Lepodisiran, an Extended-Duration Short Interfering RNA Targeting Lipoprotein(a)

JAMA, Journal Year: 2023, Volume and Issue: 330(21), P. 2075 - 2075

Published: Nov. 12, 2023

Epidemiological and genetic data have implicated lipoprotein(a) as a potentially modifiable risk factor for atherosclerotic disease aortic stenosis, but there are no approved pharmacological treatments.

Language: Английский

---

A focused update to the 2019 NLA scientific statement on use of lipoprotein(a) in clinical practice

Journal of clinical lipidology, Journal Year: 2024, Volume and Issue: 18(3), P. e308 - e319

Published: April 1, 2024

Language: Английский

---

Inflammation, Cholesterol, Lipoprotein(a), and 30-Year Cardiovascular Outcomes in Women

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 31, 2024

BackgroundHigh-sensitivity C-reactive protein (CRP), low-density lipoprotein (LDL) cholesterol, and lipoprotein(a) levels contribute to 5-year 10-year predictions of cardiovascular risk represent distinct pathways for pharmacologic intervention. More information about the usefulness these biomarkers predicting over longer periods time in women is needed because early-life intervention represents an important risk-reduction method.MethodsWe measured high-sensitivity CRP, LDL at baseline 27,939 initially healthy U.S. who were subsequently followed 30 years. The primary end point was a first major adverse event, which composite myocardial infarction, coronary revascularization, stroke, or death from causes. We calculated adjusted hazard ratios 95% confidence intervals across quintiles each biomarker, along with 30-year cumulative incidence curves age competing risks.ResultsThe mean participants 54.7 During follow-up, 3662 events occurred. Quintiles increasing all predicted risks. Covariable-adjusted comparison top bottom quintile 1.70 (95% interval [CI], 1.52 1.90) 1.36 CI, 1.23 1.52) 1.33 1.21 1.47) lipoprotein(a). Findings heart disease stroke appeared be consistent those point. Each biomarker showed independent contributions overall risk. greatest spread obtained models that incorporated three biomarkers.ConclusionsA single combined measure among predictive incident during period. These data support efforts extend strategies prevention atherosclerotic beyond traditional estimates (Funded by National Institutes Health; Women's Health Study ClinicalTrials.gov number, NCT00000479.)

Language: Английский

---

Single Ascending and Multiple-Dose Trial of Zerlasiran, a Short Interfering RNA Targeting Lipoprotein(a)

JAMA, Journal Year: 2024, Volume and Issue: 331(18), P. 1534 - 1534

Published: April 8, 2024

Lipoprotein(a) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic stenosis, with no pharmacological treatments approved by regulatory authorities.

Language: Английский

---

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

---

Lipoprotein(a) and cardiovascular disease

The Lancet, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

---

Recommendations of the Experts of the Polish Cardiac Society (PCS) and the Polish Lipid Association (PoLA) on the diagnosis and management of elevated lipoprotein(a) levels

Archives of Medical Science, Journal Year: 2024, Volume and Issue: 20(1), P. 8 - 27

Published: Jan. 30, 2024

Lipoprotein(a) [Lp(a)] is made up of a low-density lipoprotein (LDL) particle and specific apolipoprotein(a). The blood concentration Lp(a) approximately 90% genetically determined, the main genetic factor determining levels size apo(a) isoform, which determined by number KIV2 domain repeats. isoform inversely proportional to Lp(a). strong independent cardiovascular risk factor. Elevated ≥ 50 mg/dl (≥ 125 nmol/l) are estimated occur in more than 1.5 billion people worldwide. However, determination performed far too rarely, including Poland, where, fact, it only since 2021 guidelines Polish Lipid Association (PoLA) five other scientific societies that measurements have begun be performed. Determination concentrations not easy due to, among things, different sizes isoforms; however, currently available certified tests make possible distinguish between with low high degree precision. In 2022, first for management patients elevated lipoprotein(a) were published European Atherosclerosis Society (EAS) American Heart (AHA). result work experts from two their aim provide clear, practical recommendations levels.

Language: Английский

---

High lipoprotein(a): Actionable strategies for risk assessment and mitigation

American Journal of Preventive Cardiology, Journal Year: 2024, Volume and Issue: 18, P. 100651 - 100651

Published: April 3, 2024

High levels of lipoprotein(a) [Lp(a)] are causal for atherosclerotic cardiovascular disease (ASCVD). Lp(a) is the most prevalent inherited dyslipidemia and strongest genetic ASCVD risk factor. This persists in presence at target, guideline-recommended, LDL-C adherence to lifestyle modifications. Epidemiological evidence supporting its role calcific aortic stenosis continues accumulate, although various facets regarding biology (genetics, pathophysiology, expression across race/ethnic groups) not yet fully understood. The evolving nature clinical guidelines consensus statements recommending universal measurements scientific data multiple states reinforce merit start population screening now. There a current gap implementation recommendations primary secondary (CVD) prevention those with high Lp(a), part due lack protocols management strategies. Importantly, targeted apolipoprotein(a) [apo(a)]-lowering therapies that reduce patients phase 3 development. review focuses on identification Lp(a). Specifically, we highlight value measuring use determining Lp(a)-associated CVD by providing actionable guidance, based knowledge, can be utilized now mitigate caused

Language: Английский

---

Zerlasiran—A Small-Interfering RNA Targeting Lipoprotein(a)

JAMA, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

Importance Elevated lipoprotein(a) increases the risk of atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis. Objective To evaluate effects zerlasiran, a small-interfering RNA targeting hepatic synthesis apolipoprotein(a), on serum concentration. Design, Setting, Participants A multicenter trial in patients with stable ASCVD concentrations greater than or equal to 125 nmol/L at 26 sites Europe South Africa between January 3, 2023, April 27, last follow-up July 1, 2024. Interventions randomized receive subcutaneous dose placebo every 16 weeks for 3 doses (n = 23) 24 2 24) zerlasiran 450 mg 45), 300 42), 44). Main Outcome Measures The primary outcome was time-averaged percent change concentration from baseline 36 weeks, 60 weeks. Results Among 178 patients, mean (SD) age 63.7 (9.4) years, 46 (25.8%) were female, median (IQR) 213 (177-282) nmol/L; 172 completed trial. Compared pooled group, least-squares week −85.6% (95% CI, −90.9% −80.3%), −82.8% −88.2% −77.4%), −81.3% −86.7% −76.0%) groups, respectively. Median −94.5% (−97.3% −84.2%) −96.4% (−97.7% −92.3%) −90.0% (−93.7% −81.3%) group. most common treatment-related adverse injection site reactions, mild pain occurring 2.3% 7.1% participants first day following drug administration. There 20 serious events 17 none considered related study drug. Conclusions Zerlasiran well-tolerated reduced by more 80% during treatment ASCVD. Trial Registration ClinicalTrials.gov Identifier: NCT05537571

Language: Английский

---

2023: The year in cardiovascular disease - the year of new and prospective lipid lowering therapies. Can we render dyslipidemia a rare disease by 2024?

Archives of Medical Science, Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 1, 2023

In 2023 there are still even 75% of patients over the target low-density lipoprotein cholesterol (LDL-C), and hypercholesterolemia is most common worst monitored cardiovascular risk factor. How it possible, considering knowledge we have on role in process atherosclerosis, atherosclerotic disease (ASCVD) its complications, methods lipid disorders diagnosis, prevention, treatment. Nowadays, almost 4 million deaths per year attributed to LDL-C, 2/3 all CVD ASCVD, therefore hypothetically should easily prevent few several with early intensive non-pharmacological pharmacological therapies. Moreover, lipidology now, besides oncology, area highest number new ongoing trials effective safe medications that already appeared will soon be available. Therefore, no doubt called prospective lowering therapies (LLTs). this State-of-the-Art paper summarized important trials, studies, recommendations LLTs, suitable graphical summaries might helpful for physicians their practice a look nearest future being under investigation. Let's hope those helps render dyslipidemia rare next years.

Language: Английский

---