Longer-Term Elevated Cardiovascular Risks Evident From COVID-19 Infection

Elevated risks of cerebrovascular disorders, dysrhythmias, ischemic and nonischemic heart disease, pericarditis, myocarditis, heart failure, and thromboembolic disease were seen in the year following COVID-19 infection among more than 150,000 veterans in the US Department of Veterans Affairs’ national health care databases.

Outcomes were compared between 153,760 individuals with COVID-19 who survived the first 30 days after infection; 5,637,647 contemporary controls; and 5,859,411 historical controls (from before the pandemic). The findings were published in Nature Medicine, with the authors noting that previous studies in this area focused on individuals hospitalized with COVID-19 and had short follow-ups.

“The post-acute cardiovascular manifestations of COVID-19 have not yet been comprehensively characterized,” the study authors wrote. “We used national health care databases from the US Department of Veterans Affairs to estimate risks and 1-year burdens of a set of prespecified incident cardiovascular outcomes. Addressing this knowledge gap will inform post-acute COVID-19 care strategies.”

The 12-month burdens were per 1000 persons, median follow-up times ranged from 347 to 348 days in the 3 cohorts, and there were 12,095,836 total person-years of follow-up.

Among those in the COVID-19 cohort, risks of stroke and transient ischemic attack increased by 52% (HR, 1.52; 95% CI, 1.43-1.62) and 49% (HR, 1.49; 95% CI, 1.37-1.62), respectively, with corresponding burdens of 4.03 (95% CI, 3.32-4.79) and 1.84 (95% CI, 1.38-2.34). The overall risk and burden for both of these outcomes was 53% (HR, 1.53; 95% CI, 1.45-1.61) and 5.48 (95% CI, 4.65-6.35).

Heart rhythm disorders investigated were atrial fibrillation (AFib), sinus tachycardia and bradycardia, ventricular arrhythmias, and atrial flutter. All had elevated risks, with the highest seen at 84% for both sinus tachycardia (HR, 1.84; 95% CI, 1.74-1.95) and ventricular arrhythmias (HR, 1.84; 95% CI, 1.72-1.98), followed by 80% for atrial flutter (HR, 1.80; 95% CI, 1.66-1.96), 71% for AFib (HR, 1.71; 95% CI, 1.64-1.79), and 53% for sinus bradycardia (HR, 1.53; 95% CI, 1.45-1.62). Corresponding burdens were 5.78 (95% CI, 5.07-6.53), 4.18 (95% CI, 3.56-4.85), 3.10 (95% CI, 2.55-3.69), 10.74 (95% CI, 9.61-11.91), and 4.62 (95% CI, 3.90-5.38). This group of disorders also had an overall elevated risk of 69% (HR, 1.69; 95% CI, 1.64-1.75) and burden of 19.86 (95% CI, 18.31-21.46).

There was an 85% greater risk of pericarditis (HR, 1.85; 95% CI, 1.61-2.13), with a burden of 0.98 (95% CI, 0.70-1.30), and a 438% greater risk of myocarditis (HR, 5.38; 95% CI, 3.80-7.59), with a burden of 0.31 (95% CI, 0.20-0.46). Their composite overall risk increase was 102% (HR, 2.02; 95% CI, 1.77-2.30) and burden, 1.23 (95% CI, 0.93-1.57).

The ischemic heart disease with the most increased risk was ischemic cardiomyopathy, at 75% (HR, 1.75; 95% CI, 1.44-2.13), with a burden of 2.34 (95% CI, 1.37, 3.51), followed by acute coronary disease at 72% (HR, 1.72; 95% CI, 1.56-1.90), with a burden of 5.35 (95% CI, 4.13-6.70); myocardial infarction at 63% (HR, 1.63; 95% CI, 1.51-1.75), with a burden of 2.91 (95% CI, 2.38-3.49); and angina at 52% (HR, 1.52; 95% CI, 1.42-1.64), with a burden of 2.50 (95% CI, 2.00-3.03). Overall risk and burden were 66% (HR, 1.66; 95% CI, 1.52-1.80) and 7.28 (95% CI, 5.80-8.88).

Additional cardiovascular disease risks were increased by 72% for heart failure (95% CI, 1.65-1.80), 62% for nonischemic cardiomyopathy (95% CI, 1.52-1.73), 145% for cardiac arrest (95% CI, 2.08-2.89), and 143% for cardiogenic shock (95% CI, 1.86-3.16), with an overall increased risk of 72% (95% CI, 1.65-1.79). The respective burdens were 11.61 (95% CI, 10.47-12.78), 3.56 (95% CI, 2.97-4.20), 0.71 (95% CI, 0.53-0.93), and 0.51 (95% CI, 0.31-0.77), respectively, with an overall burden of 12.72 (95% CI, 11.54-13.96).

The final category of disease risk and burden investigated was thromboembolic disorders, which included a 193% higher risk of pulmonary embolism (95% CI, 2.73-3.15), with a burden of 5.47 (95% CI, 4.90-6.08); 109% for deep vein thrombosis (95% CI, 1.94-2.24), with a burden of 4.18 (95% CI, 3.62-4.79); and 95% for superficial vein thrombosis (95% CI, 1.80-2.12), with a burden of 2.61 (95% CI, 2.20-3.07). The overall risk of a thromboembolic disorder was increased by 139% (95% CI, 2.27-2.51), and the overall burden was 9.88 (95% CI, 9.05-10.74).

In addition, there was a 55% greater risk of major adverse cardiovascular events and a 63% elevated risk of any cardiovascular outcome in the COVID-19 group compared with the contemporary control group.

The authors noted that the risks in their study were seen even when accounting for demographic characteristics (age, race, sex), cardiovascular risk factors (obesity, hypertension, diabetes, chronic kidney disease, and hyperlipidemia), and no history of cardiovascular disease. As for risks and their respective burdens, both were clear among persons who did not require hospitalization and increased with greater COVID-19 severity setting, which ranged from nonhospitalized to intensive care unit admission.

“Taken together, our results show that 1-year risks and burdens of cardiovascular diseases among those who survive the acute phase of COVID-19 are substantial and span several cardiovascular disorders,” the authors concluded. “Care strategies of people who survived the acute episode of COVID-19 should include attention to cardiovascular health and disease.”

Next steps include continuously improving SARS-CoV-2 preventive measures; investigating optimal methods to overcome long COVID that cover patient care, health systems, economic productivity, and life expectancy; and furthering clinical measure and evaluation of the biologic mechanisms that underlie cardiovascular manifestations in individuals with COVID-19.

Reference

Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med. Published online February 7, 2022. doi:10.1038/s41591-022-01689-3