Factors influencing cardiovascular system-related post-COVID-19 sequelae: A single-center cohort study

1 Introduction

COVID-19 sequelae, also known as “long COVID-19,” are long-term symptoms of COVID-19. According to the clinical case definition published by the World Health Organization in October 2021, COVID-19 sequelae usually occur within 3 months after the onset of COVID-19 infection. They cannot be explained by other diagnoses. From the end of 2022 to the beginning of 2023, China experienced the peak period of COVID-19 infection. More and more studies and evidence show that most patients with COVID-19 recovery have sequelae of different systems and degrees, which may be new symptoms after recovery from infection, or the persistence of specific symptoms during acute infection. Cardiovascular disease is not only a risk factor for the occurrence of COVID-19 sequelae but also a potential result directly or indirectly caused by COVID-19 infection. It was found clinically that most patients who visited the Cardiovascular Department due to the sequelae of COVID-19 complained of chest pain and palpitations. This study collected the general information and prominent symptoms of relevant patients and systematically summarizes the relevant information of the patients to clarify the main manifestations of the sequelae of COVID-19 in the cardiovascular system, explore the influencing factors of related symptoms, and aim to raise people’s attention to the sequelae of COVID-19, to provide a basis for further formulating a reasonable treatment plan.

2 Materials and methods

3 Results

3.3 Analysis of influencing factors of cardiovascular symptoms

In the assessment of cardiovascular symptoms post-COVID-19, a comprehensive statistical approach was employed to discern the relationship between various patient characteristics and the manifestation of cardiovascular sequelae. The dependent variable in this analysis was the presence of cardiovascular symptoms, coded as binary outcomes where “yes” was assigned a value of 1 and “no” a value of 0. A range of independent variables was considered, including age classification, gender, body mass index (BMI) classification, blood pressure level classification, resting heart rate, and medical history encompassing cardiovascular disease, cerebrovascular disease, diabetes, and thyroid disease. Lifestyle factors such as smoking and drinking history were also incorporated into the analysis.

To evaluate the potential influence of these variables on the occurrence of cardiovascular sequelae, both univariate and multivariate logistic regression models were applied. The univariate analysis served as a preliminary step, identifying variables with a P-value less than 0.1, which were then included in the subsequent multivariate model. This selection criterion ensured that only variables with a potential association were considered for more complex analysis, thereby refining the model and enhancing the reliability of the results.

The multivariate logistic regression analysis utilized the forward LR method, a forward stepwise regression approach based on maximum likelihood estimation. This technique iteratively selects the most statistically significant variables, adding them to the model one at a time, and removing any that do not contribute to the model’s predictive power. This process is governed by predefined significance levels for entry and removal from the model, set at 0.05 and 0.10, respectively.

The findings from the multivariate logistic regression revealed that females exhibited a higher risk of developing cardiovascular symptoms post-COVID-19, with an OR of 2.081 and a 95% CI of 1.358–3.189. Similarly, young individuals were identified as a higher risk group, with an OR of 2.557 and a 95% CI of 1.44–4.54. Blood pressure levels were also significant predictors, with prehypertension and hypertension associated with increased risks of cardiovascular symptoms, as indicated by ORs of 1.905 (95% CI = 1.091–3.329) and 2.287 (95% CI = 1.433–3.649), respectively. Additionally, a history of cardiovascular disease and diabetes were found to be significant risk factors, with ORs of 1.862 (95% CI = 1.16–2.988) and 2.138 (95% CI = 1.058–4.319), respectively (Table 3 and Figure 1). These results were statistically significant, with P-values less than 0.05, suggesting a robust association between these factors and the development of cardiovascular symptoms post-COVID-19.

Table 3

Impact of gender, BMI, blood pressure, heart rate, medical history, smoking and drinking history, and full vaccination before COVID-19 infection on the occurrence of cardiovascular sequelae

	Patients without cardiovascular symptoms (n = 226)	Patients with cardiovascular symptoms (n = 226)	P value	Adjust-ed OR	95% CI	95% CI
Age by category
Young adult	45 (19.9)	55 (24.3)	0.001	2.557	1.44	4.54
Middle age	127 (56.2)	88 (38.9)	Ref.
Old age	54 (23.9)	83 (36.7)	0.074	1.545	0.959	2.49
Sex (female)	131 (58.0)	154 (68.1)	0.001	2.081	1.358	3.189
Blood pressure by classification
Normal blood pressure	122 (54.0)	83 (36.7)	Ref.
Prehypertension	35 (15.5)	40 (17.7)	0.024	1.905	1.091	3.329
Hypertension	69 (30.5)	103 (45.6)	0.001	2.287	1.433	3.649
Any pre-existing chronic condition
Heart disease	50 (22.1)	88 (38.9)	0.01	1.862	1.16	2.988
Diabetes	14 (6.2)	33 (14.6)	0.034	2.138	1.058	4.319

Figure 1

The forest plot for the regression analysis.

4 Discussion

The present study conducted at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine offers novel insights into the post-COVID-19 cardiovascular sequelae, revealing significant associations with demographic and pre-existing health conditions. Our findings underscore the heightened vulnerability of certain populations – particularly women, younger individuals, and those with pre-existing cardiovascular conditions – to the development of cardiovascular symptoms following COVID-19 recovery. This study is among the first to delineate the risk profile for cardiovascular sequelae in a post-COVID-19 cohort within a traditional Chinese medicine hospital setting, providing a unique perspective on the intersection of viral infection aftermath and cardiovascular health.

Heart discomfort is a common symptom of patients with COVID-19, mainly including chest pain, palpitations, fatigue, shortness of breath, etc. Previous studies have shown that the new coronavirus will cause damage to the cardiovascular system, may impact the heart, and even cause serious complications such as myocarditis and myocardial infarction. The mechanism is mainly related to myocardial injury. The first cause is that the virus directly invades the cells by binding to the angiotensin-converting enzyme 2 receptor on the surface of myocardial cells, the second is a myocardial injury caused by an immune inflammatory response and cytokine storm, and the third is an ischemic myocardial injury caused by cellular hypoxia. A cohort study involving 12,095,836 cases found that even people without high-risk factors for cardiovascular disease still had an increased risk of cardiovascular disease after infection with the new coronavirus. Paying attention to the impact of the new coronavirus on the heart and studying the risk factors of related sequelae are crucial for predicting the occurrence of sequelae and improving the quality of life of patients.

Our analysis indicates that young adults, a demographic typically perceived as having a lower risk for severe COVID-19 outcomes, are paradoxically at an elevated risk for cardiovascular sequelae. This unexpected finding challenges the prevailing understanding of COVID-19’s impact across age groups and suggests that factors such as lifestyle, stress, and possibly vaccination status may contribute to this increased susceptibility. Existing studies have shown that aging is an independent risk factor for COVID-19. Electronic health record analysis of age and long-term diagnosis of new coronavirus shows that the long-term risk of COVID-19 virus is associated with age in an inverted U shape. The risk of 45–69 years old and 55–69 years old are the highest; the risk was not higher among those aged 80 years and older than the reference population aged 18–24 [1]. This study found that young people have a higher risk of cardiovascular sequelae than middle-aged and elderly after being infected with the COVID-19. In addition, high work pressure, eating disorders, and bad living habits of young people may also be influencing factors. Studies have observed that vaccination with the second dose of mRNA-1273 vaccine may increase the probability of myocarditis in young people, so the higher risk of cardiovascular sequelae in young people may be related to vaccination [2]. In addition, Osmanov et al. believe that in children and adolescents, immune mechanisms may be responsible for the increased risk of long-term consequences of infection, and the sequelae of COVID-19 may be associated with the immune responses of mast cell activation syndrome and helper T cell type 2 in children with allergic diseases [3].

Moreover, the study’s revelation that women are disproportionately affected by long-term cardiovascular symptoms post-COVID-19 adds to the growing body of evidence on gender disparities in the pandemic’s aftermath. The potential role of immunological differences and hormonal influences in this gender-specific risk profile warrants further exploration. Studies have shown that there seem to be significant gender differences in long-term cardiovascular outcomes after COVID-19. Middle-aged women are twice as likely to suffer from long-term COVID-19 as men. The difference in inflammatory load between male and female populations may explain the gender differences in clinical manifestations and cardiovascular outcomes after COVID-19 [4]. Previous studies have also shown that women are associated with COVID-19 symptoms, especially persistent fatigue, anxiety, and depression. The reason may be that women have a stronger immune response. For example, women have a higher proportion of autoimmune diseases. It has been reported that women produce stronger immunoglobulin G antibodies in the early stage of the disease, which may lead to more favorable outcomes in women. Women recover more quickly from COVID-19 but may also play a role in perpetuating disease manifestations [5]. Even after recovery, estrogen in women may maintain the role played in the hyper-inflammatory state of the acute phase, which may also increase the risk of developing COVID-19 [6,7]. In addition, women are generally more concerned about their bodies and related pain, which may also be the reason why the survey shows that women are at higher risk of developing COVID-19 [8].

The study also reaffirms the critical influence of pre-existing cardiovascular conditions on the severity and incidence of post-COVID-19 cardiovascular symptoms. Patients with previous cardiovascular diseases are more likely to be infected with the new coronavirus. These findings emphasize the need for targeted monitoring and management strategies for patients with cardiometabolic disorders in the context of COVID-19 recovery. The virus has long-term potential effects on heart damage and is more likely to have related symptoms such as palpitations or chest pain. Patients with existing cardiometabolic diseases may have a higher risk of developing an acute state after infection with the new coronavirus, accompanied by complications and significantly affecting the prognosis [9]. On the other hand, COVID-19 itself may aggravate cardiac damage. It has been reported that previous history of coronary heart disease and elevated cardiac troponin I levels are two independent determinants of clinical status in COVID-19 patients [10]. Elderly patients with coronary heart disease, hypertension, diabetes, and chronic kidney disease are more likely to develop severe sequelae after COVID-19. Transthoracic echocardiogram imaging showed regional wall motion abnormalities, left or right ventricle abnormalities, systolic dysfunction, diastolic dysfunction, and pericardial effusion in the acute phase of COVID-19 [11]. In patients diagnosed with various heart diseases, COVID-19 infection may be one of the triggers for exacerbation and death [12]; patients with new-onset myocardial dysfunction, inflammation, or cardiovascular magnetic resonance scarring after COVID-19 may have increased risk of cardiac failure or recurrence of arrhythmia [13]. Patients with hyperglycemia have metabolic abnormalities, and patients with metabolic abnormalities have a higher risk of severe COVID-19 and COVID-19 sequelae. Obesity is a risk factor for cardiovascular disease, and the possible mechanisms include sympathetic nerve activation, endothelial dysfunction, oxidative stress, rheumatoid arthritis activation, metabolic dysfunction, etc., which can affect hemodynamics and cardiac structure, thereby increasing palpitations and the risk of developing related symptoms.

Interestingly, our data suggest a protective effect of alcohol consumption against the severity of chest pain, a finding that contrasts with the established role of alcohol as a risk factor for cardiovascular disease. This counterintuitive association may reflect complex interactions between alcohol intake, cardiovascular health, and COVID-19, which merit further investigation. It is imperative to approach these results with caution, considering the potential confounding factors and the need for larger-scale studies to validate the observed relationship. Alcohol consumption is a well-recognized risk factor for cardiovascular disease. Statistical analysis of the data in this study found that a history of alcohol consumption reduced the risk of increased chest pain severity. However, the small sample size may lead to statistical bias in the data, hence, no conclusion can be drawn. Additionally, the study demonstrated a J-shaped relationship between alcohol consumption and cardiovascular disease incidence, total mortality, and cardiovascular disease mortality in multivariate models. In a multivariable model, alcohol intake of 5–14.9 g per day was associated with a 26, 35, and 51% lower risk of cardiovascular disease, total mortality, and cardiovascular disease mortality, respectively, compared with abstainers. The mechanism may be related to the effect of alcohol on lipids and insulin sensitivity [14]; there is also evidence that alcohol consumption is positively associated with coronary artery disease, atrial fibrillation, and abdominal aortic aneurysm, but this association is attenuated after adjustment for smoking, hence smoking may have some effect in that study [15]; alcohol abuse is associated with increased odds of clinically high serum total cholesterol and triglyceride levels [16], but a short-term intervention study showed that moderate alcohol consumption reduced several cardiovascular biomarkers including high-density lipoprotein, adiponectin levels, and fibrinogen [17]. Although some studies in the past have shown that light drinking may have a protective effect on ischemic heart disease in women, the irreversible damage caused by alcohol to the cardiovascular system has offset this protective effect. The relationship between drinking history and drinking volume with COVID-19 still needs further research.

The implications of these findings are profound, highlighting the necessity for a nuanced approach to post-COVID-19 care that accounts for the diverse risk factors influencing cardiovascular sequelae. Healthcare providers should be cognizant of these risk factors when evaluating and managing patients in the post-recovery phase. Additionally, our study calls for increased vigilance in the follow-up of young adults and women who have recovered from COVID-19, as they may harbor a higher risk for long-term cardiovascular complications.

5 Conclusion

The study conducted at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine provides insights into the prevalence and risk factors associated with cardiovascular symptoms in patients who have recovered from COVID-19. Our findings suggest a correlation between certain demographic and health-related factors and the increased likelihood of experiencing cardiovascular symptoms post-COVID-19 infection.

It was observed that women, younger individuals, and the elderly exhibited a higher propensity for cardiovascular symptoms. Moreover, pre-existing conditions such as prehypertension, hypertension, cardiovascular diseases, and diabetes were identified as contributing factors to the increased risk of cardiovascular sequelae. These associations underscore the importance of vigilant monitoring and management of cardiovascular health, particularly in these identified higher-risk groups, during the post-recovery phase of COVID-19.

Additionally, the study revealed that individuals with cardiovascular symptoms post-COVID-19 were more prone to experiencing a range of other sequelae, including fatigue, shortness of breath, and gastrointestinal disturbances. This finding indicates a potential interconnection between cardiovascular symptoms and other post-COVID-19 conditions, which warrants further investigation to understand the underlying mechanisms and to develop comprehensive management strategies.

While the study provides valuable information, it is important to acknowledge its limitations, including the single-center design and the reliance on self-reported symptoms, which may introduce subjective bias. Future research with larger, multi-center cohorts and objective diagnostic measures is recommended to validate these findings and to explore the long-term implications of COVID-19 on cardiovascular health.

In conclusion, our study contributes to the growing body of evidence on post-COVID-19 sequelae and highlights the need for targeted follow-up care for patients at higher risk of cardiovascular complications. Healthcare providers should be aware of these risk factors when assessing and treating patients who have recovered from COVID-19, to mitigate the potential long-term health impacts of the disease.