Exploring Post-COVID-19 Sequelae: Elevated Arterial Blood Pressure as a Delayed Complication—A Comprehensive Narrative Analysis

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Arterial hypertension has long been recognized as a critical risk factor for cardiovascular diseases (CVD), significantly influencing the prevalence and outcomes of these conditions. The evolving understanding of hypertension’s role, particularly in the context of the COVID-19 pandemic, has highlighted the intricate connections between infectious diseases and chronic cardiovascular conditions.

Hypertension and Cardiovascular Disease: A Persistent Challenge

The definitions and guidelines for managing arterial hypertension have varied across different health organizations. The American College of Cardiology (ACC) and the American Heart Association (AHA) define hypertension with lower thresholds (≥130/80 mmHg) compared to the European Society of Cardiology and the European Society of Hypertension (ESC/ESH), which set the criteria at ≥140/90 mmHg. This discrepancy underscores the complexity of diagnosing and managing hypertension, reflecting variations in clinical practices and recommendations globally.

Hypertension’s role in cardiovascular diseases is profound and multifaceted, involving the sympathetic nervous system, the renin–angiotensin–aldosterone system (RAAS), endothelial function, and more. It is closely linked with a range of risk factors, including age, obesity, and lifestyle choices, underscoring the need for comprehensive strategies in prevention and management.

COVID-19 and Cardiovascular Impact

The COVID-19 pandemic has introduced new dimensions to the cardiovascular implications of infectious diseases. Studies have found that individuals with pre-existing cardiovascular conditions, including hypertension, face a higher risk of severe outcomes from COVID-19. Recent research indicates a significant association between COVID-19 and an increased risk of various cardiovascular complications, such as ischemic heart disease, heart failure, and thromboembolic disorders. Patients recovering from COVID-19 have shown heightened risks for acute coronary disease, myocardial infarction, and more, suggesting a lingering cardiovascular impact post-infection​​.

The Role of RAAS Inhibition in COVID-19 Outcomes

The relationship between the renin-angiotensin-aldosterone system (RAAS) inhibitors and COVID-19 outcomes has been a subject of investigation, considering the pivotal role of RAAS in cardiovascular health and its potential interaction with the SARS-CoV-2 virus. Despite initial concerns, leading cardiovascular organizations, including the ACC and AHA, have advised against discontinuing RAAS inhibitors in COVID-19 patients where clinically indicated, pending further evidence from ongoing clinical trials​​.


TABLE 1 – The Renin-Angiotensin-Aldosterone System (RAAS)

The Renin-Angiotensin-Aldosterone System (RAAS) plays a crucial role in regulating blood pressure and maintaining fluid and electrolyte balance, impacting cardiovascular health significantly. This system’s intricate workings, especially in the context of COVID-19, involve a complex interplay of enzymes, hormones, and receptors, each contributing to the pathophysiological outcomes observed in patients infected with SARS-CoV-2. Here is an in-depth look at each component and process within this system and how COVID-19 intersects with its function to potentially exacerbate hypertension risk.

The Basic Mechanism of RAAS

  • Initiation of the RAAS Cascade: The process begins with the liver producing angiotensinogen, a precursor protein. Renin, an enzyme secreted by the kidneys in response to reduced blood volume or blood pressure, or sympathetic nervous system activation, cleaves angiotensinogen to form angiotensin I (AT-I).
  • Conversion to Angiotensin II: Angiotensin I is relatively inactive until it encounters angiotensin-converting enzyme (ACE), primarily found in the lungs’ endothelial cells. ACE converts AT-I to angiotensin II (AT-II), a potent vasoconstrictor that raises blood pressure by narrowing blood vessels.
  • Effects of Angiotensin II: Beyond its vasoconstrictive action, AT-II stimulates the adrenal cortex to release aldosterone, a hormone that promotes sodium and water reabsorption by the kidneys, further increasing blood volume and pressure. AT-II also signals the release of antidiuretic hormone (ADH), which aids in water reabsorption.
  • Counter-Regulatory Mechanisms: The system also includes counter-regulatory components, such as ACE2, which converts AT-II to angiotensin 1-7 (AT-1-7). AT-1-7 acts as a vasodilator and antagonizes many AT-II effects, thereby reducing blood pressure.

COVID-19 Interaction with RAAS

  • ACE2 and SARS-CoV-2: The novel coronavirus (SARS-CoV-2) enters human cells by binding to ACE2 receptors, predominantly present in the lungs, heart, kidneys, and intestines. ACE2 serves as a counterbalance within RAAS, mitigating AT-II effects by converting it to AT-1-7. When SARS-CoV-2 binds to ACE2, it downregulates the receptor’s availability for its physiological function, disrupting the balance towards more AT-II effects.
  • Disruption of RAAS Dynamics: The binding of SARS-CoV-2 to ACE2 receptors leads to a decrease in ACE2 surface expression and activity, hindering the conversion of AT-II to the beneficial AT-1-7. This disruption shifts the balance toward AT-II’s effects, including vasoconstriction, increased aldosterone secretion, sodium and water retention, and potentially leading to higher blood pressure and exacerbated hypertension risk.
  • Inflammatory Response and Endothelial Damage: COVID-19 triggers a significant inflammatory response, with cytokine release that can cause endothelial damage. The endothelium, lining the interior surface of blood vessels, plays a vital role in vascular tone and blood pressure regulation. Inflammation and damage to the endothelium further impair its function, contributing to hypertension. The pro-inflammatory state, combined with the direct effects of SARS-CoV-2 on RAAS through ACE2, creates a conducive environment for hypertension development or exacerbation.
  • Potential Exacerbation of Hypertension Risk: Patients with pre-existing hypertension are often managed with RAAS inhibitors (e.g., ACE inhibitors or angiotensin receptor blockers). The interaction of COVID-19 with the RAAS system complicates the management of such patients, as the virus’s effect on ACE2 may alter the expected outcomes of these medications, necessitating careful consideration and potentially adjusted management strategies.

Understanding the interplay between SARS-CoV-2 and the RAAS is critical for managing COVID-19 patients, especially those with or at risk for hypertension. The virus’s impact on this regulatory system underscores the need for vigilant cardiovascular monitoring in infected individuals and may inform therapeutic approaches to mitigate adverse outcomes. Research into COVID-19’s effects on RAAS continues to evolve, highlighting the importance of integrating emerging insights into clinical practice to improve patient care and outcomes in this challenging context.


Ongoing Research and Clinical Trials

Research into the long-term cardiovascular outcomes of COVID-19 is ongoing, with studies exploring the full spectrum of post-infection complications. The pandemic has spurred a flurry of investigations to understand how SARS-CoV-2 infection may predispose individuals to cardiovascular issues, examining factors such as RAAS dysregulation and the virus’s impact on endothelial function. These efforts aim to unravel the complex interactions between COVID-19 and cardiovascular diseases, informing future therapeutic strategies and guidelines for managing patients with hypertension in the context of a global pandemic.

Discussion – Understanding the Impact of SARS-CoV-2 on Blood Pressure and Arterial Hypertension

The interplay between SARS-CoV-2 infection and arterial hypertension presents a complex picture that merits thorough investigation. This systematic review aimed to delve into the potential mechanisms by which COVID-19 may precipitate or exacerbate hypertension, drawing upon a range of studies to shed light on this critical issue.

SARS-CoV-2 Infection and Blood Pressure Elevation

The consensus among the majority of studies reviewed indicates a trend toward blood pressure elevation following SARS-CoV-2 infection, suggesting a possible link to the onset of arterial hypertension. This observation aligns with the multifactorial nature of hypertension, highlighting the need for deeper exploration into the virus’s role in cardiovascular dysregulation.

The Role of RAAS, Inflammation, and Endothelial Damage

The renin–angiotensin–aldosterone system (RAAS), along with inflammatory processes and endothelial damage, emerges as central to understanding the cardiovascular implications of COVID-19. The virus’s interaction with ACE-2 receptors and the subsequent disruption of RAAS dynamics offer a plausible pathway through which SARS-CoV-2 may influence blood pressure regulation. This disruption could lead to an imbalance between angiotensin II and its counter-regulatory peptide, angiotensin-(1-7), exacerbating hypertension risk.

Potential Mechanisms Behind Hypertension Post-COVID-19

Several mechanisms have been proposed to elucidate the observed elevation in blood pressure post-COVID-19, including:

  • Direct viral effects on the endothelium: The SARS-CoV-2 virus may directly invade endothelial cells, disrupting normal vascular function and promoting hypertension.
  • Inflammatory response: A heightened inflammatory state, triggered by the infection, could contribute to endothelial dysfunction and altered blood pressure regulation.
  • Autonomic nervous system imbalance: COVID-19 may affect the autonomic nervous system, potentially leading to increased sympathetic activity and higher blood pressure.

Exacerbation of Hypertension Risk Factors

The review also highlights the exacerbation of traditional risk factors for hypertension, such as obesity, sedentary lifestyle, and metabolic dysregulation, in the context of COVID-19. These factors may interact synergistically with the direct effects of the virus, further complicating the clinical picture.

Psychological Impacts and Hypertension

The psychological strain associated with the pandemic, including stress, anxiety, and changes in sleep patterns, has also been implicated as a contributory factor to blood pressure variations. The interrelation between mental health and physiological stress responses suggests a multifaceted impact of COVID-19 on cardiovascular health.

Autonomic Nervous System and Blood Pressure Regulation

The review points to potential alterations in the autonomic nervous system as a result of SARS-CoV-2 infection, which could impact blood pressure regulation. Damage to baroreceptors and changes in sympathetic nervous system activity post-infection are areas requiring further research to understand their roles in hypertension post-COVID-19.

Conclusion

This systematic review underscores the intricate connections between SARS-CoV-2 infection and hypertension, spotlighting the need for ongoing research to unravel the multifaceted mechanisms at play. The findings call for a holistic approach to managing patients recovering from COVID-19, considering the potential long-term cardiovascular implications and the interplay of physiological, psychological, and lifestyle factors.


reference link : https://www.mdpi.com/1422-0067/25/3/1837

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