CV Risk After Acute COVID-19 Not So High as Feared: Registry

The risk of cardiovascular events is indeed increased in patients with COVID-19, but that hazard seems to be concentrated in the first 30 days after diagnosis, with little impact beyond that, international registry data suggest.

Through 1 year of follow-up, encompassing both acute and postacute phases, patients with versus without COVID-19 had greater risks of all-cause death, venous thromboembolism, and arterial thrombotic events, but no higher rate of CV death specifically, according to researchers led by Luis Ortega-Paz, MD (University of Florida College of Medicine – Jacksonville and Hospital Clínic de Barcelona, Spain), and Victor Arévalos, MD (Hospital Clínic de Barcelona).

But, they report in a study published online recently in PLOS ONE, when events that occurred within the first 30 days were excluded, only a slightly increased risk of deep vein thrombosis remained at 1 year in patients who had recovered from COVID-19.

That suggests, Ortega-Paz indicated to TCTMD, that concerns about a lingering cardiovascular impact after the acute phase of COVID-19—spurred by prior research—may be somewhat overstated.

“I don’t think that we can say that patients after COVID have that high a risk of CV events,” he said, adding that previous studies suggesting a substantially greater risk “are a little bit difficult to . . . put in context with what we are seeing in clinical practice.”

That should put patients’ minds at ease, said Ortega-Paz, who noted that several factors in this study were associated with a greater risk of CV events and might be used to identify patients who require closer follow-up after recovering from COVID-19.

CV COVID-19 Registry

Early on in the pandemic, physicians noticed high rates of thromboembolic complications among patients hospitalized with COVID-19, a link subsequently confirmed in many studies. There is less evidence when it comes to longer-term CV outcomes, although some studies have suggested elevated risks that persist for several months.

One such study, conducted within the US Department of Veterans Affairs healthcare system, found that between 30 days and 1 year after a COVID-19 diagnosis, patients continued to be at risk for a variety of CV conditions, including cerebrovascular disorders, dysrhythmias, ischemic heart disease, and others. “Nevertheless, this study assessed administrative data, which often are collected for nonresearch purposes and may not be optimal for outcome ascertainment,” Ortega-Paz et al say in their paper.

I don’t think that we can say that patients after COVID have that high a risk of CV events. Luis Ortega-Paz

To explore this question further, the investigators turned to the CV COVID-19 registry, which collected data on adult patients who were tested for COVID-19 between February and December 2020 across 17 centers in Spain and Italy. Of 4,427 patients included in the current analysis, 80.8% had confirmed COVID-19 and 19.2% did not (and remained free from infection with SARS-CoV-2 during follow-up).

Patients with COVID-19 were more likely to require hospital admission (91.6% vs 28.6%). Among those hospitalized, patients with versus without COVID-19 had a longer median length of stay (9 vs 5 days) and higher rates of ICU admission (20.6% vs 11.5%), invasive mechanical ventilation (62.2% vs 35.7%), renal replacement therapy (4.0% vs 0.8%), and vasoactive drug use (10.4% vs 4.9%).

The primary outcome was CV death at 1 year, and there was no difference between the COVID-19 and control groups after adjustment for baseline difference (1.4% vs 0.8%; HR 1.28; 95% CI 0.56-2.91). Patients with COVID-19 did, however, have greater risks of several other outcomes:

• All-cause death (17.8% vs 4.0%; HR 2.82; 95% CI 1.99-4.00)
• Non-CV death (16.3% vs 3.2%; HR 3.22; 95% CI 2.18-4.76)
• Pulmonary embolism (2.6% vs 0.4%; HR 5.96; 95% CI 1.85-19.14)
• Serious cardiac arrhythmias (2.5% vs 0.6%; HR 3.37; 95% CI 1.35-8.46)
• Arterial thrombotic events (2.6% vs 0.9%; HR 2.25; 95% CI 1.07-4.73)
• Venous thromboembolism (3.7% vs 0.4%; HR 9.33; 95% CI 2.93-29.70)
• Composite adverse CV events (9.7% vs 3.1%; HR 2.63; 95% CI 1.75-3.96)

When the analysis was confined to the postacute phase (31 days to 1 year), however, there were no significant differences for nearly all outcomes. The exceptions were deep vein thrombosis, which occurred at a slightly higher rate in the COVID-19 group (0.6% vs zero; P = 0.028), and rehospitalization, which was less frequent in the COVID-19 group (13.9% vs 20.6%; P = 0.001).

Situation ‘Not as Dramatic as Some People Think’

Discussing these results in the context of prior studies suggesting a lasting CV impact after COVID-19, the investigators touted the rigor with which the current study was performed. “To the best of our knowledge, our data represent the largest patient-level manually abstracted cohort of consecutive COVID-19 patients and controls with the longest available follow-up,” they write. “Moreover, our data underwent external data verification, prespecified statistical analysis, and independent event adjudication, making it also of [the] highest quality reported in the literature.”

Ortega-Paz said he was not surprised by the results, because his clinical observation has been that there are high rates of cardiovascular complications when COVID-19 patients are in the hospital, particularly the ICU, but not after the acute phase.

What’s unique about this registry study compared with prior efforts, he added, is that the investigators identified nine factors associated with a greater risk of cardiovascular events during follow-up among the patients with COVID-19:

• Prior history of valvular heart disease (HR 2.57; 95% CI 1.34–4.94)
• Pulmonary hypertension (HR 2.48; 95% CI 1.61–4.94)
• Atrial fibrillation (HR 2.27; 95% CI 1.33–3.86)
• Heart failure (HR 2.27; 95% CI 1.20–4.28)
• Dependent functional health status (HR 2.16; 95% CI 1.29–3.60)
• Previous cancer (HR 2.16; 95% CI 1.33–3.52)
• Hypertension (HR 1.85; 95% CI 1.15–2.99)
• Active or former smoker (HR 1.78; 95% CI 1.18–2.70)
• ICU admission (HR 2.32; 95% CI 1.35-3.99)

Physicians might be able to use these factors to select patients who require more-careful follow-up after recovering from COVID-19, Ortega-Paz said, acknowledging, however, that such a strategy needs to be studied further.

The major takeaway, he said, is that “COVID-19 infection is associated with a high burden of cardiovascular events that are clustered within the first month. In the postacute phase beyond 30 days, I think that there is a nonsignificant or very slightly increased risk of cardiovascular events. . . . My personal opinion is it’s not as dramatic as some people think.”