LAUSR

Retinopathy is a typical microvascular complication of diabetes and is mainly caused by hyperglycemia. Cardiovascular (CV) diseases, such as coronary artery disease and stroke, are macrovascular complication of diabetes, and dyslipidemia is deeply involved in its etiology. Epidemiological studies have shown that diabetic patients with retinopathy have higher incidence of CV events and death compared to those without retinopathy. Therefore, diabetic retinopathy has a very high risk of CV disease. The intEnsive statin therapy for hyper-cholesteroleMic Patients with diAbetic retinopaTHY (EMPATHY) study was a primary prevention trial investigating the incidence of CV events with intensive or standard statin therapy in patients with hypercholesterolemia and diabetic retinopathy. As a result, there was no significant reduction in CV outcomes with intensive care, probably due to the slight difference in LDLcholesterol (-C) between the intensive and standard treatment groups. Nonetheless, a sub-analysis of the EMPATHY study provided unexpected results suggesting that dyslipidemia is associated with diabetic retinopathy. In this issue of the Journal of Atherosclerosis and Thrombosis, Nakayama et al. reported that small dense (sd) LDL-C was not only a sensitive marker for predicting CV events but also a marker for predicting the need for laser treatment. Laser treatment is used to prevent the exacerbation of retinopathy, so sdLDL-C can be considered as a predictor of exacerbation of diabetic retinopathy. This study is unique in suggesting that dyslipidemia affects both the microangiopathy and macroangiopathy. SdLDL particles are thought to be more atherogenic than large buoyant LDL particles, because they have a long residence time in the blood circulation, easily penetrate into the arterial wall, and are easily oxidized. These properties facilitate the production of toxic oxidized-LDL in the subendothelial space and promote plaque formation. We established a fully automated assay kit for quantifying sdLDL-C levels, and this assay system has been adopted in famous cohort studies, such as the Suita, the ARIC, the Hisayama, and the Framingham Offspring. All studies have consistently proven that sdLDL-C is superior to LDL-C in predicting CV events. The present study demonstrated that triglyceride (TG), TG-rich lipoprotein (TRL) -C, and sdLDL-C can all predict CV events. However, the predictive power of sdLDL-C for CV events was lost in subjects with higher TG levels (>113 mg/dl). It should be noted that unlike other studies, all participants in the EMPATHY study had type 2 diabetes. In addition, the CV events in this study included renal outcomes 2) in which TG metabolism would be significantly impaired. They may enhance the impact of TG and TRL-C on CV events and relatively mask the atherogenicity of sdLDL-C. SdLDL-C correlated more closely with apolipoprotein B than LDL-C, suggesting that the number of LDL particles is a major determinant of sdLDL-C concentration. There is plenty of evidence that LDL particle numbers are superior to LDL-C in predicting CV events. Few studies have investigated specific changes in plasma lipids in diabetic retinopathy. Diabetic retinopathy often coexists with diabetic nephropathy, and albuminuria and/or renal dysfunction strongly affects plasma lipoprotein metabolism. Therefore, the relationship between diabetic retinopathy and plasma lipids should take into account the presence of diabetic nephropathy. The authors analyzed that serum creatinine and sdLDL-C were independently associated with the need for laser treatment. Therefore, it is possible that sdLDL-C is directly associated with diabetic retinopathy, regardless of nephropathy. As the authors introduced, fenofibrate, a TG-lowering drug,