Cheese consumption on atherosclerosis, atherosclerotic cardiovascular diseases and its complications: A two-sample Mendelian randomization study.

BACKGROUND AND AIM: Evidence from prospective cohort studies has revealed an inverse association between cheese consumption and the development of atherosclerosis (AS), atherosclerotic cardiovascular diseases (ASCVD), and their complications. However, it remains unclear whether this observed association is influenced by potential confounding factors that may arise during the long-term development process of AS, ASCVD, and its complications. Therefore, to further clarify the causal relationship between cheese consumption and AS, ASCVD, and its complications, we conducted a two-sample Mendelian randomization (MR) analysis to explore the causal association between cheese intake and the aforementioned health outcomes. METHODS AND RESULTS: We employed a two-sample MR analysis based on publicly available genome-wide association studies (GWAS) to infer the causal relationship, with no overlap between their participating populations. The effect estimates were calculated using the random-effects inverse-variance-weighted method. Sensitivity analyses were conducted using Cochran's Q statistic, funnel plot, leave-one-out analysis, and MR-Egger intercept tests. The genetically predicted cheese intake was found to be associated with lower risks of coronary AS (odds ratio [OR] = 0.72, 95 % confidence interval [CI] 0.59-0.88, P = 0.001), peripheral vascular AS (OR = 0.56, 95 % CI 0.37-0.84, P = 0.006), other vascular AS (OR = 0.66, 95 % CI 0.44-0.99, P = 0.043), coronary artery disease (OR = 0.64, 95 % CI 0.56-0.74, P = 1.57e-09), angina pectoris (OR = 0.70, 95 % CI 0.58-0.84, P = 4.92e-05), myocardial infarction (OR = 0.63, 95 % CI 0.52-0.77, P = 3.56e-06), heart failure (OR = 0.62, 0.49-0.79, P = 1.20e-04), total ischemic stroke (OR = 0.76, 95 % CI 0.63-0.91, P = 0.003), peripheral artery disease (OR = 0.64, 95 % CI 0.43-0.95, P = 0.028), and cognitive impairment (OR = 0.65, 95 % CI 0.56-0.74, P = 3.40e-10). However, no associations were observed for cerebrovascular AS, arrhythmia, cardiac death, ischemic stroke (large artery AS), ischemic stroke (small vessel), ischemic stroke (cardioembolic), and transient ischemic attack. CONCLUSION: This two-sample MR analysis reveals a causally inverse association between cheese intake and multi-vascular AS (including coronary AS, peripheral vascular AS, and other vascular AS), as well as multiple types of ASCVD and its complications (such as coronary artery disease, angina pectoris, myocardial infarction, heart failure, total ischemic stroke, and peripheral artery disease). The findings from this study may lay a stronger theoretical foundation and present new opportunities for the dietary management of future atherosclerotic cardiovascular diseases.

Postprandial Triglyceride-Rich Lipoproteins-Induced Lysosomal Dysfunction and Impaired Autophagic Flux Contribute to Inflammation in White Adipocytes.

BACKGROUND: Obesity and postprandial hypertriglyceridemia, characterized by an increase in triglyceride-rich lipoproteins (TRLs), cause chronic low-grade inflammation. It is unclear how postprandial TRLs affect inflammation in white adipocytes. OBJECTIVES: The objectives of the study were to explore the inflammatory response of postprandial TRLs in white adipocytes and investigate the possible mechanism. METHODS: We measured postprandial triglyceride (TG) and high-sensitivity C-reactive protein (hsCRP) concentrations in 204 recruited subjects and treated white adipocytes from mice with postprandial TRLs from above patients with hypertriglyceridemia. RESULTS: Serum hsCRP concentrations and BMI were positively related to TG concentrations in the postprandial state. Postprandial TRLs increased mRNA and protein expression of inflammatory factors, including interleukin-1ß, via the NOD-like receptor protein 3 (NLRP3)/Caspase-1 pathway, and impaired autophagy flux in white adipocytes of mice. TRLs also induced lysosomal damage as evidenced by the reduced protein expression of lysosome-associated membrane proteins-1 and Cathepsin L. Inhibition of Cathepsin B, NLRP3, and mTOR signaling improved autophagy/lysosome dysfunction and inhibited the activation of the NLRP3/Caspase-1 pathway and inflammatory factors induced by TRLs in white adipocytes. CONCLUSIONS: Our results suggest that postprandial hypertriglyceridemia causes chronic inflammation in adipocytes through TRL-induced lysosomal dysfunction and impaired autophagic flux in an mTOR-dependent manner.

Comparison between Fasting and Non-Fasting Cut-Off Values of Triglyceride in Diagnosing High Triglyceride in Chinese Hypertensive Outpatients.

Background: Hypertension (HBP) often occurs together with hypertriglyceridemia which indicates elevated triglyceride (TG) and remnant cholesterol (RC) levels. Non-fasting (i.e., postprandial) blood lipid test after a daily meal has been recommended by the European Atherosclerosis Society (EAS). However, little is known about the difference between fasting and non-fasting cut-off values in assessing high TG (HTG) and high RC (HRC) in HBP outpatients. Methods: 225 Chinese outpatients with HBP, including 119 fasting patients (i.e., fasting group) and 106 non-fasting patients (i.e., non-fasting group) were enrolled in this study. Non-fasting levels of blood lipids at 2 h after a daily breakfast were also tested in 33 patients among the fasting group. Venous blood samples were collected. Results: The non-fasting group had significantly higher levels of TG and RC while lower levels of total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol than the fasting group (p < 0.05). According to the TG and RC cut-off values of the EAS, the percentages of HTG and HRC in the non-fasting group were 72.6% and 70.8%, respectively, whereas those in the fasting group were 57.1% and 52.9%, respectively. According to the cut-off value of marked HTG commonly used in the Chinese population in clinical practice, the percentage of marked HTG in the non-fasting group was 57.5%, whereas that in the fasting group was 34.5%. However, the percentages of HTG (57.6% vs. 51.5%) and HRC (51.5% vs. 51.5%) marked HTG (30.3% vs. 33.3%) in the fasting state and at 2 h after a daily breakfast in 33 outpatients did not reach statistical significance. Conclusion: Non-fasting blood lipid tests could find more individuals with HTG as well as those with marked HTG among Chinese outpatients with HBP. It indicates that non-fasting blood lipid tests are worth being recommended in patients with HBP.

Determination of the postprandial cut-off value of triglyceride after a daily meal corresponding to fasting optimal triglyceride level in Chinese subjects.

Background: According to the 2021 consensus statement about triglyceride (TG)-rich lipoproteins and their remnants from the European Atherosclerosis Society (EAS), fasting TG level < 1.2 mmol/L is regarded as optimal, otherwise considered as non-optimal TG (NoTG). However, the postprandial cut-off value after a daily meal corresponding to a fasting TG level of 1.2 mmol/L has not been explored. Materials and methods: Six hundred and eighteen inpatients aged 18 to 70 were recruited in this study. Among them, 219 subjects had fasting TG levels < 1.2 mmol/L (i.e., OTG group), and 399 subjects had fasting TG levels ≥ 1.2 mmol/L (i.e., NoTG group). Serum levels of blood lipids, including calculated non-high-density lipoprotein cholesterol (non-HDL-C) and remnant cholesterol (RC), were monitored at 0, 2, and 4 h after a daily Chinese breakfast according to their dietary habits. Receiver operating characteristic (ROC) curve analysis was used to determine the postprandial cut-off value corresponding to the fasting TG level of 1.2 mmol/L. Kappa statistics were performed to determine the consistency between fasting and postprandial cut-off values in determining whether TG was optimal. Univariate and multivariate logistic regression analyses were conducted to evaluate the associations between NoTG and potential confounders. Subgroup analyses were performed to explore the association between postprandial TG levels at 4h (pTG4h) and NoTG in greater detail. Results: Postprandial levels of TG and RC significantly elevated and peaked at 4h after a daily breakfast in two groups (P < 0.05). The optimal cut-off value at 4h corresponding to fasting TG of 1.2 mmol/L was 1.56 mmol/L. According to the fasting cut-off value, the percentage of patients with NoTG was 64.6% in the fasting state while increasing obviously to 73.3-78.4% at 2 and 4h, respectively, after a daily Chinese breakfast. According to the postprandial cut-off value, the percentage of patients with NoTG at 4h after a daily Chinese breakfast was 62.6% which was close to 64.6% in the fasting state. The Kappa coefficient was 0.551, indicating a moderate consistency between the fasting and postprandial cut-off values in the diagnosis of NoTG. Moreover, the subjects with NoTG determined by the postprandial TG cut-off value had an obviously higher postprandial level of RC (1.2 vs. 0.8 mmol/L) and percentage of HRC (37.1 vs. 32.1%) than those determined by the fasting TG cut-off value. Multivariate logistic regression analyses demonstrated that except for BMI, pTG4h emerged as an independent predictor of not. Subgroup analyses revealed that the association between pTG4h and NoTG was consistent across subgroups. Conclusion: Taken together, we for the first time determined TG 1.56 mmol/L as the postprandial cut-off value corresponding to fasting TG 1.2 mmol/L in Chinese subjects. This could make it more convenient to determine whether TG is optimal or not in the fasting or postprandial state.

Non-fasting Changes in Blood Lipids After Three Daily Meals Within a Day in Chinese Inpatients With Cardiovascular Diseases.

Background: Non-fasting (i.e., postprandial) lipid detection is recommended in clinical practice. However, the change in blood lipids in Chinese patients with cardiovascular diseases after three daily meals has never been reported yet. Methods: Serum levels of blood lipids were measured or calculated in 77 inpatients (48 men and 29 women) at high or very high risk of atherosclerotic cardiovascular disease (ASCVD) in the fasting state and at 4 h after three meals within a day according to their diet habits. Results: Female patients showed significantly higher level of high-density lipoprotein cholesterol (HDL-C) than male patients, and the gender difference in other lipid parameters did not reach statistical significance at any time-point. Levels of triglyceride (TG) and remnant cholesterol (RC) increased, while that of low-density lipoprotein cholesterol (LDL-C) decreased significantly after three meals (p < 0.05). Levels of HDL-C, total cholesterol (TC), and non-high-density lipoprotein cholesterol (non-HDL-C) showed smaller changes after three meals. Percent reductions in the non-fasting LDL-C levels after lunch and supper were around 20%, which were greater than that after breakfast. The percent reductions in the non-fasting non-HDL-C levels after three meals were smaller than those in the non-fasting LDL-C levels. Patients with TG level ≥ 2.0 mmol/L (177 mg/dL) after lunch had significantly greater absolute reduction of LDL-C level than those with TG level < 2.0 mmol/L (177 mg/dL) after lunch [-0.69 mmol/L (-27 mg/dL) vs. -0.36 mmol/L (-14 mg/dL), p<0.01]. There was a significant and negative correlation between absolute change in LDL-C level and that in TG level (r = -0.32) or RC level (r = -0.67) after lunch (both p<0.01). Conclusion: LDL-C level decreased significantly after three daily meals in Chinese patients at high or very high risk of ASCVD, especially when TG level reached its peak after lunch. Relatively, non-HDL-C level was more stable than LDL-C level postprandially. Therefore, when LDL-C level was measured in the non-fasting state, non-HDL-C level could be evaluated simultaneously to reduce the interference of related factors, such as postprandial hypertriglyceridemia, on detection.

Change in Postprandial Level of Remnant Cholesterol After a Daily Breakfast in Chinese Patients With Hypertension.

Background: Hypertension (HBP) is usually accompanied by hypertriglyceridemia that represents the increased triglyceride-rich lipoproteins and cholesterol content in remnant lipoproteins [i.e., remnant cholesterol (RC)]. According to the European Atherosclerosis Society (EAS), high RC (HRC) is defined as fasting RC ≥0.8 mmol/L and/or postprandial RC ≥0.9 mmol/L. However, little is known about postprandial change in RC level after a daily meal in Chinese patients with HBP. Methods: One hundred thirty-five subjects, including 90 hypertensive patients (HBP group) and 45 non-HBP controls (CON group), were recruited in this study. Serum levels of blood lipids, including calculated RC, were explored at 0, 2, and 4 h after a daily breakfast. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff point of postprandial HRC. Results: Fasting TG and RC levels were significantly higher in the HBP group (P < 0.05), both of which increased significantly after a daily meal in the two groups (P < 0.05). Moreover, postprandial RC level was significantly higher in the HBP group (P < 0.05). ROC curve analysis showed that the optimal cutoff point for RC after a daily meal to predict HRC corresponding to fasting RC of 0.8 mmol/L was 0.91 mmol/L, which was very close to that recommended by the EAS, i.e., 0.9 mmol/L. Fasting HRC was found in 31.1% of hypertensive patients but not in the controls. According to the postprandial cutoff point, postprandial HRC was found in approximately half of hypertensive patients and ~1-third of the controls. Conclusion: Postprandial RC level increased significantly after a daily meal, and hypertensive patients had higher percentage of HRC at both fasting and postprandial states. More importantly, the detection of postprandial lipids could be helpful to find HRC.

Determination of the Optimal Cutoff Value of Triglyceride That Corresponds to Fasting Levels in Chinese Subjects With Marked Hypertriglyceridemia.

The level of triglyceride (TG) ≥ 2. 3 mmol/L is suggestive of marked hypertriglyceridemia (HTG) and requires treatment with a triglyceride-lowering agent in high-risk and very high-risk patients as recommended by the 2019 ESC/EAS guidelines for the management of dyslipidemia. However, the optimal cutoff value required to diagnose non-fasting HTG that corresponds to the fasting goal level of 2.3 mmol/L in Chinese subjects is unknown. This study enrolled 602 cardiology inpatients. Blood lipid levels, including calculated non-high-density lipoprotein cholesterol (non-HDL-C) and remnant cholesterol (RC), were measured at 0, 2, and 4 h after a daily Chinese breakfast. Of these, 482 inpatients had TG levels of <2.3 mmol/L (CON group) and 120 inpatients had TG levels of ≥2.3 mmol/L (HTG group). Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff values for postprandial HTG that corresponded to a target fasting level of 2.3 mmol/L. Marked hypertriglyceridemia (≥2.3 mmol/L) was found in 120 (19.9%) patients in this study population. The levels of non-fasting TG and RC increased significantly in both groups and reached the peak at 4 h after a daily meal, especially in the HTG group (p < 0.05). The optimal cutoff value of TG at 4 h, which corresponds to fasting TG of ≥2.3 mmol/L, that can be used to predict HTG, was 2.66 mmol/L. According to the new non-fasting cutoff value, the incidence of non-fasting HTG is close to its fasting level. In summary, this is the first study to determine the non-fasting cutoff value that corresponds to a fasting TG of ≥2.3 mmol/L in Chinese patients. Additionally, 2.66 mmol/l at 4 h after a daily meal could be an appropriate cutoff value that can be used to detect non-fasting marked HTG in Chinese subjects.

Diagnostic value of monocyte to high-density lipoprotein ratio in acute aortic dissection in a Chinese han population.

Background: Recently, considerable evidence pointed out monocyte to high-density lipoprotein ratio (MHR) is highly related to inflammatory related diseases. We aim to explore the level of MHR in acute aortic dissection (AAD) patients and determine whether MHR can be a novel diagnostic marker of AAD. Research design and methods: A total of 228 subjects including 128 AAD patients and 110 healthy control were enrolled. MHR levels and other serum samples were obtained at admission. Results: The baseline MHR levels were significantly higher in patients with AAD (p < 0.0001). A cutoff value of MHR >0.37 was associated with a sensitivity of 86.70% and a specificity of 93.60% for AAD. MHR levels were positively correlated with the time from symptom onset (R2 = 0.0318, p = 0.0003). Additionally, the area under the curve (AUC) was increased to 0.979 in patients whose time from onset of symptoms >24 h, with a sensitivity of 98.04% and a specificity of 93.64%. Multivariate logistic regression demonstrated that MHR levels, history of hypertension, and coronary artery disease (CHD) emerged as independent predictors of AAD. Expert Opinion: MHR has a high diagnostic value in AAD patients, especially in those whose time from onset of symptoms >24 h.