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PURPOSE OF REVIEW: Cardiovascular disease is a leading cause of death worldwide. Dyslipidemia is a critical modifiable risk factor for the prevention of cardiovascular disease. Dyslipidemia affects a large population of women and is especially pervasive within racial/ethnic minorities. RECENT FINDINGS: Dyslipidemia in pregnancy leads to worse outcomes for patients and creates increased cardiovascular risk for women at an older age. However, women remain underscreened and undertreated compared to men. Females also comprise a small portion of clinical trial participants for lipid lowering agents with increased disease prevalence compared to trial representation. However, recent lipid trials have shown different efficacies of therapies such as ezetimibe, inclisiran, and bempedoic acid with a greater relative benefit for women. SUMMARY: Pathophysiology of dyslipidemia varies between men and women and across a womans lifetime. While increased lipid levels or lipid imbalances are more common in postmenopausal women over age 50, conditions such as PCOS and FH produce higher cardiovascular risk for young women.Best practices for management of women with dyslipidemia include early screening with lifestyle intervention and pharmacotherapy with statin and non-statin agents to achieve guideline directed LDL-C thresholds.

Statins have contributed to the prevention of numerous atherosclerotic cardiovascular (CV) events and cardiovascular deaths in the past three decades. The benefit of statins is mainly mediated by the lowering of LDLc. According to scientific evidence, the current international guidelines recommend very low LDLc goals in patients at high/very high cardiovascular risk because they are associated with fewer CV events and improvements in atherosclerotic plaques. However, these goals often cannot be obtained with statins alone. Recent RCTs have demonstrated that these CV benefits can also be obtained with nonstatin LDLc-lowering drugs such as PCSK9 inhibitors (alirocumab and evolocumab), ezetimibe and bempedoic acid, while evidence with inclisiran is upcoming. Icosapent ethyl, a lipid metabolism modifier, has also shown an effect on event reduction. Physicians should take advantage of the currently available lipid-lowering therapies, choosing the drug or combination of drugs that is most appropriate for each patient according to his or her CV risk and baseline LDLc concentration. Strategies implementing combination therapies from early stages or even from the outset may increase the number of patients attaining LDLc goals, thereby preventing new CV episodes and improving existing atherosclerotic lesions.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

ATP-citrate lyase is a central integrator of cellular metabolism in the interface of protein, carbohydrate, and lipid metabolism. The physiological consequences as well as the molecular mechanisms orchestrating the response to long-term pharmacologically induced Acly inhibition are unknown. We report here that the Acly inhibitor SB-204990 improves metabolic health and physical strength in wild-type mice when fed with a high-fat diet, while in mice fed with healthy diet results in metabolic imbalance and moderated insulin resistance. By applying a multiomic approach using untargeted metabolomics, transcriptomics, and proteomics, we determined that, in vivo, SB-204990 plays a role in the regulation of molecular mechanisms associated with aging, such as energy metabolism, mitochondrial function, mTOR signaling, and folate cycle, while global alterations on histone acetylation are absent. Our findings indicate a mechanism for regulating molecular pathways of aging that prevents the development of metabolic abnormalities associated with unhealthy dieting. This strategy might be explored for devising therapeutic approaches to prevent metabolic diseases.

After experiencing an acute coronary syndrome (ACS), patients are at a high risk of suffering from recurrent ischaemic cardiovascular events, especially in the very early phase. Low density lipoprotein-cholesterol (LDL-C) is causally involved in atherosclerosis and a clear, monotonic relationship between pharmacologic LDL-C lowering and a reduction in cardiovascular events post-ACS has been shown, a concept termed 'the lower, the better'. Current ESC guidelines suggest an LDL-C guided, step-wise initiation and escalation of lipid-lowering therapy (LLT). Observational studies consistently show low rates of guideline-recommended LLT adaptions and concomitant low rates of LDL-C target goal achievement, leaving patients at residual risk, especially in the vulnerable post-ACS phase. In addition to the well-established 'the lower, the better' approach, a 'strike early and strike strong' approach in the early post-ACS phase with upfront initiation of a combined lipid-lowering approach using high-intensity statins and ezetimibe seems reasonable. We discuss the rationale, clinical trial evidence and experience for such an approach and highlight existing knowledge gaps. In addition, the concept of acute initiation of PCSK9 inhibition in the early phase is reviewed. Ultimately, we focus on hurdles and solutions to provide high-quality, evidence-based follow-up care in post-ACS patients.

Bempedoic acid acts by inhibiting adenosine triphosphate-citrate lyase (ACL) and consequently cholesterol biosynthesis, leading to increased expression of LDL receptors and increasing low-density lipoproteins (LDL-C) plasma clearence. It is a prodrug for oral administration with intracellular activation. It is activatedin liver cells and to a lesser extent in kidney cells, being absent in adipose tissue and muscle cells. Therefore, unlike statins, its potential myotoxic effect is very limited. It has recently been approved as a lipid-lowering drug in combination with diet, with statins, or with other lipid-lowering drugs in patients with hypercholesterolaemia, mixed dyslipidaemia, statin intolerance, or when these are contraindicated. The marketing of bempedoic acid implies, in clinical practice, having a new family of lipid-lowering drugs. (c) 2021 Sociedad Espanola de Arteriosclerosis. Published by Elsevier Espana, S.L.U. All rights reserved.