Increased risk of incident CV outcomes in the post-acute phase of COVID-19

Long-term cardiovascular outcomes of COVID-19

Literature - Xie Y, Xu E, Bowe B et al. - Nat Med. 2022 Feb 7. doi: 10.1038/s41591-022-01689-3.

Introduction and methods

Aim of the study

This observational study used a cohort of individuals with COVID-19 and two sets of control cohorts to assess the risk and 1-year burden of incident CVD in the post-acute phase of COVID-19.

Methods

The study used a cohort of US veterans who survived the first 30 days of COVID-19 (n=153,760), a contemporary control group (n=5,637,647) and a historical (pre-pandemic) control group (n=5,859,411).

The investigators estimated the risk of incident CV outcomes in the COVID-19 cohort versus the contemporary control group. In addition, they estimated the adjusted excess burden of CV outcomes due to COVID-19 per 1,000 persons at 12 months, which was based on the difference between the estimated incidence rate in the COVID-19 group and the contemporary control group.

The median follow-up time was 347 days in the COVID-19 cohort, 348 in the contemporary control group and 347 in the historical control group.

Outcomes

An extensive set of pre-specified CV outcomes was investigated in this study, including cerebrovascular disorders, dysrhythmias, inflammatory disease of the heart or pericardium, ischemic heart disease, thromboembolic disorders, other CV disorders, and MACE.

Main results

Cerebrovascular outcomes

Individuals in the COVID-19 cohort had increased risks of stroke (HR 1.52, 95% CI 1.43-1.62); burden 4.03 (95% CI 3.32-4.79) per 1,000 persons at 12 months, and TIA (HR 1.49, 95% CI 1.37-1.62); burden 1.84 (95% CI 1.38-2.34), compared to the contemporary control cohort.
Risk of the composite of these cerebrovascular outcomes was HR 1.53 (95% CI 1.45-1.61) and burden was 5.48 (95% CI 4.65-6.35).

Dysrhythmia outcomes

There was an increased risk of atrial fibrillation in the COVID-19 cohort (HR 1.71, 95% CI 1.64-1.79; burden 10.74 (95% CI 9.61-11.91).
Risk of the composite of dysrhythmia outcomes (atrial fibrillation, sinus tachycardia, sinus bradycardia, ventricular arrhythmias, and atrial flutter) was HR 1.69 (95% CI 1.64-1.75) and burden was 19.86 (95% CI 18.31-21.46).

Inflammatory diseases

There was an increased risk of pericarditis and myocarditis in the COVID-19 cohort (HR 1.85, 95% CI 1.61-2.13; burden 0.98, 95% CI 0.70-1.30; and HR 5.38, 95% CI 3.80-7.59; burden 0.31, 95% CI 0.20-0.46, respectively).
Risk of the composite of these inflammatory outcomes was HR 2.02 (95% CI 1.77-2.30) and burden was 1.23 (95% CI 0.93-1.57).

Ischemic outcomes

Risk and burden of acute coronary disease was HR 1.72 (95% CI 1.56-1.90) and 5.35 (95% CI 4.13-6.70). For MI, risk and burden was HR 1.63 (95% CI 1.51-1.75) and 2.91, (95% CI 2.38-3.49).
Risk of the composite of ischemic outcomes (acute coronary disease, MI, ischemic cardiomyopathy, and angina) was HR 1.66 (95% CI 1.52-1.80) and burden was 7.28 (95% CI 5.80-8.88).

Thromboembolic disorders

There was an increased risk of PE, DVT and superficial vein thrombosis in the COVID-19 cohort (PE: HR 2.93, 95% CI 2.72-3.15; burden 5.47, 95% CI 4.90-6.08, DVT: HR 2.09, 95% CI 1.94-2.24; burden 4.18, 95% CI 3.62-4.79, superficial vein thrombosis: HR 1.95, 95% CI 1.80-2.12; burden 2.61, 95% CI 2.20-3.07).
The composite risk of these thromboembolic outcomes was HR 2.39 (95% CI 2.27-2.51) and the burden was 9.88 (95% CI 9.05-10.74).

Heart failure and other CV outcomes

There was an increased risk of HF in the COVID-19 cohort (HR 1.72, 95% CI 1.65-1.80); burden 11.61 (95% CI 10.47-12.78).
Risk of the composite of other CV outcomes (defined as the composite of HF, non-ischemic cardiomyopathy, cardiac arrest, and cardiogenic shock) was HR 2.43 (95% CI 1.86-3.16) and burden was 12.72 (95% CI 11.54-13.96).

MACE

There was also an increased risk of MACE (defined as a composite of MI, stroke and all-cause mortality) in the COVID-19 cohort (HR 1.55, 95% CI 1.50-1.60; burden 23.48, 95% CI 21.54-25.48). Risk and burden of any CV outcome was HR 1.63 (95% CI 1.59-1.68) and 45.29 (95%CI 42.22-48.45).

Subgroup analyses

The increased risks of incident CV outcomes in the COVID-19 cohort were evident in individuals with and without CVD before COVID-19. Risks were also evident regardless of age, race, sex, obesity, hypertension, diabetes, CKD, and hyperlipidemia.
Risks of incident CV outcomes increased with increasing severity of the COVID-19 in the acute phase. Risks were highest in individuals admitted in to the ICU during acute infection. Nevertheless, increased risks were also evident in those who were not hospitalized during the acute phase of COVID-19.
Results were consistent with the primary analysis when the COVID-19 cohort was compared with the historical cohort.

Conclusion

This study showed that individuals in the post-acute phase of COVID-19 had increased risks and 12-month burdens of incident CV diseases, compared to control cohorts with individuals with no evidence of SARA-CoV-2 infection.

The authors of the article wrote: “Our study shows that the risk of incident cardiovascular disease extends well beyond the acute phase of COVID-19. (…) Governments and health systems around the world should be prepared to deal with the likely significant contribution of the COVID-19 pandemic to a rise in the burden of cardiovascular diseases.”

Find this article online at Nat Med.