COVID-19 a CV risk equivalent to prior heart disease; type O blood may be protective
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Key takeaways:
- COVID-19 hospitalization may be a risk equivalent to coronary artery disease for MI and stroke.
- Having type O blood may be partly protective against risk for MI and stroke after SARS-CoV-2 infection.
Prior SARS-CoV-2 infection was associated with a twofold increased risk for heart attack and stroke for SARS-CoV-2 up to 3 years, even among people with no history of heart disease, researchers reported.
For more serious SARS-CoV-2 infection, such as those requiring hospitalization, the long-term risk was even higher.
In addition, the researchers noted that individuals with non-O blood types were at greater risk for major adverse cardiac events following COVID-19 hospitalization compared with those with the type O blood type, according to data published in Arteriosclerosis, Thrombosis, and Vascular Biology.
“It's known that there's CV risk associated with having COVID-19, but what isn't known is how long that lasts, how big an impact that has and, from a clinical perspective, should that be impacting the way we approach our patients for CV risk assessment,” Stanley L. Hazen, MD, PhD, co-section head of preventive cardiology and chair of cardiovascular and metabolic sciences at the Cleveland Clinic Lerner Research Institute, told Healio.
Using data from the UK Biobank, Hazen and colleagues examined data from nearly a quarter million people and identified 10,005 individuals with either a positive PCR test for SARS-CoV-2 or a hospital-based ICD-10 code for COVID-19 between Feb. 1, 2020, and Dec. 31, 2020. The studies explore the impact of COVID-19 effect on long-term heart disease risks pre-vaccination.
COVID-19 and risk for MI and stroke
Risk for MI and stroke following SARS-CoV-2 infection and hospitalization in this cohort was compared to risk among two control groups: a population control cohort already in the UK Biobank who never tested positive for SARS-CoV-2 or assigned a COVID-19 ICD-10 code during the study period (n = 217,730); and a propensity-matched control cohort who never tested positive (n = 38,860) to reduce confounding due to preexisting risk factors.
COVID-19 as a CAD-equivalent risk factor was also evaluated over 1,000 days of follow-up.
Major adverse CV events — defined as MI, stroke or all-cause death — were significantly elevated among those with a positive SARS-CoV-2 PCR test at all levels of infection severity (HR = 2.09; 95% CI, 1.94-2.25; P < .0005) compared with individuals without SARS-CoV-2, and was especially higher among patients hospitalized for COVID-19 (HR = 3.85; 95% CI, 3.51-4.24; P < .0005). The association between major adverse CV events and COVID-19 hospitalization was consistent when compared with propensity-matched controls (HR = 3.65; 95% CI, 3.3-4.05; P < .0005).
Risk for MI, stroke and all-cause death remained elevated out to 1,000 days follow-up among those hospitalized with COVID-19, even among those without CVD at the time of hospitalization (HR = 7.04; 95% CI, 6.25–7.92; P < .0005), according to the study.
“That's the most surprising, and important, finding. The increased risk was persistent for as long as follow-up is available with no sign of attenuation at all,” Hazen told Healio. “The heightened risk that we saw in the first year after infection was the same magnitude as the heightening of risk in between years 2 and 3 after the sentinel infection. Somehow, having COVID-19 rewires us to make us, long-term, more susceptible to CV event risk, at least for 3 years. For all we know, it could be indefinite.”
Compared with patients with CVD and no history of SARS-CoV-2 infection, individuals without CVD who were hospitalized with COVID-19 had an approximately 20% increased risk for major adverse cardiac events during follow-up (HR = 1.21; 95% CI, 1.08-1.37; P < .005).
“If someone was hospitalized for COVID-19, based on this data, their long term risk for a heart attack, stroke or dying is equivalent to a prior diagnosis of heart disease like a bypass surgery, heart attack or stroke,” Hazen said. “As a preventive cardiology physician, it makes me wonder whether or not we should be taking COVID-19 positivity into our risk assessment for CV risk reduction efforts. If you have a CAD risk equivalent, we lower the LDL goals and we are more aggressive with antiplatelet agents. All of the antiplatelet studies in primary prevention are pre-COVID-19 era endpoint trials … Should we look at a history of COVID-19, especially severe COVID-19, as a thing that changes the way that we do preventive CV risk assessment? These studies suggest we should.”
Blood type may have downstream benefit
To assess whether thrombosis risk after SARS-CoV-2 infection was affected via interaction with genetic susceptibility factors, Hazen and colleagues analyzed the ABO locus — patients’ blood type.
The researchers reported that COVID-19 hospitalization was associated with greater risk for MI and stroke in patients with non-O blood types (HR = 1.65; 95% CI, 1.29-2.09; P = .000048) compared with O blood type (HR = 0.96; 95% CI, 0.66-1.39; P = .82; P for interaction = .01).
“[We] saw the remarkable finding that your blood type is related to your downstream risk for developing heart disease post COVID-19 infection. We saw COVID-19 infection amongst the entire cohort was linked to heightened long-term risk, but the risk was especially larger among the non-O genotypes,” Hazen told Healio. “That's all we know at this point. ABO blood type is a carbohydrate group on the surface of the red blood cell, but it's also a carbohydrate group on the surface of many other cells too. If I had to guess, the blood type is having its effect on something other than a red blood cell.”
The researchers wrote that thrombosis risk among patients hospitalized with COVID-19 differs as a function of ABO blood type, but identified no interactions with genetic determinants of COVID-19 severity, SARS-CoV-2 infection susceptibility or atherosclerotic CAD.
For more information:
Stanley Hazen, MD, PhD, can be reached at 9500 Euclid Ave., Mail Code NC-I O, Cleveland, OH 44195.
Reference:
- COVID-19 infection appeared to increase risk of heart attack & stroke up to 3 years later. https://newsroom.heart.org/news/covid-19-infection-appeared-to-increase-risk-of-heart-attack-stroke-up-to-3-years-later. Published Oct. 9, 2024. Accessed Oct. 9, 2024.
Perspective
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Salim Hayek, MD
This study corroborates previous research demonstrating an elevated long-term risk for CVD in patients with COVID-19, while also confirming the protective effect associated with blood type O. The findings align with our current understanding of COVID-19 pathophysiology, particularly in severe cases requiring hospitalization. These cases typically manifest a pronounced inflammatory response, characterized by elevated levels of pro-inflammatory cytokines and acute-phase reactants. This heightened inflammatory state shares common pathways with CVD, including endothelial dysfunction, hypercoagulability and oxidative stress. The observed association between COVID-19 severity and subsequent CV risk is therefore consistent with the underlying biological mechanisms involved in both conditions.
The link between COVID-19 infection and CAD risk likely involves several interconnected mechanisms, with inflammation playing a central role. The acute inflammatory response triggered by SARS-CoV-2 infection shares many features with the chronic low-grade inflammation characteristic of atherosclerosis and CAD.
A key player in this inflammatory process that has gained significant attention is the soluble urokinase plasminogen activator receptor (suPAR) — a regulator of innate immune activity. We have identified suPAR as one of the most robust inflammatory markers associated with severe COVID-19 outcomes (Vasbinder A, et al. J Med Virol. 2024;doi:10.1002/jmv.29389). Interestingly, suPAR has also been implicated as a driver of atherosclerotic disease, providing a potential mechanistic link between COVID-19 and long-term CAD risk (Hindy G, et al. J Clin Invest. 2022;10.1172/JCI158788).
suPAR is a versatile biomarker that reflects immune activation and is elevated in various inflammatory conditions. In the context of COVID-19, high levels of suPAR have been associated with increased risk for severe disease, need for mechanical ventilation and mortality. Similarly, in CV research, elevated suPAR levels have been linked to endothelial dysfunction, plaque instability and increased risk for future CV events.
The dual role of suPAR in both COVID-19 severity and atherosclerosis progression suggests that it may be a key mediator in the observed increased CAD risk following COVID-19 infection. Elevated suPAR levels during acute COVID-19 may not only contribute to immediate disease severity but also potentially initiate or accelerate atherosclerotic processes, leading to long-term CV complications.
Furthermore, suPAR's involvement in both conditions highlights the potential for persistent immune dysregulation following COVID-19 infection, which could contribute to ongoing CV risk even after recovery from the acute illness. This shared inflammatory pathway, with suPAR as a central player, provides a plausible biological mechanism linking COVID-19 to subsequent CAD risk and warrants further investigation for potential therapeutic interventions.
There are several theories why O blood type may be protective against negative CV effects after COVID-19 infection, though none have been confirmed.
No. 1, individuals with blood type O naturally produce anti-A and anti-B antibodies. Some researchers suggest that these antibodies might interact with the SARS-CoV-2 virus, potentially inhibiting its ability to bind to host cells. Specifically, the presence of anti-A antibodies could interfere with the virus's spike protein, which utilizes the ACE2 receptor to enter cells.
No. 2, blood type can influence the levels of certain coagulation factors in the blood. For example, individuals with blood type O generally have lower levels of von Willebrand factor and factor VIII, proteins involved in blood clotting. Since severe COVID-19 has been associated with clotting complications, lower levels of these factors might reduce the risk for thrombosis in individuals with blood type O.
No. 3, the ABO blood group may affect the immune system's inflammatory response. Blood type A has been associated with higher levels of certain pro-inflammatory molecules. An exaggerated inflammatory response can lead to severe symptoms in patients with COVID-19, so variations in this response might contribute to differences in disease severity.
No. 4, there is speculation that blood type might influence the expression of receptors used by the virus to enter cells, such as the ACE2 receptor. Variations in receptor expression could affect how easily the virus infects cells in different individuals.
No. 5, the gut microbiome differs among individuals with different blood types. Since the microbiome can influence immune function, these differences might impact susceptibility to infections, including COVID-19.
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