scholarly journals Relationship between genetic polymorphism of drug transporters and the efficacy of Rosuvastatin, atorvastatin and simvastatin in patients with hyperlipidemia

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Andrey Sivkov ◽  
Natalya Chernus ◽  
Roman Gorenkov ◽  
Sergey Sivkov ◽  
Svetlana Sivkova ◽  
...  
Keyword(s):  
Genetic Polymorphism ◽  
Drug Transporters ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Hypolipidemic Effect ◽  
Low Density Lipoprotein Cholesterol ◽  
Mdr1 Polymorphism ◽  
Lipid Lowering Effect ◽  
Efficacy Of Treatment

Abstract Background To determine the effect of genetic polymorphism of drug transporters on the efficacy of treatment with Rosuvastatin, Atorvastatin and Simvastatin in patients with hyperlipidemia. Methods The study consists of 180 patients, aged 40–75 years, with hyperlipidemia. All patients were divided into two equal groups: patients with different SLCO1B1 (521CC, 521CT and 521TT) and MDR1 (3435CC, 3435TC and 3435TT) genotypes. Each group was divided into rosuvastatin-treated, atorvastatin-treated and simvastatin-treated subgroups. The lipid-lowering effect of statins was assessed by tracing changes in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. Results The use of statins over a 4-month period led to substantial reductions in TC and LDL-C levels. The hypolipidemic effect of studied agents was seen in both groups. However, it was less pronounced in patients with 521CC genotype. No statistically significantly differences were found between carriers of 3435TT, 3435CT and 3435CC genotypes. Conclusions The lipid-lowering efficacy of rosuvastatin was higher compared to other two statins. Patients with SLCO1B1 521CC genotype are more likely to encounter a decrease in the hypolipidemic effect of statins. Such a risk should be considered when treating this category of patients. MDR1 polymorphism had no significant effect on statin efficacy.

scholarly journals PCSK-9 Inhibitors in a Real-World Setting and a Comparison Between Alirocumab and Evolocumab in Heterozygous FH Patients

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
José Juan Ceballos-Macías ◽  
Carolina Lara-Sánchez ◽  
Jorge Flores-Real ◽  
Carlos Alberto Aguilar-Salinas ◽  
Guillermo Ortega-Gutiérrez ◽  
...  
Keyword(s):  
Real World ◽  
Standard Therapy ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Low Density Lipoprotein Cholesterol ◽  
Pcsk9 Inhibitors ◽  
Lipid Clinic ◽  
Real World Setting ◽  
Lipid Lowering Effect

Abstract A real-world setting study of familial hypercholesterolemia (FH) patients who received Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in a specialized referral center in Mexico City. Ten patients between the ages of 18 and 70 years, with a diagnosis of FH according to Dutch Lipid Clinic Network (DLCN) criteria, with failure to achieve their Low-density lipoprotein Cholesterol (LDL-C) goals, and with standard therapy between 2016 and 2017 enrolled in a simple randomization in which a group of 5 participants received alirocumab (75 mg every 2 weeks) and the remaining 5 patients received evolocumab (140 mg every 2 weeks). Comparative analysis was made, analyzing the means of LDL at baseline at 4, 6, and 12 weeks. The evolocumab group had an average initial LDL-C of 277 mg/dL, which, after 12 weeks of treatment, was significantly reduced to 116 mg/dL; P = 0.04 (95% confidence interval [CI]: 11.5–310.9). The alirocumab group with a mean initial LDL-C of 229 mg/dL showed a reduction of LDL-C levels at 12 weeks of treatment to 80 mg/dL; P = 0.008 (95% CI: 63.8–233.7). In conclusion, PCSK9 inhibitors are an excellent treatment option in patients with FH who do not reach their LDL-C goals with standard therapy or due to intolerance to the standard therapy. There is no difference in the lipid-lowering effect between both PSCK9 inhibitors.

scholarly journals Evaluation of two highly effective lipid-lowering therapies in subjects with acute myocardial infarction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aline Klassen ◽  
Andrea Tedesco Faccio ◽  
Carolina Raissa Costa Picossi ◽  
Priscilla Bento Matos Cruz Derogis ◽  
Carlos Eduardo dos Santos Ferreira ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Low Density Lipoprotein Cholesterol ◽  
Residual Cardiovascular Risk ◽  
St Segment Elevation ◽  
Lipidomic Analysis ◽  
St Segment ◽  
Highly Effective

AbstractFor cardiovascular disease prevention, statins alone or combined with ezetimibe have been recommended to achieve low-density lipoprotein cholesterol targets, but their effects on other lipids are less reported. This study was designed to examine lipid changes in subjects with ST-segment elevation myocardial infarction (STEMI) after two highly effective lipid-lowering therapies. Twenty patients with STEMI were randomized to be treated with rosuvastatin 20 mg QD or simvastatin 40 mg combined with ezetimibe 10 mg QD for 30 days. Fasting blood samples were collected on the first day (D1) and after 30 days (D30). Lipidomic analysis was performed using the Lipidyzer platform. Similar classic lipid profile was obtained in both groups of lipid-lowering therapies. However, differences with the lipidomic analysis were observed between D30 and D1 for most of the analyzed classes. Differences were noted with lipid-lowering therapies for lipids such as FA, LPC, PC, PE, CE, Cer, and SM, notably in patients treated with rosuvastatin. Correlation studies between classic lipid profiles and lipidomic results showed different information. These findings seem relevant, due to the involvement of these lipid classes in crucial mechanisms of atherosclerosis, and may account for residual cardiovascular risk.Randomized clinical trial: ClinicalTrials.gov, NCT02428374, registered on 28/09/2014.

scholarly journals U-Shaped Relationship of Low-Density Lipoprotein Cholesterol With Risk of Severe COVID-19 From a Multicenter Pooled Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Jiao Gong ◽  
Yaqiong Chen ◽  
Yusheng Jie ◽  
Mingkai Tan ◽  
Zhaofang Jiang ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Odds Ratios ◽  
Lowering Therapy ◽  
Severe Group

Low-density lipoprotein cholesterol (LDL-C) is a well-known risk factor for coronary heart disease but protects against infection and sepsis. We aimed to disclose the exact association between LDL-C and severe 2019 novel coronavirus disease (COVID-19). Baseline data were retrospectively collected for 601 non-severe COVID-19 patients from two centers in Guangzhou and one center in Shenzhen, and patients on admission were medically observed for at least 15 days to determine the final outcome, including the non-severe group (n = 460) and the severe group (severe and critical cases) (n = 141). Among 601 cases, 76 (12.65%) received lipid-lowering therapy; the proportion of patients taking lipid-lowering drugs in the severe group was higher than that in the non-severe group (22.7 vs. 9.6%). We found a U-shaped association between LDL-C level and risk of severe COVID-19 using restricted cubic splines. Using univariate logistic regression analysis, odds ratios for severe COVID-19 for patients with LDL-C ≤1.6 mmol/L (61.9 mg/dL) and above 3.4 mmol/L (131.4 mg/dL) were 2.29 (95% confidence interval 1.12–4.68; p = 0.023) and 2.02 (1.04–3.94; p = 0.039), respectively, compared to those with LDL-C of 2.81–3.40 mmol/L (108.6–131.4 mg/dL); following multifactorial adjustment, odds ratios were 2.61 (1.07–6.37; p = 0.035) and 2.36 (1.09–5.14; p = 0.030). Similar results were yielded using 0.3 and 0.5 mmol/L categories of LDL-C and sensitivity analyses. Both low and high LDL-C levels were significantly associated with higher risk of severe COVID-19. Although our findings do not necessarily imply causality, they suggest that clinicians should pay more attention to lipid-lowering therapy in COVID-19 patients to improve clinical prognosis.

scholarly journals Evaluation of Lipid Lowering Effect of Milk Thistle (Silybum Marianum) in Comparison with Rosuvastatin in Rats by Using Ace-alera® Analyzer

2020 ◽  
Vol 14 ◽  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Lipid Lowering ◽  
Control Group ◽  
Milk Thistle ◽  
High Dose ◽  
Hypolipidemic Effect ◽  
Low Density ◽  
Therapeutic Protocols

Dyslipidemia is a metabolic disorder that is characterized with an elevation in the cholesterol serum levels that can be treated with various hypolipidemic drugs like rosuvastatin. The present study was undertaken to determine and evaluate the hypolipidemic effect of milk thistle seeds extract in comparison with rosuvastatin and the combination of both for the treatment of dyslipidemia in rats. Also its effect on blood glucose levels on experimentally induced dyslipidemic rats. In vivo studies were conducted on wister albino laboratory rats, in which 49 rats were induced to be dyslipidemic by a daily intragastric administration of cholesterol (2 g/kg). The induction of dyslipidemia was evaluated by comparing these rats with a negative control group that was composed of 10 healthy rats. Then, after one month dyslipidemia was induced in 49 rats that were divided into 6 groups, as the following; positive control group (n=9) received cholesterol (2 g/kg) for another one month, and the other five groups each of 8 rats continued to receive cholesterol (2 g/kg) for one month along with therapy as; rosuvastatin low dose (RL) group received 10 mg/kg, rosuvastatin high dose (RH) group received 20 mg/kg, milk thistle (MT) group received 7.15 mg/kg, (RL+MT) group received a combination of 10 mg/kg of rosuvastatin and 7.15 mg/kg of milk thistle, and (RH+MT) group received a combination of 20 mg/kg of rosuvastatin and 7.15 mg/kg of milk thistle. The statistical results of biochemical analysis showed that all the studied therapeutic protocols whether given alone; RL, RH, and MT or in a combination; RL+MT and RH+MT led to a significant (p≤0.05) hypolipidemic effect that reduced the total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) and increased the high density lipoprotein (HDL) cholesterol levels. In conclusion, all therapeutic protocols were effective in treating dyslipidemia, as they all reduced the TC, TG, LDL, and VLDL, and increased the HDL cholesterol significantly (p≤0.05). Furthermore, we found that milk thistle can be used in the management of dyslipidemia, as it has a hypolipidemic effect. Also, the addition of milk thistle to rosuvastatin therapy reduced the risk of developing diabetes mellitus (DM), as it has a glucose modulating activity either when it was given alone or in combination with rosuvastatin. Moreover, the combination of milk thistle and rosuvastatin was of a great benefit, as it gave an intensive goal of therapy than each one alone in altering all lipid profile parameters.

Abstract P43: Frequency and Predictors of Low-Density Lipoprotein Cholesterol Control and Appropriate Response to Elevated LDL-C Levels in Patients with Cardiovascular Disease

2011 ◽  
Vol 4 (suppl_2) ◽  
Author(s):  
Salim S Virani ◽  
Lechauncy D Woodard ◽  
Supicha Sookanan ◽  
Cassie R Landrum ◽  
Tracy H Urech ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Medication Possession Ratio ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
To Receive

Background: Although current cholesterol performance measures define good quality as low density lipoprotein cholesterol (LDL-C) levels < 100mg/dl in cardiovascular disease (CVD) patients, they provide a snap shot at one time point and do not inform whether an appropriate action was taken to manage elevated LDL-C levels. We assessed frequency and predictors of this appropriate response (AR). Methods: We used administrative data to assess 22,902 CVD patients receiving care in a Veterans Affairs network of 7 hospitals and affiliated clinics. We determined the proportion of CVD patients at LDL-C goal <100 mg/dl, and the proportion of patients with uncontrolled LDL-C levels (>100 mg/dl) who had an AR [defined as the initiation or dosage increase of a lipid lowering medication (LLM), addition of a new LLM, receipt of maximum dosage or >1 LLM, or LDL-C reading <100 mg/dl] at 45 days follow-up. Logistic regression was performed to evaluate facility, provider and patient characteristics associated with AR. Results: LDL-C levels were at goal in 16,350 (71.4%) patients. An additional 2,110 (9.2%) had an AR at 45 days of follow-up. Controlling for clustering between facilities and patient's illness severity, history of diabetes (OR 1.18, 95% CI 1.03-1.35), hypertension (OR 1.21, 95% CI 1.02-1.44), patients showing good medication adherence (medication possession ratio > 0.8) [OR 2.29, 95% CI 1.99-2.64] were associated with AR. Older CVD patients (age >75 years) were less likely to receive AR (OR 0.60, 95% CI 0.52-0.70). Teaching vs. non-teaching facility (p=0.40), physician vs. non-physician provider (p=0.14), specialist vs. non-specialist primary care provider (p=0.12), and patient's race (p=0.12) were not predictors of AR. Conclusion: Among patients with CVD and LDL-C above guideline recommended levels, only one-third receive AR. Diabetic and hypertensive CVD patients are more likely to receive AR, whereas older Veterans with CVD receive AR less often likely reflecting providers' belief of lack of efficacy from treatment intensification in older CVD patients. Our findings are important for quality improvement and policy making initiatives as they provide more actionable information compared with isolated LDL-C goal attainment as a quality indicator.

Comparison of LDL-C calculation by friedewald and martin/hopkins methods in 12,243 adults from the United States of America

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Penson ◽  
S.S Martin ◽  
N.C Henney ◽  
M Banach
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Threshold Value ◽  
The United States ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Strongly Correlated ◽  
Low Density Lipoprotein Cholesterol

Abstract Background Low-density lipoprotein cholesterol (LDL-C) is an established risk factor for cardiovascular disease (CVD), and a target for lipid-lowering therapy. LDL-C is typically not measured directly but is estimated using the Friedewald formula, which assumes a fixed factor for the ratio of triglycerides (TG) to very low-density lipoprotein cholesterol (VLDL-C). However this assumption is sometimes not valid. The Martin/Hopkins (M/H) formula estimates LDL-C using an adjustable factor for the TG:VLDL-C ratio and is expected to improve upon Friedewald when predicting measured LDL-C, and apolipoprotein B (ApoB), one molecule of which is associated with each LDL particle. Purpose We compared values of LDL-C calculated by the Friedewald and M/H methods with respect to their correlation with non-high density lipoprotein cholesterol (non-HDL-C) and ApoB, and their classification of individuals based upon attainment of the threshold value of 70 mg/dl (1.8 mmol/l) of LDL-C. This cut-point is a treatment target for individuals at high risk of CVD in the 2019 ESC guidelines for lipid modification, and a threshold for initiating statin therapy in the 2019 ACC/AHA guidelines. Methods In this analysis we included participants in the National Health and Nutrition Examination Survey (NHANES) from 2005–2016, age ≥18, &lt;80 years who had measurements for total cholesterol (TC), TG and HDL-C. LDL-C was calculated using Friedewald and M/H. We correlated LDL-C (calculated using the two methods) with non-HDL-C and ApoB. We identified individuals with LDL-C &lt;70 mg/dl using both methods. When LDL-C (Friedewald) was &lt;70, but LDL-C (M/H) was &gt;70, we classified these participants as discordant. Statistical analyses were performed in IBM SPSS for Windows v26. Results 12,243 individuals were included. 51.8% were female, mean (±SD) age was 45.5±17.4, 15.3% were treated with statins, ApoB was available for 2179 participants. Mean lipid concentrations (mg/dl) were: TC: 191.5±41.0, TG: 120.0±67.0, HDL-C: 54.1±15.7, LDL-C (Friedewald): 113.3±35.4; LDL-C (M/H): 114.9±35.2. In the whole population, LDL-C (M/H) was more strongly correlated than LDL-C (Friedewald) with ApoB (r=0.935 v 0.894) and non-HDL-C (r=0.981 v 0.944). In statin-treated participants, LDL-C (M/H) was also more strongly correlated with ApoB (r=0.951 v 0.914) and non-HDL-C (r=0.979 v 0.928). 1139 participants had LDL-C (Friedewald) &lt;70 mg/dl. Of these, 206 individuals (18.1%) were discordant, having LDL-C (M/H) &gt;70 mg/dl. Amongst statin-treated patients, 22.9% were discordant. Only 5.5% of individuals with LDL-C (M/H) &lt;70 mg/dl showed reverse discordance (LDL-C (Friedewald) &gt;70 mg/dl). Conclusions The M/H method of calculating LDL-C correlates more strongly with non-HDL-C and ApoB than Friedewald. Importantly the discordant results confirm previous observations that Friedewald underestimates LDL-C at low concentrations. This may result in under-use of lipid-lowering therapies. Funding Acknowledgement Type of funding source: None

scholarly journals Clinical Significance of Electronegative Low-Density Lipoprotein Cholesterol in Atherothrombosis

Biomedicines ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 254 ◽  
Author(s):  
Chih-Sheng Chu ◽  
Shi Hui Law ◽  
David Lenzen ◽  
Yong-Hong Tan ◽  
Shih-Feng Weng ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Clinical Significance ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Exercise Stress ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

Despite the numerous risk factors for atherosclerotic cardiovascular diseases (ASCVD), cumulative evidence shows that electronegative low-density lipoprotein (L5 LDL) cholesterol is a promising biomarker. Its toxicity may contribute to atherothrombotic events. Notably, plasma L5 LDL levels positively correlate with the increasing severity of cardiovascular diseases. In contrast, traditional markers such as LDL-cholesterol and triglyceride are the therapeutic goals in secondary prevention for ASCVD, but that is controversial in primary prevention for patients with low risk. In this review, we point out the clinical significance and pathophysiological mechanisms of L5 LDL, and the clinical applications of L5 LDL levels in ASCVD can be confidently addressed. Based on the previously defined cut-off value by receiver operating characteristic curve, the acceptable physiological range of L5 concentration is proposed to be below 1.7 mg/dL. When L5 LDL level surpass this threshold, clinically relevant ASCVD might be present, and further exams such as carotid intima-media thickness, pulse wave velocity, exercise stress test, or multidetector computed tomography are required. Notably, the ultimate goal of L5 LDL concentration is lower than 1.7 mg/dL. Instead, with L5 LDL greater than 1.7 mg/dL, lipid-lowering treatment may be required, including statin, ezetimibe or PCSK9 inhibitor, regardless of the low-density lipoprotein cholesterol (LDL-C) level. Since L5 LDL could be a promising biomarker, we propose that a high throughput, clinically feasible methodology is urgently required not only for conducting a prospective, large population study but for developing therapeutics strategies to decrease L5 LDL in the blood.

scholarly journals GENetic characteristics and REsponse to lipid-lowering therapy in familial hypercholesterolemia: GENRE-FH study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hyoeun Kim ◽  
Chan Joo Lee ◽  
Hayeon Pak ◽  
Doo-Il Kim ◽  
Moo-Yong Rhee ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Genetic Characteristics ◽  
Pathogenic Variants ◽  
Lowering Therapy ◽  
Primary Variable

Abstract Among the 146 patients enrolled in the Korean FH registry, 83 patients who had undergone appropriate LLT escalation and were followed-up for ≥ 6 months were analyzed for pathogenic variants (PVs). The achieved percentage of expected low-density lipoprotein-cholesterol (LDL-C) reduction (primary variable) and achievement rates of LDL-C < 70 mg/dL were assessed. The correlations between the treatment response and the characteristics of PVs, and the weighted 4 SNP-based score were evaluated. The primary variables were significantly lower in the PV-positive patients than in the PV-negative patients (p = 0.007). However, the type of PV did not significantly correlate with the primary variable. The achievement rates of LDL-C < 70 mg/dL was very low, regardless of the PV characteristics. Patients with a higher 4-SNP score showed a lower primary variable (R2 = 0.045, p = 0.048). Among evolocumab users, PV-negative patients or those with only defective PVs revealed higher primary variable, whereas patients with at least one null PV showed lower primary variables. The adjusted response of patients with FH to LLT showed significant associations with PV positivity and 4-SNP score. These results may be helpful in managing FH patients with diverse genetic backgrounds.

Cardiovascular event rates increase after each recurrence and associate with poor statin adherence

2020 ◽  
pp. 204748732090433 ◽  
Author(s):  
Mariann I Lassenius ◽  
Iiro Toppila ◽  
Susanne Bergius ◽  
Julia Perttilä ◽  
KE Juhani Airaksinen ◽  
...  
Keyword(s):  
Cardiovascular Event ◽  
Cardiovascular Events ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Increased Risk ◽  
Event Rates

Aims The study evaluated the quality of cardiovascular prevention in real-world clinical practice. The recurrence of up to five cardiovascular events was assessed, as data on recurrence beyond the first event and interindividual variations in event rates past the second event have been sparse. Low-density lipoprotein cholesterol concentrations and lipid-lowering therapy use were investigated. Methods This retrospective register-based study included adult patients with an incident cardiovascular event between 2004 and 2016 treated in the hospital district of southwest Finland. Patients were followed for consecutive cardiovascular events or cardiovascular death, low-density lipoprotein cholesterol and statin purchases. The timing of event recurrence was evaluated, and predictive factors were assessed. Results A wide interindividual variation in cardiovascular event recurrence was observed, each additional event caused an increased risk, the median time of recurrence decreased from 7 to one year for the second and fifth event. Event rates increased correspondingly from 12 to 43/100 patient-years and were most pronounced in the first years following the previous event. The low-density lipoprotein cholesterol goal (<1.8 mmol/l) was reached by 18% in the year after the event and statin underuse was associated with an increased risk of recurrence. Six months after the index event high intensity statins were used by only 22% of the cohort. Conclusion The study provides new perspectives on individual risk assessment showing that event rates are not stable for all patients but increase 1.2–1.9-fold per consecutive event. The underuse of statins and poor adherence support the identification of these patients for intensified multifactorial preventive measures.

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