Insights From a Deep Dive Into CV Risk Among Hospitalized COVID-19 Patients

Mirroring other cohorts around the globe, US patients hospitalized with COVID-19 experience a high rate of cardiovascular events, but careful chart review suggests that these same patients also have a high burden of cardiovascular risk factors to begin with, according to research presented during the virtual European Society of Cardiology (ESC) Congress 2020.

That cardiovascular risk factors are associated with worse outcomes in COVID-19 is not new—early reports out of China established this link—but the extent to which cardiovascular events in infected patients are related to the virus as opposed to baseline risk is the subject of debate.

“Once you really dive deep into this population, these patients have an extremely high prevalence of cardiovascular risk factors and cardiovascular disease, and that’s really important when you consider the incident cardiovascular outcomes,” Manan Pareek, MD, PhD (Yale New Haven Hospital, CT), told TCTMD.

Pareek, who is leading the Yale COVID-19 Cardiovascular Registry with co-PI Avinainder Singh, MD, presented preliminary numbers from the project as a late-breaking clinical trial during the meeting. Unique to the registry was a detailed, manual review of individual patient medical records related to demographic characteristics, presenting signs and symptoms, comorbidities and medication use, and disease course and complications.

“There’s been a lot of talk about patients who are admitted with COVID-19 having a very high incident risk of CVD, and if you go through a lot of the other studies, you’ll see preexisting cardiovascular disease or vaguer definitions of their preadmission status,” Pareek told TCTMD. “We dissected every little detail that we could think of and found an extremely high prevalence of cardiovascular risk factors: things like hypertension, diabetes, hyperlipidemia, all exceeding prevalences of 40%, with almost half of these individuals having some sort of preexisting cardiovascular disease. And things that we included that have not necessarily been captured well in prior studies are things like history of arrhythmia, atrial fibrillation, ventricular tachycardia—we included all the conditions that we could think of, not just your classic coronary disease and history of heart failure.”

Preliminary Data

At the ESC Congress, Pareek presented results for the first 485 patients out of the more than 1,300 people now included in the registry. In this preliminary cohort, the mean age was 68, 54% were male, 49% were white, 27% were Black, and 16% were Hispanic. Half were taking statins and almost 40% were on an ACE inhibitor or ARB, with almost the same proportion taking beta-blockers and aspirin. Use of diuretics and calcium channel blockers was also common.

In terms of disease course and complications, elevations of high-sensitivity troponin and NT-proBNP were relatively frequent and 39% of patients experienced a major adverse cardiovascular event while in the hospital. The most common event was atrial fibrillation (19%), followed by MI, including type 2 MI (17%), and acute decompensated heart failure (14%). In all, 35% of patients were admitted to the ICU, 21% required mechanical ventilation, and 18% died in the hospital.

It’s really easy to make the mistake of solely focusing on the virus and attributing all symptoms and signs that these patients may develop to a severe COVID-19 course. Manan Pareek

Independent predictors of death were older age, history of ventricular tachycardia, use of P2Y12 inhibitors, lower platelet count, higher aspartate aminotransferase, lower albumin, and higher troponin T. Only a few of these overlapped with the risk of MACE—namely, troponin and lower albumin—but unique predictors were male sex, history of atrial fibrillation, use of a diuretic, and any oxygen therapy at admission.

“In consecutive patients hospitalized with COVID-19, there was a high baseline cardiovascular risk. There was high mortality and risk of CV complications, and finally, cardiovascular disease and biomarker elevation predicted poor outcomes,” Pareek reported.

Don’t Miss the Forest for the Trees

Speaking with TCTMD, Pareek stressed that it’s valuable for US physicians to get a sense of what the background cardiovascular considerations are in an American cohort of COVID-19 patients, outside of the high-profile hot spots, whose disease is severe enough to require hospital admission to tertiary centers. These data replicate findings from around the US and the globe using meticulous collection techniques, he said.

This also points to an important pathway for improving outcomes, he continued. “We believe it’s important to optimize the cardiovascular treatments that patients should be on, but honestly, that is irrespective of whether they have COVID-19 or not. This data showcases the fact that patients might not be optimized on their effective cardiovascular treatments or treatments of cardiovascular risk factors.”

This is a key lesson for patient care in the ongoing pandemic, Pareek said. “It’s really easy to make the mistake of solely focusing on the virus and attributing all symptoms and signs that these patients may develop to a severe COVID-19 course; these very high cardiovascular complication rates suggest that we have to be more vigilant in detecting and possibly treating these complications and that’s actually not easy in this population. . . . It’s really difficult to know what exactly goes on when these patients develop a cardiovascular event, because so far no one knows whether the infection is directly involved in the pathogenesis of these events or whether it’s just a trigger for cardiovascular events in those who are already high risk. So all we can do for now is optimize the treatments that we know work in other settings.”

Treatment decision-making is complicated by the fact that troponin elevations and ECG changes, for example, are routinely reported even in patients with no obstructive coronary disease, Pareek acknowledged. For now, he said, “we’re kind of stuck here because we don’t really know how to detect or predict these complications, but what we can do is be vigilant about them and know that not everything these patients exhibit is directly related to COVID-19—it’s easy to lose sight of that.”

COVID-19 and the Heart

Pareek’s presentation was part of an ESC 2020 late-breaking session devoted to COVID-19, with other talks tackling the rigor of published research during the pandemic, thromboembolic risks, clinical trial updates, and COVID-19 in women. This last, presented by Orianne Weizman, MD (Centre Hospitalier Régional Universitaire de Nancy, France), zeroed in on female patients enrolled in the COVID-19 France registry, covering 24 hospitals throughout the country. The aim, said Weizman, was to examine whether the established link between cardiovascular comorbidities and COVID-19 was seen in women, a group for whom specific information has been lacking, particularly since male sex has emerged as a key risk factor for severe COVID-19.

We have to remember that just because our hospitals have often been full of patients with COVID, that we haven’t cured the other conditions that we all worry about. Martin Landray

And indeed, among the 2,878 patients hospitalized between February 26 and April 20, 2020, 42% were women. In findings that overlap to some extent with those of the Yale COVID-19 Cardiovascular Registry, age, diabetes, and heart failure were all independently associated with ICU transfer or in-hospital death, with elevated BNP or troponin associated with double the risk of ICU death.

Importantly, while female sex was associated with a lower risk of ICU transfer, women and men had roughly the same risk of dying in the hospital, Weizman said. The oft-reported lower risk of hospitalization or ICU transfer for women “should not obscure the substantial morbidity-mortality in women with cardiovascular diseases,” she said. “We should also take into account the input of cardiac biomarkers in risk stratification of women with COVID-19, [especially] if they have no prior heart failure or coronary artery disease.”

Martin Landray, MB ChB, PhD (University of Oxford, England), the session chair, referred to both Pareek’s and Weizman’s presentations in his closing remarks, saying, “I think what this really illustrates is that, among the hospitalized patients at least, COVID really is a condition in which a lot of patients have significant comorbidity, cardiovascular as well as other comorbidities, and it is particularly a disease—at least the hospital version of it—of the elderly, those over 70 or 80. So I think there’s a lot to think about, but we have to remember that just because our hospitals have often been full of patients with COVID, that we haven’t cured the other conditions that we all worry about and especially in this setting, cardiovascular disease.”

Taking the Weizman and Pareek talks together, Landray continued, it’s clear that cardiovascular comorbidities play an important role in both men and women, but that women “do seem to have a better trajectory, better outcomes, as a general rule, than men, and that’s certainly an interesting finding and one that I know is being explored.”

As for the hot-button topic of whether COVID-19 is more directly affecting the heart, Pareek told TCTMD that his institution has been very restrictive in performing imaging on infected patients due to exposure risks to personnel. Reassuringly, however, “in these preliminary data we presented during ESC, we did not have a single case of true myocarditis. We mostly saw decompensated heart failure and we did see some patients with new-onset heart failure, but it’s unclear to us whether that was something that was waiting to happen irrespective of COVID-19 and it just kind of triggered that because of the extra physiological stress on the body.”