Cholesterol Lowering Biotechnological Strategies: From Monoclonal Antibodies to Antisense Therapies. A Pre-Clinical Perspective Review.

In recent years, the increase in available genetic information and a better understanding of the genetic bases of dyslipidemias has led to the identification of potential new avenues for therapies. Additionally, the development of new technologies has presented the key for developing novel therapeutic strategies targeting not only proteins (e.g., the monoclonal antibodies and vaccines) but also the transcripts (from antisense oligonucleotides (ASOs) to small interfering RNAs) or the genomic sequence (gene therapies). These pharmacological advances have led to successful therapeutic improvements, particularly in the cardiovascular arena because we are now able to treat rare, genetically driven, and previously untreatable conditions (e.g, familial hypertriglyceridemia or hyperchylomicronemia). In this review, the pre-clinical pharmacological development of the major biotechnological cholesterol lowering advances were discussed, describing facts, gaps, potential future steps forward, and therapeutic opportunities.

[Cardiovascular effects of omega-3 polyunsaturated fatty acids: position of omega-3 polyunsaturated fatty acids in Russian and international guidelines. Council of Experts].

This Expert Council focuses on the meta-analysis of studies on the risk of atrial fibrillation (AF) in patients taking omega-3 polyunsaturated fatty acids (PUFA) and of data on the omega-3 PUFA treatment in patients with cardiovascular and kidney diseases.The major statements of the Expert Council: the meta-analysis of AF risk in patients taking omega-3 PUFA showed an increased risk of this arrhythmia. However, it should be taken into account that the risk of complications was low, and there was no significant increase in the risk of AF when omega-3 PUFA was used at a dose of ≤1 g and a standard dose of the only omega-3 PUFA drug registered in the Russian Federation, considering all AF episodes in the ASCEND study.At the present time, according to Russian and international clinical guidelines, the use of omega-3 PUFA can be considered in the following cases: • for patients with chronic heart failure (CHF) with reduced left ventricular ejection fraction as a supplement to the basic therapy (2B class of recommendations according to the 2020 Russian Society of Cardiology guidelines (RSC) and the 2022 AHA / ACC / HFSA guidelines); • for patients with hypertriglyceridemia (>1.5 mmol/l) as a part of combination therapy (IIb class of recommendations and B level of evidence according to the 2021 European guidelines on cardiovascular disease prevention, etc.); • for adult patients with stage 3-4 chronic kidney disease (CKD), long-chain omega-3 PUFA 2 g/day is recommended for reducing the level of triglycerides (2C class of recommendations). Data on the use of omega-3 PUFA for other indications are heterogenous, which can be partially explained by using different form and doses of the drugs.

Vascular Age Concept: Which Approach Is Preferable in Clinical Practice?

AIM: to compare various approaches to estimation of vascular age in patients from sample of citizens of Saint-Petersburg (SPB) with arterial pressure (AP) above 130 / 80 mm Hg without history of cardiovascular events. MATERIALS AND METHODS: Examination of a population sample of SPB citizens (n=1600) was carried out within framework of the observational epidemiological study ESSE-RF (ЭССЕ-РФ) in 2012-2013. We selected from this sample 477 women and man aged 40-65 years without history of cardiovascular events, diabetes, or chronic kidney disease, and AP >130 / 80 mm Hg. Examination included anthropometry, sampling of fasting blood for measurement of lipids, glucose, creatinine levels, urine sampling for determination of albumin excretion, and AP measurement in ac-cordance with standard methods. The SCORE scale was used of evaluation of 10-year risk of fatal stroke and fatal myocardial infarction. Volume sphygmography (VaSera device) was applied for determination of cardio-ankle vascular index (CAVI) with calculation of vascular age, and ankle-brachial index. ASCORE scale was used for determination of сalculated vascular age was determined with help of the ASCORE scale. RESULTS: Mean age of participants (182 men [38.2 %], 295 women [61.8 %]) was 52.5±6.2 years. Calculated and instrumental methods of determination of vascular age and early vascular aging had low concordance (κ = 0.099). With elevation of cardiovascular risk early vascular aging was more frequently detected by method of its calculation ASCORE than with instrumental method (VaSera). In the absence of achievement of target AP level signs of early vascular aging were significantly more often detected by the method of vascular age calculation than by the instrumental method VaSera. CONCLUSION: Application of the concept of vascular age and early vascular aging syndrome might be an effective tool for stratification of cardiovascular risk by a physician and improvement of adherence of a patient. This is especially actual for young patients with burdened heredity. One can assume that estimation of virtual risk factor load on blood vessels by the ASCORE method of calculation is more sensitive to detection of premature vascular aging, while requiring less financial and organizational efforts.

[Adipokines Level in Metabolically Healthy Obese Saint-Petersburg Inhabitants (ESSE-RF)].

AIM: to elucidate prevalence of phenotypes of metabolically heathy obesity (MHO) among inhabitants of Saint-Petersburg using various criteria and assess dependence levels of adipokines on obesity phenotype. MATERIAL AND METHODS: Within a framework of epidemiologic study ESSE-RF we formed a random sample of 1600 Saint-Petersburg inhabitants stratified according to gender and age. Examination of participants included anthropometry with measurement of waist circumference CRP and estimation of body mass index (BMI), measurement of arterial pressure, determination of fasting blood glucose, insulin (with calculation of index of insulin resistance -IIR), lipid spectrum, C-reactive protein (CRP), adiponectin, leptin. In subjects with obesity (BMI more or equal 30 kg/m) we used Meigs and Wildman MHO criteria. To Wildman criteria we applied 3 variants of definition of elevated CRP and IIR: 90th percentile among subjects with BMI <25 kg/m (variant 1) or among all participants (variant 2), and (variant 3) definition from publication by E.Oliveros et al. (2014). RESULTS: Obesity (BMI more or equal 30 kg/m) was found in 430 participants. Numbers/rates of MHO according to the Wildman criteria were the following: variant 1 - 49/12% (among them 13/10% men and 36/14% women, =0.15); variant 2 - 85/22% (24/18% men, 61/23% women, =0.13); variant 3 - 59/15% (13/10% men, 46/18% women, =0.02). Portion of MHO according to Meigs criteria was 138/35% (among them 48/36% men, 90/35% women, =0.4). Significant differences in adipokines levels between subjects with MHO and metabolically unhealthy obesity (MUHO) were revealed only among women. There was no difference in leptin level between subjects with MHO and MUHO irrespective of gender. CONCLUSION: Rate of MHO phenotype in a sample of inhabitants of Saint-Petersburg varied from 12 to 35% depending on criteria used. Gender differences in MHO rates were minimal and depended on selected criteria. Elevated adiponectin level among obese women could be presumably related to more favorable metabolic profile.

[Gender Differences of Behavioral Risk Factors in Saint-Petersburg Inhabitants].

BACKGROUND: In developed countries there are significant gender differences in lifetime expectancy that can be explained by behavioral risk factors (RF). OBJECTIVE: The aim of our study was to estimate gender features of behavioral RF in general population of Saint-Petersburg, Russia. METHODS: As a part of all-Russian epidemiology survey ESSE-RF a random sampling of 1600 Saint-Petersburg inhabitants (25-64 y.o.) stratified by age and sex was performed. All participants filled in the questionnaire. Anthropometry (weight, height, body-mass index (BMI), waist circumference (WC) and fasting blood-tests (lipids, glucose by Abbott Architect 8000 (USA)) were performed. RESULTS: There were examined 573 (36%) men and 1027 (64%) women. No gender differences in obesity were found according to BMI criteria--in 178 (31.2%) women and 352 (35.1%) men. Obesity was more often detected in females according to WC criteria: ATPIII--44.1 vs 30.3%; IDF 51.2 vs 66.4% (p < 0.001 for both). Linear regression analysis was performed and age was associated with BMI--1.6 kg/m2/decade, WC in women--5.2 cm/decade and WC in men--2.8 cm/decade, p < 0.001 for all anthropometric parameters. Optimal level of physical activity was equally documented in both genders--540 (61.2%) women and 286 (58.9%) men. Daily intake of sweets was lower in men--228 (39.8%) vs 539 (52.5%) in women (p < 0.001). 810 (50.6%) of trial subjects were non-smokers, 395 (24.7%) were former smokers, and 395 (24.7%) were smokers at the moment of trial. The higher number of female smokers was observed--194 (19.1%). CONCLUSION: A high prevalence of obesity is observed in sample of Saint-Petersburg inhabitants--it is higher among women according to WC criteria regardless of menopause, possibly due to bigger sweets consumption. Males smoke more often and consume less fresh fruits and vegetables which is accompanied by a higher prevalence of hyperglycemia and hypertriglyceridemia.

Large artery stiffness according to different assessment methods in adult population of St.Petersburg.

OBJECTIVE: The aim of the present study was to assess the prevalence of increased arterial stiffness by different diagnostic methods and its association with cardiovascular risk in Russian population-based cohort. DESIGN AND METHODS: In terms of Russian epidemiological study ESSE-RF a random selection of 452 apparently healthy Saint-Petersburg inhabitants aged 25-65 years was performed. Fasting lipids, glucose and blood pressure measurements were performed. We used 3 diagnostic methods of arterial stiffness assessment: pulse wave velocity by applanation tonometry (SphygmoCor - PWV-S) and pulse wave velocity by volumetric sphygmography (VaSera - PWV-V), and cardio-ankle vascular index (CAVI) by VaSera. RESULTS: 341 (75,4%) had normal parameters of arterial stiffness assessed by all methods. Spearmen's coefficient of correlation and "kappa" coefficient for PWV-S and CAVI were 0,74 and 0,04, for PWV-S and PWV-V - 0,10 and 0,06, for CAVI and PWV-V - 0,28 and 0,03, respectively. There was a significant correlation between cardiovascular risk (defined by SCORE) and PWV-S (r = 0,38, p < 0,001) and a non-significant trend of increasing CAVI along with cardiovascular risk (r = 0,35, p = 0,14). CONCLUSIONS: Different methods of arterial stiffness assessment showed a weak correlation with each other. Carotid-femoral pulse wave velocity detected by applanation tonometry is associated with high cardiovascular risk score and might be considered as better additional risk marker for cardiovascular risk stratification.