Raised Troponin Linked to Worse COVID-19 Outcomes

September 03, 2020

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The link between COVID-19 and cardiovascular disease has been strengthened by new results from a US population.

The study, which systematically collected data on cardiovascular risk factors and outcomes in patients hospitalized with COVID-19, showed that these patients had a high rate of existing cardiovascular disease and a very high incidence of subsequent cardiovascular complications, with 40% of the cohort suffering an adverse cardiovascular event.

It also showed raised troponin T levels at admission were an indicator of adverse outcomes and may be useful for risk stratification. 

The study was presented at a special session on COVID-19 and cardiovascular disease at the recent European Society of Cardiology (ESC) Congress 2020.

Cardiac biomarkers troponin and B-type natriuretic peptide (BNP) were also independent prognostic indicators of poor outcome in a French study looking specifically at women hospitalized with COVID-19.

The French study, also presented during the ESC session, showed that women hospitalized with COVID-19 were older and had fewer cardiovascular morbidities than men, and had less risk for a bad outcome (defined as transfer to ICU or in-hospital death), but cardiovascular disease was also an independent predictor of adverse outcomes in women.

Dr Manan Pareek

Presenting the new US data, Manan Pareek, MD, PhD, Yale New Haven Hospital, New Haven, Connecticut, noted that there have been several reports, mainly from China, suggesting that patients with established cardiovascular disease or multiple cardiovascular risk factors are especially vulnerable to COVID-19, but "there is limited good data on this from the US."

"In addition, there are concerns that the infection itself may increase the risk of cardiovascular complications such as arrhythmias, thromboembolism, and myocarditis, so we wanted to look more thoroughly at this as well," he said.  

"Yale New Haven Hospital is near New York and we thought we would get a high caseload of COVID patients, so we instigated a study to systematically collect data on the link between cardiovascular disease and COVID-19," Pareek explained to theheart.org | Medscape Cardiology. 

"We found that having preexisting cardiovascular disease or signs of myocardial injury (raised troponin) on admission is associated with an increased risk of both in-hospital death and major cardiovascular events," he said.

"This is one of the first studies in the US to have produced high-quality, comprehensive data on cardiovascular histories and outcomes, so our results are very relevant to US clinical practice, particularly tertiary care centers," he added.

The study included all adult patients admitted to the hospital with a COVID-19 diagnosis, and researchers collected data on 200 variables related to patient demographics, biomarkers, CV risk factors, history of cardiovascular disease, as well as cardiovascular and COVID outcomes.

So far, approximately 1200 patients have been enrolled, and Pareek presented preliminary results from the first 485 patients. The average age was 68 years, 46% were female, 49% were White, 27% Black and 16% Hispanic.

Results showed a high prevalence of cardiovascular risk factors and cardiovascular disease in patients hospitalized with COVID-19, with 46% of patients having a history of CVD and more than 40% having hypertension, hyperlipidemia, and diabetes.

These patients had high rates of adverse COVID outcomes — almost 1 in 5 died in hospital, 1 in 3 were treated in the ICU, and 1 in 5 needed ventilation.

They also had high rate of cardiovascular events — with 2 in 5 experiencing a major adverse cardiovascular event, defined as an ischemic event, arrhythmia, heart failure, or vascular outcome, Pareek reported.   

The researchers conducted a multivariable logistical regression analysis to determine independent factors associated with poor outcomes.

In this analysis, the main predictors of in-hospital death were a history of ventricular arrhythmia (odds ratio [OR], 9.87; P = .004), which Pareek said is a surrogate for previous serious cardiovascular disease, and use of a P2Y12 inhibitor (OR, 4.58; P = .04), which he noted is a surrogate for underlying coronary heart disease.

Independent factors associated with a major adverse cardiovascular event while hospitalized included use of diuretic, a surrogate for a history of heart failure, and the presence of atrial arrhythmias.

On the high rate of cardiovascular events in these patients, Pareek explained that it is not known whether the virus is involved in the specific pathogenesis of cardiovascular events or if it's just the stress of infection that triggers the event. "But the cardiovascular event rates do seem to be higher than expected from experience with other respiratory infections."

Increased Troponin

Results also showed that raised levels of troponin T on admission were significantly associated with in-hospital death and with major adverse cardiovascular events.

"These troponin levels normally indicate that a patient is having an MI (myocardial infarction) but most of these patients were not having an acute cardiac event at baseline. The raised troponin seemed to be indicating isolated myocardial injury," Pareek noted.  

"We do see raised troponins in other severe infections and it is probably associated with the physiological stress associated with a severe infection," he added.  

He explained that raised troponin has been seen in other COVID cohorts, "but we performed rigorous multivariable adjustment and have shown that it is still a significant predictor of adverse outcomes."

Asked whether all patients hospitalized with COVID should have a troponin test, Pareek said: "This would be useful for risk stratification, but while we know these patients may have worse outcomes, we don't really know how to treat them differently."

"One of the challenges we have is that cardiovascular markers that normally signal MI are showing positive results in COVID patients, but these patients are not having an acute cardiovascular event at that time," he said. "Chest pain was actually inversely associated with the cardiovascular event endpoint in this study.

"This makes patients very difficult to evaluate, but this study does give us more information that confirms that the virus is triggering cardiovascular events in some way."

Pareek believes the next step is to conduct randomized trials of different treatment strategies on various different groups of patients. 

"Rather than having pragmatic protocols for all COVID patients, I think we need prospective studies on how to manage patients with different presentations," he said. "For example, in patients with raised troponins, would treatment with an anticoagulant or an antiplatelet agent lead to better outcomes? We need to conduct randomized studies on these strategies."

Risk Factors in Women

The French study looking to specifically address the link between cardiovascular morbidities and COVID-19 in women was presented by Orianne Weizman, MD, Centre Hospitalier Régional Universitaire de Nancy, France.

"While male sex is a risk factor for worse outcomes in COVID-19, 40% to 50% of hospitalized patients are women and there is little specific data on women," she noted.   

This retrospective, multicenter study involved all patients hospitalized with COVID-19 between February and April in 24 hospitals across France. Of 2878 patients in the cohort, 1212 were women (42%). Of these, 21.8% died.

Women hospitalized with COVID-19 in this cohort were older than men (average 68 vs 65 years). They had fewer cardiovascular risk factors — less smoking, heart failure, diabetes, dyslipidemia, coronary artery disease and peripheral arterial disease — but more thromboembolic disease.

Women were less likely than men to experience the primary outcome of transfer to ICU or in-hospital death (OR, 0.63; P < .001), although rates of death were similar in men and women.

Factors associated with transfer to ICU or death in women included higher age, higher body mass index (BMI), hypertension, diabetes, heart failure, and chronic kidney disease.

The most common comorbidity in women who were transferred to the ICU or died was heart failure, (38%) followed by coronary artery disease (30%), diabetes (30%), dyslipidemia (26%) and hypertension (26%).

After multivariable analysis, four factors were significantly and independently associated with the primary outcome in women: age, BMI, chronic kidney disease, and heart failure. Age, diabetes, and heart failure were independently associated with death in hospital.

In terms of biomarkers, BNP and NT pro-BNP were increased in 33% of women who were transferred to ICU or died, and raised levels of these biomarkers doubled the risk of the primary endpoint (hazard ratio, 1.96; P < .001) after adjustment for the existence of heart failure.

Similar results were found for troponin, which was raised in 35% of women experiencing the primary endpoint, with a hazard ratio of 2.0 (P < .001) after having adjusted for previous heart failure or coronary artery disease.

Commenting on the two studies, Martin Landray, MD, chair of the session and professor of Medicine and Epidemiology at the University of Oxford, UK, said: "It is notable that prior cardiovascular disease really plays a role in subsequent risk, and that is something we might want to take forward when thinking about the epidemiology of COVID and the management of individual patients and future clinical trials."

He added: "These observations from the French study emphasize the importance of considering disease patterns in women and thinking of them separately."

European Society of Cardiology (ESC) Congress 2020: Presented August 30, 2020.

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