Šlapikas, Rimvydas

This literature review investigates new treatment targets and therapeutics for dyslipidaemias and atherosclerosis and their role in decreasing the risk of cardiovascular events in adults. Apart from emerging research on new drug therapies to decrease the cardiovascular risk through LDL-C, more and more data directs attention to other markers and potential treatment targets of dyslipidaemia. Namely the focus is on high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), lipoprotein (α) (Lp(a)), apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (non-HDL-C) and their relevance in cardiovascular risk (CV) management by analysing the current scientific literature using the PubMed database, including human trials published between 2019 and 2023. The review identifies a large residual CV risk despite effective LDL-C lowering treatment approaches with statins, PCSK9 inhibitors and ezetimibe. It has been widely detected that low HDL-C level are associated with an increased CV risk but in recent studies high HDL-C levels have not only shown no protective effect on CV events but have even been associated with an increase in CV risk. HDL-C levels between 40 mg/dL (50 mg /dL in women) and 80 mg/dL appear not associated with an increased CV risk. Using these cut-offs an HDL-C measurement may be useful in a more individualized CV risk stratification. To better understand HDL-functionality more research is warranted investigating HDL-C and CEC in different settings and stages of inflammation. Apart from LDL-C and HDL-C, TGs are one of three main lipid markers in regard to CV risk modification. More than one third of patients on statins are struggling with elevated TGs. IPE, an established treatment for hypertriglyceridemia still requires further supportive data. It is also necessary to determine a common target value, possibly approaching 100 or 150 mg/dL. With the development of new drugs targeting TGs, the focus should be on determining the optimal TG level for CV event reduction. Especially ASOs, like vupanorsen and volanesorsen have shown significant reductions in TGs in phase II and III trials, respectively. The antibody evinacumab has also produced TG reductions up to 80%, even though most studies have consisted of very small cohort and apart from one exception included phase I and II studies only so far. The newer lipid markers gaining popularity and as for TG, Lp(a), apoB and non-HDL-C have as well demonstrated their significance in CV risk reduction. Lp(a) still requires a lot more research before being more thoroughly incorporated into daily clinical practice, but recent antibody trials with alirocumab and evolocumab are promising. ApoB and non-HDL-C may be measured and focused on already, their significance and practicality has been widely proven, and more precise real-life data is warranted to determine optimal goals and the effect of other drugs and individual factors. Future studies may consider a cut-off of apoB levels at around 90mg/dL as suggested by results so far. New drug classes such as siRNAs, antisense oligonucleotides and monoclonal antibodies show consistent results in reducing not only LDL-C in many cases, but also affecting TGs, Lp(a), non-HDL-C and/or ApoB. More research is warranted to identify the impact on each lipid marker individually to exclude possible interactions. The trend in treating dyslipidaemias and atherosclerosis is moving towards a more individualized approach, taking some distance from only focusing on lowering LDL-C as much as possible, but also taking other markers into account, which may be modified by the new drugs.

ABSTRACT

AIM: To assess the effect of novel approaches regarding the treatment of inflammatory residual risk.

OBJECTIVES: 1. Identifying the impact of hsCRP and IL-6 on cardiovascular disease. 2. Analyzing the effect of colchicine and methotrexate in cardiovascular diseases. 3. Examine the role of IL-1 modulators for the treatment of cardiovascular diseases. 4. Analyzing the significance of IL-6 modulators as a novel approach.

MATERIALS AND METHODS: A search for Articles from databases like MEDLINE, PubMed and Google Scholar were conducted. The keywords used during the search were “Residual risk” OR “Cardiovascular disease” OR “Atherosclerosis” AND “Inflammation” OR “Inflammatory pathway” OR “Inflammatory risk” OR “Interleukin-1” OR “Interleukin-6” OR “hsCRP” AND “Treatment” OR “Statin” OR “Canakinumab” OR “Monoclonal antibody” OR “Colchicine” OR “Methotrexate” OR “Tocilizumab” OR “Anakinra” OR “Ziltivekimab”. The articles were selected via specific inclusion and exclusion criteria. 20 articles were finally used for this review.

RESULTS: Randomized clinical trials, systemic and literature reviews and retrospective studies were reviewed. After the initial search, 20 studies were selected. Besides the investigation of the impact of inflammatory markers like hsCRP, IL-6 and IL-1 on the outcome of residual cardiovascular risk, the role of novel management approaches regarding inflammatory residual risk were assessed. This includes IL-1 and IL-6 modulators, colchicine and methotrexate.

CONCLUSION: 1. HsCRP and IL-6 are powerful biomarkers as well as good predictors for cardiovascular events. 2. The inflammatory pathway should be evaluated as a whole, rather than each individually. 3. IL-1 and IL-6 modulators show great potential for novel therapeutic options in inflammatory residual risk management. 4. Colchicine as a therapeutic option for further cardiovascular risk reduction shows promising results. 5. Methotrexate has no usefulness in cardiovascular risk management since it shows a greater harm than a benefit.

Research aim The aim of this research is to provide an account of primary literature about non-obstructive coronary artery disease, as well as the therapeutic effect statin and aspirin therapy may have on this pathology.

Objectives • To describe the significance, incidence, clinical presentation and prognosis of non-obstructive coronary artery disease. • To investigate the impact of statin therapy on all-cause mortality and coronary revascularization in patients with non-obstructive CAD. • To investigate the impact of aspirin therapy on all-cause mortality and coronary revascularization in patients with non-obstructive CAD.

Methodology This literature review involved a primary online search of the following databases: PubMed, Cochrane Library, ScienceDirect and UpToDate. A secondary manual review of the selected publications’ reference lists was also performed. Additionally, Medscape and WHO internet web pages were used to supplement missing information. Research results and conclusion The studies investigated in this review showed that non-obstructive CAD is a pathology with significant clinical risks: it is associated with an increased rate of myocardial infarction and mortality and carries a far worse prognosis than no apparent CAD. Patients suffering from this condition may benefit from statin therapy, as it is associated with a decreased mortality risk. Aspirin therapy is only beneficial to patients with non-obstructive CAD, if they have additional cardiovascular risk factors, such as >65 years, diabetes or hypertension.

Tyrimo tikslas ir uždaviniai. Nustatyti išeminės širdies ligos (IŠL) rizikos veiksnių (RV) paplitimą ir įtaką širdies vainikinių arterijų aterosklerozinės plokštelės (AP) sudėčiai, nustatomai vidukraujagyslinio ultragarso (IVUS) su virtualiaja histologija (IVUS-VH) tyrimu. Tyrimo metodika. Atliktame retrospektyviniame tyrime analizuota IVUS, IVUS-VH tyrimo metu nustatyta tiriamųjų širdies vainikinėse kraujagyslėse rastų AP sudėtis. Ieškota IŠL RV sąsajų su AP sudedamosiomis dalimis (nekrotinė šerdis (NŠ), kalcifikacija, fibrozinis audinys (FA), riebalinis audinys (RA)). Statistinės duomenų analizės atlikimui naudotas SPSS 23.0 programos paketas. Tyrimo dalyviai. Atsitiktine tvarka atrinkti 54 vyresni nei 18 metų pacientai, kuriems 2015m. lapkričio – 2016m. balandžio mėnesiais Lietuvos sveikatos mokslų universiteto ligoninės Kauno klinikų Kardiologijos klinikoje, esant ūmiam koronariniam sindromui, atliktas IVUS, IVUS-VH tyrimas.

Darbo tikslas - Vainikinių arterijų nepriežastinių aterosklerozinių plokštelių palyginimas virtualios histologijos-vidukraujagyslinio ultragarso (VH-VUG) metodu pacientams, sergantiems ūminiais koronariniais sindromais (ŪKS) be ST segmento pakilimo ir stabilia krūtinės angina (SKA). Tyrimo metodai. Buvo įvertinta ir palyginta 25 pacientų, sergančių ŪKS be ST segmento pakilimo ir 22 pacientų, sergančių SKA, vainikinių arterijų nepriežastinės aterosklerozinės plokštelės, naudojant VH-VUG. VH-VUG vainikinių arterijų aterosklerozinių plokštelių komponentai buvo suklasifikuoti į 4 grupes ir išreikšti jų procentiniai dydžiai tiriamajame aterosklerozinės plokštelės segmente. Buvo vertinami šie vainikinių arterijų aterosklerozinių plokštelių komponentai: nekrozinis, kalcifikacinis, fibro-elastinis, fibro-lipidinis. Tyrimo rezultatai. nustatyta, kad pacientų sergančių ŪKS be ST segmento pakilimo grupėje nepriežastinių aterosklerozinių plokštelių komponentų tūris buvo ženkliai mažesnis (90,8 ±21 mm3 vs. 102,6 ± 28 mm3, p >0,05) lyginant su pacientų sergančių SKA plokštelių tūriu. Lyginant vainikinių arterijų aterosklerozinių plokštelių komponentų tūrius tarp tiriamųjų grupių gauta, kad tiek nekrotinio (19,1 vs. 12,4, p<0,05), tiek kalcifikacinio (15,6 vs. 9,6 p<0,05) komponentų tūriai aterosklerozinėse plokštelėse buvo didesni vertinant absoliučiai skaičiais pacientams, sergantiems ŪKS be ST segmento pakilimo lyginant su pacientais SKA. Išvados. Pacientų, sergančių ŪKS, nepriežastinės aterosklerozinės plokštelės pasižymi mažesniu tūriu ir plokštelių sudėtis turi daugiau komponentų būdingų lengvai pažeidžiamoms plokštelėms lyginant su pacientų sergančių SKA aterosklerozinėmis plokštelėmis.