COVID-19 in Unvaccinated Patients Increases Long-Term Cardiovascular Disease Risk

Clinicians should focus on long-term cardiovascular health among patients with a history of COVID-19 infection.

Unvaccinated survivors of COVID-19 infection were found to be at increased risk for cardiovascular disease (CVD) compared with unvaccinated individuals with no history of infection. These study findings were published in eClinicalMedicine.

Investigators from the Second Affiliated Hospital of Zhejiang Chinese Medical University in China and the Chung Shan Medical University in Taiwan sourced data for this study from the TriNetX Research Network. Included patients (N=4,131,717) were unvaccinated against COVID-19 infection and had more than 2 health encounters between 2019 and 2022. The investigators compared long-term cardiovascular outcomes between patients who survived COVID-19 infection and those with no history of infection (controls). To balance for cohort differences, a 1:1 propensity matching approach was used, with adjustments for index age, race/ethnicity, sex, socioeconomic status, comorbidities, blood type, alcohol-related disorders, nicotine dependence, and BMI. The primary outcome was the incidence of CVD in the postacute phase of COVID-19 infection, assessed 30 days after the index date until month 12.

Among patients in the prematched COVID-19 (n=691,455) and control (n=2,249,533) cohorts, the mean age mean was 43.2±16.2 and 44.5±17.0 years, 56.8% and 58.0% were women, 56.4% and 58.3% were White, and 15.3% and 13.8% had a BMI of at least 30 kg/m2, respectively. After propensity matching, each cohort comprised 690,892 patients.

The investigators evaluated the risk for adverse cardiovascular outcomes at 12 months. Compared with patients in the control cohort, those who survived COVID-19 infection were found to be at increased risk for major adverse cardiac events (hazard ratio [HR], 1.871; 95% CI, 1.816-1.927), any cardiovascular-related complication (HR, 1.552; 95% CI, 1.526-1.578), and mortality (HR, 1.604; 95% CI, 1.510-1.703).

Clinicians and patients with a history of COVID-19 should pay extra attention to their cardiovascular health in [the] long term.

Stratified by cardiac event, patients in the COVID-19 cohort had an increased risk for ischemic cardiomyopathy (HR, 2.811; 95% CI, 2.477-3.190), pulmonary embolism (HR, 2.648; 95% CI, 2.443-2.870), atrial fibrillation and flutter (HR, 2.407; 95% CI, 2.296-2.523), heart failure (HR, 2.296; 95% CI, 2.200-2.396), acute coronary disease (HR, 2.048; 95% CI, 1.752-2.393), and myocardial infarction (HR, 1.979; 95% CI, 1.831-2.138) at 12 months compared with those in the control cohort. Patients who survived COVID-19 infection also had an increased risk for deep vein thrombosis (HR, 1.879; 95% CI, 1.751-2.017), tachycardia (HR, 1.682; 95% CI, 1.626-1.740), ventricular arrhythmias (HR, 1.600; 95% CI, 1.535-1.668), bradycardia (HR, 1.599; 95% CI, 1.521-1.681), superficial vein thrombosis (HR, 1.592; 95% CI, 1.442-1.756), and transient ischemic attack (HR, 1.503; 95% CI, 1.353-1.670) at 12 months.

Subgroup analyses were performed after patients were stratified on the basis of sex and age. Compared with men in the control cohort, an increased risk for myocarditis (HR, 4.116; 95% CI, 2.344-7.229), ischemic cardiomyopathy (HR, 3.189; 95% CI, 2.734-7.229), and pulmonary embolism (HR, 3.145; 95% CI, 2.792-3.543) was observed among men in the COVID-19 cohort. Compared with women in the control cohort, women who survived COVID-19 infection were at increased risk for myocarditis (HR, 3.329; 95% CI, 1.901-5.829), ischemic cardiomyopathy (HR, 3.169; 95% CI, 2.459-4.085), and atrial fibrillation and flutter (HR, 2.542; 95% CI, 2.360-2.738).

Among patients aged between 20 and 44 years, the risk for myocarditis (HR, 3.829; 95% CI, 2.361-6.211) and ischemic cardiomyopathy (HR, 2.632; 95% CI, 1.494-4.636) was significantly increased among those who survived COVID-19 infection vs those in the control group.

These results may not be generalizable to more diverse populations. Other limitations include potential misclassification bias and residual confounding.

“Clinicians and patients with a history of COVID-19 should pay extra attention to their cardiovascular health in [the] long term,” the investigators concluded.


Wang W, Wang CY, Wang SI, Wei J CC. Long-term cardiovascular outcomes in COVID-19 survivors among non-vaccinated population: a retrospective cohort study from the TriNetX US collaborative networks. EClinicalMedicine. 2022;53:101619. doi:10.1016/j.eclinm.2022.101619