In this study, we found that when LDL-C goal < 1.4 mmol/L was used for evaluating cholesterol control in Chinese CHD patients after short-term statins treatment, the target percentage attainment in the non-fasting state was significantly higher than that of the fasting state. However, the percent attainment of non-fasting non-HDL-C was close to its fasting state, suggesting that non-HDL-C is more stable than LDL-C in assessing the percent attainment of non-fasting lipid for coronary heart disease patients. Notably, according to the new non-fasting cut-off points, 1.19 mmol/L, the non-fasting goal attainment of LDL-C was close to its fasting value. This suggests that lower non-fasting targets could be needed to evaluate the efficacy of cholesterol-lowing therapy in the non-fasting state, particularly when fasting blood lipids are unavailable and the percentage reduction of LDL-C cannot be determined due to a lack of baseline non-fasting levels before treatment.
There are two targets to evaluate the efficacy of cholesterol-lowering treatment in CHD patients. First, LDL-C should achieve a ≥ 50% reduction from baseline or a goal < 1.4 mmol/L according to the 2019 European guidelines. However, this recommendation refers only to cholesterol control in the fasting state. In this study, the goal attainment of LDL-C reduction ≥ 50% could not be evaluated because the baseline fasting or non-fasting LDL-C levels before treatment could not be obtained in most patients in the CHD2 group. Under these circumstances, a physician can only make clinical judgments based on LDL-C goal levels. A considerable number of CHD patients from other locations visit physicians but forget to remain in a fasting state. This is a common situation in the outpatient department of our hospital. As a result, physicians have to assess cholesterol control using non-fasting measurement of blood lipids. According to the joint consensus statement of European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine, the non-fasting detection of blood lipids can be routinely applied in CHD patients as long as they are willing to undergo non-fasting measurement. This suggests that measurement of LDL-C level in the non-fasting state is quite important.
Compared with some studies with large population in other countries[10, 11, 17, 18], the reduction in LDL-C level in CHD patients after a daily meal was more significant in the present study. The maximum mean reduction in LDL-C or non-HDL-C was approximately 0.1–0.2 mmol/L in the European and North American subjects[10, 11, 17, 18]; however, Chinese CHD patients in this study showed a greater decrease in either directly detected LDL-C ( i.e., 0.4–0.5 mmol/L) or calculated non-HDL-C (i.e., 0.2–0.3 mmol/L) after a daily breakfast. Although our recent study showed that the postprandial decline (i.e., 0.3–0.4 mmol/L) in calculated LDL-C was less than that of the directly detected LDL at 2–4 h after a daily breakfast in Chinese CHD patients, it was still more than the reduction of above the European and North American studies[10, 11, 17, 18]. The underling mechanisms of non-fasting reduction in LDL-C may be complicated in the present study. First, in the Copenhagen General Population Study, they compared blood lipids levels of individuals at random time points after the last meal in the large-scale population. By contrast, our measurements were acquired from the same individuals at various times since the last meal, which was different from the Copenhagen General Population Study in terms of the observation time-points and monitoring method. Second, postprandial reduction in LDL-C concentration is most likely haemodilution resulting from fluid intake in relation to the meal and thus adjusting the data for albumin concentration was recommended[7, 10]. Langsted et al. observed that the non-fasting LDL-C concentration no longer changed after adjustment for albumin concentration. However, a very slight change in the postprandial albumin level was observed in our study; therefore, haemodilution may not be the only cause of postprandial decline in the LDL-C level in the Chinese. Third, the diet structures of Chinese and western people are very different. For example, the Chinese people prefer carbohydrates. It is not clear whether the high-carbohydrate diet will cause a more significant decline in cholesterol. At any rate, the obvious decrease in non-fasting LDL-C might affect the evaluation of goal attainment when the LDL-C level was detected after a meal.
Indeed, non-HDL-C was more stable than LDL-C in assessing the percent attainment of non-fasting lipid for coronary heart disease patients. Non-fasting reduction in non-HDL-C was less than that in LDL-C and the difference between fasting and non-fasting percentage attainments of non-HDL-C < 2.2 mmol/L was less than that of LDL-C < 1.4 mmol/L. Non-HDL-C represents the cholesterol content of all atherosclerotic lipoproteins in the circulation, including chylomicrons, very-low-density-lipid and their remnants, intermediate-density lipoproteins, LDL, and lipoprotein (a) particles. Takahiro found that non-HDL cholesterol levels were clearly associated with future mortality and were less affected by fasting status or serum triglyceride levels. Meta-analyses and prospective studies with large populations supported the opinion that on-treatment levels of non-HDL-C were stronger than that of LDL-C for future CVD risk estimation[20, 21]. Furthermore, non-HDL-C is a cheaper equivalent predictor of risk on and off statins, without the requirement for a fasting sample. Therefore, some scholars proposed that the clinical benefit obtained from controlling non-HDL-C would be greater than the one obtained from controlling LDL-C[19–21, 23].
Nevertheless, the percent attainment of non-HDL-C was higher than that of LDL-C in both fasting and non-fasting states according to the goals of LDL-C < 1.4 mmol/L and non-HDL-C < 2.2 mmol/L, respectively, in this study. The difference between non-HDL-C and LDL-C will increase with TG elevation, which could exert a substantial influence on evaluation of cholesterol-lowering treatment[29, 30]. The fixed difference between fasting non-HDL-C and LDL-C goals was 30 mg/dl (i.e., 0.8 mmol/L) when fasting TG level was 1.7 mmol/L, reflecting the fact that cholesterol content within TG-rich lipoproteins was about 1.7/2.2 ≈ 0.8 mmol/L. Some scholars found that the goal attainment of non-HDL-C was higher than that of LDL-C when fasting TG was < 1.7 mmol/L, while it was less than that of LDL-C when fasting TG > 2.3 mmol/L. Su et al. reported that the specific and fixed goals as non-HDL-C 0.8 mmol/L (30 mg/dL) higher than the corresponding LDL-C goals were not sufficient for Chinese patients with CHD and proposed that flexible goals basing on TG level were more appropriate. This is consistent with our findings that the percent attainment of LDL-C < 1.4 mmol/L was significantly lower than that of non-HDL-C < 2.2 mmol/L in the fasting state; however, the difference in percent attainment between LDL-C and non-HDL-C after a daily breakfast became smaller with the increase in non-fasting TG level.
It was found that the percent attainment of postprandial LDL-C was significantly higher than that of fasting values in the present study, suggesting that the fasting goals of LDL-C < 1.4 mmol/L was indeed unsuitable for the evaluation of postprandial cholesterol control. ROC analysis has been used to identify the optimal cut-off point for the diagnosis of postprandial hypertriglyceridemia[16, 31, 32] but not for determining goals of LDL-C and non-HDL-C in the non-fasting state corresponding to the fasting goals. Because the non-fasting cut-off points acquired by ROC analysis corresponded to the fasting goals of LDL-C < 1.4 mmol/L and non-HDL-C < 2.2 mmol/L, the postprandial percent attainments were very similar to their respective fasting values. This suggested that lower postprandial cut-off points, different from their fasting goals, should be adopted in the evaluation of postprandial goal attainment, unless it is possible to assess the percentage reduction in the non-fasting LDL-C level. In this study, the difference (1.19 mmol/L vs. 2.11 mmol/L) between non-fasting cut-off points of LDL-C and non-HDL-C was 0.92 mmol/L corresponding to non-fasting TG level of approximately 2.0 mmol/L (i.e. 0.92 × 2.2 = 2.024 ≈ 2.0). This suggests that a larger difference between LDL-C and non-HDL-C should be considered in the evaluation of non-fasting goal attainment even after a daily meal without high fat.
This study had some limitations. First, it was a single centre study with a small sample size of inpatients but not outpatients. In the future, the suitability of non-fasting cut-off points in a large sample of arteriosclerotic cardiovascular disease patients, including patients with ischemic stroke and peripheral vascular disease, is worth exploring. Second, only the percent attainment of the goal, but not percentage reduction of LDL-C, was evaluated because of the lack of baseline levels of blood lipids.