Pharmacogenomic biomarkers in coronary artery disease: a narrative review.

Coronary artery disease (CAD) has a high mortality rate. Despite various therapeutic targets, non-responsiveness to drugs remains a prevalent issue. Pharmacogenomics assesses the way an individual's genetic attributes affect their likely response to drug therapy. Single-nucleotide polymorphisms play a crucial role in determining these outcomes. This review offers an overview of single-nucleotide polymorphisms investigated in clinical studies and their associations with drug response/nonresponse in the treatment of CAD. A total of 104 studies of whole sets of chromosomes and several genes were explored. A total of 161 polymorphisms exhibited associations with drug response/nonresponse in CAD across diverse ethnic populations. This pool can serve as a pharmacogenomic biomarker for predicting response to drug therapy in patients with CAD.

Lp-PLA2 as a biomarker and its possible associations with SARS-CoV-2 infection.

Lp-PLA2 is an enzyme encoded by the PLA2G7 gene located at chromosome 6p12-21, which is included in different signal transduction pathways. The potential of serum levels of Lp-PLA2 as a marker of inflammation quantifying cardio-metabolic risk, renal impairment and oxidative stress has been explored in earlier studies. It has also been used in chronic obstructive pulmonary disease, hepatic disease, metabolic conditions and exercise tolerance. Additionally, it shows promising evidence for the assessment of risk for certain cardiovascular conditions in otherwise seemingly healthy individuals. COVID-19 has affected life and the economy globally. The identification of biomarkers to assess the sickness and treatment plan is the need of the hour. This review summarizes the pathophysiological inter-relationship between serum levels of Lp-PLA2 and COVID-19. The authors hypothesize that the estimation of Lp-PLA2 levels may help in the early identification of risk and thus may play a beneficial role in the proactive management of COVID-19.

Beneficial Effect of Ocimum sanctum (Linn) against Monocrotaline-Induced Pulmonary Hypertension in Rats.

BACKGROUND: The study was designed to explore any beneficial effect of Ocimum sanctum (Linn) (OS) in experimental pulmonary hypertension (PH) in rats. OS is commonly known as “holy basil” and “Tulsi” and is used in the Indian System of Medicine as antidiabetic, antioxidant, hepatoprotective, adaptogenic, and cardioprotective. METHODS: Monocrotaline (MCT) administration caused development of PH in rats after 28 days and rats were observed for 42 days. Treatments (sildenafil; 175 µg/kg, OS; 200 mg/kg) were started from day 29 after the development of PH and continued for 14 days. Parameters to assess the disease development and effectiveness of interventions were echocardiography, right and left ventricular systolic pressures, and right ventricular end diastolic pressure, percentage medial wall thickness (%MWT) of pulmonary artery, oxidative stress markers in lung tissue, NADPH oxidase (Nox-1) protein expression in lung, and mRNA expression of Bcl2 and Bax in right ventricular tissue. RESULTS: OS (200 mg/kg) treatment ameliorated increased lung weight to body weight ratio, right ventricular hypertrophy, increased RVSP, and RVoTD/AoD ratio. Moreover, OS treatment decreases Nox-1 expression and increases expression of Bcl2/Bax ratio caused by MCT. CONCLUSION: The present study demonstrates that OS has therapeutic ability against MCT-induced PH in rat which are attributed to its antioxidant effect. The effect of OS was comparable with sildenafil.

Clinical efficacy of water extract of stem bark of Terminalia arjuna (Roxb. ex DC.) Wight & Arn. in patients of chronic heart failure: a double-blind, randomized controlled trial.

BACKGROUND: The stem bark of Terminalia arjuna (Roxb. ex DC.) Wight and Arn. (Arjuna) is used in Indian system of medicine (Ayurveda) for treatment of various cardiac diseases, including heart failure. However, well designed clinical trials exploring its efficacy and safety in chronic heart failure (CHF) are lacking. PURPOSE: To ascertain the add-on efficacy and safety of a standardized water extract of stem bark of Arjuna (Arjuna extract) in CHF patients on standard pharmacotherapy. STUDY DESIGN: Double-blind, parallel, randomized, placebo-controlled add-on clinical trial. METHODS: After approval of institutional ethics committee, 100 patients of CHF of New York Heart Association (NYHA) functional class II on standard pharmacotherapy having an echocardiographic left ventricular ejection fraction (LVEF) ≤ 40% were consecutively recruited with informed consent and randomized 1:1 to Arjuna extract 750 mg or matching placebo twice daily. The primary outcome measure was change in LVEF at 12 weeks. Secondary outcome measures included changes in (i) NYHA functional class, (ii) distance covered in 6 min walk test (6MWT), (iii) quality of life (QoL), as determined by the Kansas City Cardiomyopathy Questionnaire (KCCQ), (iv) plasma brain natriuretic peptide, (v) plasma cytokines (interleukin-6, high sensitivity C-reactive protein and tumour necrosis factor-α) and (vi) oxidative stress markers [serum thiobarbituric acid reactive substances (TBARS), red blood cell (RBC) superoxide dismutase (SOD), RBC catalase and RBC glutathione (GSH)] at 6 and 12 weeks. Safety assessment was done by adverse event monitoring and laboratory investigations. Results were expressed as mean ± SD or median (interquartile range) and analysed with intention-to- treat principle using appropriate two-sided statistical tests. A p-value < 0.05 was considered significant. RESULTS: Arjuna extract was well-tolerated, but did not change LVEF (24.3 ± 7.1 versus 25.5 ± 7.7%; p = 0.4) or secondary outcome measures except preservation of RBC catalase activity [1275(104, 10350) versus 1243.5(104, 10350) U/g haemoglobin; p = 0.01] compared to placebo. Significantly greater percentage increases occurred in distance covered in 6 MWT, RBC-SOD, RBC catalase, RBC GSH and in symptom severity and stability domains of KCCQ in patients on Arjuna extract versus those on placebo, on a post-hoc analysis, between subgroups of patients who improved in these outcomes. CONCLUSION: Arjuna extract did not improve LVEF in CHF patients over 12 weeks, although there was improvement in functional capacity, antioxidant reserves and symptom-related QoL domains in some patients.