Elevated Small Dense Low-Density Lipoprotein Cholesterol as a Predictor for Future Cardiovascular Events in Patients with Stable Coronary Artery Disease

Abstract

Aim:The aim of the present study was to investigate how small dense low-density lipoprotein cholesterol (sdLDL-C) compared with LDL-C affect the long-term prognosis in patients with stable coronary artery disease (CAD). Methods: sdLDL-C measured by heparin magnesium precipitation and LDL particle size measured by non-denatured gradient-gel electrophoresis were compared in 190 consecutive CAD patients who underwent coronary arteriography between 2003 and 2004 who did or did not develop cardiovascular events during a seven-year follow-up period. Cardiovascular events were death caused by cardiovascular diseases (CVDs), onset of acute coronary syndrome, need for coronary and peripheral arterial revascularization, hospitalization for heart failure, surgical procedure for any CVDs, and/or hospitalization for stroke. Results: First-time cardiovascular events were observed in 72 patients. Those who experienced cardiovascular events were older and had higher prevalence rates of hypertension and diabetes; significantly higher Gensini coronary atherosclerotic scores; significantly higher levels of sdLDL-C, sdLDL-C/LDL-C, and LDL-C/high-density lipoprotein cholesterol (HDL-C) ratios; and greater glycated hemoglobin (Hb)A1c and brain natriuretic peptide (BNP) levels. They also had significantly smaller LDL particle sizes, HDL-C, apolipoprotein A-1, and estimated glomerular filtration rate (GFR) compared with patients without cardiovascular events. Conversely, LDL-C, non-HDL-C, apolipoprotein B, remnantlike particle cholesterol, and high-sensitivity C-reactive protein (hs-CRP) levels were similar between the two groups. A Kaplan-Meyer event-free survival curve demonstrated that patients with sdLDL-C ≥ 35 mg/dL (median level) had significantly poorer prognosis compared with those with lower sdLDL-C levels, while patients with LDL-C ≥ 100 mg/dL had a non-significantly lower survival rate. Conclusion: These results confirm that sdLDL-C is a very promising biomarker to predict future cardiovascular events in the secondary prevention of stable CAD. J Atheroscler Thromb, 2014; 21:755-767.

Non-HDL cholesterol is better than Friedewald-estimated LDL cholesterol to associate with cardiometabolic markers

“…Thus, our observation of relatively strong correlation of non-HDL-C with triglyceride is likely to reflect non only the unsurprising correlation between VLDL-triglycerides and VLDLcholesterol, but also some presence of triglyceride-rich lipoproteins, remnant, and abnormal small particles and low HDL-C concentration, which have been proposed as atherogenic lipoprotein phenotype [31,32]. Of note, the correlation coefficient of non-HDL-C with small dense LDL-C has been shown to be high (r = 0.76) compared to Friedewald-estimated LDL-C (r = 0.60) [19,20].…”

“…As occurrence of dyslipidemia is an important feature of MetS, the latter study was considered to highlight the importance of atherogenic dyslipidemia rather than high LDL-C levels [18], while both are features related to, or integrated in, non-HDL-C values. In regard of atherogenic dyslipidemia, small dense LDL-C has been shown to strongly associated with an increased risk of coronary heart disease [19]. Of note, non-HDL-C shows a better correlation with small dense LDL particles than do other lipid parameters including LDL-C [20].…”

Hepatic Effects of Estrogen on Plasma Distribution of Small Dense Low-Density Lipoprotein and Free Radical Production in Postmenopausal Women

“…In the present study, we measured the plasma concentrations of total and small dense LDL triglyceride is synthesized in the liver, our results indicate that CEE-induced hepatic stimulation may increase plasma triglyceride. Small dense LDL particles, with a diameter less than 25.5 nm and density ranging from 1.044 to 1.063 g/ml 29) , are known to be associated with an increased incidence of CVD 8,30,31) . Long residence time in the plasma, enhanced oxidizing ability, permeability through the endothelial barrier, arterial proteoglycan binding, and lower affinity for LDL receptors have been proposed as factors for 36) demonstrated that plasma levels of lipid peroxide correlate positively with Cu and the Cu/Zn ratio and negatively with Zn.…”

State of the Art: Blood Biomarkers for Risk Stratification in Patients with Stable Ischemic Heart Disease

“…Accordingly, in a recent study of stable IHD patients treated with atorvastatin, plasma concentrations of NT-proBNP, neopterin, lipoprotein(a) [Lp(a)], and soluble receptor for advanced glycation end-products (sRAGE) were predictive of major cardiovascular events, whereas LDL-cholesterol, HDL-cholesterol, triglycerides, hs-CRP, adiponectin, cystatin C, Lp-PLA2, monocyte chemotactic protein-1, matrix metalloproteinase-9, myeloperoxidase, osteopontin, soluble CD-40 ligand, sICAM-1, and soluble vascular cell adhesion molecule 1 (sVCAM-1) were not (55 ). Measurement of other lipid elements believed to be highly atherogenic, including small dense LDL particles may provide prognostic information independently of traditional risk factors concerning cardiovascular events in the secondary prevention setting (56 ), but it is unclear whether they provide prognostic information incremental to high-sensitivity troponins and natriuretic peptides.…”