Tactics of managing a cardiac patient with comorbidity: promising opportunities for correction of endothelial dysfunction
Background. Arterial hypertension (AH) and heart diseases are the leading causes of morbidity, mortality and the number of visits to the doctor. Cardiac patients are characterized by the frequent polymorbidity. The cardiovascular continuum, which predicts the course of events from atherosclerosis to the final stages of cardiovascular diseases (CVD), includes the following pathogenetic links: oxidative stress, inflammation and endothelial dysfunction (ED).
Objective. To describe the management of a cardiac patient with comorbidity and promising options for the ED correction.
Materials and methods. Analysis of the literature on this issue.
Results and discussion. The previous paradigm of CVD development involved damage to target organs due to hypertension. Instead, according to the current paradigm, CVD are the result of the vascular dysfunction. The recently proposed paradigm indicates that all CVD are based on ED. Nitric oxide (NO) is the main molecule necessary for the proper functioning of the endothelium. NO takes part in the relaxation of blood vessels and smooth muscles, regulates the synthesis and secretion of a number of hormones, controls platelet activity and the interaction of leukocytes with vascular walls, participates in antipathogenic reactions of the immune system. ED is known to be a predictor of complications and poorer survival in patients with coronary heart disease. Dysfunctional endothelium promotes vasoconstriction, oxidation, inflammation and thrombosis. To improve the condition of the endothelium, it is advisable to increase the NO content. The increase in NO content can be the result of angiotensin-converting enzyme inhibitors, calcium channel blockers, sartans, statins, estrogens, antioxidants, and aspirin intake, as well as exercise. L-arginine is the substrate for the NO formation in human body. Potential mechanisms of L-arginine effect in AH include improvement of endothelial function, increase of vascular NO synthesis, decrease of endothelin-1 and angiotensin II activity, modulation of renal hemodynamics and reduction of oxidative stress. L-arginine therapy (9 g per day for 4 weeks) reduced systolic blood pressure by 4 mm Hg and diastolic – by 2.6 mm Hg. L-arginine also has a beneficial effect on the metabolic profile via increasing insulin sensitivity. The use of L-arginine is well studied in patients with chronic heart failure (HF) with preserved ejection fraction. In this category of patients, such treatment leads to an increase in glomerular filtration rate, improvement of endothelium-dependent vasodilation, reduction of the functional class of HF. The ESPEN guidelines on parenteral nutrition state that the use of L-arginine has both NO-dependent and NO-independent effects. The latter include the synthesis of creatine, proline and polyamines; stimulation of insulin and growth hormone secretion. Administration of L-arginine in combination with L-carnitine helps to eliminate the advanced glycation end products and to increase the rate of glomerular filtration.
Conclusions. 1. The cardiovascular continuum includes such elements as oxidative stress, inflammation and endothelial dysfunction. 2. NO is the main molecule necessary for the proper functioning of the endothelium. 3. L-arginine is the substrate for the NO formation in human body. L-arginine also helps to improve endothelial function, to reduce the activity of endothelin-1 and angiotensin II, to modulate renal hemodynamics and to reduce oxidative stress. 4. L-arginine also has a beneficial effect on the metabolic profile via increasing insulin sensitivity. 5. In patients with chronic HF with preserved ejection fraction, treatment with L-arginine leads to an increase in glomerular filtration rate, improvement of endothelium-dependent vasodilation, reduction of the functional class of HF.
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