Menopause and women’s cardiovascular health: is it really an obvious relationship?

Archives of Medical Science, Journal Year: 2022, Volume and Issue: 19(2), P. 458 - 466

Published: Dec. 10, 2022

Cardiovascular diseases are common for men and women but there differences between the sexes in terms of clinical symptoms, pathophysiology response to treatment. (CVD) is commonly underdiagnosed often tend have a lower perception risk. That can lead delayed diagnosis failed recognition symptoms. Women develop heart later than because protection reproductive phase their life. Once they enter menopause risk increases. Estrogen provides protective effect against disease women. Therefore, CVD increases after most cases. The presented work emphasizes importance menopausal period as time increasing It also monitoring health middle age, critical which early intervention strategies should be implemented reduce CVD.

Language: Английский

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Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Jan. 8, 2024

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has evolved as a pivotal enzyme in lipid metabolism and revolutionary therapeutic target for hypercholesterolemia its related cardiovascular diseases (CVD). This comprehensive review delineates the intricate roles wide-ranging implications of PCSK9, extending beyond CVD to emphasize significance diverse physiological pathological states, including liver diseases, infectious autoimmune disorders, notably, cancer. Our exploration offers insights into interaction between PCSK9 low-density lipoprotein receptors (LDLRs), elucidating substantial impact on cholesterol homeostasis health. It also details evolution PCSK9-targeted therapies, translating foundational bench discoveries bedside applications optimized patient care. The advent clinical approval innovative inhibitory therapies (PCSK9-iTs), three monoclonal antibodies (Evolocumab, Alirocumab, Tafolecimab) one small interfering RNA (siRNA, Inclisiran), have marked significant breakthrough medicine. These demonstrated unparalleled efficacy mitigating hypercholesterolemia, reducing risks, showcased profound value applications, offering novel avenues promising future personalized medicine disorders. Furthermore, emerging research, inclusive our findings, unveils PCSK9's potential role indicator cancer prognosis prospective application transformative treatment. highlights aberrant expression various forms, association with prognosis, crucial carcinogenesis immunity. In conclusion, this synthesized integrates existing knowledge providing holistic perspective reshaping paradigms across emphasizes effect PCSK9-iT, underscoring advancing landscape biomedical research capabilities heralding new eras

Language: Английский

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Bempedoic acid in the management of lipid disorders and cardiovascular risk. 2023 position paper of the International Lipid Expert Panel (ILEP)

Progress in Cardiovascular Diseases, Journal Year: 2023, Volume and Issue: 79, P. 2 - 11

Published: March 7, 2023

Cardiovascular disease (CVD) is a chronic non-communicable (NCD) and the predominant cause of morbidity mortality worldwide. Substantial reductions in CVD prevalence have been achieved recent years by attenuation risk factors (particularly hypertension dyslipidaemias) primary secondary prevention. Despite remarkable success lipid lowering treatments, statins particular, reducing CVD, there still an unmet clinical need for attainment guideline lipid-targets even 2/3 patients. Bempedoic acid, first in-class inhibitor ATP-citrate lyase presents new approach to lipid-lowering therapy. By endogenous production cholesterol, upstream rate-limiting enzyme HMG-CoA-reductase, i.e., target statins, bempedoic acid reduces circulating plasma concentrations low-density lipoprotein cholesterol (LDL-C), major adverse events (MACE). has potential contribute reduction not only as monotherapy, but further part combination therapy with ezetimibe, LDL-C up 40%. This position paper International Lipid Expert Panel (ILEP) summarises evidence around efficacy safety practical recommendations its use, which complement 'lower-is-better-for-longer' management, applied across international guidelines management risk. Practical evidence-based guidance provided relating use atherosclerotic familial hypercholesterolaemia, statin intolerance. Although are no sufficient data avilable role prevention favourable effects on glucose inflammatory markers makes this drug rational choice patient-centred care specific groups

Language: Английский

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Low-Density Lipoprotein Cholesterol, Cardiovascular Disease Risk, and Mortality in China

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(7), P. e2422558 - e2422558

Published: July 18, 2024

Importance Limited evidence supports the association between low-density lipoprotein cholesterol (LDL-C) and mortality across different atherosclerotic cardiovascular disease (ASCVD) risk stratifications. Objective To explore associations LDL-C levels to identify optimal ranges of with lowest in populations diverse ASCVD profiles. Design, Setting, Participants The ChinaHEART project is a prospective cohort study that recruited residents aged 35 75 years from 31 provinces mainland China November 2014 December 2022. were categorized into low-risk, primary prevention, secondary prevention cohorts on basis their medical history risk. Data analysis was performed 2022 October 2023. Main Outcomes Measures end point all-cause mortality, points included cause-specific mortality. Mortality data collected National Surveillance System Vital Registration. assessed by using Cox proportional hazard regression models various adjusted variables. Results A total 4 379 252 individuals recruited, 3 789 025 (2 271 699 women [60.0%]; mean [SD] age, 56.1 [10.0] years) current study. median (IQR) concentration 93.1 (70.9-117.3) mg/dL overall at baseline. During follow-up 4.6 (3.1-5.8) years, 92 888 deaths recorded, including 38 627 deaths. or (CVD) U-shaped both low-risk 838 354 participants) (829 567 participants), whereas it J-shaped (121 104 participants). corresponding CVD 117.8 group, 106.0 cohort, 55.8 cohort. associated (90.9 vs 117.0 mg/dL) (87 114.6 lower diabetes than without Conclusions Relevance This found varied among cohorts, suggesting stricter lipid control targets may be needed for higher those diabetes.

Language: Английский

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Ultrasound-assisted extraction, purification, sulfation of Perilla leaves polysaccharide and hypoglycemic and hypolipidemic activities

Ultrasonics Sonochemistry, Journal Year: 2025, Volume and Issue: unknown, P. 107269 - 107269

Published: Feb. 1, 2025

Perilla leaves are a common traditional medicinal and edible crop, in order to further explore its value, after determining the optimal ultrasound-assisted extraction conditions neutral polysaccharide was extracted. Its structure analyzed, sulfation modification carried out. After purification by different column chromatography, process for of PLP-2-1 established, sulfated modified (S-PLP-2-1) successfully prepared. The potential structural framework molecular weight were determined high performance liquid chromatography (HPLC), methylation analysis, nuclear magnetic resonance (NMR) techniques, while S-PLP-2-1 maintained degree similarity PLP-2-1. Particle size Zeta measurement, infrared spectroscopy, NMR analysis confirmed presence sulfate groups S-PLP-2-1, thermogravimetric rheological analyses provided support development utilization these two polysaccharides. safe concentration range vitro, antioxidant hypoglycemic activities measured. Besides, effects on levels total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C), low-density (LDL-C) oleic acid (OA) induced high-fat HepG2 cells both polysaccharides determined. results indicated that various biological significantly enhanced modification. Therefore, have be developed as drugs anti-glycolipid metabolism disorders.

Language: Английский

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Beyond statins: New pharmacological targets to decrease LDL-cholesterol and cardiovascular events

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 250, P. 108507 - 108507

Published: Aug. 9, 2023

The pharmacological treatment of dyslipidemia, a major modifiable risk factor for developing atherosclerotic cardiovascular disease (ASCVD), remains debated and controversial issue, not only in terms the most appropriate therapeutic range lipid levels, but also with regard to optimal strategy sequence approach (stepwise vs upstream therapy). Current guidelines management dyslipidemia focus on intensity low-density lipoprotein cholesterol (LDL-C) reduction, stratified according ASCVD. Beyond statins ezetimibe, different medications targeting LDL-C have been recently approved by regulatory agencies potential innovative mechanisms action, including proprotein convertase subtilisin/kexin type 9 modulators (monoclonal antibodies such as evolocumab alirocumab; small interfering RNA molecules inclisiran), ATP-citrate lyase inhibitors (bempedoic acid), angiopoietin-like 3 (evinacumab), microsomal triglyceride transfer protein (lomitapide). An understanding their aspects, benefit-risk profile, impact hard endpoint beyond advantages from patient perspective (e.g., adherence) - this evidence-based review is crucial practitioners across medical specialties minimize inertia support clinical practice.

Language: Английский

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Oxidative Stress, Atherogenic Dyslipidemia, and Cardiovascular Risk

Biomedicines, Journal Year: 2023, Volume and Issue: 11(11), P. 2897 - 2897

Published: Oct. 26, 2023

Oxidative stress is the consequence of an overproduction reactive oxygen species (ROS) that exceeds antioxidant defense mechanisms. Increased levels ROS contribute to development cardiovascular disorders through oxidative damage macromolecules, particularly by oxidation plasma lipoproteins. One most prominent features atherogenic dyslipidemia accumulation small dense LDL (sdLDL) particles, characterized increased susceptibility oxidation. Indeed, a considerable and diverse body evidence from animal models epidemiological studies was generated supporting modification sdLDL particles as earliest event in atherogenesis. Lipid peroxidation results formation various bioactive atherosclerotic process different pathophysiological mechanisms, including foam cell formation, direct detrimental effects, receptor-mediated activation pro-inflammatory signaling pathways. In this paper, we will discuss recent data on role their interplay atherosclerosis. addition, special focus be placed clinical applicability novel, promising biomarkers these processes.

Language: Английский

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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

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Clinical potential of inclisiran for patients with a high risk of atherosclerotic cardiovascular disease

Cardiovascular Diabetology, Journal Year: 2023, Volume and Issue: 22(1)

Published: Jan. 30, 2023

Abstract Elevated low-density lipoprotein cholesterol (LDL-C) level is associated with an increased risk of atherosclerotic cardiovascular disease. Although high-intensity lipid-lowering therapies statins and ezetimibe are highly effective for reducing LDL-C levels, over half high-risk patients do not achieve guideline-recommended goals. Thus, there a significant gap between treatment guidelines their implementation in daily clinical practice. The major causes individual variability the response to variation adherence. Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies combined provide marked consistent reduction levels; however, poor adherence due need subcutaneous injections every 2 or 4 weeks high cost obstacles use real-world settings. Inclisiran, recently approved novel small interfering ribonucleic acid (siRNA) molecule that inhibits PCSK9 synthesis, provides robust long-term levels low inter-individual LDL-C-lowering response. Moreover, its administration by biannual injection expected greatly improve Clinical trials this drug lasting up years showed acceptable safety profiles, ongoing studies accumulate evidence longer-term safety. This narrative review summarizes available on efficacy inclisiran analyzes potential overcome guideline recommendations practice current therapies, focus reduced improved

Language: Английский

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Obicetrapib on top of maximally tolerated lipid‐modifying therapies in participants with or at high risk for atherosclerotic cardiovascular disease: rationale and designs of BROADWAY and BROOKLYN

American Heart Journal, Journal Year: 2024, Volume and Issue: 274, P. 32 - 45

Published: May 4, 2024

Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] increases high-density (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential lower atherogenic lipoproteins in patients atherosclerotic cardiovascular disease (ASCVD) heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment available maximally tolerated lipid-modifying therapies, addressing an unmet medical need patient population at risk for events. BROADWAY (NCT05142722) BROOKLYN (NCT05425745) are ongoing placebo-controlled, double-blind, randomized Phase III trials designed examine efficacy, safety, tolerability of as adjunct dietary intervention therapies participants history ASCVD and/or underlying HeFH is not adequately controlled. The primary efficacy endpoint was percent change from baseline day 84. Other endpoints included changes Apo non-HDL-C, HDL-C, A1, Lp(a) triglycerides addition parameters evaluating tolerability, pharmacokinetics. also adjudicated assessment major adverse events, measurements glucose homeostasis, ambulatory blood pressure monitoring substudy. A total 2532 were 354 receive 10 mg placebo (2:1) 365 days follow-up through 35 after last dose. Results both anticipated 2024. These will provide safety data support use among elevated whom existing sufficiently effective well-tolerated.

Language: Английский

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