scholarly journals Genetics of severe hypercholesterolemia in the general population: Insights from the STANISLAS cohort

2021 ◽  
Vol 12 (3) ◽  
pp. 73-83
Author(s):  
Constance Xhaard ◽  
João Pedro Ferreira ◽  
Edith Le Floch ◽  
Zohra Lamiral ◽  
Claire Dandine-Roulland ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Total Cholesterol ◽  
Low Density Lipoprotein ◽  
Strong Association ◽  
Density Lipoprotein ◽  
Lipid Levels ◽  
Ldlr Gene ◽  
Low Density Lipoprotein Cholesterol ◽  
Heritability Estimation ◽  
Healthy Cohort

Background: Severe hypercholesterolemia (SH) is a common condition characterized by increased levels of total and low-density lipoprotein cholesterol (LDLc). Methods: The aim of this study is to screen for prevalence of hypercholesterolemia, perform heritability estimation of circulating lipoproteins and study the association between SH cases and surrogate cardiovascular disease markers among participants of STANISLAS cohort. Gene candidate analyses were utilized to investigate the association between lipid levels, SH and polymorphisms from the three commonly reported genes (APOB, LDLR and PCSK9). Results: Participants with SH (n=102; 6.9%) were older (58 vs. 51yr), had higher total cholesterol (290 vs. 209mg/dL), LDLc (206 vs. 136mg/dL) and triglycerides (114 vs. 88 mg/dL). Despite smoking less, they had carotid plaques more frequently (21.2 vs. 9.3%), higher cIMT (676 vs. 597µm), and had more frequent family history cardiovascular disease. The circulating lipid levels have an important heritability: LDLc 51.6%, HDLc 66.6%, total cholesterol 49.8%, and triglycerides 41.4%. The SNPs located in LDLR gene present the strongest association with LDLc levels: rs55997232, rs17242395, rs1010679, and rs11668477. Conclusion: In a healthy cohort, participants with SH had premature vascular damage. LDLc had an important component of heritability and SNPs linked to the LDLR gene presented a strong association with LDLc. These findings reinforce the need for an early identification and treatment of SH subjects, which is mostly polygenic.

scholarly journals 10-YEAR RISK ESTIMATION OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASE IN HYPERTENSIVE PATIENTS

2021 ◽  
Vol 9 (2) ◽  
pp. 145-150
Author(s):  
Olha M. Chernatska ◽  
Xaba Sibongumusa
Keyword(s):  
Cardiovascular Disease ◽  
Arterial Hypertension ◽  
Total Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Hypertensive Patients

Arterial hypertension is one of the most common causes of atherosclerotic cardiovascular disease, which is still the reason of mortality for a lot of persons. Assessment of 10-year risk of atherosclerotic cardiovascular disease in hypertensive patients is very important for further treatment improvement. The aim is the absolute 10-year risk assessment of atherosclerotic cardiovascular disease in hypertensive patients for further correction of treatment. We included 61 patients with stage 1 to 2 arterial hypertension into our study. Most of them are women (70%). The patients were (56.84 ± 8.1) years old. The total cholesterol was (4.32 ± 1.0) mmol/l, high and low density lipoprotein cholesterol – (1.35 ± 0.2) mmol/l and (2.44 ± 0.7) mmol/l, respectively. Online calculator «ASCVD Risk Estimator Plus» was used. It included the assessment of age, sex, race, systolic and diastolic blood pressure, total cholesterol, high and low density lipoprotein cholesterol, presence of diabetes, smoking status, hypertension treatment, consumption of statins or aspirin. The risk was classified as low (< 5%), borderline (5% to < 7.5%), intermediate (≥ 7.5% to < 20%), or high (≥ 20%). The results were analyzed statistically using Microsoft Excel. For five persons it was not possible to calculate this risk using the online calculator because of too low values of total cholesterol and low density lipoprotein cholesterol. Low 10-year risk of atherosclerotic cardiovascular disease was confirmed in 30 (53.6%) people, borderline – in 2 (3.6 %), intermediate – in 11 (19.6%), high – in 13 (23.2%). Low absolute 10-year risk of atherosclerotic cardiovascular disease was determined in more than half (53.6%) of patients, high – in about quarter (23.2%), intermediate – in the fifth part (19.6%) of patients with arterial hypertension. For patients with borderline and intermediate risks, it is reasonable to continue therapy with moderate-intensity statins. For hypertensive patients with high risk, high-intensity statin therapy can be recommended and low-dose aspirin might be considered if bleeding risk is not increased. If the absolute 10-year risk of atherosclerotic cardiovascular disease is low, it is reasonable to assess additionally total cardiovascular risk categories and continue moderate-intensity statin therapy in the case of absence of low-density lipoprotein cholesterol goal levels with the next lipid profile assessment in 8 (± 4) weeks.

Risk predictors of arterial hypertension development in population of Mountain Shoriya of various ethnical origins

2019 ◽  
Vol 1 (3) ◽  
pp. 39-42
Author(s):  
T. A. Mulerova ◽  
M. Yu. Ogarkov ◽  
O. L. Barbarash
Keyword(s):  
Cardiovascular Diseases ◽  
Total Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density Lipoprotein Cholesterol ◽  
Type Settlement ◽  
The Family ◽  
Genotype C ◽  
Hypertension Development ◽  
Risk Predictors

1409 people (901 Shors, 508 non-indigenous people) from remote villages of Mountain Shoriya (Orton and Ust-Kabyrsa) and urban-type settlement Sheregesh took part in the survey. In Shors, the risk of developing hypertension was determined by elevated levels of total cholesterol and low density lipoprotein cholesterol, violation of carbohydrate metabolism, obesity, including its abdominal type, the family anamnesis of early cardiovascular diseases, and a carriage of prognostically unfavorable genotypes D/D and C/C of the corresponding genes ACE and AGTR 1 candidates; in the cohort of non-indigenous ethnos-elevated levels of total cholesterol and triglycerides, obesity, abdominal obesity, the family anamnesis of early cardiovascular diseases, a carrier of the minor genotype C/C of the AGTR 1 gene

Low-density lipoprotein cholesterol goal attainment and treatment patterns in a cohort of >143,000 patients with atherosclerotic cardiovascular disease in Ontario, Canada

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Fairbairn ◽  
P Oh ◽  
R Goeree ◽  
R.M Rogoza ◽  
M Packalen ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Goal Attainment ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Data Repository ◽  
Funding Source ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

Abstract Background/Introduction Limited real-world data are available on attainment of low-density lipoprotein cholesterol (LDL-C) treatment goals in patients with atherosclerotic cardiovascular disease (ASCVD) in Canada. Purpose A retrospective observational study was conducted to describe types of ASCVD events/procedures, time between events and use of lipid lowering treatment (LLT) in patients who did not achieve LDL-C goal. Methods Patients in Ontario ≥65 years with a primary ASCVD event/procedure between 1 Apr 2005 and 31 Mar 2016, treated with an LLT and with index and follow up LDL-C values were identified from claims data at the Institute for Clinical Evaluative Sciences data repository. Patients were assessed over a 1-year follow up period for LDL-C goal attainment (&lt;2.0 mmol/L or 50% reduction from index LDL-C) and analysed by LLT and by index event type. Results Overall, 28% of 143,302 patients ≥65 years on LLT failed to attain LDL-C goal at follow up (Figure). The proportion of patients failing to achieve LDL-C goal decreased from 35% to 22% over the 11-year study period. Mean time between index and follow up LDL-C (based on lowest score &gt;2 weeks and up to 1 year after index LDL-C) was 203±97 days. When analysed by low-, moderate- or high-intensity statin, 57%, 30%, and 22% of patients failed to achieve LDL-C goal at follow up, respectively. Conclusions In this study, more than 1 in 4 patients with ASCVD in Ontario failed to achieve guideline recommended LDL-C goal despite treatment. In particular, ∼1 in 3 patients with cerebral and peripheral arterial disease were not at goal. An opportunity exists to better manage these high risk ASCVD patients with further statin intensification and additional LLTs This study made use of de-identified data from the ICES Data Repository, which is managed by the Institute for Clinical Evaluative Sciences with support from its funders and partners: Canada's Strategy for Patient-Oriented Research (SPOR), the Ontario SPOR Support Unit, the Canadian Institutes of Health Research and the Government of Ontario. The opinions, results and conclusions reported are those of the authors. No endorsement by ICES or any of its funders or partners is intended or should be inferred. Parts of this material are based on data and/or information compiled and provided by CIHI. However, the analyses, conclusions, opinions and statements expressed in the material are those of the author(s), and not necessarily those of CIHI Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen Canada Inc.

Eligibility for PCSK9 inhibitors based on the 2019 ESC/EAS and 2018 ACC/AHA guidelines

2020 ◽  
pp. 204748732094010
Author(s):  
Konstantinos C Koskinas ◽  
Baris Gencer ◽  
David Nanchen ◽  
Mattia Branca ◽  
David Carballo ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Coronary Syndrome ◽  
Coronary Syndromes

Aims The 2018 American College of Cardiology (ACC)/American Heart Association (AHA) and 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) lipid guidelines recently updated their recommendations regarding proprotein convertase subtilisin/kexin-9 inhibitors (PCSK9i). We assessed the potential eligibility for PCSK9i according to the new guidelines in patients with acute coronary syndromes. Methods and results We analysed a contemporary, prospective Swiss cohort of patients hospitalised for acute coronary syndromes. We modelled a statin intensification effect and an incremental ezetimibe effect on low-density lipoprotein-cholesterol levels among patients who were not on high-intensity statins or ezetimibe. One year after the index acute coronary syndrome event, treatment eligibility for PCSK9i was defined as low-density lipoprotein-cholesterol of 1.4 mmol/l or greater according to ESC/EAS guidelines. For ACC/AHA guidelines, treatment eligibility was defined as low-density lipoprotein-cholesterol of 1.8 mmol/l or greater in the presence of very high-risk atherosclerotic cardiovascular disease, defined by multiple major atherosclerotic cardiovascular disease events and/or high-risk conditions. Of 2521 patients, 93.2% were treated with statins (53% high-intensity statins) and 7.3% with ezetimibe at 1 year, and 54.9% had very high-risk atherosclerotic cardiovascular disease. Low-density lipoprotein-cholesterol levels less than 1.8 mmol/l and less than 1.4 mmol/l at 1 year were observed in 37.5% and 15.7% of patients, respectively. After modelling the statin intensification and ezetimibe effects, these numbers increased to 76.1% and 49%, respectively. The proportion of patients eligible for PCSK9i was 51% according to ESC/EAS criteria versus 14% according to ACC/AHA criteria. Conclusions In this analysis, the 2019 ESC/EAS guidelines rendered half of all post-acute coronary syndrome patients potentially eligible for PCSK9i treatment, as compared to a three-fold lower eligibility rate based on the 2018 ACC/AHA guidelines.

Abstract P102: Variability In Lipid Levels And Risk For Cardiovascular Disease: An Electronic Health Record-based Population Cohort Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Sheila M Manemann ◽  
Suzette J Bielinski ◽  
Ethan D Moser ◽  
Jennifer L St. Sauver ◽  
Paul Y Takahashi ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Electronic Health Record ◽  
Total Cholesterol ◽  
Index Date ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Health Record ◽  
Lipid Levels ◽  
Population Cohort ◽  
Increased Risk

Background: Larger within-patient variability of lipid levels has been associated with an increased risk of cardiovascular disease (CVD). However, measures of lipid variability are not currently used clinically. We investigated the feasibility of calculating lipid variability within a large electronic health record (EHR)-based population cohort and assessed associations with incident CVD. Methods: We identified all individuals ≥40 years of age who resided in Olmsted County, MN on 1/1/2006 (index date) without prior CVD. CVD was defined as myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention or stroke. Patients with ≥3 measurements of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and/or triglycerides during the 5 years before the index date were retained in the analyses. Lipid variability was calculated using variability independent of the mean (VIM). Patients were followed through 9/30/2017 for incident CVD (including CVD death). Cox regression was used to investigate the association between quintiles of lipid VIMs and incident CVD. Results: We identified 18,642 individuals (mean age 60; 55% female) who were free of CVD at baseline and VIM calculated for at least one lipid measurement. After adjustment, those in the highest VIM quintiles of total cholesterol had a 25% increased risk of CVD (Q5 vs. Q1 HR: 1.25, 95% CI: 1.08-1.45; Table). We observed similar results for LDL-C (Q5 vs. Q1 HR: 1.20, 95% CI: 1.04-1.39) and HDL-C (Q5 vs. Q1 HR: 1.25, 95% CI: 1.09-1.43). There was no association between triglyceride variability quintiles and CVD risk. Conclusion: In a large EHR-based population cohort, high variability in total cholesterol, HDL-C and LDL-C was associated with an increased risk of CVD, independently of traditional risk factors, suggesting it may be a target for intervention. Lipid variability can be calculated in the EHR environment but more research is needed to determine its clinical utility.

scholarly journals Study on the influence of 7-β-hydroxy-γ-aryloxypropylxanthinyl-8-thioalkanic acid derivatives on the lipid metabolism in experiment

2021 ◽  
Vol 23 (3) ◽  
pp. 411-416
Author(s):  
I. M. Bilai ◽  
M. I. Romanenko ◽  
D. H. Ivanchenko
Keyword(s):  
Side Effects ◽  
Total Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Lipoprotein Cholesterol ◽  
Atherogenic Index ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Xanthine Derivatives

Statin side effects are not a rare occurrence, in particular dyspeptic disorders, insomnia, headache, skin erythema, rash are often noted. All of this determines scientists to find new effective and low-toxic hypolipidemic agents. Various natural and synthetic xanthine derivatives have been recognized as therapeutically potential compounds and reported to control various diseases. Therefore, the study of new xanthine derivatives and their hypolipidemic effects, which would have a significant therapeutic effect with minimal side effects, is relevant. The aim of the study was to examine the effect of 7-β-hydroxy-γ-aryloxypropylxanthinyl-8-thioalkanic acid derivatives on lipidogram parameters in experimental laboratory rats. Materials and methods. The objects of the study were 7-β-hydroxy-γ-aryloxypropylxanthinyl-8-thioalkanic acid derivatives. The experiments were performed in white laboratory Wistar rats weighing 180–220 g. Experimental modeling of hyperlipidemia – tween model: intraperitoneal administration of tween-80 at a dose of 200 mg/100 g body weight. The test compounds were administered orally, simultaneously with tween, at a dose of 1/10 of LD50 (previously calculated by Prozorovsky express method) for 6 days. The following indicators of lipidogram were determined: total cholesterol (TC), high-density lipoprotein cholesterol (HDL cholesterol), low-density lipoprotein cholesterol (LDL cholesterol), triglycerides (TG) and atherogenic index of plasma: TC – HDL cholesterol / HDL cholesterol. The experiments were carried out with respect to Bioethical rules and norms. Results. The studies have shown data on the hypolipidemic activity of 7-β-hydroxy-γ-aryloxypropylxanthinyl-8-thioalkane acid derivatives. According to the conditional efficiency index Ʃ, which included the overall percentage of the following indicators – total cholesterol, low-density lipoprotein cholesterol and triglycerides, the leading compounds were 2439 (87.47 %), 6047 (82.30 %). The reference drug atorvastatin had a value of 82.98 %. Conclusions. The major compound was 2439 identified among all compared to the control group. The prospect of further research is a more detailed study on the ability of xanthine derivatives to exhibit hypolipidemic effects and to influence oxidative stress in various hyperlipidemic models.

scholarly journals PSV-15 Influence of the temperament of water buffaloes on the serum lipid levels

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 221-222
Author(s):  
Caroline L Francisco ◽  
André M Castilhos ◽  
Daiane C Marques da Silva ◽  
Fabiola Martinez da Silva ◽  
Aline S Aranha ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Repeated Measures ◽  
Serum Lipid ◽  
Fixed Effects ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipid Levels ◽  
Water Buffaloes ◽  
Serum Lipid Levels

Abstract This study evaluated the effect of the temperament of 75 water buffaloes of three genetic groups (GG: Jafarabadi, Mediterranean, and Murrah; n = 25 for each GG) on serum lipid levels. The animals were classified for temperament through the temperament score (TSc) obtained by the mean of the sum of the scores of the entry time into the squeeze chute (1 to 5: 1=greater time spent for entry, and 5=less time spent for entry) and the exit velocity score (1 to 5: 1=lower speed, and 5=higher speed) calculated after the period of adaptation to the feedlot (d0). The animals were categorized into adequate (ADQ; TSc≤3) or excitable (EXC; TSc &gt;3) temperaments. Blood samples were collected from the jugular vein on days -28, 0, and 84, and evaluated for serum levels of total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) using colorimetric enzymatic analyses performed by commercial kits. Data were analyzed using MIXED procedure in SAS, considering the GG, temperament, day, and the resulting interactions as fixed effects. The term day was used for repeated measures in time. Correlations were estimated using the CORR procedure in SAS. There were no interactions for the variables evaluated (P ≥ 0.11). ADQ animals showed lower levels of total cholesterol (65.95 vs 70.96mg/dL for ADQ and EXC, respectively; SEM=2.33; P = 0.04) and LDL (26.74 vs 30.40mg/dL for ADQ and EXC, respectively; SEM=1.57; P = 0.02) than EXC animals. There was no effect of temperament for the triglycerides (P = 0.41), HDL (P = 0.47), and VLDL (P = 0.46). Positive correlations were verified between both the TSc and triglycerides (r=0.32; P &lt; 0.01), and TSc and VLDL (r=0.33; P &lt; 0.01). Tendency for a positive correlation was detected between TSc and LDL (r=0.20; P = 0.09). In conclusion, there are differences in serum lipid levels between water buffalo temperaments which deserves further investigation. Supported by FAPESP (#2018/25939-1; #2014/05473-7).

scholarly journals Focus on… Praluent®

2020 ◽  
pp. 175-178
Author(s):  
L Steyn
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Pivotal Role ◽  
Atherosclerotic Cardiovascular Disease ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipoprotein Receptors

Cholesterol plays a pivotal role in the functioning of healthy cells. Being mostly lipophilic, cholesterol is transported in the blood inside lipophilic particles, e.g. high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL). Hypercholesterolaemia refers to elevated low-density lipoprotein cholesterol (LDL-C) levels, and increases the risk for premature atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein receptors (LDL-R) on the surface of hepatocytes, are the primary receptors involved in clearing circulating LDL-C.

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