Factors Determining the Three-Year Dynamics of Lipid Metabolism Indicators in Residents of a Large Industrial Region of Siberia

Aim. To assess the contribution of traditional and socio-economic factors to the development and dynamics of dyslipidemia based on the results of an epidemiological study in a large region of Siberia.Material and methods. Clinical and epidemiological prospective study of the population 35-70 years old was carried out. At the basic stage, 1600 participants were examined, including 1124 women and 476 men, the prospective stage included 807 respondents (the response was 84.1%). A survey was carried out to find out the state of health (presence of diseases, taking medications), socio-economic status (level of education and income, marital status) and the presence of behavioral risk factors (tobacco and alcohol use).Results. The proportion of people with hypercholesterolemia increased 1.2 times, low LDL – 1.1 times, and hypertriglyceridemia and low HDL – 1.7 times. In persons with hypertriglyceridemia, the frequency of detected obesity and hypertension decreased by 7.9% and 4.6%, respectively (p = 0.046). Obesity was associated with an increased risk of developing hypercholesterolemia (OR = 1.49, CI: 1.0-2.2), hypertriglyceridemia (OR = 2.14, CI: 1.5-3.0), high LDL cholesterol (OR = 2.16, CI: 1.3-3.6) and low HDL cholesterol (OR = 2.07, CI: 1.5-2.9). The presence of hypertension - with an increased risk of developing hypertriglyceridemia (OR = 2.19, CI: 1.5-3.1) and low HDL (OR = 2.49, CI: 1.8-3.5). Among people with low HDL levels, the number of smokers and drinkers decreased (by 7.0% and 5.7%, respectively), as well as those with obesity by 8.6%. The prevalence of dyslipidemia increased in all socioeconomic groups.Conclusion. Over 3 years of follow-up, there was a statistically significant increase in the proportion of persons with dyslipidemia in all socio-economic groups. There was a significant decrease in such risk factors as obesity, hypertension, smoking, alcohol consumption and an increase in the number of respondents taking lipid-lowering therapy.

PCSK9 Inhibitors in Clinical Practice: Experience of a Specialized Lipid Center

Aim. To characterize patients receiving PCSK9 inhibitors, and assess the efficiency of their treatment in a specialized lipid center.Material and methods. A retrospective analysis of the medical records of patients who visited the Lipid clinic of the National Medical Research Center for Therapy and Preventive Medicine (Moscow, Russia), receiving PCSK9 inhibitor and having lipid profile in dynamics, was carried out (n=77). Cardiovascular risk (CVR) and low-density lipoprotein cholesterol (LDL-C) target levels were evaluated in accordance with the Russian guidelines for the diagnostics and correction of dyslipidemias 2020.Results. Of 77 patients taking PCSK9 inhibitors (44.2% males, the median of age 56 [47; 66] years), the majority (64.0%) had a probable or definite familial hypercholesterolemia (FH). The proportion of other lipid metabolism disorders, pure hypercholesterolemia and combined hyperlipidemia was 21% and 15%. More than half of the patients (68.8%) had a very high CVR, mainly due to the presence of coronary heart disease (84.9%). The proportion of patients receiving PCSK9 inhibitors as monotherapy was 7.8%, in combination with high-intensity statin therapy – 33.8%, as part of triple lipid-lowering therapy (high-intensity statin, ezetimibe, PCSK9 inhibitors) – 50.6%. Addition of PCSK9 inhibitors to combined lipid-lowering therapy enabled to reduce the LDL-C level to 1.02 [0.62; 1.39] mmol/l with its total decrease from the baseline by 87.3%. While taking PCSK9 inhibitors, LDL-C <1.8 mmol/l and <1.4 mmol/l achieved at 78.3% and 57.7% FH patients with high and very high CVR, respectively. Among patients with other hyperlipidemias, 74.1% of patients with very high CVR was achieved the target LDL-C level <1.4 mmol/l.Conclusion: In a specialized lipid center, PCSK9 inhibitors are prescribed to patients with high or very high CVR, most of whom are FH patients. The effectiveness of the use of PCSK9 inhibitors in real-world practice is comparable to the results of clinical trials.

Unsolved Issues of Atherosclerosis Prevention and of Adequate Lipid-lowering Therapy in Patients with Acute Ischemic Cerebrovascular Accident

The existing system of medical care for patients with acute cerebrovascular accident of atherothrombotic genesis, namely lipid metabolism disorders, the modern evidence base for lipid-lowering therapy in this category of patients and the feasibility of interdisciplinary interaction of cardiologists and neurologists were discussed at a meeting of the expert council of cardiologists and neurologists in Moscow on 2021 July 7.

Effectiveness of lipid-lowering therapy in outpatients with coronary artery disease living in a large industrial center of Eastern Siberia

Aim. To study the prescription rate of lipid-lowering therapy and achieving the target low-density lipoprotein cholesterol (LDL-C) values in outpatients with coronary artery disease (CAD) living in Krasnoyarsk.Material and methods. The study included all patients with CAD hospitalized in the cardiology department of the clinic of the Research Institute of Medical Problems of the North (Krasnoyarsk) in 2018-2019. The analysis included data from 1671 patients (men, 770; women, 901). During hospitalization, an in-depth survey of patients was carried out on the subject of prescribing and taking lipid-lowering drugs. On admission, lipid profile was assessed in all patients.Results. At the time of admission, only 51,4% of patients received lipidlowering therapy. The majority received statin monotherapy (99,2%). Only 0,8% of patients received combination therapy (statin+ezetimibe). The most frequently prescribed statin in the study was atorvastatin — 74,6%. Rosuvastatin was received by 17,1% of patients. In most cases, the doses of atorvastatin and rosuvastatin corresponded to the moderate-intensity statin therapy regimen. The frequently prescribed dose of atorvastatin was 20 mg/day — 54,4%, rosuvastatin — 10 mg/day — 68,7%. The target level of LDL-C <1,8 mmol/L was reached by 16,3%, <1,5 mmol/L — by 9,0%, <1,4 mmol/L — only 6,5% of patients. Most often, the target LDL-C levels were achieved by patients receiving high-intensity statin (HIS) therapy. The target level of LDL-C <1,8 mmol/L was reached by 37,5%, <1,5 mmol/L — 23,9%, LDL cholesterol <1,4 mmol/L — 20,7% of patients, receiving HIS.Conclusion. In patients with CAD living in Krasnoyarsk, the most commonly prescribed statins were atorvastatin and rosuvastatin, but only 32% of patients received HIS. Combination lipid-lowering therapy has been used extremely rarely. Among the surveyed patients, the current target level of LDL-C for patients with CAD (<1,4 mmol/L) was achieved only in 6,5% of patients. In the group of patients receiving high-intensity statin therapy, this target level was achieved in 20,7% of patients, which indicates the need for strict adherence to current clinical guidelines.

NAFLD fibrosis score is correlated with PCSK9 and improves outcome prediction of PCSK9 in patients with chest pain: a cohort study

Background The risk of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) can be easily evaluated by noninvasive scoring systems, of which the NAFLD fibrosis score (NFS) is the most commonly used. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a new predictor of cardiovascular events, has been reported to be associated with cardiovascular outcomes and NAFLD. However, the relationship of NFS with PCSK9 and their prognostic abilities in cardiovascular risks are unknown. Methods A total of 2008 hospitalized subjects who had chest pain without lipid-lowering therapy were consecutively included. Baseline clinical data were collected, and the NFS was calculated. The circulating PCSK9 concentration was determined by enzyme immunoassay. The major adverse cardiovascular event (MACE) occurrences were recorded in the follow-up period. Associations of PCSK9 concentration with NFS were examined. All of the participants were categorized into three groups according to NFS levels and were further stratified by PCSK9 tertiles to evaluate the MACEs. Results 158 (7.87%) MACEs were observed during a mean of 3.2 years of follow-up. NFS levels were independently related to higher PCSK9 levels according to multivariable linear regression analysis. Furthermore, elevated PCSK9 and NFS concentrations were respectively associated with increased MACE incidence in multivariable Cox regression models. When combining NFS status with PCSK9 tertiles as a stratifying factor, patients with intermediate-high NFS and high PCSK9 levels had higher risks of events than those with low NFS and low PCSK9 levels. Conclusions This study revealed for the first time that NFS is positively related to PCSK9 and that the combination of NFS and PCSK9 greatly increased the risk of MACEs in patients with chest pain, providing a potential link between NFS and PCSK9 for predicting cardiovascular events.

ST-elevation myocardial infarction complicated by cardiac arrest in a young patient with familiar dyslipidemia

Coronary heart disease in young patients always poses great challenges for every healthcare system with differences in clinical manifestations, etiology, epidemiology, angiographic characteristics and prognosis. The objective of this study was to describe a case of ST-elevation myocardial infarction complicated by cardiac arrest in a young patient with familial dyslipidemia. A 30-year-old male visited our hospital with typical angina. During the examination, he suffered a sudden loss of consciousness, the monitor showed ventricular fibrillation. After successful resuscitation of cardiac arrest, electrocardiography showed apparent ST-elevation from V2 to V6 leads consistent with the diagnosis of anterolateral infarction. Emergency coronary angiogram showed severe three-vessel lesions including complete occlusion of the LAD artery and 80 - 90% stenosis of the other two coronary branches. Our patient’s coronary arteries were revascularized using drug-eluting stents in LAD artery and subsequently RCA artery, stem cell therapy was applied during the interventional process. Routine laboratory test results showed dyslipidemia and his family records suggested familiar (hereditary) dyslipidemia which affected his mother and sister. 1-month follow-up echocardiography showed a drastic improvement of LVEF by roughly 15%. The combination of revascularization, stem cell therapy, and lipid-lowering therapy has shown a good therapeutic effect.

Inclisirán as an alternative treatment for Hypercholesterolemia

Hypercholesterolemia (CH) is defined as the elevation of serum cholesterol levels, especially low-density lipoprotein (LDL) cholesterol, which is considered to be one of the most relevant risk factors for triggering cardiovascular disease, for This is vitally important to start treatment, there are several highly useful pharmacological groups for lipid-lowering therapy, among them we highlight the PCSK9 inhibitors, among the molecules that are part of this group we find inclisirán, this being a structure that promises a lot in regarding the management of hypercholesterolemia.

Control of Low-Density Lipoprotein Cholesterol in Secondary Prevention of Coronary Artery Disease in Real-Life Practice: The DAUSSET Study in French Cardiologists

Introduction: Patients with established coronary artery disease (CAD) are at very high risk for cardiovascular events. Methods: The DAUSSET study is a national, multicenter, non-interventional study that included very high-risk CAD patients followed by French cardiologists. It aimed to describe real-life clinical practices for low-density lipoprotein (LDL) cholesterol control in the secondary prevention of CAD. Results: A total of 912 patients (mean age, 65.4 years; men, 76.1%; myocardial infarction, 69.4%; first episode, 80.1%) were analyzed. The LDL cholesterol goal was 70 mg/dL in most cases (84.9%). The LDL cholesterol goal <70 mg/dL was achieved in 41.7% of patients. Of the 894 (98.0%) patients who received lipid-lowering therapy, 81.2% had been treated more intensively after the cardiac event, 27.0% had been treated less intensively and 13.1% had been maintained. Participating cardiologists were very satisfied or satisfied with treatment response in 72.6% of patients. Moderate satisfaction or dissatisfaction with lipid-lowering therapy was related to not achieving objectives (100%), treatment inefficacy (53.7%), treatment intolerance (23.4%) and poor adherence (12.3%). Conclusion: These real-world results show that lipid control in very high-risk patients remains insufficient. More than half of the patients did not achieve the LDL cholesterol goal. Prevention of cardiovascular events in these very high-risk patients could be further improved by better education and more intensive lipid-lowering therapy.

Pharmacogenetic loci for rosuvastatin are associated with intima-media thickness change and coronary artery disease risk

Aim: Polymorphisms at LPA, LDLR, APOE, APOC1, MYLIP and ABCG2 are attractive targets for assessment of their impact on lipid-lowering therapy with rosuvastatin. The present study investigated whether polymorphisms at these genes are associated with the risk of coronary artery disease (CAD) development, and reduction of atherogenic lipids and carotid intima-media thickness (CIMT) in CAD patients, taking rosuvastatin. Materials & methods: 190 CAD patients and 1697 subjects were enrolled in pharmacogenetic and genetic association study, respectively. SNP genotyping was done using the MassARRAY-4 system. Results: MYLIP rs6924995, rs3757354, APOC1 rs445925, LDLR rs6511720, APOE rs7412, ABCG2 rs2199936, rs1481012 variants were significantly associated with CAD susceptibility (p = 0.016, 0.0003, <0.0001, <0.0001, 0.013, 0.016, 0.0035, respectively), as well as with CIMT regression (except ABCG2 variants; p = 0.05, 0.039, 0.039, 0.016, 0.0065), and changes in plasma lipids during rosuvastatin therapy. Conclusion: The studied polymorphisms possess pleiotropic effects on plasma lipids and CIMT, CAD susceptibility, and determine lipid-lowering response to rosuvastatin.

Lipid lowering therapy in primary and secondary prevention in Austria: are LDL-C goals achieved?

Summary Background Cardiovascular disease (CVD) is the most frequent cause of death in Austria. The European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines recommend intensive lipid lowering therapy (LLT) in patients at high or very high CV risk. Lipid management and achievement of low-density lipoprotein cholesterol (LDL-C) goals in Austria have not recently been assessed. Methods Subgroup analysis for Austria of a European 18 country, cross-sectional, observational study. Patients received LLT for primary (PP) or secondary prevention (SP). Data including LLT in the preceding 12 months and most recent LDL‑C were collected during a single visit between June 2017 and November 2018. Achievement of the risk-based 2016 and 2019 ESC/EAS LDL‑C goal while receiving stabilized LLT was assessed. Results A total of 293 patients were enrolled from 8 Austrian sites, of which 200 (PP = 104, SP = 96) received stabilized LLT at the LDL‑C measurement date. Overall, 58% (71% PP, 43% SP) and 38% (52% PP, 23% SP) achieved the risk-based 2016 and 2019 goals, respectively. Most patients received moderate-intensity statin monotherapy (46%), while 34% used high-intensity statin monotherapy. Combination therapy of moderate/high-intensity statin with ezetimibe (12%), or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors with statin ± ezetimibe (1%), was used infrequently. Conclusion The current Austrian routine lipid management using mainly moderate-intensity or high-intensity statin monotherapy is insufficient to attain ESC/EAS guideline goals, in particular the more stringent 2019 recommendations, a situation comparable to other participating European countries. In addition to switching to and optimizing doses of high-intensity statins, a combination with ezetimibe or PCSK9 inhibitors will be needed in many cases.