Chronic heart failure (CHF) is a complex syndrome that results from structural and functional disturbances that affect the ability of the heart to supply oxygen to tissues. It largely affects and reduces the patient’s quality of life, socio-economic status, and imposes great costs on health care systems worldwide. Endothelial dysfunction (ED) is a newly discovered phenomenon that contributes greatly to the pathophysiology of numerous cardiovascular conditions and commonly co-exists with chronic heart failure. However, the literature lacks clarity as to which heart failure patients might be affected, its significance in CHF patients, and its reversibility with pharmacological and non-pharmacological means. This review will emphasize all these points and summarize them for future researchers interested in vascular pathophysiology in this particular patient population. It will help to direct future studies for better characterization of these two phenomena for the potential discovery of therapeutic targets that might reduce future morbidity and mortality in this “at risk” population.

Summary: Aim: Oxidative stress and endothelial dysfunction are two inter‐related conditions commonly seen in patients with cardiovascular risk factors. The enzyme, xanthine oxidase, is an important contributor to these phenomena but to a variable degree in different patient populations. This meta‐analysis will summarize the effect of allopurinol, an established xanthine oxidase inhibitor, on endothelial function among patients with different comorbidities.Methods: Medline Complete, PubMed, ProQuest, ClinicalKey, Wiley Online Library, and Cochrane Central Register of Controlled Trials were searched till July 29, 2017. Meta‐analysis was planned for randomized controlled trials (RCTs) that investigated allopurinol effects on endothelial function. A random effect model was used to calculate the standardized mean difference (with 95% confidence intervals: CI) as an estimate of effect size. Heterogeneity was quantified by four types of information: Q statistics, I² statistic, Tau‐squared (T²), and Tau (T).Results: Thirty eligible studies were identified; 12 were included in the final analysis and subdivided among 3 patient’s groups: patients with chronic heart failure (CHF; 197 patients), patients with chronic kidney disease (CKD; 183 patients), and patients with type 2 diabetes mellitus (DM; 170 patients). Allopurinol was found to have a statistically significant benefit on endothelial function in patients with CHF and CKD but not in type 2 DM. The standardized mean differences and CI in the three patient’s groups were 0.776 (0.429, 1.122), 0.350 (0.009, 0.690), and 1.331 (−0.781, 3.444), respectively.Conclusion: Allopurinol has an antioxidant property that might partially reverse endothelial dysfunction in patients with certain comorbidities. The importance of this property and the magnitude of the beneficial effect are likely to be related to the relative contribution of xanthine oxidase into the oxidative stress associated with different underlying pathologies.

Erectile dysfunction (ED) is a public health concern worldwide. In the past, it was perceived as a phenomenon attributed to age advancement. However, more individuals are affected every year that do not fall under that age criterion. Epidemiological research revealed that this abnormality has an association with endothelial dysfunction connected to several cardiovascular (CV) risk factors. Currently, ED is interpreted as a clinical marker for future adverse events and not only as a present health issue that negatively affects the quality of life. The management of ED involves lifestyle modifications, therapeutic optimization for comorbid conditions, and pharmacological and psychosexual therapy. Phosphodiesterase type 5 (PDE5) inhibitors are the first-line pharmacological agents to be prescribed for such a condition. Nonetheless, other pharmacological pathways and agents remain underinvestigated or were investigated at some stage. This review aimed to present to future researchers interested in this field with some pharmacological agents that showed favorable effects on a limited number of studies on human subjects or experimental models.

The xanthine oxidase inhibitor allopurinol improves endothelial function in different populations, including patients with chronic heart failure (CHF). Its effect on arterial stiffness parameters is less clear. We investigated the effect of short-term low-dose allopurinol therapy on arterial stiffness in Saudi patients with stable mild-moderate CHF. A prospective, randomized, double-blind, placebo-controlled study was performed on 73 patients with mild-moderate CHF. In all, 36 patients were randomized to allopurinol 300 mg daily for 3 months, while 37 patients were randomized to placebo. Arterial stiffness parameters, aortic pulse wave velocity (Ao-PWV) and heart rate corrected augmentation index (c-AIx), were assessed before and after treatment along with serum uric acid. A total of 66 patients completed the study. Both groups were matched for age, sex, severity of heart failure, and arterial stiffness. Compared with placebo, allopurinol recipients had a significant fall in uric acid concentration from 6.31 ± 1.4 (SD) mg/dL to 3.81 ± 1.2 (P < .001). Despite that, there was no significant change in arterial stiffness parameters between allopurinol and placebo groups. Post-treatment Ao-PWV was 9.79 ± 2.6 m/s in the allopurinol group and 10.07 ± 3.4 m/s in the placebo group, P = .723. Post-treatment c-AIx was 24.0% ± 9.1% and 22.0% ± 9.9%, respectively, P = .403. We have shown that allopurinol significantly reduced uric acid concentration in Saudi patients with CHF but was not associated with a change in arterial stiffness. Our cohort of patients had worse arterial stiffness values at baseline, which might make them more resistant to change using our study regimen. The study has been registered with the International Standard Randomized Controlled Trial Number registry with an identifier number of ISRCTN58980230.

Background: Globally, unjustified medication use during pregnancy, a critical phase in human life, is a threat that compromises the safety of both, the mother and the child. We aim to investigate the prevalence of over-the-counter (OTC) or non-prescription and prescription medication use during pregnancy in women from the city of Riyadh, Saudi Arabia, the level of prior knowledge, and the sources of their information about medication hazard/safety. Methods: A cross-sectional study was performed using a self-administered questionnaire for 287 pregnant women visiting King Saud Medical City (KSMC) – outpatient departments for routine antenatal care during 3 months (1st Mar– 31st May 2021). The questionnaire was developed by Navaro et al with 4 sections: socio-demographic data, medication use during pregnancy, level of knowledge, and relevant sources of information. Results: The participants had a mean age of 32.21 years ± 6.41 (SD), and gestational age of 23.67 weeks ± 8.47. About 76.66% of them reported using medication during their current pregnancy: predominantly prescribed (86.36%). Women who used medication during pregnancy were slightly older; the mean difference was 1.97 years (95% CI 0.23– 3.71) (P=0.027). Women living in an urban environment as compared with rural had a higher prevalence of medication use (79.01% vs 52%) (P=0.002). Overall, 58.19% reported using non-prescribed medications during pregnancy, with analgesics as the most frequently used class (70.30%). The mild nature of the illnesses and availability of an old prescription and information from pharmacists were the main reasons for self-medication. About 40.77% denied receiving any information about medication use during pregnancy. Conclusion: The prevalence of the medication use during pregnancy in our population is alarmingly high. Analgesics were the most frequently used. Lack of adequate information from treating physicians appears to be contributory to self-medication during this critical time.

Background: Chronic heart failure (CHF) is a global health burden. Despite advances in treatment, there remain well-recognised morbidity and mortality. Risk stratification requires the identification and validation of biomarkers, old and new. Hyponatremia has re-emerged as a prognostic marker in CHF patients. Methods: This is a retrospective cohort study on 241 CHF patients recruited from King Fahd Hospital of the University, Al-Khobar, Saudi Arabia (January 2005–December 2016). Their serum sodium and biochemical parameters were measured at baseline, along with 2-D echocardiographic assessments of left ventricular mass and ejection fraction. The primary endpoint was the association between hyponatremia and all-cause mortality (ACM) after a follow-up period of 24 months. Results: Mean age of patients was 60.61 ± 12.63 (SD) years; 65.1% were males, and type 2 diabetes mellitus (DM) was present in 71%. Baseline serum sodium was 138.00 (136, 140) (median and interquartile range). Hyponatremia (< 135 meq/L) was present in 14.1%. After follow-up, 46 deaths had occurred. Multivariate Cox-proportional hazard model showed that type 2 DM, New York Heart Association (NYHA) class (III–IV vs I–II), age, and left ventricular mass index (LVMI) were significant and independent predictors of ACM, with HR 3.03 (95% CI; 1.13, 8.16) (P=0.028), HR 2.31 (95% CI; 1.11, 4.82) (P=0.026), HR 1.06 (95% CI; 1.03, 1.09) (P< 0.001), and HR 1.01 (95% CI; 1.00, 1.02) (P=0.039), respectively. Estimated glomerular filtration rate (eGFR) was not a significant predictor. Kaplan–Meier survival analysis was used for the analysis of NYHA class and hyponatremia interactions and showed that hyponatremia had an association with poorer survival in patients with NYHA class III–IV rather than I–II (Log-rank test, P= 0.0009). Conclusion: Hyponatremia was a feature in CHF patients, and ACM was predicted by type 2 DM, NYHA class, age, and LVMI. Hyponatremia impact on survival was in patients with more advanced disease.