Statin Hyperlipidaemia: What Else?

The fraction of the populace aged 60–65 years and over is growing more quickly compared to those of lower age.[1,2] It interprets that the proportion of worldwide people aged 65 years and exceeding is predicted to escalate from 10% (2022) to 16% by 2050.[1] The United Nations reported that there were 703 million people 65 years and above globally in 2019. It has been estimated that the geriatric community will be doubled, and 1.5 billion elderly people will live on our planet by 2050.[3] Hypercholesterolaemia is candidly associated with atherosclerotic cardiovascular disease, which endure the dominant basis of fatal outcomes amongst the elderly population.[4] The US Preventive Services Task Force recommended that with the practical assertion that regular statin (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) [Figure 1] intake prevents cardiovascular disease (CVD) calamity and every single issue that led to death toll amongst adults aged 40–75-year age range with no antiquity of CVD.[5-7] In addition, statin prevents CVD issues amongst individuals who have one or multiple CVD risk features, such as smoking, diabetes mellitus, bad serum lipid profile and essential hypertension.[6-9] Furthermore, it has been appraised that individuals who have a 10-year CVD episode possibility of 10% or above have a considerable advantage with statin medication.[6,10] The US Food and Drug Administration permitted and licensed statins include atorvastatin, rosuvastatin, simvastatin, pravastatin, fluvastatin, lovastatin and pitavastatin.[11,12]Figure 1: Illustration showing the mechanism of action of statin. This figure has been drawn with the premium version of BioRender[ 13 ] (https://biorender.com/accessedon12thAugust2024) with the license number YE2768VV7B. Image credit: Susmita Sinha.Contemporary research reported that statin possesses several pleiotropic (cholesterol-independent) pharmacodynamics, thereby enriching atherosclerotic plaques' immovability, improving endothelial physiology, deterring the thrombogenic and inflammatory retort and minimising oxidative stress [Figure 2].[14-18] Statins also possess valuable extrahepatic positive pharmacological actions on the bone, immune system and central nervous system.[14,19,20] The pleiotropic pharmacology of statins is often put in a nutshell in four tiers: anti-inflammatory, anti-invasive, antiangiogenic and antiproliferative.[21] The current editorial primarily concentrates on statin pleiotropic pharmacodynamics for gynaecological purposes, for example antiphospholipid syndrome, pre-eclampsia, adhesion prevention, ovarian carcinoma, polycystic ovary syndrome and endometriosis,[21] with especial attention towards endometriosis.Figure 2: Illustration showing the effects of statin. This figure has been drawn with the premium version of BioRender[ 13 ] (https://biorender.com/accessedon12thAugust2024) with the license number MJ27692L9Z. Image credit: Susmita Sinha.Endometriosis is a chronically oestrogen-dependent and inflammatory gynaecological disease. Around 5%–10% of women of reproductive age frequently have endometrium that occurs outside the uterine cavity. It causes lower abdominal pain, fretfulness and even childlessness.[22-24] Statins effectively antagonise the endogenous mevalonate pathway, i.e., regulate the biogenesis of cholesterol and isoprenoids.[25-27] The mevalonate pathway generates isoprenoid and is responsible for monocyte chemotactic protein 1 (MCP-1) expression in endometriotic cells.[26,28] MCP-1 is a potent chemokine controlling the migration and infiltration of monocytes/macrophages.[29,30] MCP-1 has been raised to the highest level in women's peritoneal environment, even with nominal endometriosis.[31] It has been reported that patients who have endometriosis synthesise more MCP-1, hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1).[32,33] MCP-1,[31] HGF[34] and IGF-1[35] growth factors play essential roles in the pathology of endometriosis. It has been reported that statins possess a negative impact on the synthesis of a lot of growth factors, including vascular endothelial growth factor, primary fibroblast growth factors (FGFs), insulin-like growth factor-1 and HGF, which play imperative functions in the instigation of the PI3K/AKT trajectory.[36] Madanes et al. revealed that the PI3K/AKT signalling system materialises the evolution of endometriosis because of its hormone dependency and inflammatory quality.[37] Driva et al., 2023, reported that the conversion course from normal endometrium to endometriosis to endometriosis-associated ovarian cancer is instigated by the PI3K/AKT/mTOR signalling force. The distorted expression of principal alleyway factors equally in eutopic and ectopic endometrium was responsible for the pathological process.[38] Pharmacological management (gonadotropin-releasing hormone agonists), oral contraceptive pills and medroxyprogesterone acetate) of endometriosis is particularly symptomatic.[39-41] Medication is unable to address endometriosis pathology, such as cytoreductive and hypo-oestrogenic situations, permanently, relatively only short-lived relief through the hormonal clampdown.[42-44] As soon as medical intervention stopped, endometriosis recurred.[40] This does not mean pharmacological intervention is ineffective. Many NCDs need to take medication lifelong. On the contrary, Dillon et al. reported that petite duration oral statin therapy enhanced cutaneous microvascular endothelium-dependent vasodilation amongst patients with endometriosis by intensifying nitric oxide reliant pathways,[45] thereby cutting down endometriotic damaged tissue in terms of both quantity and dimensions.[45]Per se, pharmacological intervention should precisely pursue decreasing cholesterol levels, diminishing systemic inflammation and lectin-like oxidised low-density lipoprotein receptor-1 receptor antagonism for alleviating vascular deterioration amongst those with endometriosis.[45] Hence, statins with anti-inflammatory and antioxidant properties can defend against the evolution of endometriosis [Figure 3].[46]Figure 3: Schematic diagram showing the effects of statin in endometriosis. Here, ↑and ↓ denote increased or decreased expression or function, respectively. CRP indicates C-reactive protein; MCP, monocyte chemoattractant protein; MMP, matrix metalloproteinase; TIMP, tissue inhibitor of matrix metalloproteinases; TNF, tumour necrosis factor; VEGF, vascular endothelial growth factor. This figure has been drawn with the premium version of BioRender[ 13 ] (https://biorender.com/accessedon12thAugust2024) with the license number BT2769864P. Image credit: Susmita Sinha.To conclude, plenty of research[25,44-47] reported that statin has been evidenced statin capability to prevent the progression of endometriosis. Conversely, apprehensions still endure about the possibility of statin-related adverse drug reactions on ovarian physiological performance.[48,49] Consent for publication The author reviewed and approved the final version and has agreed to be accountable for all aspects of the work, including any accuracy or integrity issues. Disclosure The author declares that they do not have any financial involvement or affiliations with any organisation, association or entity directly or indirectly related to the subject matter or materials presented in this editorial. This includes honoraria, expert testimony, employment, ownership of stocks or options, patents or grants received or pending royalties. Data availability Information is taken from freely available sources for this editorial. Authorship contribution All authors contributed significantly to work, whether in the conception, design, utilisation, collection, analysis and interpretation of data or all these areas. They also participated in the paper's drafting, revision or critical review, gave their final approval for the version that would be published, decided on the journal to which the article would be submitted and made the responsible decision to be held accountable for all aspects of the work.