The Impact of CYP2C19 Genotype on the Platelet Reactivity Index (PRI) among Chronic Coronary Syndromes (CCS) Patients Undergoing Percutaneous Coronary Intervention (PCI): Affectability of Rapid Genetic Testing.

BACKGROUND: In the Asian population, the presence of the CYP2C19 loss-of-function (LOF) allele is a known genetic variation. This allele is associated with a reduced capacity to metabolize clopidogrel into its active forms through the CYP2C19 enzyme, resulting in diminished platelet inhibition and an elevated risk of recurrent cardiovascular events. Regulatory authorities have recommended an alternative P2Y12 inhibitor, ticagrelor, for individuals carrying the LOF allele. Consequently, this study seeks to assess the impact of the CYP2C19 genotype on the Platelet reactivity index (PRI) using a rapid genetic testing approach in Asian patients with chronic coronary syndromes (CCS) who undergo percutaneous coronary intervention (PCI). METHODS: This prospective study employed a parallel design, single-center design, and randomized approach. Genotyping for the CYP2C19*2 and *3 polymorphisms was conducted using the Nested Allele-Specific Multiplex PCR (NASM-PCR) technique. Patients meeting the inclusion criteria underwent genotyping for CYP2C19 polymorphisms. Following PCI, patients were randomly assigned to receive either ticagrelor or clopidogrel. PRI assessments were performed four hours after loading dose administration. The trial was registered with ClinicalTrials.gov under the identifier NCT05516784. RESULTS: Among the 94 patients recruited for the study, 40 (42.55%) were identified as carriers of the LOF allele for CYP2C19*2 and *3 (*1/*2, *2/*2, *1/*3). Out of the 84 patients evaluated for PRI (44 receiving clopidogrel and 40 receiving ticagrelor), 21 (47.7%) of the clopidogrel group and 39 (97.5%) of the ticagrelor group exhibited a favorable response to antiplatelet therapy (PRI < 50). Patients treated with ticagrelor demonstrated superior antiplatelet responses compared to those receiving clopidogrel, regardless of LOF carrier status (P = 0.005 and < 0.001 for non-LOF and LOF carriers, respectively). CONCLUSION: NASM-PCR as a rapid genetic test holds promise for personalizing antiplatelet therapy in Asian CCS patients.

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 Role of Genetic Polymorphism and Other Factors on Clopidogrel Resistance (CR) in an Asian Population with Coronary Heart Disease (CHD).

Clopidogrel is a widely-used antiplatelet drug. It is important for the treatment and prevention of coronary heart disease. Clopidogrel can effectively reduce platelet activity and therefore reduce stent thrombosis. However, some patients still have ischemic events despite taking the clopidogrel due to the alteration in clopidogrel metabolism attributable to various genetic and non-genetic factors. This review aims to summarise the mechanisms and causes of clopidogrel resistance (CR) and potential strategies to overcome it. This review summarised the possible effects of genetic polymorphism on CR among the Asian population, especially CYP2C19 *2 / *3 / *17, where the prevalence rate among Asians was 23.00%, 4.61%, 15.18%, respectively. The review also studied the effects of other factors and appropriate strategies used to overcome CR. Generally, CR among the Asian population was estimated at 17.2-81.6%. Therefore, our overview provides valuable insight into the causes of RC. In conclusion, understanding the prevalence of drug metabolism-related genetic polymorphism, especially CYP2C19 alleles, will enhance clinical understanding of racial differences in drug reactions, contributing to the development of personalised medicine in Asia.

Dietary factors in relation to hypertension: a mendelian randomization study.

BACKGROUND: Observational studies have elucidated the associations between dietary factors and hypertension. Nevertheless, the exploration of these relationships using Mendelian randomization remains scarce currently. METHODS: The Mendelian randomization approach investigated the potential causal relationships between 16 dietary factors and hypertension. To achieve this, we identified genetic variants associated with these dietary factors by utilizing data from European-descent genome-wide association studies with a stringent significance threshold (P < 5 × 10 - 8). Subsequently, we obtained genetic associations with hypertension from the extensive FinnGen Study, encompassing 92,462 cases and 265,626 controls. Our primary analytical method was the inverse variance weighted method, and we also conducted assessments for heterogeneity and pleiotropy to ensure the robustness and reliability of our findings. RESULTS: The study revealed significant associations with hypertension risk for various dietary factors. Specifically, higher weekly alcohol consumption (OR: 1.53, 95% CI: 1.19-1.96) and more frequent alcohol intake (OR: 1.20, 95% CI: 1.08-1.33) were positively correlated with an increased risk of hypertension. Likewise, increased poultry intake (OR: 3.25, 95% CI: 1.83-5.78) and beef intake (OR: 1.80, 95% CI: 1.09-2.97) were also linked to a higher risk of hypertension. Conversely, there were protective factors associated with a decreased risk of hypertension. These included consuming salad and raw vegetables, dried fruits, cheese, and cereals. It is important to note that no evidence of pleiotropy was detected, underscoring the robustness of these findings. CONCLUSIONS: This study uncovered causal relationships between various dietary factors and hypertension risk. Specifically, alcohol consumption in terms of drinks per week and intake frequency, as well as poultry and beef intake, were causally associated with an elevated risk of hypertension. In contrast, consuming salad/raw vegetables, dried fruits, cheese, and cereals demonstrated an inverse causal association with hypertension, suggesting a potential protective effect.

Assessing the predictive value of neutrophil percentage to albumin ratio for ICU admission in ischemic stroke patients.

Background: Acute ischemic stroke (AIS) remains a substantial global health challenge, contributing to increased morbidity, disability, and mortality. This study aimed at investigating the predictive value of the neutrophil percentage to albumin ratio (NPAR) in determining intensive care unit (ICU) admission among AIS patients. Methods: A retrospective observational study was conducted, involving AIS cases admitted to a tertiary hospital in Jordan between 2015 and 2020. Lab data were collected upon admission, and the primary outcome was ICU admission during hospitalization. Descriptive and inferential analyses were performed using SPSS version 29. Results: In this study involving 364 AIS patients, a subset of 77 (21.2%) required admission to the ICU during their hospital stay, most frequently within the first week of admission. Univariable analysis revealed significantly higher NPAR levels in ICU-admitted ischemic stroke patients compared to those who were not admitted (23.3 vs. 15.7, p < 0.001), and multivariable regression models confirmed that higher NPAR (≥19.107) independently predicted ICU admission in ischemic stroke patients (adjusted odds ratio [aOR] = 4.85, 95% CI: 1.83-12.83). Additionally, lower GCS scores and higher neutrophil-to-lymphocyte ratio (NLR) were also associated with increased likelihood of ICU admission. In terms of predictive performance, NPAR showed the highest accuracy with an AUC of 0.885, sensitivity of 0.805, and specificity of 0.854, using a cutoff value of 19.107. NPAR exhibits an AUC of 0.058, significantly outperforming NLR (Z = 2.782, p = 0.005). Conclusion: NPAR emerged as a robust independent predictor of ICU admission in ischemic stroke patients, surpassing the predictive performance of the NLR.

Acupuncture in Traditional Chinese Medicine: A Complementary Approach for Cardiovascular Health.

Cardiovascular diseases (CVDs) are increasingly prevalent in clinical settings. With the continuous improvement of people's living standards, the gradual acceleration of the pace of life, and the deterioration of the living environment in recent years, the incidence of CVDs is increasing annually. The prevalence of CVDs among individuals aged 50 and above is notably elevated, posing a significant risk to patients' well-being and lives. At this juncture, numerous clinical treatment choices are available for managing CVDs, with traditional Chinese medicine (TCM) therapy standing out as a practical, safe, and reliable option. Over the recent years, there has been growing acknowledgement among both medical professionals and patients. With the expanding integration of TCM in the treatment of various clinical conditions, the use of TCM in managing CVDs has gained significant attention within the medical community, potentially emerging as an efficacious approach for addressing cardiovascular diseases. This article conducts a comprehensive review of the TCM approach, particularly acupuncture, as a supplementary treatment for CVDs, highlighting its ability to effectively lower blood pressure, decrease coronary artery events, mitigate arrhythmias, and enhance cardiac function when used alongside conventional medication. The review underscores the promise of acupuncture in enhancing cardiovascular health, although variations in research methodologies necessitate standardized applications.

Detection of CTLA-4 level and humeral immune response after the second dose of COVID-19 vaccine in certain Iraqi provinces participants.

BACKGROUND: Evaluating immune responses following COVID-19 vaccination is paramount to understanding vaccine effectiveness and optimizing public health interventions. This study seeks to elucidate individuals' immune status after administering a second dose of diverse COVID-19 vaccines. By analyzing immune responses through serological markers, we aim to contribute valuable insights into the uniformity of vaccine performance. METHODS: A total of 80 participants were enrolled in this study, with demographic and COVID-19 infection-related data collected for categorization. Serum samples were acquired within a specified timeframe, and SARS-CoV-2 IgM/IgG rapid tests were conducted. Moreover, CTLA-4 levels were measured through ELISA assays, allowing us to assess the immune responses comprehensively. The participants were divided into eight groups based on various factors, facilitating a multifaceted analysis. RESULTS: The outcomes of our investigation demonstrated consistent immune responses across the diverse types of COVID-19 vaccines administered in Iraq. Statistical analysis revealed no significant distinctions among the vaccine categories. In contrast, significant differences were observed in CTLA-4 among the control group (non-infected/non-vaccinated, infected/non-vaccinated) and infected/Pfizer, non-infected/Pfizer, and infected/Sinopharm, non-infected/sinopharm (P = 0.001, < 0.001, 0.023, respectively). This suggests that these vaccines exhibit comparable effectiveness in eliciting an immune response among the study participants. CONCLUSIONS: In conclusion, our study's results underscore the lack of discriminatory variations between different COVID-19 vaccine types utilized in Iraq. The uniform immune responses observed signify the equitable efficacy and performance of these vaccines. Despite minor quantitative discrepancies, these variations do not hold statistical significance, reaffirming the notion that the various vaccines serve a similar purpose in conferring protection against COVID-19.

The Management of Myocardial Injury Related to SARS-CoV-2 Pneumonia.

The global evolution of the SARS-CoV-2 virus is known to all. The diagnosis of SARS-CoV-2 pneumonia is expected to worsen, and mortality will be higher when combined with myocardial injury (MI). The combination of novel coronavirus infections in patients with MI can cause confusion in diagnosis and assessment, with each condition exacerbating the other, and increasing the complexity and difficulty of treatment. It would be a formidable challenge for clinical practice to deal with this situation. Therefore, this review aims to gather literature on the progress in managing MI related to SARS-CoV-2 pneumonia. This article reviews the definition, pathogenesis, clinical evaluation, management, and treatment plan for MI related to SARS-CoV-2 pneumonia based on the most recent literature, diagnosis, and treatment trial reports. Many studies have shown that early diagnosis and implementation of targeted treatment measures according to the different stages of disease can reduce the mortality rate among patients with MI related to SARS-CoV-2 pneumonia. The reviewed studies show that multiple strategies have been adopted for the management of MI related to COVID-19. Clinicians should closely monitor SARS-CoV-2 pneumonia patients with MI, as their condition can rapidly deteriorate and progress to heart failure, acute myocardial infarction, and/or cardiogenic shock. In addition, appropriate measures need to be implemented in the diagnosis and treatment to provide reasonable care to the patient.

A review of the effects of ticagrelor on adenosine concentration and its clinical significance.

BACKGROUND: Ticagrelor is an oral antiplatelet drug that can reversibly bind to the platelet P2Y12 receptor. Ticagrelor is metabolized mainly by CYP3A4 and produces a rapid blood concentration-dependent platelet inhibitory effect. Unlike other P2Y12 receptor antagonists, many clinical features of ticagrelor are not related to P2Y12 receptor antagonism. PURPOSE: This review aims to gather existing literature on the clinical effects of ticagrelor after inhibiting adenosine uptake. METHODOLOGY: The current study reviewed literature related to the effects of ticagrelor on adenosine metabolism. The review also examined the drug's biological effects and clinical characteristics to see how it could be used in a clinical setting. RESULTS: Many studies have shown that ticagrelor can inhibit equilibrative nucleoside transporter 1 (ENT1). This inhibition leads to intracellular adenosine uptake, increased adenosine half-life and plasma concentration levels and an enhanced adenosine-mediated biological effect. CONCLUSIONS: Based on the studies reviewed, it was found that ticagrelor essentially inhibits adenosine absorption of adenosine into cells through ENT1, which increases the concentration in the blood and subsequently increases the protection of the heart muscle by adenosine. It also prevents platelet aggregation, and extends the biological effects of coronary arteries. Moreover, it leads to a lower mortality rate in acute coronary syndrome (ACS) patients.

Coronary Heart Disease (CHD) in Elderly Patients: Which Drug to Choose, Ticagrelor and Clopidogrel? A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: A new generation P2Y12 receptor inhibitor (ticagrelor) is recommended in current therapeutic guidelines to treat patients with coronary heart disease (CHD). However, it is unknown if ticagrelor is more effective than clopidogrel in elderly patients. Therefore, a systematic review was done to assess the effectiveness and safety of ticagrelor and clopidogrel in older patients with CHD to determine the appropriate antiplatelet treatment plan. METHODOLOGY: We performed a systematic review of randomized controlled trials (RCTs) to compare the effectiveness and safety of ticagrelor vs. clopidogrel in elderly patients with CHD. We selected eligible RCTs based on specified study criteria following a systematic search of PubMed and Scopus databases from January 2007 to May 2021. Primary efficacy outcomes assessed were major adverse cardiovascular events (MACEs), myocardial infarction (MI), stent thrombosis (ST), and all-cause death. The secondary outcome assessed was major bleeding events. We used RevMan 5.3 software to conduct a random-effects meta-analysis and estimated the pooled incidence and risk ratios (RRs) with 95% confidence intervals (CIs) for ticagrelor and clopidogrel. RESULTS: Data from 6 RCTs comprising 21,827 elderly patients were extracted according to the eligibility criteria. There was no significant difference in the MACE outcome (incidence: 9.23% vs. 10.57%; RR = 0.95, 95% CI = 0.70-1.28, p = 0.72), MI (incidence: 5.40% vs. 6.23%; RR = 0.94, 95% CI= 0.69-1.27, p = 0.67), ST (incidence: 2.33% vs. 3.17%; RR = 0.61, 95% CI= 0.32-1.17, p = 0.13), and all-cause death (4.29% vs. 5.33%; RR = 0.86, 95% CI = 0.65-1.12, p = 0.25) for ticagrelor vs. clopidogrel, respectively. In addition, ticagrelor was not associated with a significant increase in the rate of major bleeding (incidence: 9.98% vs. 9.33%: RR = 1.37, 95% CI = 0.97-1.94, p = 0.07) vs. clopidogrel. CONCLUSIONS: This study did not find evidence that ticagrelor is significantly more effective or safer than clopidogrel in elderly patients with CHD.