The importance of LDL-C lowering in atherosclerotic cardiovascular disease prevention: Lower for longer is better

American Journal of Preventive Cardiology, Journal Year: 2024, Volume and Issue: 18, P. 100649 - 100649

Published: March 18, 2024

Cumulative exposure to low-density lipoprotein cholesterol (LDL-C) is a key driver of atherosclerotic cardiovascular disease (ASCVD) risk. An armamentarium therapies achieve robust and sustained reduction in LDL-C can reduce ASCVD The gold standard for assessment ultracentrifugation but routine clinical practice usually calculated the most accurate calculation obtained through Martin/Hopkins equation. For primary prevention, consideration estimated risk frames decision making regarding use statins other therapies, tools such as enhancing factors coronary artery calcium enable tailoring making. In patients with diabetes, lipid lowering therapy recommended an opportunity tailor based on factors. Patients hypercholesterolemia familial (FH) baseline greater than or equal 190 mg/dL are at elevated risk, high-intensity statin often combined non-statin prevent ASCVD. Secondary prevention ASCVD, including prior myocardial infarction stroke, requires intensive lifestyle modification approaches. There no established level below which benefit ceases safety concerns arise. When further required beyond modifications therapy, additional medications include oral ezetimibe bempedoic acid, injectables PCSK9 monoclonal antibodies siRNA therapy. A novel agent that acts independently hepatic LDL receptors evinacumab, approved homozygous FH. Other emerging agents targeted Lp(a) CETP. Given dyslipidemia, this manuscript reviews importance early, intensive, LDL-C-lowering secondary

Language: Английский

---

A novel small-molecule PCSK9 inhibitor E28362 ameliorates hyperlipidemia and atherosclerosis

Acta Pharmacologica Sinica, Journal Year: 2024, Volume and Issue: 45(10), P. 2119 - 2133

Published: May 29, 2024

Language: Английский

---

The impact of SLCO1B1 rs4149056 on LDL-C target achievement after lipid lowering therapy optimization in men and women with familial hypercholesterolemia

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 8, 2024

Background and aims FH women are less likely to receive intensive statin treatment obtain a 50% reduction of LDL-C from baseline compared men with FH. SLCO1B1 rs4149056 might influence therapy compliance thus target achievement. Our aim was evaluate the impact on achievement after lipid lowering (LLT) optimization in Methods This retrospective observational study involving 412 subjects probable or defined clinical diagnosis who had genetic analysis June 2016 September 2022. Biochemical obtained all at last follow-up LLT optimization. Results After percentage high-intensity statins decreased M/SLCO1B1- group W/SLCO1B1+ same found distribution (for both p for trend < 0.01). The prevalence SASE fear increased observed reported myalgia Logistic regression showed that W/SCLO1B1-, M/SCLO1B1+ W/SCLO1B1+ groups were inversely associated ( 0.001) exhibited strongest association. Conclusion A low high intensity they rarely achieved target. genotype effect could be more pronounced than men.

Language: Английский

---

Ezetimibe-Loaded Nanostructured Lipid Carrier for Oral Delivery: Response Surface Methodology; In Vitro Characterization and Assessing the Antihyperlipidemic Effect in Rats

ACS Omega, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 11, 2024

Among the independent risk factors for occurrence of cardiovascular diseases like atherosclerosis is hyperlipidemia. To decrease events and patient mortality, antihyperlipidemia therapy crucial. Our study aimed to enhance solubility poorly soluble lipid-lowering agent ezetimibe (EZ), a member class II as per Biopharmaceutics Classification System (BCS). The drug was formulated nanostructured lipid carrier (NLC) employing ultrasonication technique. A response surface D-optimal design employed effect changing liquid type percentage with respect total amount on particle size, zeta potential, entrapment efficiency, released after 24 h. Nine NLC formulations were prepared pharmaceutically evaluated, optimized formulation selected, further characterized, evaluated well. Optimized EZ-NLC assessed in high-fat diet model induce hyperlipidemia rats comparison EZ suspension. results showed that NLCs spherical no aggregation having size 204.3 ± 19.17 nm, potential equal −32 7.59 mV, efficiency 81.5 3.58% 72.15 4.58% significantly decreased elevated serum parameters, including cholesterol, triglycerides, LDL-C, but normalized HDL-C levels kept diet. demonstrated improved efficacy ameliorating parameters compared EZ.

Language: Английский

---

The effect of lipid-lowering therapy on lipid-related residual risk factors: a prospective study

Lipids in Health and Disease, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 7, 2024

Abstract Background Remnant cholesterol (RC) and nonhigh-density lipoprotein (nonHDL-C) are key risk factors for atherosclerotic cardiovascular disease (ASCVD), with apolipoprotein B (apoB) lipoprotein(a) [Lp(a)] also contributing to its residual risk. However, real-world population-based evidence regarding the impact of current clinical LDL-C-centric lipid-lowering therapy (LLT) on achieving RC nonHDL-C goals, as well modifying CVD is limited. Methods This prospective observational study enrolled 897 patients from September, 2020 July, 2021. All participants had previously received low-/moderate-intensity LLT were discharged either or high-intensity LLT. After a median follow-up 3 months, changes in RC, nonHDL-C, other biomarkers assessed. Multivariate logistic regression was performed analyze goal attainment. Results Among all patients, 83.50% transitioned low moderate. follow-up, group saw significantly greater reductions (-20.51% vs. -3.90%, P = 0.025), (-25.12% 0.00%, < 0.001), apoB (-19.35% -3.17%, triglycerides (-17.82% -6.62%, LDL-C total cholesterol. Spearman correlation analysis revealed that reduction strongly correlated ( r 0.87, 0.001). Patients who significant improvements attainment (from 44.2% 60.7%, χ² 39.23, 0.001) 19.4% 56.9%, 226.06, goals. Furthermore, multivariate showed protective factor [odds ratio (OR) 0.66; 95% confidence intervals (CI), 0.45–0.97; 0.033] (OR 0.51; CI, 0.34–0.75; without increase adverse reactions. Conclusion Current levels clinically prescribed treatment can reduce lipid-related factors, but better at goals than LLT, good safety profile. More targeted treatments still needed lipid further.

Language: Английский

---

Cardiovascular Risk Estimation and Stratification Among Individuals with Hypercholesterolemia

Current Atherosclerosis Reports, Journal Year: 2024, Volume and Issue: 26(9), P. 537 - 548

Published: July 5, 2024

Language: Английский

---

Ezetimibe Loaded Nanostructured Lipid Carriers Tablets: Response Surface Methodology, In-vitro Characterization, and Pharmacokinetics Study in Rats

Journal of Pharmaceutical Innovation, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 9, 2025

Language: Английский

---

Characterization and interactions between piperine and ezetimibe in their Anti-hyperlipidemic efficacy using Biopharmaceutics and Pharmacokinetics

BMC Pharmacology and Toxicology, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 14, 2025

Piperine, a secondary metabolite, affects the antihyperlipidemic effect of Ezetimibe (EZ). Hyperlipidemia is one independent risk factors for cardiovascular disorders such as atherosclerosis. Antihyperlipidemic drugs are essential reducing events and patient mortality. Our study aimed to improve solubility EZ, lipid-lowering drug that belongs BCS II has low solubility. bioenhancer, can increase bioavailability other pharmaceuticals without modifying their fundamental characteristics or enhancing efficacy. The objective this was EZ while also improving its potency toxicity by using piperine bioenhancer. Therefore, rats were given combined with activity assessed fed high-fat diet. in vivo at doses 10 5–20 mg/kg b.w. evaluation conducted propylthiouracil-induced triton X-100-induced hyperlipidemia rats. Give 400 body weight propylthiouracil along piperine. Serum levels total cholesterol (TC) (p < 0.01), triglycerides (TG) low-density lipoprotein (LDL) very (VLDL) 0.01) all went up significantly. Additionally, it led induction high-density (HDL) 0.01). Administration Triton X-100 via intraperitoneal injection single dose resulted an elevation lipid levels. Lower (LDL), (TC), (TG), significantly reduced 20 b.w., respectively 0.01 p 0.05). Liver histology studies provided further evidence supporting present findings. Areas concentrated periportal lymphocytes hepatocytes formed cord pattern hyperlipidaemia. It seemed like hepatocytes, area, centrilobular part liver normal group who had treatment. An analysis plasma concentration time carried out research. medication's most effective (Cmax) determined be within 4 h after delivery, quantified active medication detectable bloodstream 24 h. In combination piperine, demonstrated significant antioxidant effects. This indicates could utilised treating atherosclerosis due potential boost oral absorption drug.

Language: Английский

---

Genetic association analysis of lipid-lowering drug target genes in chronic kidney disease

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 14, 2025

The impact of lipid-lowering medications on chronic kidney disease (CKD) remains a subject debate. This Mendelian randomization (MR) study aims to elucidate the potential effects drug targets CKD development. We extracted 11 genetic variants encoding drugs from published genome-wide association (GWAS) summary statistics, encompassing LDLR, HMGCR, PCSK9, NPC1L1, APOB, ABCG5/ABCG8, LPL, APOC3, ANGPTL3, and PPARA. A analysis was conducted targeting these drug-related genes. risk designated as primary outcome, while estimated glomerular filtration rate (eGFR) blood urea nitrogen (BUN) were assessed secondary outcomes. Additionally, mediation performed utilizing 731 immune cell phenotypes identify mediators. meta-analysis revealed significant between ANGPTL3 inhibitors reduced (OR [95% CI] = 0.85 [0.75-0.96]). Conversely, LDLR agonists significantly linked an increased 1.11 [1.02-1.22]). Regarding outcomes, did not affect eGFR BUN levels. Mediation indicated that reduction in by mediated through modulation phenotype, specifically HLA-DR CD14+ CD16+ monocytes (Mediated proportion: 4.69%; Mediated effect: -0.00899). Through drug-targeted MR analysis, we identified causal relationship CKD. may represent promising candidate for treatment.

Language: Английский

---

Screening for Dyslipidemia Among Patients Admitted With Acute Coronary Syndrome at the Jakaya Kikwete Cardiac Institute, Tanzania: A Retrospective Cohort Study

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Language: Английский

---