiratory complications, he said. Cardiac complications accounted for 10% of deaths, while 18% were linked to other causes.
A composite cardiovascular outcome of cardiovascular death, myocardial infarction (MI), stroke, heart failure and shock occurred in just over 8% of individuals, De Lemos added.
The individual endpoint of MI occurred in 4% of individuals, while stroke, heart failure and cariogenic or mixed shock each occurred in less than 2%.
“Myocarditis, which has emerged as an important potential risk even in young people and athletes, is uncommon, occurring in only 0.3% of hospitalized COVID patients,” De Lemos said.
Atrial fibrillation was the most common cardiovascular complication, with a rate of around 8%, while “surprisingly, deep vein thrombosis and pulmonary embolism were only seen in under 4%, a significantly lower proportion than had been reported in single-center studies and those with active surveillance for these endpoints,” he added.
In any case, although cardiac complication numbers were better than expected, De Lemos stressed that, given the scale of the pandemic, with 70,000 U.S. people hospitalized with the illness, “the absolute number of these cardiac complications is still high.”
Panelists at the Scientific Sessions aired their hopes that the new collaborative and rapid methods used to devise the registry during an “unprecedented” situation could be used more widely in future studies.
De Lemos said it was recognized early on that usual methods – which often have a “dwell time” of around 12 to 18 months – would not serve the needs of the clinical community in the pandemic setting.
AHA researchers therefore devised a “disruptive and democratized process” for the research leveraging the organization’s Precision Medicine Platform; a secure cloud-based environment that has allowed dozens of teams of investigators to work in parallel on the same curated and de-identified data set in a ‘learn-as-we-go’ approach, De Lemos said.
“This has had the advantage of shortening the time to discovery and dissemination of results for presenting three abstracts,” he said, adding that this was done in under 6 months from the registry launch at lower cost and higher yield for knowledge acquisition from a much larger group of investigators than may have otherwise been possible.
Asked in the Q&A session about plans for the registry to give information back to participating centers, thus allowing them to “activate” the data, De Lemos said: “It’s actually a major focus and the sites are already getting data.”
Although he conceded that there still remain challenges to this approach – including maintaining scientific rigor despite less central control of the research process – he and other experts were hopeful of positive downstream effects.
“The pandemic has driven disruptive and, we believe, likely enduring innovations to registry research,” De Lemos said.