Longitudinal trajectories of blood lipid levels in an ageing population sample of Russian Western-Siberian urban population

This study investigated 12-year blood lipid trajectories and whether these trajectories are modified by smoking and lipid lowering treatment in older Russians. To do so, we analysed data on 9,218 Russian West-Siberian Caucasians aged 45-69 years at baseline participating in the international HAPIEE cohort study. Mixed-effect multilevel models were used to estimate individual level lipid trajectories across the baseline and two follow-up examinations (16,445 separate measurements over 12 years). In all age groups, we observed a reduction in serum total cholesterol (TC), LDL-C and non-HDL-C over time even after adjusting for sex, statin treatment, hypertension, diabetes, social factors and mortality (P 60 years at baseline). In smokers, TC, LDL-C, non-HDL-C and TG decreased less markedly than in non-smokers, while HDL-C decreased more rapidly while the LDL-C/HDL-C ratio increased. In subjects treated with lipid-lowering drugs, TC, LDL-C and non-HDL-C decreased more markedly and HDL-C less markedly than in untreated subjects while TG and LDL-C/HDL-C remained stable or increased in treatment naïve subjects. We conclude, that in this ageing population we observed marked changes in blood lipids over a 12 year follow up, with decreasing trajectories of TC, LDL-C and non-HDL-C and mixed trajectories of TG. The findings suggest that monitoring of age-related trajectories in blood lipids may improve prediction of CVD risk beyond single measurements

Changes induced in mouse lipid metabolism by simultaneous impact of antisense oligonucleotide derivatives to <i>apoB</i>, <i>PCSK9</i>, and <i>apoCIII</i> mRNAs

Development of new drugs able to decrease the level of “bad” cholesterol, in particular, based on antisense oligonucleotide derivatives (ASOs), remains relevant for the patients with familial hypercholesterolemia and/or intolerant to statins. The goal of the work was to assess the changes in the lipid metabolism caused by variants of joint impact of the ASOs targeted to the mRNAs of its key genes: apoB, PCSK9, and apoCIII. Female C57BL/6J mice; nuclease-protected 13- and 20-nucleotide ASOs, and standard protocols for quantification of lipoproteins (HDL CHL, non-HDL CHL, and total CHL) and ALT in the blood serum were used in the work. The following combinations of ASOs were four times injected to the mouse caudal vein: 1) ASO to apoB, 2) ASO to apoCIII, 3) ASO to apoB and ASO to PCSK9, 4) ASO to apoB, ASO to PCSK9, and ASO to apoCIII, 5) ASO to apoB (three doses), ASO to PCSK9, and ASO to apoCIII (two doses), 6) ASO to PCSK9 and (ASO to apoCIII – only in the fourth administration). Triple weekly administration of these ASO combinations resulted in a decrease in non-HDL CHL by 25, 16, 35, 47, 60, and 7 %, respectively, as compared with the control and 1.8-, 1.5-, 1.9-, 2.4-, 3.1, and 1.24-fold higher HDL CHL/ non-HDL CHL ratio. The subsequent ASO injection with concurrent switching to a high-fat diet after 1 week resulted in a decrease in the non-HDL CHL by 28, 2, 28, 70, 33, and 49 % for ASOs (1–6), respectively, as compared with the control; the HDL CHL/non-HDL CHL ratio was 1.5-, 1.1-, 2-, 3.7-, 1.9-, and 2-fold better. The ALT concentration for all ASO combinations remained within the norm for the control animals, demonstrating the absence of any hepatotoxic effect. The best efficiency of ASOs requires selection of concentrations for single ASOs and their combinations as well as of the order and timing of administration. Thus, a new antisense approach is proposed

Половозрастные особенности распространенности метаболически здорового фенотипа ожирения

Aim. The study objective was to assess the age and gender characteristics of the metabolically healthy obesity phenotype (MHO) prevalence, taking into account various classifications.Materials and methods. The materials used are the cross-sectional studies of the population cohort (Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) project, Novosibirsk), with the total of 3,197 people, among them 857 men (26.8%) and 2,340 women (73.2%), with BMI ≥30 kg/m². The MHO is defined according to different classifications: 1. IDF (International Diabetes Federation, 2005) – Waist circumference (WC) ≥ 94 cm in men and ≥80 cm in women and one or none of the components of metabolic syndrome (MS); 2. NCEP ATP III (the National Cholesterol Education Program Adult Treatment Panel III, 2001) in the presence of 2 and / or less components of the metabolic syndrome and 3. RSC (The Royal Society of Chemistry) – the index of waist circumference / hip circumference (WC / HC) ≤0.9 in men and ≤0.85 in women.Results. According to IDF the frequency of MHO in the group was 23.2%; NCEP ATP III – 41.8; RSC criteria – 27.1%. The frequency of MHO was higher in women than in men, and it significantly decreased with the age in women population. In all classifications, increased average blood pressure (BP) level, with normal average values of the level of triglycerides (TG) and high-density lipoprotein (HDL) is typical for persons with MHO. The surveyed according to the RSC criteria people with MHO demonstrate higher frequency levels of all cardio metabolic risk factors than those surveyed with the use of other criteria of MHO.Conclusion. The frequency of MHO varies depending on the used classification. In women, the frequency of MHO is reliably higher than in men. With the age, a significant reduction of the frequency of MHO in women is manifested. The frequency of arterial hypertension and abdominal obesity, the level of fasting blood glucose and LDL (low density lipoprotein), hypertriglyceridemia is higher in persons with MHO according to the criteria RSC.Цель. Изучить половозрастные особенности метаболически здорового фенотипа ожирения (МЗФО).Материалы и методы. Использованы материалы кросс-секционного исследования популяционной когорты (проект HAPIEE, г. Новосибирск) (n = 3 197 человек, среди них 857 (26,8%) мужчин и 2 340 (73,2%) женщин, с индексом массы тела (ИМТ) ≥30 кг/м²). МЗФО определен в соответствии с различными классификациями: 1) IDF (2005) – окружность талии (ОТ) ≥94 см у мужчин и ≥80 см у женщин и любой компонент метаболического синдрома (МС) по IDF или без него; 2) NCEP ATP III (2001) при наличии 2 и (или) менее компонентов МС; 3) критерии РКО (2017) – индекс окружность талии / окружность бедер (ОТ / ОБ) ≤0,9 у мужчин и ОТ / ОБ ≤ 0,85 у женщин.Результаты. Среди лиц с ожирением частота МЗФО по критериям IDF – 23,2%; NCEP ATP III – 41,8%; РКО – 27,1%. Частота МЗФО выше у женщин, чем у мужчин, и она значимо снижается с возрастом в женской популяции. Для лиц с МЗФО по всем классификациям характерно повышенное среднее значение артериального давления при нормальных средних значениях уровня триглицеридов и холестерина липопротеидов высокой плотности. Обследованные с МЗФО по критериям РКО демонстрируют более высокие показатели частоты всех изучаемых кардиометаболических факторов риска, чем при использовании других критериев МЗФО.Выводы. Частота МЗФО варьирует в зависимости от используемой классификации. У женщин частота МЗФО достоверно выше, чем у мужчин. С возрастом отмечается значимое снижение частоты МЗФО у женщин. Частота артериальной гипертонии, абдоминального ожирения, уровень глюкозы крови натощак, холестерина липопротеидов низкой плотности и гипертриглицеридемия выше у лиц с наличием МЗФО по критериям РКО

INCREASED LDLP SENSITIVITY TO OXIDATION AS A RISK FACTOR FOR ATHEROSCLEROSIS

Increased LDLP sensitivity to oxidation as a risk factor for atherosclerosis

Association of SP-A and SP-D Surfactant Proteins with the Severity of CommunityAcquired Pneumonia

Relevance. In current clinical practice, there is a need for research to find new diagnostic tests for the purpose of determining the patients with the highest risk of death from pneumonia. Surfactant proteins SP-A and SP-D play a key role in the pathogenesis of the response to microbial invasion of lung tissue, which participate in a cascade of reactions of both innate and adaptive immunity, and therefore proteins SP-A and SP-D may be considered as markers of the severity of community-acquired pneumonia (CAP).Aim of study. To evaluate the associations of surfactant proteins SP-A and SP-D in blood plasma with the severity of CAP.Material and methods. The study included 247 patients admitted to the therapeutic department. The group of patients with CAP (n=188) was divided into groups of severe (n=103) and non-severe (n=85) pneumonia. The comparison group (n=59) consisted of patients without acute and chronic diseases of the bronchi and lungs. The mean age (years, Me, 25th; 75th percentile) of patients was 55 (47; 68), 55 (47; 70), and 61 (37; 63) years, respectively. All patients underwent clinical, functional, diagnostic and laboratory studies (including determination of the content of SP-A and SP-D proteins by enzyme immunoassay).Results. In the group of patients with severe pneumonia unlike mild pneumonia, and group of comparison higher levels of proteins SP-A and SP-D were observed. Correlation analysis described below revealed statistically significant connection: protein SP-D — direct relation with leukocyte levels (r=0.320, p&lt;0.0001), erythrocyte sedimentation rate (r=0.331, p&lt;0.0001), inverse relation with blood oxygen saturation (r=-0.407, p&lt;0.0001), for SP-A protein — direct relation with body temperature (r=0.355, p&lt;0.0001), erythrocyte sedimentation rate (r=0.369, p&lt;0.0001) in the blood C-reactive protein (r=0.446, p&lt;0.0001), SP-D (r=0.357, p&lt;0.0001), and also relation with the duration of clinical symptoms (r=0.528, p&lt;0.0001) and blood oxygen saturation (r=-0.401, p&lt;0.0001). When conducting ROCanalysis for the surfactant protein SP-A, the area under the ROC- curve was 0.70, the optimal sensitivity for severe pneumonia was 68%, the specificity was 69% at the SP-A level in blood plasma equal to 42.9 ng/ml. When performing ROC analysis for the surfactant protein SP-D, the area under the ROC curve was 0.64 for severe pneumonia, the optimal sensitivity was 62%, and the specificity was 62% at the SP-D content in blood plasma equal to 319.2 ng/ml.Conclusion. According to the results of this study, the SP-A and SP-D proteins are associated with clinical and laboratory signs that reflect the severity of CAP. Thus, SP-A and SP-D are new laboratory markers of CAP severity

P57

Gastric cancer (GC) remains one of the most important gastrointestinal cancers worldwide. The incidence and mortality rate from GC in Russia is higher in comparison with other European countries and USA. It should be noted that riskometry for the GC doesn’t exist. Parallel assessment of pepsinogen I (PG I), pepsinogen II (PG II), PG I/PG II ratio and gastrin-17 (G-17), as well as antibodies to Helicobacter pylori is an exact and validated set of stomach-specific biomarkers that reflect the extent and grade of gastric atrophy as a main premalignant condition for GC. Aim: To study the diagnostic and predicting value of biomarkers of atrophic gastritis (AG) in retro-prospective cohort case-control study in Siberian population. Object and methods: General population sample was surveyed in Novosibirsk in 2003–2005 (10.000 subjects aged 45–69 years). Each serum sample was deeply frozen and stored. In 2008 and 2012 this database was compared with the data of the Population Cancer Registry. As a result of cross-sectional analysis of two databases 60 novel cases of GC were identified until 2011. For each case of GC, an appropriate control case was selected at the ratio 1:2 matching the area of residence, sex and age. Finally, 156 serum samples (52 – GC group and 104 – control group) were available for the analysis using a panel of serum biomarkers “Gastropanel” (Biohit, Finland). Criteria for “Gastropanel” in the diagnosis of AG were used: PG I <30μg/l, PG II <3μg/l, the ratio PG I/PG II <3, the level of basal G-17<1 pmol/l, and the presence of antibodies to H. pylori. Results: Mean level of biomarkers did not differ between those with, and without GC, with the exception for PG I/PGII ratio, which was significantly lower in GC group. Indicators of gastric atrophy (OR; 95% CI) were associated with GC for PG I (2.9; 1.3–6.4), PG II (9.0; 1.8–44.3), and PG I/PG II (3.3; 1.5–7.3), but neither for G-17 (0.7, 0.4–1.6), nor for the presence of antibodies to H. pylori (0.4; 0.1–1.3). Multivariate regression analysis including sex, age of the patients, all biomarkers of “Gastropanel” confirmed PG I and PGI/PGII ratio as the most powerful indicators in the model. Atrophy Index (AI) was calculated as a sum of abnormal parameters of gastric atrophy (PG I, PG I/PG II ratio and G-17, see Table, ∗p < 0.019; ∗∗p < 0.006). AI 3 (all biomarkers below normal range) was more common in GC patients than in controls. Groups Severity of atrophy (Atrophy Index score) (%) 3 2 1 0 Gastric cancer 14.0∗∗ 20.0 10.0 56.0 Control 2.2 10.8 11.8 75.3∗ Conclusion: As a first step in the development of GC riskometry was found that noninvasive set of serological biomarkers is an informative and non-expensive tool for the early detection of GC in population-based retrospective cohort survey in Siberian population. Low levels of PGI and PGI/PGII ratio were proven as the most valuable prognostic factors. The low level of G-17 as a single index did not significantly predict the risk of GC

P83

To evaluate the clinical symptoms in pancreatic cancer patients (PCa) and compare some biochemical blood serum parameters in patients with different pathology of the pancreas (PCa, acute (OP) and chronic pancreatitis (CP)). Materials and methods: During a one-time clinical research on the type of “series of cases” 130 patients were examined (42 patients with OP, 81 – CP and 7 patients with PCa). The diagnosis of PCa, OP, CP was verified by clinical and instrumental methods. Glucose, cholesterol, triglyceride and bilirubin serum levels were determined by ELISA. Results: The mean age of patients with PCa was 63.6 ± 4.9 years, morbidity duration of PCa – 3.5 ± 1.1 months. Among patients with PCa, 83.3% of people – smoked, 16.7% – smoked every day. Half of the respondents PCa patients noted that over the last year they did not drink alcohol; 16.7% of people – drank alcohol several times a year, and 33.3% of patients consumed alcohol 1–2 times a month. BMI of PCa patients was equal to 26.3 ± 3.5 kg/m2, in OP patients – 23.8 ± 1.0 kg/m2, in CP patients – 26.3 ± 0.6 kg/m2, p > 0.05. In this case, 85.7% of PCa patients noted a significant decrease in body weight (11.7 ± 6.0 kg) for 3–4 months after the onset of symptoms. There was no pain in 42.8% of PCa patients, and frequent pain noted only in 28.6% of persons. Among CP patients, frequent and persistent pain noted in 65.5% of patients and among OP patients in 48.6% of cases. All PCa patients experienced pain in the right upper quadrant. Pain was of low intensity in 75% of cases and moderate in 25% of cases. Elimination of pain was observed in half of the PCa patients, and 1/4 of patients continued to experience pain. Episodes of nausea and vomiting noted in 25% of PCa patients. Bloated feeling in the stomach and overflow were noted in 42.8% of the all surveyed PCa persons. The level of glucose in PCa patients exceeded the normal limits and was significantly higher compared to that in OP and CP patients (8.5 ± 1.4 mmol/L, 5.4 ± 0.3 and 5.1 ± 0.1 mmol/L, respectively, p  0.05). However, the total cholesterol in CP patients was significantly higher than that in PCa and OP patients (5.8 ± 0.1, 5.0 ± 0.6 and 4.1 ± 0.2 mmol/L, p < 0.05). In PCa patients, the elevated levels of some markers of cholestasis and hepatocyte injury were also found: ALP – 185.0 ± 12.7 IU/L, ALT – 108.4 ± 33.5 IU/L, AST – 85.3 ± 31.5 IU/L, amylase – 44.9 ± 14.9 IU/L, fibrinogen – 2696.6 ± 398.6 g/L. Conclusion: The combination of nonspecific clinical signs (pain, dyspepsia) with biochemical markers of biliary pathology and endocrine pancreatic insufficiency – of PCa patients demonstrates the obligatoriness of differential diagnostic pancreatic and biliary pathology in their earlier stages

Assessment of calcification of the coronary arteries and long-term prognosis of cardiovascular disease

Vascular calcification is a distinctive feature of cardiovascular diseases of atherosclerotic origin. Visualization of calcifications is carried out by invasive and non-invasive methods. Knowledge of the presence and degree of calcification can predict clinical outcomes in patients at high risk of coronary events, help in the prevention and treatment of coronary heart disease.The article presents a brief description of the methods of visualization of vascular calcium and a review of studies on the relationship of calcification with the risk of long-term adverse cardiovascular events