LDL cholesterol

Overview

Low-density lipoprotein cholesterol (LDL-C), often referred to as “LDL cholesterol,” is a major circulating cholesterol fraction and a central biomarker in cardiovascular medicine. It is widely used to assess atherosclerotic cardiovascular disease risk, and elevated LDL-C is considered a causal and modifiable risk factor for myocardial infarction and other ischemic events. In clinical practice, LDL-C is a primary treatment target in dyslipidemia, with goal attainment used to guide lipid-lowering therapy in patients with diabetes, pre-diabetes, normoglycaemia, familial hypercholesterolemia, and established cardiovascular disease.

Biologically, LDL particles transport cholesterol in the bloodstream, and excess LDL-C contributes to cholesterol deposition in arterial walls. This makes LDL-C a key endpoint in studies of statins, PCSK9 inhibitors, inclisiran, bempedoic acid, antisense therapies, and emerging genome-editing or peptide-based approaches. LDL-C is also frequently interpreted alongside apolipoprotein B, non-HDL cholesterol, triglycerides, remnant cholesterol, and inflammatory markers such as hs-CRP, because these measures together better characterize residual atherosclerotic risk.

Focus of Latest Publications

Recent publications on LDL cholesterol have focused heavily on real-world goal attainment and treatment intensification in high-risk cardiovascular populations. In the European prospective SANTORINI study, investigators examined changes in lipid-lowering therapy use and LDL-C goal attainment over 1 year, stratified by diabetes status, in patients with diabetes, pre-diabetes, and normoglycaemia. Similar implementation-focused work in a West London secondary prevention pathway evaluated whether automated detection and referral to a pharmacist-led lipid clinic improved LDL-C attainment after acute coronary syndrome, with attention to differences by sex, ethnicity, and socioeconomic deprivation. Real-world analyses from the All of Us Research Program likewise assessed lipid-lowering therapy use and LDL-C control across patients with coronary artery disease, peripheral artery disease, cerebral atherosclerosis, and polyvascular disease, highlighting persistent management gaps despite guideline recommendations for aggressive LDL-C lowering.

Several studies addressed LDL cholesterol in specific high-risk or inherited dyslipidemia settings. The Canadian HoFH Registry study described homozygous familial hypercholesterolemia as a condition marked by extremely elevated LDL-C and premature cardiovascular disease, and aimed to characterize treatment patterns and cardiovascular outcomes. Another pilot study compared plasma proteome profiles in heterozygous familial hypercholesterolemia and non-FH patients treated with PCSK9 inhibitors, reflecting ongoing interest in LDL-C reduction with PCSK9-targeted therapy. In VESALIUS-CV, evolocumab was evaluated for intensive LDL-C lowering to reduce first major cardiovascular events in patients with diabetes but without known significant atherosclerosis, underscoring the expanding use of PCSK9 inhibition beyond established atherosclerotic disease.

Other publications examined LDL-C as part of broader risk stratification or therapeutic target assessment. In post-acute myocardial infarction patients, one study assessed failure to achieve dual LDL-C and hs-CRP targets, emphasizing residual risk from both dyslipidemia and inflammation. A UK Biobank analysis explored whether combining genomics with LDL-C, lipoprotein(a), and hsCRP could improve prediction of coronary artery disease risk. A cost-effectiveness study compared LDL-C, non-HDL-C, and apoB goals for primary prevention lipid-lowering therapy, noting that the relative value of these targets has not been established. In statin-treated patients with ischemic heart disease, high LDL cholesterol was investigated as a determinant of greater risk of STEMI than NSTEMI, while another study in Japanese patients undergoing PCI for chronic coronary syndrome examined the association of high-intensity statin therapy and LDL-C with cardiovascular outcomes.

LDL cholesterol was also studied in relation to non-cardiovascular metabolic disease and dietary interventions. In patients with type 2 diabetes mellitus, one study evaluated the association of remnant cholesterol and its discordance with LDL-C with the risk of metabolic dysfunction-associated steatotic liver disease. A randomized crossover trial of Chardonnay grape marc/grape seed extract blends in adults with mild dyslipidemia hypothesized reductions in LDL-C, although the reported findings emphasized effects on triglycerides and HDL cholesterol rather than LDL-C. Together, these publications show LDL-C being used both as a treatment target and as a marker of residual risk across cardiovascular prevention, inherited lipid disorders, diabetes, and metabolic disease.

Key Publications

• NEWJul Low-density lipoprotein cholesterol management and goal attainment at 1 year in patients with diabetes, pre-diabetes and normoglycaemia: results from the European, prospective, observational SANTORINI study. (BMJ open, 2026, PMID 42373176): "To assess changes in lipid-lowering therapy (LLT) use and low-density lipoprotein cholesterol (LDL-C) goal attainment through 1-year follow-up in patients stratified by diabetes status in SANTORINI (Treatment of High and Very High riSk Dyslipidemic pAtients for the PreveNTion of CardiOvasculaR Events in Europe - a MultInatioNal ObservatIonal study)."
• NEWJun Equitable lipid optimisation through a data-driven, pharmacist-led secondary prevention pathway. (Open heart, 2026, PMID 42331567): "This study evaluates whether automating the detection and referral of high-risk patients to a pharmacist-led clinic is associated with improved attainment of low-density lipoprotein cholesterol (LDL-C) among post-acute coronary syndrome patients in a West London borough."
• NEWJun Discordant high remnant cholesterol with LDL-C increases the metabolic dysfunction-associated steatotic liver disease risk in patients with type 2 diabetes mellitus. (BMJ open diabetes research & care, 2026, PMID 42303421): "We aimed to examine the association of RC, its discordance with low-density lipoprotein cholesterol (LDL-C) in terms of MASLD risk in patients with T2DM."
• NEWJun Persistent gaps in management and risk factor control among patients with atherosclerotic cardiovascular disease: All of us research program. (Atherosclerosis, 2026, PMID 42270564): "Contemporary guidelines recommend aggressive low-density lipoprotein cholesterol (LDL-C) lowering in patients with atherosclerotic cardiovascular disease (ASCVD), yet significant treatment gaps persist in clinical practice."
• May Homozygous familial hypercholesterolemia (HoFH) in Canada. (Atherosclerosis, 2026, PMID 42229223): "Homozygous familial hypercholesterolemia (HoFH) is a rare disorder of lipid metabolism, characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C) levels and marked premature cardiovascular disease."
• May Failure to achieve LDL-C and HS-CRP targets in post-acute myocardial infarction patients: prevalence and predictors. (La Clinica terapeutica, 2026, PMID 42047130): "High-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C) represent two independent and complementary biomarkers of risk."
• May Cost-Effectiveness of ApoB, Non-HDL-C, and LDL-C Goals for Primary Prevention Lipid-Lowering Therapy. (JAMA, 2026, PMID 41949879): "Apolipoprotein B (apoB) is a superior marker of residual atherosclerotic cardiovascular disease risk in patients treated with lipid-lowering therapy (LLT) compared with low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C)."
• May Proteome Profiles of Hypercholesterolemic Patients with and Without FH Treated with a PCSK9 Inhibitor: A Comparison of Depleted and Nondepleted Samples in a Pilot Study. (Proteomics. Clinical applications, 2026, PMID 41906435): "Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors offer a novel approach for reducing low-density lipoprotein cholesterol (LDL-C) levels in patients with familial hypercholesterolemia (FH)."
• Mar Impact of High-Intensity Statins and Low-Density Lipoprotein Cholesterol on the Outcomes of Coronary Intervention for Chronic Coronary Syndrome in Japan. (Journal of atherosclerosis and thrombosis, 2026, PMID 41905939): "The clinical effect of high-intensity statin therapy after percutaneous coronary intervention (PCI) in Japanese patients with chronic coronary syndrome (CCS) remains unclear."
• Apr Evolocumab to Reduce First Major Cardiovascular Events in Patients Without Known Significant Atherosclerosis and With Diabetes: Results From the VESALIUS-CV Trial. (JAMA, 2026, PMID 41903215): "Intensive lowering of low-density lipoprotein cholesterol (LDL-C) levels with PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors for cardiovascular event reduction has largely been reserved for patients with significant atherosclerosis."