HFpEF and sex: understanding the role of sex differences.

Heart failure is a complex clinical syndrome with many etiological factors and complex pathophysiology affecting millions worldwide. Males and females can have distinct clinical presentation and prognosis, and there is an emerging understanding of the factors that highlight the similarities and differences to synthesize and present available data for sex-specific differences in heart failure with preserved ejection fraction (HFpEF). While the majority of data demonstrate more similarities than differences between females and males in terms of heart failure, there are key differences. Data showed that females have a higher risk of developing HFpEF, but a lower risk of mortality and hospitalization. This can be conditioned by different profiles of comorbidities, postmenopausal changes in sex hormone levels, higher levels of inflammation and chronic microvascular dysfunction in females. These factors, combined with different left ventricular dimensions and function, which are more pronounced with age, lead to a higher prevalence of LV diastolic dysfunction at rest and exercise. As a result, females have lower exercise capacity and quality of life when compared to males. Females also have different activities of systems responsible for drug transformation, leading to different efficacy of drugs as well as higher risk of adverse drug reactions. These data prove the necessity for creating sex-specific risk stratification scales and treatment plans.

Homocysteine and atrial fibrillation: novel evidences and insights.

Atrial fibrillation (AF) is one of the most prevalent rhythm disorders worldwide, with around 37.574 million cases around the globe (0.51 % global population).  Different studies showed a high informative value of different biomarkers, including such related to the systemic inflammation, biomechanical stress and fibrosis. In this review article we aimed to study only the relation of homocysteine to the AF development. Homocysteine is a sulfur-containing amino acid, that is produced in the process of methionine metabolism. Which is a non-canonical amino acid, that is derived from the food proteins. From the scientific point of view there is a relation between hyperhomocysteinemia and myocardial fibrosis, but these mechanisms are complicated and not sufficiently studied. Homocysteine regulates activity of the ion channels through their redox state. Elevated homocysteine level can condition electrical remodeling of the cardiomyocytes through the increase of sodium current and change in the function of rapid sodium channels, increase of inwards potassium current and decrease in amount of rapid potassium channels. High homocysteine concentration also leads to the shortening of the action potential, loss of the rate adaptation of the action potential and persistent circulation of the re-entry waves. In a series of experimental studies on mice there was an association found between the homocysteine level and activity of vascular inflammation. Elevation of homocysteine level is an independent factor of the thromboembolic events and AF relapses. Population studies showed, that homocysteine is an independent risk factor for AF. So, homocysteine is an interesting target for up-stream therapy.

Clinical course of COPD in patients with Arg16Gly (rs1042713) polymorphism of ADRB2 gene.

The ADBR2 gene has been studied for its possible relationship with the development and clinical course of chronic obstructive pulmonary disease (COPD), including response to beta-2 agonists, with existing data being contentious on the subject. So, the purpose of this study was to look into the potential impact of the arginine-16-glycine (Arg16Gly) polymorphism on the clinical course and drug utilization in COPD patients. Data show that patients with Arg16Arg have a lower number of hospital admissions for exacerbations (p=0.048), but only in the total number of exacerbations, including those treated out-patients (p=0.086). Each glycine (Gly) copy was associated with a higher number of exacerbations (OR: 0.25; 95% CI: 0.00-055; p=0.048). The number of exacerbations after LABA/LAMA treatment was similar across groups, indicating that all ADRB2 variants responded well to the treatment. Furthermore, there were no statistically significant differences in mMRC and CAT values across all study visits. Interestingly, groups differed in their use of antibiotics (AB) at all visits, with Arg16Arg being associated with the least amount of AB use. There was also a link discovered between clycine copies and increased use of glucocorticoids. As a result, Arg16Gly is involved in the clinical course of COPD as well as the utilization of drug groups. Based on the findings, we can speculate that the cross-talk between the ADRB2 gene and the corticosteroid receptor is altered in patients with the Gly16Gly genotype.