Small, dense low‐density lipoproteins (LDL) are predictors of cardio‐ and cerebro‐vascular events in subjects with the metabolic syndrome

Abstract

Summary Objective Small, dense low‐density lipoproteins (LDL) are a feature of the metabolic syndrome (MS) but their predictive role still remains to be established. We performed a 2‐year follow‐up study in 124 subjects with MS (63 ± 6 years), as defined by the American Heart Association/National Heart, Lung and Blood Institute guidelines, to assess clinical and biochemical predictors of cerebro‐ and cardio‐vascular events. Methods and results Beyond traditional cardiovascular risk factors, we measured LDL size and subclasses by gradient gel electrophoresis. Clinical events were registered in the 25% of subjects. At univariate analysis subjects with events had increased prevalence of elevated fasting glucose (P = 0·0117), smoking (P = 0·0015), family history of coronary artery disease (P = 0·0033) and higher levels of total‐ and LDL‐cholesterol (P = 0·0027 and P = 0·0023, respectively); LDL size was lower (P < 0·0001), due to reduced larger subclasses and increased small, dense LDL (all P < 0·0001). At multivariate analysis the following were independent predictors of events (univariate odd ratios were calculated): low HDL‐cholesterol (OR 15·4, P = 0·0238), elevated fasting glucose (OR 12·1, P = 0·0102), elevated small, dense LDL (OR 11·7, P = 0·0004), elevated blood pressure (OR 9·2, P = 0·0392), smoking (OR 4·8, P = 0·0054). Conclusions This is the first study that assessed the predictive role of small, dense LDL beyond traditional cardiovascular risk factors in subjects with MS.

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

“…Numerous studies have reported that sdLDL is strongly associated with CVDs 2-4, 13, 23,26,27,[36][37][38][39][40][41] . A recent study investigating the association of cellular carotid plaque composition with cholesterol concentrations in lipoprotein sub-fractions evaluated by density gradient ultracentrifugation reported that the cholesterol content in the sdLDL fraction, but not the plasma LDL-C or HDL-C positively correlated with present study compared sdLDL-C to LDL-C, non-HDL-C, triglyceride, apolipoprotein B, lipoprotein(a), RLP-C, HDL-C, LDL-C/HDL-C ratio, and apolipoprotein A1 in the fasting state.…”

Colesevelam improved lipoprotein particle subclasses in patients with prediabetes and primary hyperlipidaemia

“…2 Although reducing LDL-C is considered the main objective of lipid-lowering therapy to reduce cardiovascular risk, 3,4 studies have demonstrated that lipoprotein subfractions may provide more information on cardiovascular risk than the standard lipid profile. Thus, increased LDL particle concentration (LDL-P) is an important predictor of cardiovascular risk [5][6][7][8][9][10][11][12][13] and may be a better predictor of cardiovascular risk than LDL-C. 7,9,11,13,14 There is conflicting information regarding whether LDL particle size predicts cardiovascular risk, [5][6][7][8][9]13,15,16 and noted associations may be merely due to its relationship with LDL-P. 3,11,16 Reduced HDL particle concentration (HDL-P) has also been associated with increased cardiovascular risk in multivariate models that include major risk factors and LDL-P. 17,18 It has been suggested that smaller VLDL particles and their catabolic product, intermediate-density lipoprotein (IDL) particles, could contribute substantially to atherosclerosis because of their ability to enter the subendothelial space, 3 but larger VLDL particles are usually unable to penetrate the endothelium to enter the vascular wall, so their atherogenic potential is unclear.…”

Circulating Lp-PLA2 activity correlates with oxidative stress and cytokines in overweight/obese postmenopausal women not using hormone replacement therapy

“…LysoPC induces inflammatory cytokine expression, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) (Carlquist et al 2007). In addition, the major part of LDL-associated Lp-PLA 2 is bound to the atherogenic small dense LDL (sdLDL) particles, and serum Lp-PLA 2 enzyme activity is a marker of circulating sdLDL particles (Tsimihodimos et al 2002;Rizzo and Berneis 2006;Rizzo et al 2009;Gazi et al 2005). There has been a growing interest in Lp-PLA 2 because of its key roles in lipid metabolism and initiating inflammation .…”