Clinical Significance of Electronegative Low-Density Lipoprotein Cholesterol in Atherothrombosis

Abstract

Despite the numerous risk factors for atherosclerotic cardiovascular diseases (ASCVD), cumulative evidence shows that electronegative low-density lipoprotein (L5 LDL) cholesterol is a promising biomarker. Its toxicity may contribute to atherothrombotic events. Notably, plasma L5 LDL levels positively correlate with the increasing severity of cardiovascular diseases. In contrast, traditional markers such as LDL-cholesterol and triglyceride are the therapeutic goals in secondary prevention for ASCVD, but that is controversial in primary prevention for patients with low risk. In this review, we point out the clinical significance and pathophysiological mechanisms of L5 LDL, and the clinical applications of L5 LDL levels in ASCVD can be confidently addressed. Based on the previously defined cut-off value by receiver operating characteristic curve, the acceptable physiological range of L5 concentration is proposed to be below 1.7 mg/dL. When L5 LDL level surpass this threshold, clinically relevant ASCVD might be present, and further exams such as carotid intima-media thickness, pulse wave velocity, exercise stress test, or multidetector computed tomography are required. Notably, the ultimate goal of L5 LDL concentration is lower than 1.7 mg/dL. Instead, with L5 LDL greater than 1.7 mg/dL, lipid-lowering treatment may be required, including statin, ezetimibe or PCSK9 inhibitor, regardless of the low-density lipoprotein cholesterol (LDL-C) level. Since L5 LDL could be a promising biomarker, we propose that a high throughput, clinically feasible methodology is urgently required not only for conducting a prospective, large population study but for developing therapeutics strategies to decrease L5 LDL in the blood.

An Evidence Based Assessment of Most Common Risk Factors of Myocardial Infarction: Analysis From a Local Population

“…The exact toxic components of cigarette smoke and the mechanisms involved in CS-related cardiovascular dysfunction are largely unknown, because it is also observed that non-smoker without family history develop MI even in the early ages of the life span. but CS increases inflammation, thrombosis, and oxidation of lowdensity lipoprotein cholesterol (Chu et al, 2020). Recent experimental and clinical data support the hypothesis that cigarette smoke exposure increases oxidative stress as a potential mechanism for initiating cardiovascular dysfunction.…”

“…Smoking proved to be the significant risk factor for both genders and remained the major health hazard leading to MI. Cigarette smoking ( CS) impacts all phases of atherosclerosis from endothelial dysfunction to acute clinical events, the latter being largely thrombotic (d'Alessandro et al, 2020;Head et al, 2017). The exact toxic components of cigarette smoke and the mechanisms involved in CS-related cardiovascular dysfunction are largely unknown, because it is also observed that non-smoker without family history develop MI even in the early ages of the life span.…”

Circulating Biomarkers Reflecting Destabilization Mechanisms of Coronary Artery Plaques: Are We Looking for the Impossible?

“…Electronegative LDL (LDL(−)) is a modified fraction of the LDL that holds physical and chemical characteristics that differ from those of native LDL, such as increased lipoprotein-associated phospholipase A2 activity (Lp-PLA2), ceramide, clusterine, nonesterified fatty acid content, as well as increased aggregation level [117]. LDL(−) normally comprises around 3−5% of the total LDL plasma quantity, yet in certain CV pathologies this fraction rises [118]. A moderate rise of LDL(−) is commonly observed in patients with classical CV risk factors such as hypercholesterolemia, active smoking, diabetes, and metabolic syndrome [119][120][121][122].…”

Autoimmune Rheumatic Diseases: An Update on the Role of Atherogenic Electronegative LDL and Potential Therapeutic Strategies

“…The therapeutic goal of controlling L5 should be to lower its plasma concentration below 1.7 mg/dL. If the L5 concentration is higher than 1.7 mg/dL, a lipid-lowering treatment, such as statins or PCSK9 inhibitors, may be required regardless of the absolute LDL level [ 130 ].…”