Small dense low-density lipoprotein cholesterol is an effective target marker for predicting cardiovascular events and laser treatment for retinopathy in diabetic patients

Abstract

Background Small dense low-density lipoprotein cholesterol (sdLDL-C) has been recently reported as a sensitive marker for cardiovascular diseases. Objective We explored the superiority of sdLDL-C as a marker for predicting cardiovascular (CV) events and the need for laser treatment in patients with hypercholesterolemia and diabetic retinopathy. Methods We performed a sub-analysis of the intEnsive statin therapy for hyper-cholesteroleMic Patients with diAbetic retinopaTHY (EMPATHY) study (n = 5042), in which patients were assigned randomly to intensive or standard statin therapy targeting low-density lipoprotein cholesterol < 70 mg/dl or 100–120 mg/dl. Using the Cox hazard analysis and Kaplan-Meier analysis, the risks for CV events and the need for laser treatment were evaluated according to the following lipids: total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B (ApoB), and sdLDL-C one year after registration. Results The patients were 63 ± 11 years old and 48% of them were male. LDL-C and sdLDL-C levels were 98 ± 25 and 32 ± 14 mg/dl, respectively, one year after registration. The sdLDL-C level had a strong positive correlation with ApoB level (r = 0.83). SdLDL-C was a sensitive marker for predicting CV events when comparing among the quartiles according to sdLDL-C levels (hazard ratios: HR for quartiles 1–4 were 1.0, 1.4, 1.6, and 2.5, respectively; p for trend < 0.01). Also, sdLDL-C was a sensitive marker for predicting the need for laser treatment among lipids (log rank, p = 0.009), especially in patients with elderly (> 65 yrs) and obesity (BMI > 25 kg/m2). Conclusions SdLDL-C is a sensitive target marker to predict cardiovascular events as well as the need for laser treatment in patients with hypercholesterolemia and diabetic retinopathy. Trial registration: UMIN000003486, www.umin.ac.jp/ctr/.

Excessive Visit-to-Visit Small and Dense Low-Density Lipoproteins Elevate Cerebral Small Vessel Disease Progression Risk in the Elderly

“…The sdLDL faction of LDL is strongly associated with atherosclerotic disease (19,20,30,31), possibly due to the greater susceptibility of sdLDL particles to oxidation, higher cell membrane permeability than other fractions, and lower LDL receptor affinity (17,18). Several reports have document associations between sdLDL level and both carotid artery intima-media thickness and plaque progression (32)(33)(34).…”

“…Low-density lipoprotein cholesterol particles are heterogeneous and fractionated based on size and density into large buoyant and small dense particles (16,17). The small dense particles, constituting the so-called small and dense low-density lipoprotein (sdLDL) fraction, are more atherogenic than the large buoyant particles due to greater susceptibility to oxidation, higher cell membrane permeability, and reduced affinity for the LDL receptor (17,18). Therefore, sdLDL has been suggested as a sensitive predictive biomarker for the early diagnosis of cardiovascular diseases, particularly atherosclerosis (17,(19)(20)(21).…”

“…The small dense particles, constituting the so-called small and dense low-density lipoprotein (sdLDL) fraction, are more atherogenic than the large buoyant particles due to greater susceptibility to oxidation, higher cell membrane permeability, and reduced affinity for the LDL receptor (17,18). Therefore, sdLDL has been suggested as a sensitive predictive biomarker for the early diagnosis of cardiovascular diseases, particularly atherosclerosis (17,(19)(20)(21). However, the association between sdLDL and CSVD progression remains unclear.…”