Cardiovascular Risk Factors and Cholesterol Management

Cardiovascular disease remains the principal cause of mortality worldwide, driven by a complex interplay of modifiable and non-modifiable factors. Dyslipidaemia—characterised by elevated low-density lipoprotein cholesterol, raised triglycerides and reduced high-density lipoprotein cholesterol—promotes atherosclerotic plaque formation, while genetic determinants such as apolipoprotein B concentration and lipoprotein(a) levels confer additional, heritable risk. Hypertension, diabetes mellitus, smoking and obesity further exacerbate endothelial dysfunction and inflammatory pathways. Comprehensive risk assessment utilises multivariable algorithms that integrate demographic, clinical and emerging biomarker data to personalise prevention and guide therapeutic intensity. Management strategies combine lifestyle intervention—dietary modification, exercise and weight optimisation—with pharmacotherapy. Statins remain first line for cholesterol synthesis inhibition, complemented by agents such as ezetimibe, PCSK9-targeted monoclonal antibodies, siRNA therapeutics and novel inhibitors of angiopoietin-like protein 3 or apolipoprotein(a) assembly. This evolving arsenal enables precision approaches to reduce residual risk, informed by genetic profiling and global epidemiological trends.

Research from Nature Portfolio

Recent advances have focused on disrupting pathogenic lipid particles at the molecular level. Small-molecule inhibitors designed to bind the kringle IV domains of apolipoprotein(a) have demonstrated subnanomolar potency in preventing lipoprotein(a) assembly, reducing circulating levels in preclinical models and establishing a pathway for oral therapies to target this independent risk factor. In parallel, therapeutic blockade of angiopoietin-like protein 3 using monoclonal antibodies has been evaluated in patients with severe hypertriglyceridaemia, revealing substantive triglyceride reductions across distinct genetic subtypes and informing the design of larger trials aimed at improving chylomicron clearance and preventing pancreatitis.

Cardiovascular Risk Factors and Cholesterol Management publication trend

The graph below shows the total number of articles in cardiovascular risk factors and cholesterol management across all publications each year (not limited to Nature Index journals).

Technical terms

Low-density lipoprotein (LDL) cholesterol: A lipoprotein fraction that transports cholesterol to peripheral tissues and contributes to plaque formation when elevated.

Lipoprotein(a) [Lp(a)]: A variant lipoprotein comprising an LDL-like particle bound to apolipoprotein(a), recognised as an independent cardiovascular risk factor.

Proprotein convertase subtilisin/kexin type 9 (PCSK9): A hepatic enzyme that regulates LDL receptor recycling and modulates plasma cholesterol levels.

Inclisiran: A small interfering RNA therapeutic that inhibits hepatic PCSK9 synthesis, enabling twice-yearly LDL cholesterol reduction.

Evinacumab: A monoclonal antibody targeting angiopoietin-like protein 3 to reduce triglyceride levels in severe hypertriglyceridaemia.

References

1. Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside. Signal Transduction and Targeted Therapy (2024).
2. Discovery of potent small-molecule inhibitors of lipoprotein(a) formation. Nature (2024).
3. Evinacumab in severe hypertriglyceridemia with or without lipoprotein lipase pathway mutations: a phase 2 randomized trial. Nature Medicine (2023).
4. Long-term efficacy and safety of inclisiran in patients with high cardiovascular risk and elevated LDL cholesterol (ORION-3): results from the 4-year open-label extension of the ORION-1 trial. The Lancet Diabetes & Endocrinology (2023).
5. Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019 Update From the GBD 2019 Study. Journal of the American College of Cardiology (2020).