Particle Number and Characteristics of Lipoprotein(a), LDL, and apoB

Journal of the American College of Cardiology, Год журнала: 2024, Номер 83(3), С. 396 - 400

Опубликована: Янв. 1, 2024

Язык: Английский

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Lipid Toxicity in the Cardiovascular-Kidney-Metabolic Syndrome (CKMS)

Biomedicines, Год журнала: 2024, Номер 12(5), С. 978 - 978

Опубликована: Апрель 29, 2024

Recent studies of Cardiovascular-Kidney-Metabolic Syndrome (CKMS) indicate that elevated concentrations derivatives phospholipids (ceramide, sphingosine), oxidized LDL, and lipoproteins (a, b) are toxic to kidney heart function. Energy production for renal proximal tubule resorption critical fuels electrolytes is required homeostasis. Cardiac energy ventricular contraction/relaxation preferentially supplied by long chain fatty acids. Metabolism acids accomplished within the cardiomyocyte cytoplasm mitochondria means glycolytic, tricarboxylic acid, electron transport cycles. Toxic lipids excessive lipid may inhibit cardiac contraction requires calcium movement from sarcoplasmic reticulum a high low concentration at relatively cost. relaxation involves return lower higher more consumption. Diastolic dysfunction occurs when conversion inadequate. diminished ATP availability in presence inadequate blood pressure, glycemia, or control lead failure. Similar disruption tubular fuels/electrolytes has been found be associated with phospholipid (sphingolipid) accumulation. Elevated tissue low-density lipoprotein cholesterols loss filtration efficiency level glomerular podocyte. Macroscopically deposits epicardial intra-nephric adipose vascular pathology, fibrosis, inhibition essential functions both kidney. Chronic triglyceride accumulation fibrosis liver, structures. Successful kidney, allograft these vital organs does not eliminate risk toxicity. Lipid lowering therapy assist protecting organ function before after transplantation.

Язык: Английский

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Impact of Lipoprotein(a) Level on Low-Density Lipoprotein Cholesterol– or Apolipoprotein B–Related Risk of Coronary Heart Disease

Journal of the American College of Cardiology, Год журнала: 2024, Номер 84(2), С. 165 - 177

Опубликована: Июль 1, 2024

Язык: Английский

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Intra-individual variability in lipoprotein(a): the value of a repeat measure for reclassifying individuals at intermediate risk

European Heart Journal Open, Год журнала: 2024, Номер 4(5)

Опубликована: Авг. 31, 2024

Abstract Aims Lipoprotein(a) [Lp(a)] levels are predominantly genetically determined and repeat measurements generally considered unlikely to be clinically useful. However, the temporal variation of Lp(a) is not well characterized. Our aim was determine intra-individual variability whether a repeated measure reclassified Lp(a)-specific cardiovascular risk using European Atherosclerosis Society (EAS) consensus statement categories. Methods results This retrospective cohort study analysed initial serum measured same methodology from 609 individuals in Nashville Biosciences database, de-identified electronic medical records database. Baseline follow-up paired values were significantly different (P < 0.05), with an absolute change ≥10 mg/dL 38.1% [95% CI 34.2–42%] >25% 40.5% 36.6–44.3%] individuals. Although categories those whose EAS low-risk high-risk did change, 53% intermediate ‘grey-zone’ category transitioned either (20%) or (33%) category. Black exhibited greater than White women men. There positive correlation between baseline changes Lp(a), (r = 0.59, P 0.01). Conclusion Temporal-related present many A may allow more precise prediction for value EAS-defined should included calculating expected effect sizes future clinical research studies targeting Lp(a).

Язык: Английский

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In the Beginning, Lipoproteins Cross the Endothelial Barrier

Journal of Atherosclerosis and Thrombosis, Год журнала: 2024, Номер 31(6), С. 854 - 860

Опубликована: Апрель 12, 2024

Atherosclerosis begins with the infiltration of cholesterol-containing lipoproteins into arterial wall. White blood cell (WBC)-associated inflammation follows. Despite decades research using genetic and pharmacologic methods to alter WBC function, in humans, most effective method prevent initiation progression disease remains low-density lipoprotein (LDL) reduction. However, additional approaches reducing cardiovascular would be useful as residual risk events continues even currently LDL-reducing treatments. Some this may due vascular toxicity triglyceride-rich (TRLs). Another option is that LDL transcytosis continues, albeit at reduced rates lower circulating levels lipoprotein. This review will address these two topics. The evidence TRLs promote atherosclerosis processes allow taken up by endothelial cells leading their accumulation subendothelial space.

Язык: Английский

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Early-onset atherosclerotic cardiovascular disease

European Journal of Preventive Cardiology, Год журнала: 2024, Номер unknown

Опубликована: Июль 20, 2024

Abstract Recent trends indicate a concerning increase in early-onset atherosclerotic cardiovascular disease (ASCVD) among younger individuals (men aged <55 years women <65 years). These findings highlight the pathobiology of ASCVD as process that begins early life and underscores need for more tailored screening methods preventive strategies. Increasing attention has been placed on growing burden traditional cardiometabolic risk factors young while also recognizing unique mediate pre-mature atherosclerosis this demographic such substance use, socioeconomic disparities, adverse pregnancy outcomes, chronic inflammatory states contribute to increasing incidence ASCVD. Additionally, mounting evidence pointed out significant disparities diagnosis management outcomes based sex race. Moving towards personalized approach, emerging data technological developments using diverse tools polygenic scores coronary artery calcium scans have shown potential earlier detection risk. Thus, we review current causal drive improve assessment individuals.

Язык: Английский

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Lipoprotein(a) as a Pharmacological Target: Premises, Promises, and Prospects

Circulation, Год журнала: 2025, Номер 151(6), С. 400 - 415

Опубликована: Фев. 10, 2025

Atherosclerotic cardiovascular disease is a major health concern worldwide and requires effective preventive measures. Lp(a) (lipoprotein [a]) has recently garnered attention as an independent risk factor for astherosclerotic disease, with proinflammatory prothrombotic mechanisms contributing to its atherogenicity. On equimolar basis, ~5 6 times more atherogenic than particles that have been widely associated adverse outcomes, such LDL (low-density lipoprotein). can enter the vessel wall, leading accumulation of oxidized phospholipids in arterial intima, which are crucial initiating plaque inflammation triggering vascular progression. In addition, may cause atherothrombosis through interactions between apoA (apolipoprotein A) platelet PAR-1 (protease-activated receptor 1) receptor, well competitive inhibition plasminogen. Because mostly determined on genetic bases, 1-time assessment lifetime suffice identify patients elevated levels. Mendelian randomization studies post hoc analyses randomized trials cholesterol–lowering drugs showed causal link concentrations therapeutic reduction expected contribute estimated mitigation. Many Lp(a)-lowering drugs, including monoclonal antibodies, small interfering ribonucleic acids, antisense oligonucleotides, molecules, gene editing compounds, at different stages clinical investigation show promise use. particular, increased testing treatment substantial impact population level, enabling identification high-risk individuals subsequent prevention large number events. Ongoing phase 3 will further elucidate benefits over long term, offering potential avenues targeted interventions improved outcomes.

Язык: Английский

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Therapeutic PCSK9 targeting: Inside versus outside the hepatocyte?

Pharmacology & Therapeutics, Год журнала: 2025, Номер unknown, С. 108812 - 108812

Опубликована: Фев. 1, 2025

Язык: Английский

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Coronary Artery Calcium Scoring in the Context of Widespread Lipoprotein(a) Testing: Clinical Considerations and Implications for Lipid-Lowering Therapies

Current Cardiology Reports, Год журнала: 2025, Номер 27(1)

Опубликована: Фев. 11, 2025

Язык: Английский

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Rethinking Cardiovascular Risk: The Emerging Role of Lipoprotein(a) Screening

American Journal of Preventive Cardiology, Год журнала: 2025, Номер 21, С. 100945 - 100945

Опубликована: Фев. 14, 2025

Lipoprotein(a) [Lp(a)] is a genetically inherited, independent risk factor for cardiovascular disease (CVD), affecting approximately 20-25% of the global population. Elevated Lp(a) levels are associated with 2-3-fold increased myocardial infarction and aortic valve stenosis, comparable to seen in individuals familial hypercholesterolemia. Despite its clinical relevance, integration screening into routine practice has been limited by inconsistent measurement techniques lack targeted treatments. Recent advancements, including improved assays development potential Lp(a)-lowering therapies, have renewed focus on importance screening. This review aims clarify role health examining current evidence who should be screened, when occur, most accurate methods measuring Lp(a). Key recommendations include universal, one-time adults, selective high-risk pediatric patients, special considerations conditions such as hypercholesterolemia chronic kidney disease. Advances assay technology now allow more precise measurement, supporting better stratification. Additionally, emerging therapies that specifically target elevated could lead personalized management CVD risk. Our findings support assessment, highlighting improve early detection prevention strategies across diverse patient populations.

Язык: Английский

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