COVID-19 pandemic and hypertension: an updated report from the Japanese Society of Hypertension project team on COVID-19.

The number of reported cases with coronavirus disease 2019 (COVID-19) has exceeded 620 million worldwide, still having a profound impact on people's health and daily lives since its occurrence and outbreak in December 2019. From the early phase of the COVID-19 pandemic, there has been a concern that the rapid spread of this communicable disease can negatively influence non-communicable diseases. Accumulating data indicate that the restriction on the access to medical care, psychological distress, and life-style changes triggered by the pandemic have indeed affected blood pressure control in hypertensive patients. Since our previous report in 2020 that summarized the findings of the literature related to COVID-19 and hypertension, there has been a considerable progress in our understanding of the association between these two disorders; nonetheless, there are remaining challenges and emerging questions in the field. In this article, we aim to summarize the latest information on the impact of the pandemic on blood pressure control, the use of the renin-angiotensin system inhibitors in patients with COVID-19, and the blood pressure changes as one of the possible post-acute sequelae of COVID-19 (also known as long COVID). We also summarize the evidence of telemedicine and COVID-19 vaccination in hypertensive subjects, based on data available as of June 2022.

Hypertension management before and under the COVID-19 pandemic: lessons and future directions.

Hypertension is a significant risk factor for cardiovascular diseases. The prevalence of hypertension and its complications is increasing yearly, yet it remains inadequately controlled worldwide. It has already been recognized that self-management, including self-measured blood pressure monitoring at home, is more important than office blood pressure monitoring. The practical application of telemedicine using digital technology was already underway. COVID-19 has promoted the popularization of these management systems in primary care, although the COVID-19 pandemic disrupted lifestyle and healthcare access. At the beginning of the pandemic, we were at the mercy of information on whether certain antihypertensive drugs, for example, might pose a risk of infection in the face of unknown infectious diseases. Over the past three years, however, much knowledge has been accumulated. It has been scientifically proven that there is no serious problem in managing hypertension in the same way as before the pandemic. That is to control blood pressure mainly through home blood pressure monitoring and continuing conventional drug therapy while modifying lifestyle. On the other hand, in the New Normal era, it is necessary to accelerate digital hypertension management and the establishment of new social networks and medical systems to prepare for the re-emergence of future pandemics while continuing to protect against infection. This review will summarize the lessons and future directions we learned from the impact of the COVID-19 pandemic on hypertension management. The COVID-19 pandemic has disrupted our daily life, restricted access to healthcare, and altered some of the conventional management of hypertension.

Long COVID and hypertension-related disorders: a report from the Japanese Society of Hypertension Project Team on COVID-19.

The coronavirus disease 2019 (COVID-19) affects infected patients even after the acute phase and impairs their health and quality of life by causing a wide variety of symptoms, referred to as long COVID. Although the evidence is still insufficient, hypertension is suspected to be a potential risk factor for long COVID, and the occurrence of cardiovascular diseases seems to be a key facet of multiple conditions observed in long COVID. Nonetheless, there are few reports that comprehensively review the impacts of long COVID on hypertension and related disorders. As a sequel to our previous report in 2020 which reviewed the association of COVID-19 and hypertension, we summarize the possible influences of long COVID on hypertension-related organs, including the cardiovascular system, kidney, and endocrine system, as well as the pathophysiological mechanisms associated with the disorders in this review. Given that the clinical course of COVID-19 is highly affected by age and sex, we also review the impacts of these factors on long COVID. Lastly, we discuss areas of uncertainty and future directions, which may lead to better understanding and improved prognosis of clinical problems associated with COVID-19.

The relationship between changes in exercise habits and psychosomatic activities in older hypertensive patients during the COVID-19 pandemic.

We conducted a one-year follow-up study to determine the temporal change in exercise habits and the related factors during the COVID-19 pandemic in older hypertensive patients. A total of 190 patients were 76.1 ± 5.7 years, and 44.7% (n = 85) were male. One-hundred fifty-one and 138 patients had exercise habits at baseline and a year later, respectively (p = 0.053). We categorized patients based on the change in exercise habits (at baseline/a year later): Group A: +/+ (n = 122); Group B: +/- (n = 29); Group C: -/+ (n = 16); and Group D: -/- (n = 23). In women, the geriatric depression scale and the incidence of falls in a year were higher in group B (n = 18) than (n = 61) in group A. Such a trend was not observed in men. In conclusion, although exercise habit in older hypertensive patients was well-maintained in our survey, reduced physical activity was associated with depression and risk of fall only in women.

Tryptophan Metabolism and COVID-19-Induced Skeletal Muscle Damage: Is ACE2 a Key Regulator?

The severity of coronavirus disease 2019 (COVID-19) is characterized by systemic damage to organs, including skeletal muscle, due to excessive secretion of inflammatory cytokines. Clinical studies have suggested that the kynurenine pathway of tryptophan metabolism is selectively enhanced in patients with severe COVID-19. In addition to acting as a receptor for severe acute respiratory syndrome coronavirus 2, the causative virus of COVID-19, angiotensin converting enzyme 2 (ACE2) contributes to tryptophan absorption and inhibition of the renin-angiotensin system. In this article, we review previous studies to assess the potential for a link between tryptophan metabolism, ACE2, and skeletal muscle damage in patients with COVID-19.

A pressor dose of angiotensin II has no influence on the angiotensin-converting enzyme 2 and other molecules associated with SARS-CoV-2 infection in mice.

In the early phase of the Coronavirus disease 2019 (COVID-19) pandemic, it was postulated that the renin-angiotensin-system inhibitors (RASi) increase the infection risk. This was primarily based on numerous reports, which stated that the RASi could increase the organ Angiotensin-converting enzyme 2 (ACE2), the receptor of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in rodents. RASi can theoretically antagonize the potential influence of angiotensin II (Ang II) on ACE2. However, while Ang II decreases the ACE2 levels in cultured cells, there is little evidence that supports this phenomenon in living animals. In this study, we tested whether Ang II or Ang II combined with its antagonist would alter the ACE2 and other molecules associated with the infection of SARS-CoV-2. Male C57BL6/J mice were administered vehicle, Ang II (400 ng/kg/min), or Ang II with losartan (10 mg/kg/min) for 2 weeks. ACE2 knockout mice were used as a negative control for the ACE2 assay. We found that both Ang II, which elevated blood pressure by 30 mm Hg, and Ang II with losartan, had no effect on the expression or protein activity of ACE2 in the lung, left ventricle, kidney, and ileum. Likewise, these interventions had no effect on the expression of Transmembrane Protease Serine 2 (TMPRSS2) and Furin, proteases that facilitate the virus-cell fusion, and the expression or activity of Tumor Necrosis Factor α-Convertase (TACE) that cleaves cell-surface ACE2. Collectively, physiological concentrations of Ang II do not modulate the molecules associated with SARS-CoV-2 infection. These results support the recent observational studies suggesting that the use of RASi is not a risk factor for COVID-19.

ACE2, angiotensin 1-7 and skeletal muscle: review in the era of COVID-19.

Angiotensin converting enzyme-2 (ACE2) is a multifunctional transmembrane protein recently recognised as the entry receptor of the virus causing COVID-19. In the renin-angiotensin system (RAS), ACE2 cleaves angiotensin II (Ang II) into angiotensin 1-7 (Ang 1-7), which is considered to exert cellular responses to counteract the activation of the RAS primarily through a receptor, Mas, in multiple organs including skeletal muscle. Previous studies have provided abundant evidence suggesting that Ang 1-7 modulates multiple signalling pathways leading to protection from pathological muscle remodelling and muscle insulin resistance. In contrast, there is relatively little evidence to support the protective role of ACE2 in skeletal muscle. The potential contribution of endogenous ACE2 to the regulation of Ang 1-7-mediated protection of these muscle pathologies is discussed in this review. Recent studies have suggested that ACE2 protects against ageing-associated muscle wasting (sarcopenia) through its function to modulate molecules outside of the RAS. Thus, the potential association of sarcopenia with ACE2 and the associated molecules outside of RAS is also presented herein. Further, we introduce the transcriptional regulation of muscle ACE2 by drugs or exercise, and briefly discuss the potential role of ACE2 in the development of COVID-19.

Hypertension and related diseases in the era of COVID-19: a report from the Japanese Society of Hypertension Task Force on COVID-19.

Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected more than seven million people worldwide, contributing to 0.4 million deaths as of June 2020. The fact that the virus uses angiotensin-converting enzyme (ACE)-2 as the cell entry receptor and that hypertension as well as cardiovascular disorders frequently coexist with COVID-19 have generated considerable discussion on the management of patients with hypertension. In addition, the COVID-19 pandemic necessitates the development of and adaptation to a "New Normal" lifestyle, which will have a profound impact not only on communicable diseases but also on noncommunicable diseases, including hypertension. Summarizing what is known and what requires further investigation in this field may help to address the challenges we face. In the present review, we critically evaluate the existing evidence for the epidemiological association between COVID-19 and hypertension. We also summarize the current knowledge regarding the pathophysiology of SARS-CoV-2 infection with an emphasis on ACE2, the cardiovascular system, and the kidney. Finally, we review evidence on the use of antihypertensive medication, namely, ACE inhibitors and angiotensin receptor blockers, in patients with COVID-19.