[Albuminuria as a marker of atherosclerosis burden and a possible predictor of adverse events in patients with polyvascular disease].

BACKGROUND: The role of albuminuria as a marker of the atherosclerosis burden and a predictor of prognosis in patients with polyvascular disease (PD) has been little studied. AIM: To evaluate the prevalence, association with atherosclerosis burden, and prognostic value of albuminuria in relation to cardiovascular and bleeding complications in patients with PD. MATERIALS AND METHODS: The data was obtained from the prospective registry REGATA-1 (NCT04347200). Seventy four patients (75.7% males, median age 67 [61-69] years) with PD (CAD and peripheral arterial disease) were enrolled. All patients received aspirin and rivaroxaban 2.5 mg. The albumin-creatinine ratio in a single morning urine sample, estimated glomerular filtration rate (eGFR), and von Willebrand factor levels were determined. RESULTS: Mild albuminuria (10-29 mg/g) was detected in 45.9% of patients, moderate and severe (≥30 mg/g) - in 29.7%; eGFR<60 ml/min - in 21.7%, chronic kidney disease (CKD) according to the full KDIGO criteria (eGFR and/or albuminuria ≥30 mg/g) - twice as often (39.2%). The frequency of nephroprotective therapy prescription was insufficient. The level of albuminuria did not correlate with von Willebrand factor (endothelial dysfunction marker), but was associated with affecting of 4-5 vascular beds (ROC AUC 0.775; p=0.011). During the follow-up (12 [8-18] months) 3 patients developed MACE, 11 - BARC 2-3 bleedings. Neither albuminuria nor eGFR were predictors of MACE, bleeding, or net clinical benefit. CKD (KDIGO) was also not associated with bleedings. CKD (KDIGO) was independent predictor of MACE (in significant multiple regression model beta - coefficient for CKD was 0.097; p=0.042), however, the small number of end points allows us to speak only of a hypothesis-generating trend. The implementation of CKD (KDIGO) has increased the predictive value of the REACH score. CONCLUSION: Albuminuria is highly prevalent in patients with PD. It is a marker of atherosclerosis burden. CKD, diagnosed taking into account the level of albuminuria, can be used in a comprehensive assessment of cardiovascular risk in this category of patients.

[Upper gastrointestinal bleeding in patients with stable coronary artery disease (registry of antithrombotic therapy "REGATТA" results)].

INTRODUCTION: Upper gastrointestinal (UGI) bleeding is a common complication of antiplatelet therapy. Data from real clinical practice that characterize the range of risk factors for UGI bleeding, prophylactic proton pump inhibitors (PPIs) therapy, bleeding frequency and their long-term effects in patients with stable coronary artery disease (CAD) are limited. AIM: To identify predictors of UGI bleeding in patients with stable CAD, to assess the role of PPI in the prevention of bleeding and the long-term prognosis of patients after bleeding. MATERIALS AND METHODS: 934 patients with stable CAD (median age 61 [5368] years, 78.6% men) were included in the single institution prospective REGistry of Long-term AnTithrombotic TherApy (REGATTA). Atherosclerosis of peripheral arteries (APA) and abdominal aortic aneurysm (AAA) screening was performed by doctor decision, as well as esophagogastroduodenoscopy. 76% of patients received dual antiplatelet therapy for 612 months after elective PCI. PPIs were prescribed in 28.3% of cases. RESULTS: The median follow-up was 2.5 [1.15.1] years. The frequency of overt UGI bleeding was 1.9 per 100 patients per year. Anamnesis of peptic ulcer disease (OR 4.7; 95% CI 1.911.8;p=0.001), erosion of the upper gastrointestinal tract (OR 6.7; 2.716.6;p=0.00004 ), as well as concomitant diseases associated with a decrease in blood supply to the mucosa, such as heart failure HF (OR 6.1; 2.316.0;p=0.0002), AAA (OR 9.3; 2.534.2;p=0.0008) and APA (OR 2.3; 0.985.5;p=0.05) turned out to be independent predictors of UGI bleeding. The frequency of AAA among those who underwent UGI bleeding was 19.6% (in patients without bleeding 1.4%;p0.001). 90.2% of patients with UGI bleeding received PPI; the frequency of UGI bleeding in patients receiving pantoprazole and omeprazole did not differ significantly. After UGI bleeding, rebleeding rate was 7.8%, thrombotic events (TE) rate 31.4%, mortality rate 17.7% for 30 days, 19.4% for 1 year and 35.3% for the entire observation period. The predictors of deaths were AAA (OR 92.5; 7.7107.9;p0.0001), APA (OR 4.2; 1.0317.2;p=0.045) and HF (OR 34.5; 8.5140.6;p0.0001). The worst prognosis was expected for patients who underwent UGI bleeding and thrombotic events: 2/3 of these patients died. CONCLUSION: In a prospective analysis of patients with stable CAD, we identified UGI bleeding was a significant risk factor for late thromboembolism and death, compared with patients without bleeding. Predictors of UGI bleeding and poor prognosis are factors that indicate atherothrombotic burden abdominal aortic aneurysm, peripheral atherosclerosis and HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04347200.

[The balance of benefit and risk in prescribing antithrombotic therapy for patients with coronary artery disease. How to deal with the gastrointestinal bleeding problem?]

The review focuses on upper gastrointestinal (GI) bleeding in patients with ischemic heart disease (IHD) receiving an antithrombotic therapy. Approaches to risk stratification for GI bleeding and correction of modifiable factors that determine the probability of such events are addressed in detail. Recommendations are provided for administration of stomach-protecting drugs. The interrelation of risk factors for thromboses and bleedings is stressed, and possible indications for a multicomponent antithrombotic therapy in patients with stable IHD are discussed.

Proton pump inhibitors receiving and prognosis of patients after scheduled percutaneous coronary interventions.

AIM: The urgency of the study is determined by the lack of data necessary in order to assess the safety of prolonged use of proton pump inhibitors (PPI) in patients with IHD combined with anti-aggregant therapy. The aim of the study was to study the relationship between the use of PPI and the risk of thrombotic complications in patients undergoing planned procedures of percutaneous coronary interventions (PCI) and receiving dual antiplatelet therapy. MATERIALS AND METHODS: The study is a prospective register of patients who successfully underwent planned percutaneous coronary intervention (PCI). The effect of PPI (omeprazole and pantoprazole) on the frequency of the combined end point cardiovascular death, ACS, AI, TIA, peripheral arterial thrombosis and PE was assessed using the Log-Rank criterion, as well as in a multivariate analysis (Cox proportional risk regression model). RESULTS: A total of 391 patients were included in the study (23.1% women, mean age 61.2 years ± 10.4 years). The median duration of follow-up was 18 months. During this period of time, 34 adverse events were recorded. Log-Rank analysis showed that the proportion of patients without adverse events in the omeprazole group was significantly lower in comparison with patients who did not receive PPI (0.56 vs. 0.84, Log-Rank p=0.003), and for pantoprazole no such pattern was found (0.89 against 0.84, Log-Rank p=0.21). The average level of residual platelet reactivity (ORT), as well as the number of patients with high ORT (> 208 PRU), did not differ significantly between the groups of omeprazole, pantoprazole and the group of patients not receiving PPI. According to multivariate analysis, omeprazole was an independent predictor of thrombotic complications after a planned PCI (OR 3.75, 95% confidence interval 1.72-8.17, p=----0.0009). CONCLUSION: Long-term use of omeprazole (at least 30 days) is an independent predictor of thrombotic complications in patients who underwent planned PCI.

[Comparative efficacy of conservative and invasive treatment of patients with stable form of ischemic heart disease (according to results of five year prospective study)].

Despite high immediate efficacy of percutaneous coronary interventions (PCI) in relation to symptoms of angina the problem of influence of this method of treatment on duration of life and prognosis in stable ischemic heart disease (IHD) remains unsolved. Aim of our study was to compare efficacy of conservative therapy with drugs of proven effect on prognosis and of percutaneous coronary interventions in combination with optimal drug therapy in patients with stable ischemic heart disease (IHD) during 5 years of follow up. We included into this study 503 patients (387 men and 116 women, mean age 59 years). Groups of conservative and invasive treatments comprised 179 and 302 patients, respectively; mean durations of follow-up were 5.6+/-1.3 and 4.1+/-1.6 years, respectively, p=0.001. Study end points were fatal and nonfatal cardiovascular complications (CVC) (cardiovascular death, acute coronary syndrome, transitory ischemic attack, peripheral arterial thrombosis) and composite endpoint defined as sum of all CVC and cases of revascularization of the involved vascular bed. Cumulative rates of all fatal and nonfatal CVCs was 5.3 and 4.8 per 100 patient/years in groups of conservative and invasive treatment, respectively (relative risk [RR] 0.96, 95% confidence interval [CI] 0.6 to 1.5; p=0.9). Rates of composite end point were 7.1 and 7.3 per 100 years in groups of conservative and invasive treatment, respectively (relative risk [RR] 1.02, 95% confidence interval [CI] 0.7 to 1.3; p=0.8). According to the presence of independent clinical predictors of worst prognosis (class II-III angina, history of myocardial infarction, three vessel or left main stem coronary artery disease, concomitant signs of atherothrombosis in cerebral and peripheral vascular beds, obesity, abnormal renal function, history of erosive gastritis) all patients were divided in groups of low, moderate, and high risk. In low risk IHD patients invasive strategy worsened remote prognosis of myocardial infarction, stroke, and cardiovascular death, as well as of repetitive revascularization.

[Factors determining prognosis of patients with stable ischemic heart disease (results of a five years prospective study)].

Risk stratification seems to be very important in patients with stable coronary artery disease (CAD). However, the prognostic scales are now available only for the early risk assessment in patients with acute coronary syndromes and in patients undergoing percutaneous coronary interventions. Aim of the study was to assess the frequency of cardiovascular events (CVE) during 5 years of follow-up in patients with stable CAD and to construct a long-term risk prediction model for these patients. 503 patients (mean age 59.4 years) were included in the study. The follow-up period ranged between 3.0 and 7.5 years (mean 5.0 years). Main end points were fatal and non-fatal cardiovascular events: cardiovascular death, acute coronary syndromes, ischemic stroke, transient ischemic attack, peripheral arterial thrombosis, and need for revascularization in any affected vascular area. Total frequency of events was 31.0% (5.7/100 patient years). Independent predictors of events were: severity of angina, three vessel coronary disease, previous myocardial infarction, previous stroke/ transient ischemic attack, peripheral arterial disease, obesity, chronic kidney disease and history of erosive gastritis. The presence of more or equal 3 risk factors was significantly associated with increased frequency of CVE.

[Factors determining clinical effectiveness of clopidogrel and prognosis of patients with stable ischemic heart disease].

Aim of the study was to elucidate genetic and drug factors affecting efficacy of clopidogrel in patients with ischemic heart disease - inhabitants of central region of Russian Federation. We included 399 patients with IHD (79% men, mean age 58.3+/-9 years) receiving long term therapy with clopidogrel 75 mg/day (during stable manifestations of the disease) or 75-150 mg/day in combination with aspirin (in relation with recent elective percutaneous interventions). We studied carriage of polymorphisms of genes controlling intestinal absorption of clopidogrel (ABCB1 C3435T), activation of clopidogrel in the liver (CYP2C19 *1 *2), and also registered concomitant administration of proton pump inhibitors (PPI). Then we determined relationship of these factors to development of vascular complications (vascular death/myocardial infarction/requirement in revascularization) during 18 months followup. Among studied genetic factors carriage of allele variants CYP2C19 *1/*2 and *2/* (found in 25.5 and 1.8% of patients, respectively), possessed prognostic significance. In the group of clopidogrel monotherapy carriage of at least one *2 allele was associated with increased rate of vascular complications (33.3% vs. 11.3%) including thrombotic complications (27.7% vs. 3.2%; =0.01). In patients receiving 75 mg/day of clopidogrel in combination with aspirin total rate of thrombotic complications as well as of all adverse unfavorable outcomes was higher in *2 carriers compared with wild type homozygotes (14.0% vs.8.7% and 21.0% vs. 15.8%, respectively). In patients receiving double dose clopidogrel in combination with aspirin we found no worsening of outcomes associated with CYP2C19*2 carriage. In the multifactorial risk model independent predictors of vascular complications turned out to be CYP2C19 *2/*2 homozygosity (RR 4.9; =0.02) and concomitant PPI administration ( 1.8; p=0.05).

[Disturbances of homocysteine metabolism as a risk factor of cardiovascular diseases development: effect on prognosis and possibilities of correction with drugs].

Classical risk factors of development of cardiovascular diseases does not allow to detect all persons needing active prevention. Because of this reason great attention is given to novel biomarkers one of which is homocysteine. Most widely-spread causes of elevation of homocysteine level are such factors as deficit of folic acid and B6 and B12 vitamins, as well as genetic peculiarities. Main damaging effect of homocysteine is activation of atherothrombosis. Therapy with folic acid causes significant lowering of homocysteine level. Effect of therapy with vitamins on the risk of development of cardiovascular diseases has been assessed both in observational epidemiological studies and large prospective randomized trials. Their results are controversial. The present review is devoted to the analysis of these trials.