Role of Angiotensin II in Cardiovascular Diseases: Introducing Bisartans as a Novel Therapy for Coronavirus 2019.

Cardiovascular diseases (CVDs) are the main contributors to global morbidity and mortality. Major pathogenic phenotypes of CVDs include the development of endothelial dysfunction, oxidative stress, and hyper-inflammatory responses. These phenotypes have been found to overlap with the pathophysiological complications of coronavirus disease 2019 (COVID-19). CVDs have been identified as major risk factors for severe and fatal COVID-19 states. The renin-angiotensin system (RAS) is an important regulatory system in cardiovascular homeostasis. However, its dysregulation is observed in CVDs, where upregulation of angiotensin type 1 receptor (AT1R) signaling via angiotensin II (AngII) leads to the AngII-dependent pathogenic development of CVDs. Additionally, the interaction between the spike protein of severe acute respiratory syndrome coronavirus 2 with angiotensin-converting enzyme 2 leads to the downregulation of the latter, resulting in the dysregulation of the RAS. This dysregulation favors AngII/AT1R toxic signaling pathways, providing a mechanical link between cardiovascular pathology and COVID-19. Therefore, inhibiting AngII/AT1R signaling through angiotensin receptor blockers (ARBs) has been indicated as a promising therapeutic approach to the treatment of COVID-19. Herein, we review the role of AngII in CVDs and its upregulation in COVID-19. We also provide a future direction for the potential implication of a novel class of ARBs called bisartans, which are speculated to contain multifunctional targeting towards COVID-19.

Newer alternatives for resistant hypertension: Beyond 2022 paradigms.

Given the increased incidence of resistant hypertension and no novel agents to manage hypertension for more than 15 years, there has been an increase in the development of newer agents with unique mechanisms that will hopefully aid in getting this subset of patients under control. More recent classes of agents include nonsteroidal mineralocorticoid receptor blockers, aminopeptidase A inhibitors, dual endothelin A and B antagonists and aldosterone synthetase inhibitors, and novel agents affecting angiotensinogen mRNA in the liver. All these agents are under different levels of development and, if all goes well, should be available to the public within the next 2-5 years. In addition to these agents, renal denervation is anticipated to be approved in the United States within the next 6-9 months, whereas it has already been authorized in certain European countries. Thus, by 2025 and later, we will have a more extensive armamentarium to help quell the rise in resistant hypertension. From early actuarial data associating elevated blood pressure with mortality to the first trials of blood pressure-lowering medications to contemporary American and European hypertension guidelines, the beneficial impact of blood pressure lowering in individuals with hypertension is well established1,2-4. Population-level decreases in incident cardiovascular disease and mortality over the past 50 years reflect this well-established impact. Yet, the year-over-year decline in the incidence of cardiovascular disease has now plateaued, and concomitantly rates of uncontrolled hypertension have increased5,6. Additionally, how the global COVID-19 pandemic impacts cardiovascular disease and hypertension-related outcomes is yet to be determined, but early data suggests population-level increases in blood pressure7.

Vascular mechanisms of post-COVID-19 conditions: Rho-kinase is a novel target for therapy.

BACKGROUND: In post-coronavirus disease-19 (post-COVID-19) conditions (long COVID), systemic vascular dysfunction is implicated, but the mechanisms are uncertain, and the treatment is imprecise. METHODS AND RESULTS: Patients convalescing after hospitalization for COVID-19 and risk factor matched controls underwent multisystem phenotyping using blood biomarkers, cardiorenal and pulmonary imaging, and gluteal subcutaneous biopsy (NCT04403607). Small resistance arteries were isolated and examined using wire myography, histopathology, immunohistochemistry, and spatial transcriptomics. Endothelium-independent (sodium nitroprusside) and -dependent (acetylcholine) vasorelaxation and vasoconstriction to the thromboxane A2 receptor agonist, U46619, and endothelin-1 (ET-1) in the presence or absence of a RhoA/Rho-kinase inhibitor (fasudil), were investigated. Thirty-seven patients, including 27 (mean age 57 years, 48% women, 41% cardiovascular disease) 3 months post-COVID-19 and 10 controls (mean age 57 years, 20% women, 30% cardiovascular disease), were included. Compared with control responses, U46619-induced constriction was increased (P = 0.002) and endothelium-independent vasorelaxation was reduced in arteries from COVID-19 patients (P < 0.001). This difference was abolished by fasudil. Histopathology revealed greater collagen abundance in COVID-19 arteries {Masson's trichrome (MT) 69.7% [95% confidence interval (CI): 67.8-71.7]; picrosirius red 68.6% [95% CI: 64.4-72.8]} vs. controls [MT 64.9% (95% CI: 59.4-70.3) (P = 0.028); picrosirius red 60.1% (95% CI: 55.4-64.8), (P = 0.029)]. Greater phosphorylated myosin light chain antibody-positive staining in vascular smooth muscle cells was observed in COVID-19 arteries (40.1%; 95% CI: 30.9-49.3) vs. controls (10.0%; 95% CI: 4.4-15.6) (P < 0.001). In proof-of-concept studies, gene pathways associated with extracellular matrix alteration, proteoglycan synthesis, and viral mRNA replication appeared to be upregulated. CONCLUSION: Patients with post-COVID-19 conditions have enhanced vascular fibrosis and myosin light change phosphorylation. Rho-kinase activation represents a novel therapeutic target for clinical trials.

The impact of statin therapy on in-hospital prognosis and endothelial function of patients at high-to-very high cardiovascular risk admitted for COVID-19.

Statins may protect against adverse outcomes from Coronavirus disease 2019 (COVID-19) through their pleiotropic effects. Endothelial dysfunction seems to be implicated in the pathophysiology of COVID-19, and can be attenuated by statins. This study assessed the role of preadmission statin therapy and its interaction with endothelial function, measured using flow-mediated dilation (FMD) at hospital admission, in predicting in-hospital outcomes among patients with COVID-19 having high-to-very high cardiovascular (CV) risk. We conducted a retrospective cohort study of hospitalized patients with COVID-19 having high-to-very high CV risk, including a subgroup of patients who underwent FMD assessment. Among 342 patients, 119 (35%) were treated with statins at study baseline. Preadmission statin therapy was independently associated with a 75% risk reduction of intensive care unit admission/in-hospital death (adjusted hazard ratio 0.252, 95% confidence interval 0.122-0.521, p < 0.001). In the subgroup of patients with an FMD assessment (245 patients, 40% statin-treated), preadmission statin therapy was independently associated with higher FMD values (ß = 0.159, p = 0.013). However, preadmission statin therapy × FMD interaction was not associated with in-hospital outcomes (F = 0.002, pinteraction = 0.960). Preadmission statin therapy is associated with better in-hospital outcomes among patients with COVID-19 having high-to-very high CV risk, independent of the endothelium-protective effects of these drugs.

Cardiovascular Disease Risk in a Cohort of Virologically Suppressed People Living with HIV Switching to Doravirine: Preliminary Data from the Real Life.

Aim of this study is to assess the impact of doravirine (DOR)-based regimens on cardiovascular risk in treatment-experienced people living with HIV (PLWHIV). We retrospectively analyzed a cohort of 40 treatment-experienced PLWHIV switching to a DOR-based three-drug regimen, evaluating 10-year risk of manifesting clinical cardiovascular diseases (CD) through the Framingham Risk Score at baseline, 12, and 24 weeks of follow-up. At baseline, median predicted 10-year risk of cardiovascular disease (10Y-CD) was 8.0% (interquartile range 4.0-13.0). After 12 weeks, we observed a significant reduction in 10Y-CD (mean decrease -2.21, p = .012); similarly, we observed a nonsignificant reduction at week 24 (p = .336). Regarding metabolic parameters, after 24 weeks we observed a significant reduction in total cholesterol (median change -8.8 mg/dL, p = .018), low-density lipoprotein cholesterol (median -9.5 mg/dL, p = .007), and triglycerides (median -19.8 mg/dL, p < .001). Our results show a favorable metabolic impact of DOR-based regimens along with a promising reduction in 10-year risk of cardiovascular disease.

Prevalence of Statin Use for Primary Prevention of Atherosclerotic Cardiovascular Disease by Race, Ethnicity, and 10-Year Disease Risk in the US: National Health and Nutrition Examination Surveys, 2013 to March 2020.

Importance: The burden of atherosclerotic cardiovascular disease (ASCVD) in the US is higher among Black and Hispanic vs White adults. Inclusion of race in guidance for statin indication may lead to decreased disparities in statin use. Objective: To evaluate prevalence of primary prevention statin use by race and ethnicity according to 10-year ASCVD risk. Design, Setting, and Participants: This serial, cross-sectional analysis performed in May 2022 used data from the National Health and Nutrition Examination Survey, a nationally representative sample of health status in the US, from 2013 to March 2020 (limited cycle due to the COVID-19 pandemic), to evaluate statin use for primary prevention of ASCVD and to estimate 10-year ASCVD risk. Participants aged 40 to 75 years without ASCVD, diabetes, low-density lipoprotein cholesterol levels 190 mg/dL or greater, and with data on medication use were included. Exposures: Self-identified race and ethnicity (Asian, Black, Hispanic, and White) and 10-year ASCVD risk category (5%-<7.5%, 7.5%-<20%, ≥20%). Main Outcomes and Measures: Prevalence of statin use, defined as identification of statin use on pill bottle review. Results: A total of 3417 participants representing 39.4 million US adults after applying sampling weights (mean [SD] age, 61.8 [8.0] years; 1289 women [weighted percentage, 37.8%] and 2128 men [weighted percentage, 62.2%]; 329 Asian [weighted percentage, 4.2%], 1032 Black [weighted percentage, 12.7%], 786 Hispanic [weighted percentage, 10.1%], and 1270 White [weighted percentage, 73.0%]) were included. Compared with White participants, statin use was lower in Black and Hispanic participants and comparable among Asian participants in the overall cohort (Asian, 25.5%; Black, 20.0%; Hispanic, 15.4%; White, 27.9%) and within ASCVD risk strata. Within each race and ethnicity group, a graded increase in statin use was observed across increasing ASCVD risk strata. Statin use was low in the highest risk stratum overall with significantly lower rates of use among Black (23.8%; prevalence ratio [PR], 0.90; 95% CI, 0.82-0.98 vs White) and Hispanic participants (23.9%; PR, 0.90; 95% CI, 0.81-0.99 vs White). Among other factors, routine health care access and health insurance were significantly associated with higher statin use in Black, Hispanic, and White adults. Prevalence of statin use did not meaningfully change over time by race and ethnicity or by ASCVD risk stratum. Conclusions and Relevance: In this study, statin use for primary prevention of ASCVD was low among all race and ethnicity groups regardless of ASCVD risk, with the lowest use occurring among Black and Hispanic adults. Improvements in access to care may promote equitable use of primary prevention statins in Black and Hispanic adults.

Fixed dose combination drugs for cardiovascular disease in a prolonged humanitarian crisis in Lebanon: an implementation study.

OBJECTIVES: This pre-post implementation study evaluated the introduction of fixed dose combination (FDC) medications for atherosclerotic cardiovascular disease (ASCVD) secondary prevention into routine care in a humanitarian setting. SETTING: Two Médecins sans Frontières (MSF) primary care clinics serving Syrian refugee and host populations in north Lebanon. PARTICIPANTS: Consenting patients ≥18 years with existing ASCVD requiring secondary prevention medication were eligible for study enrolment. Those with FDC contraindication(s) or planning to move were excluded. Of 521 enrolled patients, 460 (88.3%) were retained at 6 months, and 418 (80.2%) switched to FDC. Of these, 84% remained on FDC (n=351), 8.1% (n=34) discontinued and 7.9% (n=33) were lost to follow-up by month 12. INTERVENTIONS: Eligible patients, enrolled February-May 2019, were switched to Trinomia FDC (atorvastatin 20 mg, aspirin 100 mg, ramipril 2.5/5/10 mg) after 6 months' usual care. During the study, the COVID-19 pandemic, an economic crisis and clinic closures occurred. OUTCOME MEASURES: Descriptive and regression analyses compared key outcomes at 6 and 12 months: medication adherence, non-high density lipoprotein cholesterol (non-HDL-C) and systolic blood pressure (SBP) control. We performed per-protocol, intention-to-treat and secondary analyses of non-switchers. RESULTS: Among 385 switchers remaining at 12 months, total adherence improved 23%, from 63% (95% CI 58 to 68) at month 6, to 86% (95% CI 82 to 90) at month 12; mean non-HDL-C levels dropped 0.28 mmol/L (95% CI -0.38 to -0.18; p<0.0001), from 2.39 (95% CI 2.26 to 2.51) to 2.11 mmol/L (95% CI 2.00 to 2.22); mean SBP dropped 2.89 mm Hg (95% CI -4.49 to -1.28; p=0.0005) from 132.7 (95% CI 130.8 to 134.6) to 129.7 mm Hg (95% CI 127.9 to 131.5). Non-switchers had smaller improvements in adherence and clinical outcomes. CONCLUSION: Implementing an ASCVD secondary prevention FDC improved adherence and CVD risk factors in MSF clinics in Lebanon, with potential for wider implementation by humanitarian actors and host health systems.

Improving Initial Medication Adherence to cardiovascular disease and diabetes treatments in primary care: Pilot trial of a complex intervention.

Introduction: The Initial Medication Adherence (IMA) intervention is a multidisciplinary and shared decision-making intervention to improve initial medication adherence addressed to patients in need of new treatments for cardiovascular diseases and diabetes in primary care (PC). This pilot study aims to evaluate the feasibility and acceptability of the IMA intervention and the feasibility of a cluster-RCT to assess the effectiveness and cost-effectiveness of the intervention. Methods: A 3-month pilot trial with an embedded process evaluation was conducted in five PC centers in Catalonia (Spain). Electronic health data were descriptively analyzed to test the availability and quality of records of the trial outcomes (initiation, implementation, clinical parameters and use of services). Recruitment and retention rates of professionals were analyzed. Twenty-nine semi-structured interviews with professionals (general practitioners, nurses, and community pharmacists) and patients were conducted to assess the feasibility and acceptability of the intervention. Three discussion groups with a total of fifteen patients were performed to review and redesign the intervention decision aids. Qualitative data were thematically analyzed. Results: A total of 901 new treatments were prescribed to 604 patients. The proportion of missing data in the electronic health records was up to 30% for use of services and around 70% for clinical parameters 5 months before and after a new prescription. Primary and secondary outcomes were within plausible ranges and outliers were barely detected. The IMA intervention and its implementation strategy were considered feasible and acceptable by pilot-study participants. Low recruitment and retention rates, understanding of shared decision-making by professionals, and format and content of decision aids were the main barriers to the feasibility of the IMA intervention. Discussion: Involving patients in the decision-making process is crucial to achieving better clinical outcomes. The IMA intervention is feasible and showed good acceptability among professionals and patients. However, we identified barriers and facilitators to implementing the intervention and adapting it to a context affected by the COVID-19 pandemic that should be considered before launching a cluster-RCT. This pilot study identified opportunities for refining the intervention and improving the design of the definitive cluster-RCT to evaluate its effectiveness and cost-effectiveness. Clinical trial registration: ClinicalTrials.gov, identifier NCT05094986.

The Impact of Prior Antithrombotic use on Thromboembolic Events in Patients with Cardiovascular Disease and Severe COVID-19 Infection.

OBJECTIVE: Our objective in this study was to determine the predictive factors of thromboembolic complications in patients with previous heart disease and severe covid-19 infection and the impact of previous use of antithrombotics on protection against these complications. METHODS: We conducted a single-center retrospective study of 158 patients with heart disease admitted to an intensive care unit for severe SARS-COV-2 infection. In order to determine the predictive factors, we used logistic regression analysis. RESULTS: Out of 158 patients, 22 were complicated by a thrombo-embolic event (13.9%), mean age of our population 64.03 (SD = 15.27), with a male predominance of 98 (62%). For the predictive factors of thromboembolic complications, and after multivariate analysis, we find the short duration of hospitalization (OR = 0.92; 95%CI (0.863-0.983), P = .014, previous use of antithrombotic drugs ((OR = 0.288, 95%CI (0.091-0.911), P = .034 for antiplatelet agents) and (OR = 0.322, 95% CI (0, 131-0.851), P = .021) for anticoagulants) as protective factors, and admission thrombocytosis as a risk factor (OR = 4.58, 95%CI (1.2-10.627), P = .021). D-dimer was not detected as a risk factor, and this can be explained by the characteristics of our population. Although prior use of antithrombotic drugs protects against thromboembolic complications during severe infection, there was no benefit in mortality. CONCLUSION: Prior use of antithrombotic drugs is a protective factor against thromboembolic complications in patients with a history of heart disease but without effect on mortality.

Impact of the COVID-19 pandemic on cardiovascular heart disease medication use: time-series analysis of England's prescription data during the COVID-19 pandemic (January 2019 to October 2020).

BACKGROUND: Management of high blood pressure (BP) typically requires adherence to medication regimes. However, it is known that the COVID-19 pandemic both interrupted access to some routine prescriptions and changed some patient health behaviours. AIM: This study, therefore, retrospectively investigated prescription reimbursement of cardiovascular (CVD) medicines as a proxy measure for patient adherence and access to medicines during the pandemic. METHODS: A cohort study of all primary care patients in England prescribed CVD medicines. The exposure was to the global pandemic. Prescriptions were compared before and after the pandemic's onset. Statistical variation was the outcome of interest. RESULTS: Descriptive statistics show changes to monthly prescriptions, with wide confidence intervals indicating varying underlying practice. Analysis of variance reveals statistically significant differences for bendroflumethiazide, potassium-sparing diuretics, nicorandil, ezetimibe, ivabradine, ranolazine, colesevelam and midodrine. After the pandemic began (March-October 2020), negative parameters are observed for ACE inhibitors, beta-blockers, calcium channel blockers, statins, antiplatelet, antithrombotics, ARBs, loop diuretics, doxazosin, bendroflumethiazide, nitrates and indapamide, indicating decelerating monthly prescription items (statistically significant declines of calcium channel blockers, antithrombotic, adrenoreceptor blockers and diuretics) of CVD medicines within the general population. Many data points are not statistically significant, but fluctuations remain clinically important for the large population of patients taking these medications. CONCLUSION: A concerning decline in uptake of CVD therapies for chronic heart disease was observed. Accessible screening and treatment alongside financial relief on prescription levies are needed. A video abstract is (4 min 51 s) available: https://bit.ly/39gvEHi.

The Complexity and Multiplicity of the Specific cAMP Phosphodiesterase Family: PDE4, Open New Adapted Therapeutic Approaches.

Cyclic nucleotides (cAMP, cGMP) play a major role in normal and pathologic signaling. Beyond receptors, cyclic nucleotide phosphodiesterases; (PDEs) rapidly convert the cyclic nucleotide in its respective 5'-nucleotide to control intracellular cAMP and/or cGMP levels to maintain a normal physiological state. However, in many pathologies, dysregulations of various PDEs (PDE1-PDE11) contribute mainly to organs and tissue failures related to uncontrolled phosphorylation cascade. Among these, PDE4 represents the greatest family, since it is constituted by 4 genes with multiple variants differently distributed at tissue, cellular and subcellular levels, allowing different fine-tuned regulations. Since the 1980s, pharmaceutical companies have developed PDE4 inhibitors (PDE4-I) to overcome cardiovascular diseases. Since, they have encountered many undesired problems, (emesis), they focused their research on other PDEs. Today, increases in the knowledge of complex PDE4 regulations in various tissues and pathologies, and the evolution in drug design, resulted in a renewal of PDE4-I development. The present review describes the recent PDE4-I development targeting cardiovascular diseases, obesity, diabetes, ulcerative colitis, and Crohn's disease, malignancies, fatty liver disease, osteoporosis, depression, as well as COVID-19. Today, the direct therapeutic approach of PDE4 is extended by developing allosteric inhibitors and protein/protein interactions allowing to act on the PDE interactome.

Global, regional and national trends in statin utilisation in high-income and low/middle-income countries, 2015-2020.

OBJECTIVE: Prior studies have reported inequitable global access to essential medicines for cardiovascular disease (CVD) prevention, especially statins. Here we examine recent trends and disparities in statin utilisation at the income group, regional and country levels. DESIGN: Ecological study. Pharmaceutical sales data were used to examine statin utilisation in high-income counties (HICs) and low/middle-income countries (LMICs) from 2015 to 2020. Population estimates were obtained from the Global Burden of Disease. Fixed-effects panel regression analysis was used to examine associations between statin utilisation and country-level factors. SETTING: Global, including 41 HICs and 50 LMICs. PARTICIPANTS: Population older than 40 years of age. PRIMARY AND SECONDARY OUTCOME MEASURES: Statin utilisation was measured using defined daily doses (DDDs) per 1000 population ≥40 years per day (TPD). RESULTS: Globally, statin utilisation increased 24.7% from 54.7 DDDs/TPD in 2015 to 68.3 DDDs/TPD in 2020. However, regional and income group disparities persisted during this period. In 2020, statin utilisation was more than six times higher in HICs than LMICs (192.4 vs 28.4 DDDs/TPD, p<0.01). Substantial disparities were also observed between LMICs, ranging from 3.1 DDDs/TPD in West African nations to 225.0 DDDs/TPD in Lebanon in 2020. While statin utilisation increased in most LMICs between 2015 and 2020, several experienced declines in utilisation, most notably Venezuela (-85.1%, from 92.3 to 14.0 DDDs/TPD). In LMICs, every $100 increase in per capita health spending was associated with a 17% increase in statin utilisation, while every 10% increase in out-of-pocket health spending was associated with a 11% decline (both p<0.05). CONCLUSIONS: Despite global increases in statin utilisation, there are substantial regional and country-level disparities between HICs and LMICs. To address global CVD disparities, policymakers should promote increased and equitable access to statins in LMICs.

A prospective longitudinal study with treated hypertensive patients in Northern Bangladesh (PREDIcT-HTN) to understand uncontrolled hypertension and adverse clinical events: A protocol for 5-years follow-up.

INTRODUCTION: Uncontrolled hypertension is the most common cause of major adverse clinical events (MACE), such as myocardial infarction, strokes, and death due to CVDs, in both developed and developing countries. Western-led studies found that treated hypertensive adults with uncontrolled hypertension were more at-risk of all-cause and CVD-specific mortality than normotensives. The PRospEctive longituDInal sTudy of Treated HyperTensive patients of Northern-Bangladesh (PREDIcT-HTN) study principally aims to estimate the incidence of MACE in treated hypertensive patients and identify the determinants of MACE. The secondary objective is to find the prevalence of uncontrolled hypertension in treated hypertensive patients and the associated risk factors. METHODS AND ANALYSIS: The treated hypertensive patients were obtained from the Hypertension and Research Center (H&RC), Rangpur, Bangladesh, from January to December 2020. Based on the eligibility criteria, 2643 patients were included to constitute the PREDIcT-HTN cohort. Baseline data was retrieved from the H&RC registry, and five follow-up waves are planned yearly (2021-2025). A questionnaire will be administered at each follow-up visit on hypertension control status, behavioral factors, quality of life, dietary adherence, and high blood pressure compliance-related variables. The participant will be right censored if the patient develops MACE, death due to any cause, loss to follow-up, or at the end of the study. A proportional hazard model will identify the risk factors of MACE. Multinomial logistic regression analyses will be performed to determine the predictors of the hypertension control status by medication and dietary adherence after adjusting confounders. ETHICS AND DISSEMINATION: The ethical approval for this study was obtained from the Institutional Review Board, North South University [Ref: 2019/OR-NSU/IRB-No.0902]. The participants will provide written consent to participate. The findings will be disseminated through manuscripts in clinical/academic journals and presentations at professional conferences and stakeholder communication.

Papaverine, a promising therapeutic agent for the treatment of COVID-19 patients with underlying cardiovascular diseases (CVDs).

The causative agent of coronavirus disease-2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enters the host cells via an angiotensin-converting enzyme 2 (ACE2)-mediated endocytosis-dependent manner. Because ACE2 is highly expressed in the heart, SARS-CoV-2 can severely infect heart tissue and arteries, causing acute and chronic damage to the cardiovascular system. Therefore, special attention should be paid to finding appropriate agents to protect this vital system during COVID-19 treatment. Papaverine is a unique vasodilator alkaloid that is clinically used in the treatment of vasospasm. Interestingly, this compound has potent and direct effects on a wide range of viruses, and could also prevent viral exploitation mechanisms of the host cell facilities by inhibiting some cellular signaling pathways such as p38 MAPK. This pathway was recently introduced as a promising target for the treatment of COVID-19. Papaverine also has anti-inflammatory effects which is useful in combating the hyper-inflammatory phase of the COVID-19. Unlike some medications that have severe dosage-restrictions in the treatment of COVID-19 due to cardiac side effects, papaverine is recommended for use in many heart disorders. The ability of papaverine to treat COVID-19 has become more promising when the results of some extensive screenings showed the strong ability of this compound to inhibit the cytopathic effects of SARS-CoV-2 with EC50 of 1.1 µM. Having several therapeutic effects along with desired safety profile raises this hypothesis that papaverine could be a promising compound for the suppression of SARS-CoV-2 and prevention of ischemia/vasoconstriction-related complications in COVID-19 disease, especially in patients with underlying cardiovascular diseases (CVDs).

Association of Statins for Primary Prevention of Cardiovascular Diseases With Hospitalization for COVID-19: A Nationwide Matched Population-Based Cohort Study.

Background There is little evidence on the relationship between statin use and the risk of hospitalization attributable to COVID-19. Methods and Results The French National Healthcare Data System database was used to conduct a matched-cohort study. For each adult aged ≥40 years receiving statins for the primary prevention of cardiovascular diseases, one nonuser was randomly selected and matched for year of birth, sex, residence area, and comorbidities. The association between statin use and hospitalization for COVID-19 was examined using conditional Cox proportional hazards models, adjusted for baseline characteristics, comorbidities, and long-term medications. Its association with in-hospital death from COVID-19 was also explored. All participants were followed up from February 15, 2020, to June 15, 2020. The matching procedure generated 2 058 249 adults in the statin group and 2 058 249 in the control group, composed of 46.6% of men with a mean age of 68.7 years. Statin users had a 16% lower risk of hospitalization for COVID-19 than nonusers (adjusted hazard ratio [HR], 0.84; 95% CI, 0.81-0.88). All types of statins were significantly associated with a lower risk of hospitalization, with the adjusted HR ranging from 0.75 for fluvastatin to 0.89 for atorvastatin. Low- and moderate-intensity statins also showed a lower risk compared with nonusers (HR, 0.78 [95% CI, 0.71-0.86] and HR, 0.84 [95% CI, 0.80-0.89], respectively), whereas high-intensity statins did not (HR, 1.01; 95% CI, 0.86-1.18). We found similar results with in-hospital death from COVID-19. Conclusions Our findings support that the use of statins for primary prevention is associated with lower risks of hospitalization for COVID-19 and of in-hospital death from COVID-19.

The impact of SARS-CoV-2 treatment on the cardiovascular system: an updated review.

The coronavirus disease-2019 (COVID-19) pandemic has become a major global health problem. COVID-19 is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and exhibits pulmonary and extrapulmonary effects, including cardiovascular involvement. There are several attempts to identify drugs that could treat COVID-19. Moreover, many patients infected with COVID-19 have underlying diseases, particularly cardiovascular diseases. These patients are more likely to develop severe illnesses and would require optimized treatment strategies. The current study gathered information from various databases, including relevant studies, reviews, trials, or meta-analyses until April 2022 to identify the impact of SARS-CoV-2 treatment on the cardiovascular system. Studies have shown that the prognosis of patients with underlying cardiovascular disease is worsened by COVID-19, with some COVID-19 medications interfering with the cardiovascular system. The COVID-19 treatment strategy should consider many factors and parameters to avoid medication-induced cardiac injury, mainly in elderly patients. Therefore, this article provides a synthesis of evidence on the impact of different COVID-19 medications on the cardiovascular system and related disease conditions.

The Effects of the SARS-CoV-2 Virus on the Cardiovascular System and Coagulation State Leading to Cardiovascular Diseases: A Narrative Review.

The novel coronavirus pandemic has led to morbidity and mortality throughout the world. Until now, it is a highly virulent contagion attacking the respiratory system in humans, especially people with chronic diseases and the elderly who are most vulnerable. A majority of afflicted are those suffering from cardiovascular and coronary diseases. In this review article, an attempt has been made to discuss and thoroughly review the mode of therapies that alleviate cardiac complications and complications due to hypercoagulation in patients infected with the SARS-CoV-2 virus. Presently a host of thrombolytic drugs are in use like Prourokinase, Retelapse, RhTNK-tPA and Urokinase. However, thrombolytic therapy, especially if given intravenously, is associated with a serious risk of intracranial haemorrhage, systemic haemorrhage, immunologic complications, hypotension and myocardial rupture. The effects of the SARS-CoV-2 virus upon the cardiovascular system and coagulation state of the body are being closely studied. In connection to the same, clinical prognosis and complications of thrombolytic therapy are being scrutinized. It is noteworthy to mention that myocardial oxygen supply/demand mismatch, direct myocardial cells injury and acute plaque rupture are the multiple mechanisms responsible for acute coronary syndrome and cardiac complications in Covid-19 infection. However, this review has limitations as data available in this context is limited, scattered and heterogenous that questions the reliability of the same. So, more multi-centric studies involving representative populations, carried out meticulously, could further assist in responding better to cardiac complications among Covid-19 patients.

A biological rationale for the disparate effects of omega-3 fatty acids on cardiovascular disease outcomes.

The omega-3 fatty acids (n3-FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) rapidly incorporate into cell membranes where they modulate signal transduction pathways, lipid raft formation, and cholesterol distribution. Membrane n3-FAs also form specialized pro-resolving mediators and other intracellular oxylipins that modulate inflammatory pathways, including T-cell differentiation and gene expression. Cardiovascular (CV) trials have shown that EPA, administered as icosapent ethyl (IPE), reduces composite CV events, along with plaque volume, in statin-treated, high-risk patients. Mixed EPA/DHA regimens have not shown these benefits, perhaps as the result of differences in formulation, dosage, or potential counter-regulatory actions of DHA. Indeed, EPA and DHA have distinct, tissue-specific effects on membrane structural organization and cell function. This review summarizes: (1) results of clinical outcome and imaging trials using n3-FA formulations; (2) membrane interactions of n3-FAs; (3) effects of n3-FAs on membrane oxidative stress and cholesterol crystalline domain formation during hyperglycemia; (4) n3-FA effects on endothelial function; (5) role of n3-FA-generated metabolites in inflammation; and (6) ongoing and future clinical investigations exploring treatment targets for n3-FAs, including COVID-19.