BackgroundHigh serum concentrations of small dense low-density lipoprotein cholesterol (sd-LDL-c) particles are associated with risk of cardiovascular disease (CVD). Their clinical application has been hindered as a consequence of the laborious current method used for their quantification.ObjectiveOptimize a simple and fast precipitation method to isolate sd-LDL particles and establish a reference interval in a Mediterranean population.Materials and methodsForty-five serum samples were collected, and sd-LDL particles were isolated using a modified heparin-Mg2+ precipitation method. sd-LDL-c concentration was calculated by subtracting high-density lipoprotein cholesterol (HDL-c) from the total cholesterol measured in the supernatant. This method was compared with the reference method (ultracentrifugation). Reference values were estimated according to the Clinical and Laboratory Standards Institute and The International Federation of Clinical Chemistry and Laboratory Medicine recommendations. sd-LDL-c concentration was measured in serums from 79 subjects with no lipid metabolism abnormalities.ResultsThe Passing–Bablok regression equation is y = 1.52 (0.72 to 1.73) + 0.07x (−0.1 to 0.13), demonstrating no significant statistical differences between the modified precipitation method and the ultracentrifugation reference method. Similarly, no differences were detected when considering only sd-LDL-c from dyslipidemic patients, since the modifications added to the precipitation method facilitated the proper sedimentation of triglycerides and other lipoproteins. The reference interval for sd-LDL-c concentration estimated in a Mediterranean population was 0.04–0.47 mmol/L.ConclusionAn optimization of the heparin-Mg2+ precipitation method for sd-LDL particle isolation was performed, and reference intervals were established in a Spanish Mediterranean population. Measured values were equivalent to those obtained with the reference method, assuring its clinical application when tested in both normolipidemic and dyslipidemic subjects.

Background LDL‐C lowering is the main measure in cardiovascular disease prevention but a residual risk of ischemic events still remains. Alterations of lipoproteins, specially, increase in small dense LDL (sdLDL) particles are related to this risk. Objective To investigate the potential use of sdLDL cholesterol concentration (sdLDL‐C) isolated by an easy precipitation method and to assess the impact of a set of clinical and biochemical variables determined by NMR on sdLDL concentration. Methods sdLDL‐C and NMR lipid profile were performed in 85 men samples. Association among them was evaluated using Pearson coefficients ( r xy ). A multivariate regression was performed to identify the influence of NMR variables on sdLDL‐C. Results A strong association between sdLDL‐C and LDLLDL‐P ( r xy = 0.687) and with LDL‐Z ( r xy = −0.603) was found. The multivariate regression explained a 56.8% in sdLDL‐C variation ( P = 8.77.10‐12). BMI, ApoB, triglycerides, FFA, and LDL‐Z showed a significant contribution. The most important ones were ApoB and LDL‐Z; a 1nm increase (LDL‐Z) leads to decrease 126 nmol/L in sdLDL‐C. Conclusion The association between sdLDL‐C, LDL‐Z, and LDL‐P is clear. From a large number of variables, especially LDL‐Z and apoB influence on sdLDL‐C. Results show that the smaller the LDL size, the higher their cholesterol concentration. Therefore, sdLDL‐C determination by using this easy method would be useful to risk stratification and to uncover cardiovascular residual risk.

Some lipoprotein disorders related to the residual risk of premature cardiovascular disease (PCVD) are not detected by the conventional lipid profile. In this case-control study, the predictive power of PCVD of serum sdLDL-C, measured using a lipoprotein precipitation method, and of the physicochemical properties of serum lipoproteins, analyzed by nuclear magnetic resonance (NMR) techniques, were evaluated. We studied a group of patients with a first PCVD event (n = 125) and a group of control subjects (n = 190). Conventional lipid profile, the size and number of Very Low Density Lipoproteins (VLDL), Low Density Lipoproteins (LDL), High Density Lipoproteins (HDL) particles, and the number of particles of their subclasses (large, medium, and small) were measured. Compared to controls, PCVD patients had lower concentrations of all LDL particles, and smaller and larger diameter of LDL and HDL particles, respectively. PCVD patients also showed higher concentrations of small dense LDL-cholesterol (sdLDL), and triglycerides (Tg) in LDL and HDL particles (HDL-Tg), and higher concentrations of large VLDL particles. Multivariate logistic regression showed that sdLDL-C, HDL-Tg, and large concentrations of LDL particles were the most powerful predictors of PCVD. A strong relationship was observed between increased HDL-Tg concentrations and PCVD. This study demonstrates that beyond the conventional lipid profile, PCVD patients have other atherogenic lipoprotein alterations that are detected by magnetic resonance imaging (MRI) analysis.

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