In this retrospective cohort study in a racially diverse population of women military veterans, we found that women veterans with COVID-19 were at nearly 4 times higher risk of mortality but at a lower risk of experiencing cardiovascular events and developing new heart disease within 60 days compared to those without COVID-19.
The current study confirms older age4,7,22,23,24, obesity25,26,27, and prior CVD4,14 and COPD4,14 conditions as risk factors for mortality in COVID-19 disease. We observed only weak associations of prior CKD4,14 with COVID-19 mortality risk. While SARS-CoV-2 positive women veterans were at lower risk of CVD events at 60 days, positive subjects showed strong associations of older age, obesity, and prior diagnoses of CVD, COPD, and CKD with increased risk of CVD events. Unlike previous studies14,23,28, we found that having diabetes prior to a positive test was not a significant risk factor for 60-day mortality3, but might increase risk of a new onset of heart disease29.
The US veteran population differs from the general population in the prevalence of pre-existing conditions. Moreover, compared to the general population of women, women veterans differ from the general population of women in terms of socio-demographic characteristics. The women veteran population is slightly older (median age 50) than the general population of women (median age 45), and Black women comprise a greater portion of the veteran population (19% vs. 12%). Additionally, Veteran women have a lower rate of being uninsured (4% vs. 9%) and a higher rate of being college educated (35% vs. 28%) and employed (72% vs. 70%)30. Overall, minority women veterans may have better access to care than women of minority background in the general population31. Nevertheless, the current study, using VA national data, was able to confirm several previously reported risk factors of COVID-19-associated mortality and cardiovascular complications.
Racial and ethnic minority women are understudied in COVID-19 research due to their under-representation in available data sets10,32, despite the fact that these groups are disproportionately affected by COVID-1933. By focusing on a racially diverse cohort of women veterans, our study can disentangle the effects of race, sex, and access to care on risk factors for COVID-associated mortality and cardiovascular outcomes. Demographic and health data on women veterans are readily available from VA national COVID-19 shared resources built from VA national EHRs. The current study provides a better understanding of this understudied population10,32. A further advantage of VA EHR data is that there is no confounding effect of access to care on disease outcomes. Despite the elevated rate of SARS-CoV-2 positivity observed among minority women veterans, there was no accompanying elevated mortality rate. This is in stark contrast to other studies that have suggested that racial and socioeconomic disparities in access to care contribute to the higher mortality rates in minority women diagnosed with COVID34,35,36,37,38. Although the cohort of women veterans may not exactly mirror the general population, our study does provide important insight into the effect of COVID on a racially diverse group of women in the absence of confounders such as access to care.
We found that SARS-CoV-2 infection itself does not increase a short-term CVD disease risk in women veterans, which may be explained by the observation that women veterans who tested positive were overall younger and healthier than those who tested negative prior to index date. Although there was an association with early troponin elevation, it is unknown whether this was associated with any cardiac symptoms or EKG changes. Furthermore, as depicted in Fig. 2, there were no increases in new-onset heart disease after 60 days. However, longer-term ramifications of SARS-CoV-2 infection on cardiovascular disease are still unknown. The clinical presentation of COVID-19-associated cardiovascular disease in women may be delayed beyond 60 days. Thus, longer follow-up is warranted.
A history of treatment with either an antiplatelet or antithrombotic medication was consolidated into a single field in the VA COVID-19 shared data repository. Although the current analysis found that there is a significant association between prior antiplatelet or antithrombotic therapy and a cardiovascular event within 60 days of being diagnosed with COVID-19, the lack of granularity in the data collection complicates the interpretation of this result. A history of treatment with an antithrombotic may reflect a patient’s pre-existing risk of deep vein thrombosis or venous thromboembolism, Arterial Fibrillation (A-Fib), or stroke, or a hypercoagulable state prior to COVID-19 infection, which may be associated with worse outcomes39,40,41. Similarly, prior treatment with antiplatelet medications may reflect underlying coronary artery disease or peripheral artery disease. While some clinicians and investigators have proposed anticoagulants as a successful treatment of COVID-19 infected patients with a complication of coagulopathy42,43, their effectiveness in improving survival and CVD outcomes is yet to be proven44,45. Separate analyses of the role of antiplatelets and antithrombotics in CVD outcomes and mortality after diagnosis with COVID-19, though not feasible with the current data set, would improve our understanding of risk factors driving adverse outcomes in patients with COVID-19. Finally, we did not include post-index pharmacotherapy in a final model to examine factors associated with COVID-19-related mortality or cardiovascular outcomes, since at the time of this writing, there is no single known medication proven to be effective to treat severely ill COVID-19 patients44.
Our finding that COVID-19-positive women veterans are much younger and have higher BMI compared to COVID-19 tested negative women veterans may partially reflect that racial and ethnic minority groups had higher prevalence of COVID-19 and were more likely to be obese (Black women veterans)15 and younger (Hispanic women veterans)20. Thus, it is essential to adjust for these confounding factors, which we have done using Cox and logistic regression models including to test associations with COVID-19 and 60-day mortality and CVD outcomes, respectively.
Our study has some limitations: First, we used CVD event occurrence and new onset of CVD at 60 days as binary outcomes due to data availability; a time-to-event analysis would provide a more detailed picture of the natural history of COVID. Second, the study did not include post-index medications (such as antithrombotics, antiplatelets, angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), hydroxychloroquine, losartan, and corticosteroids) to examine COVID-associated mortality and cardiovascular complications with respect to pharmacologic interventions, due to limited availability of data on timing and use of concomitant drugs. Third, we cannot rule out human errors in the entry of ICD codes into the VA EHR system; thus, variable construction may be susceptible to coding errors. Additional future studies investigating the long-term consequences of COVID-19 on women’s cardiovascular health are necessary to understand the full societal impact of the COVID-19 pandemic.