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Beyond LDL-C: unravelling the residual atherosclerotic cardiovascular disease risk landscape-focus on
Bilal Bashir1,2,3, Jonathan Schofield2, Paul Downie4
1Faculty of Biology Medicine and Health, University of Manchester, Manchester, United Kingdom.
Insights
High triglycerides remain a key cardiovascular risk even with low LDL-C. Pure EPA shows promise for reducing atherosclerotic cardiovascular disease risk, necessitating updated guidelines and further research into novel therapies.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Lipidology
Background:
- Atherosclerotic cardiovascular disease (ASCVD) risk management traditionally focuses on low-density lipoprotein cholesterol (LDL-C).
- Residual ASCVD risk persists despite optimal LDL-C control, particularly in patients with hypertriglyceridaemia.
- Hypertriglyceridaemia is linked to increased ASCVD risk, often coexisting with low high-density lipoprotein cholesterol.
Purpose of the Study:
- To review the residual ASCVD risk profile beyond LDL-C.
- To explore the role of hypertriglyceridaemia and recent therapeutic trials.
- To discuss novel approaches for other residual ASCVD risk factors.
Main Methods:
- Narrative review of existing literature and clinical trial data.
- Analysis of observational studies on hypertriglyceridaemia and ASCVD.
- Evaluation of therapeutic agents targeting triglyceride levels and other ASCVD risk factors.
Main Results:
- Hypertriglyceridaemia is a significant ASCVD risk factor, even with low LDL-C.
- Fibrates' efficacy in lowering triglycerides for ASCVD risk reduction is questionable.
- Purified eicosapentaenoic acid (EPA) demonstrates ASCVD risk reduction, unlike EPA/docosahexaenoic acid (DHA) combinations.
Conclusions:
- Hypertriglyceridaemia represents a critical residual ASCVD risk.
- Evidence supports pure EPA for ASCVD risk reduction in specific patient groups.
- Clinical guidelines require updates, and novel therapies targeting non-conventional risks need further investigation.
Aims:
Historically, atherosclerotic cardiovascular disease (ASCVD) risk profile mitigation has had a predominant focus on low density lipoprotein cholesterol (LDL-C). In this narrative review we explore the residual ASCVD risk profile beyond LDL-C with a focus on hypertriglyceridaemia, recent clinical trials of therapeutics targeting hypertriglyceridaemia and novel modalities addressing other residual ASCVD risk factors.
Findings:
Hypertriglyceridaemia remains a significant ASCVD risk despite low LDL-C in statin or proprotein convertase subtilisin/kexin type 9 inhibitor-treated patients. Large population-based observational studies have consistently demonstrated an association between hypertriglyceridaemia with ASCVD. This relationship is complicated by the co-existence of low high-density lipoprotein cholesterol. Despite significantly improving atherogenic dyslipidaemia, the most recent clinical trial outcome has cast doubt on the utility of pharmacologically lowering triglyceride concentrations using fibrates. On the other hand, purified eicosapentaenoic acid (EPA), but not in combination with docosahexaenoic acid (DHA), has produced favourable ASCVD outcomes. The outcome of these trials suggests alternate pathways involved in ASCVD risk modulation. Several other pharmacotherapies have been proposed to address other ASCVD risk factors targeting inflammation, thrombotic and metabolic factors.
Implications:
Hypertriglyceridaemia poses a significant residual ASCVD risk in patients already on LDL-C lowering therapy. Results from pharmacologically lowering triglyceride are conflicting. The role of fibrates and combination of EPA and DHA is under question but there is now convincing evidence of ASCVD risk reduction with pure EPA in a subgroup of patients with hypertriglyceridaemia. Clinical guidelines should be updated in line with recent clinical trials evidence. Novel agents targeting non-conventional ASCVD risks need further evaluation.
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