In this study, the patients consumed an identical breakfast before and after six weeks of Xuezhikang treatment, and nonfasting blood lipids were detected at the same time-points after breakfast. It was found that the percent reduction in LDL-C at any time point after breakfast was similar to that in the fasting state, suggesting that the percent reduction in nonfasting LDL-C level can be used to evaluate the efficacy of cholesterol control for CHD patients who are unwilling or unable to keeping the fast state, as can the nonfasting non-HDL-C level. This means that nonfasting LDL-C and non-HDL-C levels can be used in place of their fasting values when evaluating the efficacy of statin treatment in specific CHD patients if the following conditions can be met: the same breakfast has been eaten, and blood lipids are detected by the same commercial kits at the same time points after a meal.
It is noteworthy that the detection of nonfasting blood lipids in clinical practice was originally recommended to be carried out after a daily meal[8, 9]. The CHD patients recruited for this study regularly consumed a daily breakfast of > 800 kcal and > 50 g of fat. The standard breakfast in this study can be regarded as a customary breakfast. Thus, the findings from this study could apply to CHD patients with similar dietary habits.
Among all cholesterol parameters, LDL-C levels were obviously reduced after breakfast. TC levels were the most stable after breakfast, followed by HDL-C and non-HDL-C levels, whose changes did not exceed 0.1 mmol/L in this study. However, the RC level increased with increasing TG levels. Some scholars speculated that a reduction in nonfasting LDL-C levels was likely induced by hemodilution due to fluid intake[11, 28]. Others attributed the decrease to biological rhythm and found that LDL-C and HDL-C levels were significantly lower from after breakfast until midnight than they were before breakfast[29]. Although the potential cause of the reduction in nonfasting LDL-C levels in this study was not very clear, we should cautiously evaluate the cholesterol-lowering effect during follow-up if the LDL-C level is detected in a nonfasting state. For example, if the fasting LDL-C goal was < 1.8 mmol/L, it was difficult to decide whether a nonfasting LDL-C level of 1.65 mmol/L reached the target. This result indicates that it could be inappropriate to evaluate the nonfasting LDL-C level according to the fasting LDL-C goal.
With the update of the Chinese and Western guidelines for the management of dyslipidemia in adults, evaluation of the percent reduction in LDL-C level has become increasingly important[16, 30, 31]. For the nonnegligible reduction in LDL-C levels after breakfast in this study, the percent reduction was calculated to compare the effects of Xuezhikang on LDL-C levels between the fasting level and the levels at the nonfasting time points. After six weeks, LDL-C levels presented parallel changes at four different time points, with a percent reduction between 25.3% and 28.2%. More importantly, there was no significant difference in the percent reductions in LDL-C level among the four different time points. This suggested that if the LDL-C level was detected after a habitual breakfast in the first visit in one patient, it can be detected repeatedly at the same time point after an identical breakfast at the second visit six weeks later. That is, nonfasting LDL-C levels could even be used to evaluate cholesterol control in unstable patients.
In the present study, the percent reduction in LDL-C level was less than 27.8%, which was very close to that reported by other studies, including 28.5% by the China Coronary Secondary Prevention Study (CCSPS) and 27% by a Food and Drug Administration Phase II clinical study [32]. It is known that with every 1% decrease in LDL-C level, the relative risk of cardiovascular events is reduced by 1% [33]. Because Chinese patients with CHD had lower baseline LDL-C levels than Western patients[1, 34, 35], a nearly 30% reduction in LDL-C induced by a six-week Xuezhikang treatment made the mean fasting LDL-C level < 2.6 mmol/L in 76% of CHD patients, which was the LDL-C goal recommended by the guidelines of the National Cholesterol Education Program in 2002 [36]. Considering that this study was completed in 2002, a nearly 30% reduction in LDL-C level was clinically significant at that time.
Compared to LDL-C levels, non-HDL-C levels changed mildly after breakfast in this study, which could be related to the obvious increase in RC levels. The non-HDL-C level includes the LDL-C level and the RC level at each time-point. The percent reduction in non-HDL-C level was slightly greater than that in LDL-C level at each nonfasting time point, which could be due to Xuezhikang inhibiting the increment in the nonfasting TG and RC levels. Similar to the LDL-C level, the non-HDL-C level also showed very similar percent reductions among the four different time points. This finding supports that non-HDL-C levels can be detected and evaluated in the nonfasting state during follow-up for those who are unwilling or unable to keep fasting state[30, 37, 38].
The mechanism of Xuezhikang in reducing blood lipids is complex. Xuezhikang contains natural lovastatin (i.e., monacolin K) and 12 other kinds of natural monacolins (24 mg in each Xuezhikang capsule) that are homologs of statins. Additionally, it comprises other ingredients, such as sterols[39]. Compared with 10 mg lovastatin, 1200 mg Xuezhikang showed more potent effects for lowering cholesterol and TG levels[40]. CCSPS demonstrated that Xuezhikang significantly decreased the risk of cardiovascular events and total mortality by 30% and 33%, respectively, in Chinese patients with CHD, which was not completely explained by the decrease in LDL-C induced by natural statins in Xuezhikang[32]. Other components of Xuezhikang, such as unsaturated fatty acids, sterols and flavonoids, may also play essential roles in cardiovascular protection [39]. New evidence has shown that unsaturated fatty acids not only have antioxidative and TG-lowering effects but also further reduce cardiovascular events based on statin treatment[41–43].
At one point, there was concern about the safety of Xuezhikang[44]. According to a recent meta-analysis of 53 randomized controlled trials with a total of 8,535 patients (4,437 in the red yeast rice treatment arm and 4,303 in the control arm), the use of monacolin K is not associated with an increased risk of muscular adverse events (OR 0.94, 95% CI, 0.53–1.65)[45]. In the real world, some patients could take Xuezhikang because of their intolerance to synthetic statins[46]. Xuezhikang should be taken as two capsules orally after meals twice a day[47]. Combining other cholesterol-lowering drugs, such as proprotein convertase subtilisin/kexin type 9 inhibitor and ezetimibe, can achieve a better therapeutic effect if needed by the patient.
Several limitations existed in this study. First, this study was a single-blind clinical observational study with a small sample. According to the previous recommendations of international guidelines around 2000[36]. statin treatment was initiated after ineffective lifestyle interventions in CHD patients. That was why half of the participants in this study did not receive Xuezhikang treatment immediately after the diagnosis of CHD. It is worth carrying out a randomized, double-blind clinical trial with a larger sample in the future. Second, more relevant lipid profiles and inflammatory markers should be detected during throughout the day in the future, although a certain type of breakfast may trigger the fluctuation of inflammation and metabolism parameters that are linked to biological rhythms.
In conclusion, six weeks of Xuezhikang treatment (1200 mg/d) significantly decreased LDL-C and non-HDL-C levels, with similar percent reductions between the fasting and nonfasting states, in CHD patients. This result indicates that nonfasting blood lipids detected at the same time point after a standard meal could replace fasting blood lipids when evaluating the efficacy of cholesterol control in CHD patients who are unwilling or unable to fast.