The aim of this study was to investigate the major factors that characterize the LDL phenotypes and the levels of LDL particle size, a potential risk factor for CVD and related diseases, in healthy Korean women. The present results confirmed that LDL particle size (LDL phenotype) was closely correlated with circulating TG levels and demonstrated, for the first time, that LDL particle size was significantly associated with dietary carbohydrate intake in Korean women.
Many studies have reported that sd-LDL, LDL III, or the LDL phenotype B are associated with elevated circulating TG levels, abdominal adiposity, increased concentrations of apolipoprotein B, and decreased concentrations of HDL-cholesterol [7
]. In addition, sd-LDL has been postulated to be a major risk factor for CVD [7
]. According to a report by Austin et al. [6
], subjects with a LDL profile dominated by sd-LDL have a three-fold increased CVD risk. Griffin et al. [8
] also reported a seven-fold increase in CVD risk for sd-LDL concentrations > 100 mg/dl. Several physiological mechanisms have been attributed to the greater atherogenicity of dense than buoyant LDL [18
]. sd-LDLs are taken up less readily by LDL receptors, penetrate more readily into arterial tissue, bind more tightly to arterial proteoglycans, and are oxidized more rapidly than larger LDL particles [18
sd-LDL prevalence in Asian Indians is significantly higher than that in Caucasians [21
]. Cho et al. [4
] also reported that both male and female Koreans have higher relative proportions of LDL III compared to those in Scots. The elevated level of sd-LDL might be due to differences in genetics or environmental factors such as dietary habits among ethnic groups. Additionally, several studies have confirmed that the predominance of sd-LDL is also significantly influenced by specific genes related to lipid metabolism, including the cholesteryl ester transfer protein, the LDL receptor, manganese superoxide dismutase, lipoprotein lipase, APOE
, and APOA5
] In the present study, the regression analysis revealed that serum levels of TG and dietary carbohydrate intake were independent factors for LDL particle size, which is supported by previous reports [21
]. It is well known that circulating TG is strongly associated with LDL particle size and density [22
]. There is also evidence that LDL III concentration increases linearly through the whole range of circulating TG concentration in Korean men, whereas in Scottish men, there was a threshold of 108 mg/dl triglyceride above which there was a positive association [4
], suggesting that circulating TG may interact with certain dietary patterns (i.e., high or low carbohydrate intake) and/or with genetic backgrounds (Asians or Caucasians) to form sd-LDLs. LDL particle size was also correlated with circulating levels of HDL-cholesterol, apoB, apoAI, and apoCIII. However, these associations were no longer significant after adjusting for serum TG levels, suggesting that they were mediated through metabolic associations with high levels of circulating TG. In contrast, numerous studies have investigated the association between dietary macronutrient proportions and lipid profiles, particularly the effects of alterations in dietary carbohydrate on fasting blood TG concentrations in postmenopausal women [23
]. The increased carbohydrate intake observed in this study may cause the synthesis of free fatty acids in the liver, which, in turn, could potentially stimulate the production of large TG-rich very low density lipoprotein, a precursor of sd-LDL particles [26
]. Despite rapid transitions in dietary patterns over time in Korea [27
], dietary carbohydrates are still the major source of energy intake in Korea. Thus, it is possible that high carbohydrate intake is somehow related to the expression of these phenotypes through its metabolic associations.
We focused on female subjects in this study because dyslipidemia characterized by lower HDL cholesterol, smaller LDL cholesterol particle size, and higher TG is a strong contributing factor to the increased CVD risk, which is more remarkable in females than males [28
]. The influence of MetS on the increased risk for CVD is greater among women than among men [29
]. Particularly, pregnancy, lactation, gestational diabetes mellitus, preeclampsia, polycystic ovary syndrome, hormonal contraceptives, and menopause are considered factors influencing MetS and CVD risk together with central adiposity, dyslipidemia, hypertension, and hyperglycemia in women [31
]. In addition, a study conducted in Koreans [32
] reported that abdominal obesity is significantly related to carbohydrate intake in women but not in men. Furthermore, the Korean National Health and Nutrition Examination Survey reported that subjects with MetS consume a higher percentage of energy from carbohydrates than those without MetS, which was remarkable in women [33
]. Therefore, special dietary efforts emphasizing the limitation of high carbohydrate intake for Korean women would improve the increasing burden of CVD risk. Krauss [22
] showed a strong linear relationship between decreased fat/increased carbohydrate intake and the prevalence of the LDL subclass pattern B in healthy men, indicating that the prevalence of pattern B in men consuming 30% fat is ~30-35%, which corresponds to the consumption of > 55% carbohydrate [22
]. Taken together, the cut-off point for carbohydrate intake in Koreans to maintain a healthy LDL phenotype needs to be established, as Koreans consume a relatively higher percentage of energy from carbohydrates compared to that of Western people, although the effect of ethnicity still must be considered.
This study had several limitations. It was a cross-sectional study and had a small sample size. Additionally, information such as glycemic index needs to be included to address the associations more precisely. Nevertheless, the present study was meaningful because it was conducted in a very homogenous group of Koreans. In summary, the present study showed that LDL particle size (LDL phenotype) was closely correlated with circulating TG levels and demonstrated, for the first time, that particle size is significantly associated with dietary carbohydrate intake in Korean women.