2025 Expert Consensus Recommendations on Vaccinations in Adults with High Cardiovascular Risk and Cardiovascular Disease: A Report of the Task Force of the Taiwan Society of Cardiology and the Infectious Diseases Society of Taiwan

Abstract

Cardiovascular disease (CVD) is a leading cause of death worldwide, and infections often worsen the clinical condition of these patients. Respiratory infections, either bacterial or viral sources, are important causes of high morbidity and mortality in older adults. Beyond the burden of infection-related complications, they are also associated with non-infection-related complications such as cardiovascular (CV) events. For example, herpes zoster is associated with an increased risk of stroke and myocardial infarction. Vaccination is an effective preventive strategy for patients with CVD by reducing viral and bacterial infections, and minimizing systemic inflammatory responses to support plaque stability and reduce the likelihood of CV events in high-risk patients, thereby reducing the risks of CV and non-CV hospitalizations and mortality. Despite evidence on the effectiveness, safety, and benefits of vaccines and recommendations to vaccinate older patients and those with risk factors, vaccination rates remain sub-optimal in this population. The Taiwan Society of Cardiology and the Infectious Diseases Society of Taiwan recently appointed a task force to formulate a consensus on vaccinations for adults with high CV risk or CVD. Based on the most up-to-date information, the consensus provides current evidence-based important recommendations.

Abbreviations

ACE2, Angiotensin-converting enzyme 2

ACIP, Advisory Committee on Immunization Practices

ARIs, Acute respiratory infections

CAD, Coronary artery disease

CDC, Centers for Disease Control and Prevention

CI, Confidence interval

COR, Class of recommendation

COVID-19, Coronavirus disease 2019

CV, Cardiovascular

CVD, Cardiovascular disease

HF, Heart failure

HR, Hazard ratio

HZ, Herpes zoster

ICU, Intensive care unit

LOE, Level of evidence

MI, Myocardial infarction

NR, Non-randomized

oxLDL, Oxidized low-density lipoprotein

PCV, Pneumococcal conjugate vaccine

PPV, Pneumococcal polysaccharide vaccine

RSV, Respiratory syncytial virus

RZV, Recombinant zoster vaccine

SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2

US, United States

ZVL, Zoster vaccine live

INTRODUCTION

Cardiovascular disease (CVD) is a leading cause of death worldwide, with a mortality rate approximately equal to that of all cancers combined. In recent decades, significant progress has been made in the treatment of CVD, especially in the identification and management of major traditional risk factors for atherosclerotic CVD, as well as other related comorbid conditions such as diabetes and chronic kidney disease. However, the prevalence of CVD remains high, with an estimated 48.6% of Americans aged ≥ 20 years affected by CVD, including coronary artery disease (CAD), heart failure (HF), stroke, and hypertension. In the United States (US), CVD-related deaths declined during the early 2010s; however, the rate began to increase again in the late 2010s and continued rising through 2020.¹ In Taiwan, CVD is the second leading cause of death behind cancer, accounting for over 30,000 deaths annually.²

Conditions that increase cardiovascular (CV) risk include age more than 40 years, male gender, a family history of premature CAD, diabetes, hypertension, hyperlipidemia, obesity, smoking, and microalbuminuria. In addition, several non-traditional risk factors have also become major contributors, such as infection, which is a significant factor leading to mortality in CVD patients,^3-6 particularly following HF and CV events. Infections often worsen the clinical condition of these patients and cause complications,^7,8 as they increase the metabolic demands of the heart and oxygen consumption, making it harder for the already compromised heart to cope, leading to acute decompensation and even cardiogenic shock. Meanwhile, patients with HF have compromised immune systems, and they are more susceptible to infections, which trigger a systemic inflammatory response, increase myocardial workload, and further worsen cardiac function, ultimately increasing the risk of mortality. Systemic inflammation also damages the vascular endothelium, promotes thrombosis, and increases the risk of myocardial infarction (MI) and stroke. In addition, CVD patients often have multiple comorbidities including diabetes and chronic kidney disease, which further increase their susceptibility to infection. During hospitalization, these patients are exposed to the hospital environment and may acquire healthcare-associated infections such as pneumonia or urinary tract infections, further elevating their risk of mortality. The mortality rate of CVD patients with concurrent infections is significantly higher than that of those without infections. Therefore, preventing and promptly treating infections in CVD patients is crucial.

In patients with high CV risk and CVD, infections increase the risk of serious complications such as myocardial ischemia, MI, stroke, and HF, and 20% of patients with acute decompensated HF have concomitant infections at the time of hospitalization. These patients have longer lengths of stay, as well as higher rates of readmission and mortality.^9,10 Chen et al. reported that the risk of infection within 1 year following hospitalization for HF was 17%. They also found that lower respiratory tract infection or pneumonia was the most prevalent infectious disease (43.9%), followed by urinary tract and soft tissue infections.¹¹ Vaccination is an effective preventive strategy for CVD patients.^12-14 Although the mechanisms of virus-induced pathological vascular remodeling are not fully understood, recent research indicates that inflammation plays a significant role. In addition to reducing bacterial and viral infections, vaccination can minimize systemic inflammatory responses and endothelial injury, thereby preventing plaque instability and lowering the likelihood of CV events in high-risk patients and those with CVD. Vaccination can further reduce the risk of hospitalization, severe complications, and mortality related to infections in these patients. On the other hand, in patients without CVD who are hospitalized due to severe infections, the incidence of CV complications, including MI, stroke, and CV mortality, ranges from approximately 4-6%. The risk of CV complications significantly increases (hazard ratio [HR], 7.87) within the first month following infection. Furthermore, the likelihood of developing CVD continues to increase over the subsequent 10-year period. Vaccines, and particularly influenza¹⁵ and pneumococcal vaccines¹⁶ have been shown to reduce the risks of MI, stroke and other serious CV complications. Therefore, influenza and pneumococcal vaccines are generally recommended for people with CVD as an important part of multidisciplinary team management for the prevention and treatment of HF^17,18 and chronic coronary syndromes.^19,20

Coronavirus disease 2019 (COVID-19) has been linked with many manifestations in multiple organ systems along with several CV pathologies, and COVID-19 vaccination has been shown to reduce the risk of CV events following infection.²¹ Respiratory syncytial virus (RSV) is traditionally known for causing respiratory illness in young children; however, its impact on older adults has gained increasing attention.^22,23 Varicella-zoster virus infection is an intriguing medical entity that involves many medical specialties, including infectious diseases, immunology, dermatology, and neurology. A few studies have reported an association between herpes zoster (HZ) with a higher long-term risk of major CV events.²⁴ The benefit-risk ratio of vaccination is highly favorable in patients with CVD. Therefore, the reductions in major CV events, hospitalizations, and mortality significantly outweigh the minor and rare vaccine-related side effects. Adequate patient self-care is essential for the effective management of CVD, and this includes immunization. Misunderstandings, misconceptions, and lack of knowledge all contribute to insufficient self-care. Physicians should therefore discuss the benefits and possible barriers with their patients and give advice regarding local immunization practice.

This consensus aims to summarize the impact of vaccinations against influenza, pneumococcus, COVID-19, RSV and HZ in patients with high CV risk or CVD. The draft of this consensus was developed by the joint task force from the Taiwan Society of Cardiology and the Infectious Diseases Society of Taiwan, and the final document was endorsed by both societies. The recommendations in this consensus are made based on updated scientific evidence but modified by the expert opinions along with local, pragmatic considerations in Taiwan. Similar to the previously published guidelines from the Taiwan Society of Cardiology, the consensus uses an evidence-based classification system including three classes of recommendation (COR) and three levels of evidence (LOE). For the COR, Class I recommendations indicate that they are useful and beneficial for the patients. Class IIa recommendations indicate that the evidence favors the recommendations and could be used for the patients. Class IIb recommendations are those that may be considered but the scientific strength is less well-established. Class III recommendations indicate that the treatment is unnecessary or harmful. There are also three levels of LOE. LOE A recommendations are supported by multiple randomized clinical trials or meta-analyses of randomized clinical trials. LOE B recommendations are from only one randomized clinical trial or non-randomized (NR) observational studies. LOE C recommendations are from case series, case reports or consensus of expert opinions.

INFLUENZA VACCINATION

A relationship between influenza and CVD has been demonstrated (Figure 1). Patients with viral respiratory infections are prone to CV events and deaths. On the other hand, underlying CVD is also associated with an increased risk of viral respiratory infections and their complications.^25,26 Chow et al. reported that sudden serious cardiac events are common among adults hospitalized with influenza.²⁷ They investigated more than 80,000 adult patients hospitalized with influenza over eight influenza seasons and found that almost 12% of the patients had an acute cardiac event such as acute HF or acute ischemic heart disease. Of these patients, 30% were admitted to the intensive care unit (ICU) and 7% died while in the hospital. Even during the mildest influenza season, infec-tion was found to increase the risk of MI and stroke within 14 days by two to four times among those over 50 years old.²⁸ Influenza vaccination reduces the risk of CV events regardless of an individual’s history of CVD. Research has shown that influenza vaccination can be used as both a primary and secondary prevention strategy for CVD, and that it protects against acute CV events for at least 1 year.¹⁵ In a meta-analysis of four randomized controlled trials and 12 observational studies, influenza vaccination was associated with a reduction in the incidence of CV mortality by 18%, major adverse cardiac events by 13%, and total mortality by 25% in CVD patients.²⁹ For patients admitted for MI, early influenza vaccination has been shown to reduce the risk of stent thrombosis, death due to MI, CV death and all-cause death within 1 year.³⁰ In addition, a study on patients with recent acute coronary syndrome and stable CVD reported that influenza vaccination led to a significant 28% reduction in major adverse CV events and a 41% reduction in CV mortality.³¹ Another study reported no significant difference between high-dose trivalent and standard-dose quadrivalent vaccine formulations [64.9% vs. 62.2% (p = 0.44)] on CV death, total cardiopulmonary hospitalizations, or all-cause death across all enrollment seasons in patients hospitalized for MI within 1 year or HF within 2 years.³²

Figure 1.

For patients with pre-existing atherosclerotic cardiovascular disease (ASCVD), once infected with influenza, the inflammatory response caused by infection increases the risk of recurrence and death from cardiovascular disease (CVD). On the other hand, for patients who do not have CVD history but other comorbidities such as chronic obstructive pulmonary disease, diabetes mellitus, and chronic kidney disease, once infected with influenza, the inflammatory reaction may cause subclinical asymptomatic atheroma to become unstable and even rupture, leading to acute cardiovascular (CV) events. Therefore, influenza vaccination may reduce the risk of CV events regardless of an individual’s history of CVD. CKD, chronic kidney disease; COPD, chronic obstruction pulmonary disease; DM, diabetes mellitus.

In Taiwan, lower risks of CV death and hospitalization for HF have been reported in older patients with MI who received influenza vaccination.³³ In patients with HF and New York Heart Association functional class II-IV during the peak influenza season, influenza vaccination was shown to reduce pneumonia by 42% and all-cause hospitalizations by 16%, and also significantly lower the co-primary outcomes of CV death and non-fatal MI.³⁴ Influenza vaccination is effective in reducing the risk of all-cause death in patients with HF. However, due to data quality issues, the overall confidence is relatively low, and further reliable data are needed to determine the effectiveness of such vaccination.³⁵ HF is often associated with multiple comorbidities and non-CV death is common, especially in patients with HF with preserved ejection fraction. Influenza vaccination is recommended for patients with HF, and especially for those who are older.¹⁸ Currently, there is no definite conclusion on the timing of vaccination for patients hospitalized due to acute CVD; however, vaccination is usually recommended 3 months after hospital discharge and when their clinical condition is stable.

The Taiwan Advisory Committee on Immunization Practices recommends³⁶ that children over 6 months of age and adults should receive an influenza vaccine before each influenza season, especially for those aged 6 months to 18 years, those over 65 years of age, those with underlying diseases, pregnant women, care recipients in nursing homes and long-term care institutions, and medical, health and epidemic prevention personnel. Attention should be paid to adequate vaccination protection in the general population, hospitalized patients with CVD, and end-stage patients, especially in the early stages of the winter epidemic. Increasing vaccination rates may help reduce the risk of a first acute CV event in those already eligible for seasonal influenza vaccination.

Influenza vaccination is the most effective public health strategy to protect people against seasonal influenza. High-dose trivalent vaccines induce a greater humoral response in patients with HF or previous MI, and no association has been reported between their effectiveness and the risk of cardiorespiratory hospitalization or all-cause death.³⁷ Adjuvanted influenza vaccines produce a stronger immune response and are recommended as the first choice for those aged ≥ 65 years.³⁸ Therefore, adjuvant trivalent influenza vaccines are suitable for people over 65 years old due to better immunogenicity. Common side effects include pain, redness and swelling at the injection site. Systemic mild reactions can sometimes occur, such as fever, headache, muscle ache, nausea, itchy skin, urticaria, rash, etc., which usually occur 1-2 days after the injection and subside within a few days. The risk of serious side effects is very low.

In conclusion, influenza vaccination is associated with significant risk reductions in CV and respiratory adverse outcomes as well as all-cause mortality. This preventive measure can benefit the general population as well as older people and those with pre-existing specific diseases, including CVD.³⁹

Recommendations

• In patients with chronic coronary syndrome, annual influenza vaccination is recommended to prevent major adverse CV events. (COR I, LOE A)

• In patients with HF, annual influenza vaccination is recommended, especially for older patients. (COR I, LOE B)

• For early post-MI patients, influenza vaccination is recommended to prevent major adverse CV events. (COR I, LOE B)

• Influenza vaccination is reasonable in patients with multiple risk factors such as hypertension, hyperlipidemia, diabetes, and chronic kidney disease to prevent CV events. (COR IIa, LOE B)

PNEUMOCOCCAL VACCINATION

Pneumococcal pneumonia is a severe respiratory infection caused by Streptococcus pneumoniae, and it is the most common bacterial cause of community-acquired pneumonia. The resultant development of often fatal CV events, particularly during the first 7 days of acute infection, is now recognized as a relatively common complication of invasive pneumococcal disease.^16,40-42 Effective vaccination schedules for individuals with CVD or at a very high risk of developing CVD are therefore important.

Two types of pneumococcal vaccines: polysaccharide vaccine and protein-polysaccharide conjugate vaccine

There are two main types of pneumococcal vaccines: pneumococcal polysaccharide vaccine (PPV) and pneumococcal conjugate vaccine (PCV). As of 2024, PPV23 and PCV13 are both available in Taiwan. While both vaccines protect against Streptococcus pneumoniae infection, they differ in their composition and the immune responses they elicit. Understanding these differences is crucial when examining their potential cardioprotective effects. The differences in immunogenicity mechanisms between the two types of pneumococcal vaccines are illustrated in Figure 2.

Figure 2.

Differences in immunogenicity mechanisms between the two types of pneumococcal vaccines (modified from ref. 40). The vaccine-induced immunogenicity is longer by protein-polysaccharide conjugate vaccines (PCV) because PCVs could induce the development of memory B cells by T cells, which are co-stimulated via carrier proteins of conjugate vaccines. BCR, breakpoint cluster region; CD, cluster of differentiation; MHC, major histocompatibility complex; TCR, T cell receptor.

Potential cardioprotective mechanisms of PPV23

The potential cardioprotective effects of PPV23 are thought to stem from the following two mechanisms:

1. Reduction of Pneumococcal Infections and Subsequent CV Complications: Pneumococcal pneumonia is known to increase the risk of acute cardiac events.^16,41,43 PPV23 may indirectly lower this risk by reducing the incidence of pneumococcal pneumoniae infection.^16,41,43,44 A reduction in pneumococcal disease also prevents potentially systemic effects such as sympathetic activation, tissue hypoxemia, release of pro-inflammatory cytokines, and hypercoagulability.⁴⁵

2. Molecular Mimicry and Atherosclerosis: A key mechanism proposed for the cardioprotective effect of PPV23 is molecular mimicry. The phosphorylcholine antigens found on the cell wall of Streptococcus pneumoniae are similar to those found in oxidized low-density lipoprotein (oxLDL), a significant component of atherosclerotic plaques.^41,43,45,46 PPV23 vaccination induces the production of antibodies against these antigens, which may cross-react with oxLDL, potentially reducing plaque formation and atherosclerosis.^41,43,45-47 This cross-reactivity has been demonstrated in animal studies where PPV23 vaccination led to decreased atherosclerotic lesion formation. In humans, a significant association has been observed between pneumococcal IgG and anti-oxLDL antibody titers following PPV23 vaccination.⁴³

PPV23 vaccination, all-cause mortality, and events

Several observational studies have suggested that the PPV23 vaccination is associated with a reduction in certain CV events:

1. All-Cause Mortality: In individuals with established CVD or at a very high risk of developing CVD, several reviews found that pneumococcal vaccination was associated with a 24% reduction in all-cause mortality.^41,45 In addition, a meta-analysis of 15 studies found that PPV23 vaccination was associated with a decreased risk of all-cause mortality, particularly in individuals older than 65 years.⁴⁸

2. CV Events: Evidence has shown that dual vaccination with PPV23 and influenza vaccine is more effective than either vaccine alone in reducing the incidence of MI in older individuals.⁴⁹ A systematic review and meta-analysis of cohort studies found that PPV23 vaccination was associated with a decreased risk of CV events, and that the protective effect was more pronounced in older individuals and those at higher CV risk.⁵⁰ Several studies also reported that older individuals who received PPV23 had reductions in MI (27%) and cerebrovascular events.^45,50

Effect of sequential PCV13 and PPV23 vaccinations on CVD among older adults

A previous study reported that sequential vaccinations including PCV13 were associated with a lower risk of CVD compared to a single vaccination with either PCV13 or PPV23 alone.¹⁶ The study suggested that this protective effect may be mediated by a reduction in all-cause pneumonia.¹⁶ This finding suggests a potential indirect mechanism by which PCV13 contributes to CV health.

With the recent availability of PCV20 in Taiwan, the recommendations and guidance for pneumococcal vaccination in adults aged ≥ 18 years in Taiwan will be updated soon, and the effectiveness of PCV20 has been demonstrated to be non-inferior to PCV13 and PPV23.^51,52 PCV20 is expected to allow for a less complicated pneumococcal vaccination schedule compared to PCV13 and PPV23.⁵³ Therefore, the latest pneumococcal vaccination schedules should be followed according to the Taiwan Centers for Disease Control and Prevention (CDC) website.⁵⁴

Recommendation

• Pneumococcal vaccination is recommended to reduce the risk of major adverse CV events in patients with CVD or at high CV risk. (COR: I, LOE: B-NR)

COVID-19 VACCINATION

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and it has been linked with many disease manifestations in multiple organ systems in addition to pulmonary manifestations. Individuals infected with COVID-19 are at an increased risk of CV events due to a complex interplay of mechanisms. Studies have reported significantly higher mortality rates in patients infected with SARS-CoV-2 who have underlying conditions such as diabetes, hypertension, and other CVDs. In addition, COVID-19 can lead to acute myocardial injury, arrhythmias, and thrombosis, as well as triggering acute coronary syndromes and HF.⁵⁵ The mechanisms by which COVID-19 contributes to CV events are described as follows and illustrated in Figure 3.

Figure 3.

The mechanisms by which COVID-19 contributes to cardiovascular events (modified from ref. 55). COVID-19 infection could cause inflammatory injury to myocardial cells; and it also could induce dysfunction of coronary arterial smooth cells and endothelial cells, and instability of atheroma plaques, thus leading to myocardial damage. COVID-19, coronavirus disease 2019; SIRS, systemic inflammatory response system.

1. Direct Viral Invasion of Cells Expressing Angiotensin-converting Enzyme2 (ACE2): The SARS-CoV-2 virus uses ACE2 receptors to enter cells.^56,57 ACE2 is prevalent in the lungs, heart, and CV system.⁵⁶ The interaction of SARS-CoV-2 with ACE2 may lead to alterations in ACE2 pathways, resulting in acute lung injury and damage to endothelial cells and the heart.⁵⁶ Myocardial injury may be mediated by direct injury of myocardial tissues when SARS-CoV-2 enters cells via ACE2.⁵⁶ Pre-existing cardiac dysfunction may increase ACE2 levels, making the patients more vulnerable to serious complications from COVID-19.

2. Cytokine Storm and Systemic Inflammation: An intense systemic inflammatory response, i.e. a "cytokine storm", may contribute to myocardial injury.^56-60 Viral particles spreading through respiratory mucosa can infect cells, initiating a cascade of immune responses and the release of inflammatory cytokines.⁵⁷ This inflammation cascade is marked by elevated levels of inflammatory biomarkers such as interleukin-6, ferritin, lactate dehydrogenase, and D-dimer.⁵⁷ Cytokine storm may lead to a reduction in coronary blood flow, decreased oxygen supply, destabilization of coronary plaque, and microthrombogenesis.⁵⁷

3. Endothelial Dysfunction and Microthrombi: Endothelial dysfunction is impairment of the inner lining of blood vessels, and it can lead to a hypercoagulable state and increase the risk of thrombosis.^60,61 Microthrombi (small blood clots) are frequently found in the hearts of COVID-19 patients. These microthrombi can contribute to cardiac injury and other CV events.^59,62

4. Hyperactivated Platelets and Immunothrombosis: COVID-19 leads to hyperactivated platelets, including those carrying viral RNA.^59,60 These platelets express and release factors that stimulate microvascular endothelial activation and weaken endothelial junctions.⁵⁹ This interaction initiates immunothrombosis, a process where the immune system and clotting system are inappropriately activated, further contributing to the formation of microthrombi.⁵⁹

5. Vulnerable Plaque Rupture: Pre-existing CV conditions and atherosclerosis, especially in the context of adipokine expression and cytokine storm, can aggravate cardiac injury and HF.⁶¹ Systemic inflammation may further impair micro- and macro-circulation, leading to plaque rupture. In addition, oxygen desaturation can impair the microcirculation and myocardial performance.⁶¹

6. Myocarditis: Myocarditis can present as fulminant HF and is more likely in patients with concurrent COVID-19 pneumonia.⁵⁹ Pericytes, which are cells that support the microvasculature, are believed to be the primary target of SARS-CoV-2 infection in the heart.⁵⁹

Post-infection COVID-19 severity and CV complications

Researchers have found a significant association between the severity of COVID-19 infection and the subsequent risk of developing CV events. Wiemken et al. reported that patients who required hospitalization, particularly those admitted to the ICU, had a much higher risk of CV events compared to those who only required outpatient care.⁶³ Moreover, this increased risk persisted even after adjusting for various demographic and clinical characteristics.⁶³ Their results also showed a dose-response relationship, indicating that the risk of CV events increased with the severity of the initial COVID-19 infection.⁶³ At 9 months post-diagnosis, the weighted cumulative incidence rates of any CV event were 14%, 10%, and 8% for patients requiring ICU care, non-ICU hospitalization, and outpatient care, respectively.⁶³ These findings highlight the need for preventive measures such as vaccination and prompt treatment to mitigate severe disease and complications. The main mechanism potentially associated with this outcome is direct viral invasion of heart cells through ACE2 receptors, leading to myocardial injury.^56,63 Another major contributor is cytokine storm.^56,63 The excessive release of pro-inflammatory molecules can damage the heart and blood vessels and potentially lead to CV events.⁵⁶

Acute risks of MI and stroke

COVID-19 has been demonstrated to increase the risks of MI and ischemic stroke within weeks post-infection. For patients hospitalized with COVID-19, the risk of such adverse events approaches that observed in patients with CAD. A 2- to 6-fold increased risk of MI and 2- to 8-fold increased risk of stroke has been reported, along with an increased risk of major adverse CV events for up to 1000 days.^64,65 This underscores the profound impact of COVID-19 on CV health.

Persistent CV risks

A previous study demonstrated that long-term CV complications could persist for up to 1 year post-COVID-19. In addition, the risks of dysrhythmias, myocarditis, HF, and thromboembolic disorders were significantly elevated, even among non-hospitalized patients, the severity of which was associated with the intensity of the acute phase.⁶⁶

Atherosclerotic inflammation

Autopsy findings have shown that SARS-COV-2 can infect macrophages within coronary plaques, increasing inflammation and predisposing patients to acute coronary syndromes.⁶⁷

COVID-19 vaccination helps lower CV events and mortality

Full vaccination against COVID-19 has been reported to reduce the incidence of major adverse CV events by up to 41%, offering significant protection for high-risk groups.⁶⁸ In addition, vaccination has been shown to reduce the inflammatory response, thereby mitigating risks associated with cytokine storm.⁵⁵

COVID-19 vaccination significantly reduces the risk of acute/post-acute CV complications after SARS-CoV-2 infection. A previous study demonstrated a 45-81% risk reduction in thromboembolic and cardiac events in the acute phase (30 days) of COVID-19 among vaccinated individuals, and this effect persisted for up to 1 year for conditions including venous or arterial thromboembolism and HF.⁶⁹ The primary mechanism behind this protective effect is the reduction in SARS-CoV-2 infection and disease severity.⁶⁹ Vaccines help prevent infection, and if breakthrough infections occur, vaccinated individuals have milder illness, leading to fewer CV complications.⁶⁹ Vaccines are highly effective in preventing severe COVID-19 and associated deaths, particularly in high-risk groups.⁷⁰ By reducing the incidence of severe COVID-19, vaccines indirectly protect against long-term CV consequences associated with the virus.

Vaccines including BNT162b2 and ChAdOx1 have been shown to be effective in preventing MI and ischemic stroke, with studies reporting significant reductions in adverse events in vaccinated individuals, including those with pre-existing CVD.^70,71 These findings underscore the protective effect of vaccines not only against infection but also in reducing the CV burden associated with post-acute COVID-19 syndrome, also known as long COVID.⁷⁰

Regarding safety, while slight increases in rare adverse events such as myocarditis and pericarditis have been reported in younger males after mRNA vaccinations, the overall risk of such events is much lower compared to the risk of CV events after COVID-19 infection.^72,73 The risk of myocarditis after vaccination is significantly lower than that after COVID-19 infection itself. A meta-analysis reported that the incidence of vaccine-related myocarditis was 14.8 cases per million people, compared to much higher rates following COVID-19 infection.^72,73 The benefits of vaccination in preventing severe disease and long-term CV complications far outweigh the risks.^70,72

Reinfection and long COVID

Reinfections have been shown to have similar severity as the first infection,⁷⁴ and they also pose substantial risks for long COVID, including CV complications. Vaccination significantly mitigates these risks, emphasizing its role in preventing long-term sequelae.^74,75 The Vaccine Effectiveness, Networking, and Universal Safety Study in Japan explored the protective effects of vaccination against these sequelae, and found that individuals vaccinated within 149 days prior to infection had significantly reduced risks of developing long-term complications across various organ systems, including respiratory, CV, and neurological systems. Vaccination has been shown to be especially effective in mitigating conditions such as ischemic heart disease, arrhythmias, stroke, and cognitive disorders, even among high-risk populations with pre-existing comorbidities.⁷⁶ In a parallel study, Ye et al. demonstrated the efficacy of COVID-19 vaccines, specifically BNT162b2 and CoronaVac, in lowering the risks of MI and stroke within 28 days post-infection among individuals with CVD. The protective effects were dose-dependent, with the greatest reduction observed after three doses. This underscores the importance of full vaccination in not only improving severe acute-phase outcomes but also in averting long-term CV complications.⁷⁷

Recommendation

• Up-to-date COVID-19 vaccination is recommended to reduce the risk of COVID-19-related CV complications in patients with and without pre-existing CVD. (COR: I, LOE: B-NR)

RESPIRATORY SYNCYTIAL VIRUS VACCINATION

RSV was first identified in 1957 as a cause of bronchiolitis in young children; however, its potential severity in older adults had not been recognized until the 1970s, following outbreaks in long-term care facilities.⁷⁸ Each year, RSV infects 3-7% of healthy older individuals and 4-10% of high-risk adults, such as those with immunosuppression, hemato-oncologic disease, CVD, and chronic lung disease, and those hospitalized with acute cardiopulmonary conditions.⁷⁸

In Taiwan, the estimated prevalence of RSV among hospitalized adults with respiratory symptoms is around 2%, with higher rates in older adults and those with chronic cardiopulmonary diseases.⁷⁹ A global meta-analysis on RSV-acute respiratory infections (ARIs) reported approximately 336,000 hospitalizations (range: 186,000-614,000) and around 14,000 in-hospital deaths related to RSV-ARIs.⁸⁰ With an annual incidence of 44.2 to 58.9 per 100,000, a population-based surveillance study showed that RSV-ARIs are not rare.⁸¹ Higher hospitalization and mortality rates from RSV have been reported in older adults with high-risk cardiac conditions such as CAD and HF compared to those at lower risk.^25,82

RSV is an increasingly recognized cause of illness in adults, with an incidence in older and high-risk adults sometimes surpassing that of influenza.⁷⁸ As with other pathogens, RSV has been linked to the development of atherosclerosis and increased risk of MI. A UK case series found a higher risk of first and recurrent MI and stroke following respiratory tract infections compared to asymptomatic periods.²⁵ Patients hospitalized with RSV were more likely to require invasive mechanical ventilation or die, as compared to those hospitalized with influenza (adjusted odds ratio, 2.08; 95% confidence interval [CI], 1.33-3.26). Although less common, RSV in hospitalized older adults was associated with more severe disease than COVID-19 or influenza. This severity is crucial for shared clinical decision making regarding RSV vaccination.⁸³ Patients with underlying cardiopulmonary diseases have a higher risk of symptomatic RSV and increased morbidity.²⁵

Data on the epidemiology and clinical effects in community-dwelling older and high-risk adults can help in assessing the need for vaccine development.⁷⁸ The RSV genome encodes 11 proteins, of which glycoprotein G, responsible for viral attachment, and fusion protein F, which facilitates viral penetration and syncytium formation, play key roles in the pathogenesis and protective immunity.²⁵ Two different subtypes of the virus, RSV A and RSV B, are circulating concurrently, and they are distinguished mainly by variations in the G protein. Most RSV vaccines target the RSV F glycoprotein, which mediates viral fusion and host-cell entry, elicits neutralizing antibodies, and is highly conserved across the two RSV subtypes (A and B).²⁵ A phase III trial (AReSVi-006) investigated the efficacy of a single dose of RSV PreF3-adjuvanted vaccine over 3 years with annual revaccinations thereafter in adults aged ≥ 60 years. The results showed high vaccine efficacy of 82.6% against RSV-associated lower respiratory tract disease, 94.6% in those with pre-existing comorbidities, and 93.8% in those aged 70-79 years.⁸⁴ The recently approved RSV preF vaccine, similar to RSV preF3 but without an adjuvant, is licensed in the US for older adults and pregnant women. In the RENOIR trial, it showed 65.1% efficacy for ≥ 2 symptoms and 88.9% for ≥ 3 symptoms, with mostly mild to moderate reactions.⁸⁵ The definition of RSV symptoms includes systemic symptoms (fever or feverishness, fatigue, body aches, headache, and decreased appetite), upper respiratory symptoms (nasal congestion and sore throat), and lower respiratory symptoms (sputum production, cough, and shortness of breath) along with signs such as wheezing, crackles or rhonchi, rapid breathing (tachypnea), low oxygen levels (hypoxemia), and the need for supplemental oxygen.⁸⁵ The respective pivotal studies showed a very high efficacy of the vaccine in preventing severe RSV-associated respiratory infections. Therefore, the Standards for Adult Immunization Practices highlight the essential role of clinicians in encouraging patients to receive annual vaccinations, including RSV, to improve the outcomes of HF patients.⁸⁶ On June 26, 2024, the CDC Advisory Committee on Immunization Practices (ACIP) recommended RSV vaccinations for all adults aged ≥ 75 years and in adults aged 60-74 at increased risk of severe RSV disease; and on April 16, 2025, the ACIP voted in favour of recommending the use of RSV vaccines in adults aged 50-59 who are at increased risk for severe RSV disease, offered to adults using shared clinical decision-making, as summarized in Table 1.⁸⁷ In addition, we recommend use of the vaccination in adults of any age with severe pulmonary or pre-existing CV conditions, as well as in significantly immunocompromised adults, after consultation with a physician.²³

Table 1.

Although the original vaccination schedules in the trials were a single lifetime dose, all vaccines showed a reduction in efficacy in the 3 years following the vaccination against lower respiratory tract infections (Figure 4).⁸⁸

Figure 4.

Overview of the findings on the decline in vaccine efficacy against lower respiratory tract infections during the first, second and third RSV seasons with different medical conditions.⁸⁹ LRTD: ≥ 2 lower respiratory symptoms/signs for ≥ 24 hours including ≥ 1 lower respiratory sign or ≥ 3 lower respiratory symptoms for ≥ 24 hours; Severe LRTD: LRTD with ≥ 2 lower respiratory signs, or an LRTD episode assessed as severe by the investigator. Cardiorespiratory: chronic obstructive pulmonary disease, asthma, any chronic respiratory or pulmonary disease, chronic heart failure; Metabolic condition: Diabetes mellitus type 1 or 2, advanced liver or renal disease. LRTD, lower respiratory tract disease; RSV, respiratory syncytial virus.

Recommendation

• RSV vaccination is recommended for adults aged ≥ 75 years and those aged 50-74 years with established CVD, chronic lung disease, or living in nursing homes, to prevent RSV and related complications. (COR: I, LOE: B)

HERPES ZOSTER VACCINATION

HZ is caused by reactivation of the latent varicella-zoster virus in sensory ganglia, typically presenting as a painful blistering rash.⁸⁹ The disease shows different clinical stages with variable clinical manifestations, some of which are associated with a higher risk of complications. These complications include postherpetic neuralgia and HZ ophthalmicus, which affect 5-30% and 10-15% of patients, respectively, and significantly impact the quality of life.^89,90 Renal and gastrointestinal complications have also been reported. HZ may trigger inflammation and vasculitis or vasculopathy, increasing the risk of CV complications and consequently morbidity and mortality.⁹⁰ A Korean study found a bidirectional association between HZ and CVD, with severe HZ increasing the risk of MI, ischemic stroke, and HF. Similarly, MI, ischemic stroke, and HF episodes were shown to increase the risk of HZ hospitalization.⁹¹ In addition, severe HZ requiring hospitalization was found to increase the risk of subsequent MI (HR, 1.831; 95% CI, 1.354-2.476), ischemic stroke (HR, 1.523; 95% CI, 1.212-1.915) and HF (HR, 2.034; 95% CI, 1.615-2.562); similarly, patients with MI (HR, 1.625; 95% CI, 1.144-2.308), ischemic stroke (HR, 1.518; 95% CI, 1.177-1.957) or HF (HR, 1.485, 95% CI 1.041-2.117) were also found to be at an increased risk of hospitalization for HZ.⁹¹ The cornerstone of treatment is early intervention with acyclovir or brivudine. Pain management is essential. For (secondary) prophylaxis, vaccination can prevent HZ and its complications.

Since HZ is secondary to varicella, its incidence increases with age. HZ is rare in children and adolescents, and it is associated with metabolic and neoplastic disorders. In adults, advanced age, chronic illnesses such as CVD, distress, other infectious diseases (such as the acquired immunodeficiency syndrome or COVID-19), and immunosuppression are the most common risk factors. The reactivation of latent varicella-zoster virus has recently been observed after COVID-19 vaccination.⁹² In Taiwan, the lifetime risk of HZ is 32.2%,⁹³ with the incidence increasing sharply after 50 years of age due to waning immunity, chronic conditions, and the immunocompromised state.^89,90 Several Taiwanese studies reported an increased HZ risk in patients with CVD, particularly in the first month post-HF (HR, 4.52) and within the first year post-stroke (HR, 25.27).^94,95

There are two licensed vaccines for prevention of HZ: zoster vaccine live (ZVL) and recombinant zoster vaccine (RZV). Of these vaccines, RZV is preferred,⁹³ and ZVL is no longer available in the US since November 18, 2020 as lower vaccine efficacy and a contraindication in immunocompromised patients. RZV contains varicella-zoster virus glycoprotein E and the AS01_B adjuvant system, and it was approved by the Taiwan Food and Drug Administration in 2021 for use in individuals aged ≥ 50 years and those ≥ 18 years who are at increased risk of HZ.⁹⁶ In the pivotal phase III trials, RZV showed 97.2% and 91.3% efficacy in adults aged ≥ 50 (ZOE-50) and ≥ 70 (ZOE-70) years, respectively, over a median follow-up of 4 years. A post-hoc analysis of the pooled data demonstrated 91.9% efficacy in hypertensive patients and 97.0% in those with coronary heart disease.⁹⁷ Long-term follow-up studies have shown that RZV remains effective for at least 11 years in adults aged ≥ 50 years.⁹⁸ A meta-analysis also reported a 22% reduction in stroke risk for those vaccinated against HZ.⁹⁹ Related information is summarized in Figure 5.

Figure 5.

A summary of the incidence, high-risk populations for herpes zoster, and recommendations for vaccination.^{91,93,94,96-99} CVD, cardiovascular disease; HF, heart failure; HZ, herpes zoster; IS, ischemic stroke; MI, myocardial infarction; VZV, varicella-zoster virus.

RZV has a favorable safety profile, with injection site pain and fatigue as the most common side effects.^96-98 It can be co-administered with other vaccines, including influenza vaccine, pneumococcal vaccines such as PPV23 or PCV, diphtheria-tetanus-acellular pertussis vaccine, and COVID-19 mRNA vaccines.⁹⁶

Recommendation

• RZV is recommended for adults aged ≥ 50 years and those aged 18-49 years with CVD to prevent HZ and related complications. (COR: I, LOE: B)

CONSENSUS STATEMENTS

Vaccination coverage needs to be increased in patients with high CV risk or CVD. Appropriate and timely vaccination programs are recommended for these patients as in the general elderly population. Recommendations for vaccinations (influenza, pneumococcal, COVID-19, RSV, and HZ) should be made when managing this high-risk population. In addition, Taiwan CDC also recommend the diphtheria toxoid-, tetanus toxoid-, and acellular pertussis-containing vaccine for adults aged ≥ 65 years, particularly those who have never received it, and for booster doses every 10 years. Based on the most updated information, it is important to counsel high-risk patients on the CV benefits of these vaccinations, and this consensus provides rationales for prioritizing vaccinations for patients with high CV risk and CVD. Because aging is accompanied by increased susceptibility to bacterial and viral infections indicative of a decline in immunity, it is important to stay up to date with recommended vaccines, including boosters for enhanced protection. However, the members of the joint task force fully realize that the recommendations should be updated and individualized to address the circumstance of each patient, including national public health policies.

FUTURE PERSPECTIVE

Although foundational therapies significantly improve outcomes in patients with CVD and HF, the residual risk of CV death and hospitalization remains elevated in this high-risk patient group. Increased vaccination coverage may be associated with a decreased risk of respiratory complications, CV and non-CV hospitalizations, and CV death in patients with high CV risk or CVD.

DECLARATION OF CONFLICT OF INTEREST

All of the authors declare no conflict of interest.