To evaluate the reproducibility and validity of a 93-item food frequency questionnaire (FFQ) designed to assess usual dietary habits over the past year among adults in the southeast coastal region of China.

Qualified dietary data of 477 subjects (75.26% female, mean age = 59.7 years) were collected via two FFQs over approximately 15 months, alongside four 4-day 24-hour dietary recalls (24 h-DRs) at average intervals of four months. The analysis included 25 general nutrients, 14 particular nutrients and 12 food groups. Wilcoxon signed-rank test, correlation coefficients, cross-classification with weighted kappa statistic and Bland-Altman plots were used for comparison.

For reproducibility, the Spearman, Pearson, and intraclass correlation coefficients between two FFQs ranged from 0.24 to 0.53, 0.21 to 0.53 and 0.19 to 0.53, respectively. After adjusting for energy intake, most coefficients either decreased or remained unchanged. The rates of agreement in classifying subjects in the same or adjacent quartile fell between 62% and 84% for both FFQs. Regarding validity, the crude Spearman, energy-adjusted and de-attenuated Pearson correlation coefficients between FFQs and 24 h-DRs ranged from 0.17 to 0.59, 0.12 to 0.54, and 0.13 to 0.57, respectively. Over 58% of subjects were classified into the same and adjacent categories by both methods. Weighted kappa statistic and Bland-Altman plots demonstrated acceptable concordance.

The FFQ developed for adults in the specific coastal region of China, aiming to be used in a population-based cohort study, demonstrates acceptable reproducibility and validity to measure the dietary intakes of certain nutrients and foods.

BackgroundAtherosclerosis contributes to cognitive dysfunction and Alzheimer's disease-related pathologies. Atherogenic index of plasma (AIP) is a novel and composite biomarker can predict atherosclerosis.ObjectiveThis study aims to (1) examine the association between the AIP and cognitive performance, and (2) explore the mediating role of oxidative stress biomarkers in this relationship.Methods1466 participants over the age of 60 were included from 2011-2014 NHANES. AIP was calculated through log-transformed triglyceride to high-density lipoprotein cholesterol ratios. The assessment of cognition was conducted using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test. Weighted linear regression model and restricted cubic spline were carried out to determine the associations between AIP and CERAD scores. The mediation analyses were conducted to assess whether oxidative stress mediates the association.ResultsHigher AIP levels were associated with lower CERAD learning scores. The highest quartile of AIP showed a 0.67-fold decrease (95%CI: -1.30, -0.03; p = 0.041) on the CERAD total score than that in the lowest quartile. Each 1-unit increase in AIP corresponded to reductions in CERAD total and delayed recall scores of approximately 1.09 and 0.54 points, respectively, in the sub-population under 70 years. Moreover, 25(OH)D, an oxidative stress indicator, partially mediated 24% of the association between AIP and the CERAD total score.ConclusionsAIP has the potential to indicate the risk of cognitive aging, especially that for young-old or female older adults. The supplementation of 25(OH)D may reduce atherosclerosis-related cognitive decline, which could provide some strategies for the prevention of dementia.

To explore the influence of the serum total bilirubin to total cholesterol (TBIL/TC) ratio on the progression of chronic kidney disease (CKD) in people with type 2 diabetes.

The present retrospective discovery cohort investigated 4282 patients. The exposure was baseline TBIL/TC ratio. The outcome was the first time to progressing CKD, defined by a drop in the estimated glomerular filtration rate (eGFR) category, along with a reduction in eGFR of at least 25% compared to the baseline value. Hazard ratios (HRs) for CKD progression were evaluated based on the Cox proportional hazards approach. Dose-response relationships were conducted using Restricted Cubic Splines (RCS). Additionally, 758 patients were enrolled as an independent validation cohort.

During a median observation period of 2.4 years (interquartile range 1.3-3.8 years) within the discovery cohort, 522 individuals showed progression in CKD. The analysis revealed a negative association between the TBIL/TC ratio and the risk of CKD progression, with an adjusted HR of 0.17 and a 95% CI ranging from 0.07 to 0.41. After adjusting for confounding variables, the HRs for the second, third, and fourth quartiles of the TBIL/TC ratio were recorded at 0.61 (95% CI 0.48, 0.78), 0.55 (95% CI 0.42, 0.72), and 0.55 (95% CI 0.41, 0.74), respectively. Analysis with RCS indicated an optimal TBIL/TC ratio threshold of 0.25%. Similar results were also observed in the validation cohort.

A higher TBIL/TC ratio was significantly associated with a reduced risk of CKD progression in patients with type 2 diabetes.

The rising rates of obesity worldwide have increased the incidence of cardiovascular disease (CVD), making it the number one cause of death. Higher plasma bilirubin levels have been shown to prevent metabolic dysfunction and CVD. However, reducing levels leads to deleterious outcomes, possibly due to reduced bilirubin half-life that escalates the production of its catabolized product, urobilinogen, produced by gut bacteria and naturally oxidized to urobilin. Recent findings suggest that the involvement of the microbiome catabolism of bilirubin to urobilin and its absorption via the hepatic portal vein contributes to CVD, suggesting a liver-gut axis involvement. We discuss the studies that demonstrate that urobilin is frequently raised in the urine of persons with CVD and its probable role in acquiring the disease. Urobilin is excreted from the kidneys into the urine and may serve as a biomarker for Cardiovascular-Kidney-Metabolic (CKM) Syndrome. We deliberate on the newly discovered bilirubin reductase (BilR) bacterial enzyme that produces urobilin. We discuss the bacterial species expressing BilR, how they impact CVD, and whether suppressing urobilin production and increasing bilirubin may provide new therapeutic strategies for CKM. Possible therapeutic mechanisms for achieving this goal are discussed.

Apigenin is a natural flavonoid abundantly found in fruits, vegetables, and medicinal plants. It possesses protective effects against cancer, metabolic syndrome, dyslipidemia, etc. Atherosclerosis, a chronic immune-mediated inflammatory disease, is the underlying cause of coronary heart disease, stroke, and myocardial infarction. Numerous in vivo and in vitro studies have shown a protective effect of apigenin against atherosclerosis, attributed to its antioxidant and anti-inflammatory properties, as well as its antihypertensive effect and regulation of lipid metabolism. This study aimed to review the effects and mechanisms of apigenin against atherosclerosis for the first time. Apigenin displays encouraging results, and this review confirms the potential value of apigenin as a candidate medication for atherosclerosis.

Diabetic Cardiomyopathy (DCM), a common complication of Type 2 Diabetic Mellitus (T2DM), has been emerging as one of the leading causes of mortality in T2DM patients. During the past decade, although, clinical studies concerning DCM are increasing at an exponential rate, mechanisms underlying this disease still can't be clearly defined. Here, we aim to recognize the function of Suv39h1 in DCM and to explore underlying mechanisms during this disease, providing new insights into DCM and novel guide for clinical therapy development.

We employed cardiac specific Suv39h1 knockout mice to reveal the role of Suv39h1 in high-fat diet induced DCM and using human cardiomyocyte line AC16 cells treated with Suv39h1 siRNA or inhibitor Chaetocin to further explore the mechanism during lipotoxicity condition.

Cardiac Suv39h1 knockout ameliorated manifestations of DCM, including cardiac function indexes, cardiomyocyte hypertrophy, interstitial fibrosis, along with improved metabolic disorder in mice. Further, interfering human AC16 cardiomyocytes with siSuv39h1 down-regulated lipotoxicity induced cardiac hypertrophy, inflammation, and fibrosis markers. Subsequent mRNA-seq using siSuv39h1 and SCR AC16 cells discovered a well-recognized cytoprotective, anti-oxidant, and anti-inflammation factor-Hmox1, prominently upregulated in Suv39h1 ablation cells versus SCR under lipotoxicity condition. ChIP assay revealed that Suv39h1 could bind to Hmox1 promoter and reversed by Chaetocin or small interfering RNA.

These results suggested that the protective effects in DCM rendered by Suv39h1 ablation may work through activating Hmox1 transcription and protein function, providing new insights into pathogenesis of DCM and novel epigenetic target for clinical DCM therapies.

Obesity has been linked to arterial stiffness, while no consensus was reached on the association. We aimed to clarify the association of general and central obesity with arterial stiffness by combining observational studies and Mendelian randomization (MR) study.

Two cross-sectional studies were performed in UK Biobank and Fuqing Cohort, respectively. Two-sample MR study was conducted using summary data of GWASs from GIANT consortium and UK Biobank. General obesity and central obesity were measured using body mass index (BMI) and waist circumference (WC), respectively. Arterial stiffness was measured by arterial stiffness index (ASI) in UK Biobank or branchial-ankle pulse wave velocity (baPWV) in Fuqing Cohort.

Two observational studies found a consistent positive association of BMI and WC with arterial stiffness when adjusting for age, sex, education, smoking, alcohol drinking, physical activity, and LDL cholesterol. However, when additionally adjusting for metabolic traits (i.e., systolic blood pressure, diastolic blood pressure, blood glucose, triglycerides, high-density lipoprotein cholesterol, and WC or BMI), the association with BMI changed to be inverse. As compared to the lowest quintile group, the adjusted ORs across groups of second to fifth quintile were 0.93, 0.90, 0.83, and 0.72 in UK Biobank and 0.88, 0.65, 0.63, and 0.50 in Fuqing Cohort. In contrast, the positive relationship with WC remained stable with the adjusted ORs of 1.23, 1.46, 1.60, and 1.56 in UK Biobank and 1.35, 1.44, 1.77, and 1.64 in Fuqing Cohort. MR analyses provided supportive evidence of the negative association with BMI (OR = 0.97, 95%CI = 0.94-1.00) and the positive association with WC (OR = 1.14, 95%CI = 1.08-1.20).

Observational and genetic analyses provide concordant results that central obesity is independently related to arterial stiffness, while the role of general obesity depends on metabolic status.

Low-density lipoprotein cholesterol (LDLc) and body mass index (BMI) are not always correlated and their relationship is probably dependent on age, indicating differential age-specific associations of these factors with health outcomes. We aim to discriminate the roles of LDLc and BMI in coronary heart disease (CHD) across different age groups.

This is a prospective cohort study of 368,274 participants aged 38-73 years and free of CHD at baseline. LDLc and BMI were measured at baseline, and incident CHD was the main outcome. Cox proportional hazards model and restricted cubic spline (RCS) regression were used to estimate hazard ratio (HR) and 95% confidence interval (CI) of exposure on CHD.

After a mean of 12 years of follow-up, similar relationships of LDLc and BMI with CHD risk were observed in the overall population but in differential age-specific patterns. Across the age groups of <50, 50-54, 55-59, 60-64 and ≥ 65 years, the LDLc-CHD association diminished with the adjusted HRs decreasing from 1.35, 1.26, 1.19, 1.11 to 1.08; while no declining trend was found in BMI-CHD relationship with the adjusted HRs of 1.15, 1.11, 1.12, 1.13 and 1.15, respectively. The interaction and mediation between LDLc and BMI on CHD risk were more pronounced at young-age groups. LDLc-CHD but not BMI-CHD association was dependent on sex, metabolic syndrome and lipid-lowering drugs use.

There were differential age-specific associations of LDLc and BMI with the risk of developing CHD, calling for future efforts to discriminate the age-different benefits from lipids management or weight control on the primary prevention for CHD.

Atherosclerosis is closely associated with metabolic disorders such as cholesterol accumulation, bile acid metabolism, and gut dysbiosis. Neoagarotetraose supplementation has been shown to inhibit obesity and alleviate type 2 diabetes, but its effects on modulating the development of atherosclerosis remain unexplored. Therefore, the present study was conducted to investigate the protective effects and potential mechanisms of neoagarotetraose on high-fat, high-cholesterol diet (HFHCD)-induced atherosclerosis in ApoE-/- mice. The results showed that neoagarotetraose supplementation decreased the atherosclerotic lesion area by 50.1% and the aortic arch lesion size by 80.4% compared to the HFHCD group. Furthermore, neoagarotetraose supplementation led to a significant reduction in hepatic lipid content, particularly non-high-density lipoprotein cholesterol. It also resulted in a substantial increase in total bile acid content in both urine and fecal samples by 3.0-fold and 38.7%, respectively. Moreover, neoagarotetraose supplementation effectively downregulated the intestinal farnesoid X receptor by 35.8% and modulated the expressions of its associated genes in both the liver and intestine. In addition, correlation analysis revealed strong associations between gut microbiota composition and fecal bile acid levels. These findings highlight the role of gut microbiota in neoagarotetraose-mitigating atherosclerosis in HFHCD-fed ApoE-/- mice. This study indicates the potential of neoagarotetraose as a functional dietary supplement for the prevention of atherosclerosis.

Adequate experimental animal models play an important role in an objective assessment of the effectiveness of medicines and functional foods enriched with biologically active substances. The aim of our study was a comparative assessment of the effect of consumption of 1 or 2% cholesterol with and without regular (two times a week), moderate running exercise on the main biomarkers of lipid and cholesterol metabolism, as well as the intestinal microbiota of male Wistar rats. In experimental rats, a response of 39 indicators (body weight, food consumption, serum biomarkers, liver composition, and changes in intestinal microbiota) was revealed. Total serum cholesterol level increased 1.8 times in animals consuming cholesterol with a simultaneous increase in low-density lipoprotein cholesterol (2 times) and decrease in high-density lipoprotein cholesterol (1.3 times) levels compared to the control animals. These animals had 1.3 times increased liver weight, almost 5 times increased triglycerides level, and more than 6 times increased cholesterol content. There was a tendency towards a decrease in triglycerides levels against the background of running exercise. The consumption of cholesterol led to a predominance of the Bacteroides family, due to a decrease in F. prausnitzii (1.2 times) and bifidobacteria (1.3 times), as well as an increase in Escherichia family (1.2 times). The running exercise did not lead to the complete normalization of microbiota.

Bile acids (BAs) and bilirubin, primarily known for their role in lipid metabolism and as heme catabolite, respectively, have been found to have diverse effects on various physiological processes, including oxidative stress and inflammation. Indeed, accumulating evidence showed that the interplay between BAs and bilirubin in these processes involves intricate regulatory mechanisms mediated by specific receptors and signaling pathways under certain conditions and in specific contexts. Oxidative stress plays a significant role in the development and progression of cardiovascular diseases (CVDs) due to its role in inflammation, endothelial dysfunction, hypertension, and other risk factors. In the cardiovascular (CV) system, recent studies have suggested that BAs and bilirubin have some opposite effects related to oxidative and inflammatory mechanisms, but this area of research is still under investigation. This review aims to introduce BAs and bilirubin from a biochemical and physiological point of view, emphasizing their potential protective or detrimental effects on CVDs. Moreover, clinical studies that have assessed the association between BAs/bilirubin and CVD were examined in depth to better interpret the possible link between them.

Although the impact of hypertension on carotid intima-media thickness (IMT) and plaques has been well established, its association with femoral IMT and plaques has not been extensively examined. In addition, the role of the ratio of systolic and diastolic pressure (SDR) in the subclinical atherosclerosis (AS) risk remains unknown. We assessed the relationship between SDR and carotid and femoral AS in a general population.

A total of 7,263 participants aged 35-74 years enrolled from January 2019 to June 2021 in a southeast region of China were included in a cross-sectional study. Systolic and diastolic blood pressure (SBP and DBP) were used to define SDR. Ultrasonography was applied to assess the AS, including thickened IMT (TIMT) and plaque in the carotid and femoral arteries. Logistic regression and restricted cubic spline (RCS) models were the main approaches.

The prevalence of TIMT, plaque, and AS were 17.3%, 12.4%, and 22.7% in the carotid artery; 15.2%, 10.7%, and 19.5% in the femoral artery; and 23.8%, 17.9% and 30.0% in either the carotid or femoral artery, respectively. Multivariable logistic regression analysis found a significant positive association between high-tertile SDR and the higher risk of overall TIMT (OR = 1.28, 95% CI = 1.10-1.49), plaques (OR = 1.36, 95%CI = 1.16-1.61), or AS (OR = 1.36, 95% CI = 1.17-1.57), especially in the carotid artery. RCS analysis further revealed the observed positive associations were linear. Further analyses showed that as compared to the low-tertile SDR and non-hypertension group, high-tertile SDR was associated with increased risks of overall and carotid TIMT, plaques, or AS in both groups with or without hypertension.

SDR is related to a higher risk of subclinical AS, regardless of hypertension or not, suggesting that as a readily obtainable index, SDR can contribute to providing additional predictive value for AS.

Cardiovascular disease is a major complication of diabetes mellitus (DM). Type-2 DM (T2DM) is associated with an increased risk of cardiovascular events and mortality, while serum biomarkers may facilitate the prediction of these outcomes. Early differential diagnosis of T2DM complicated with acute coronary syndrome (ACS) plays an important role in controlling disease progression and improving safety.

To investigate the correlation of serum bilirubin and γ-glutamyltranspeptidase (γ-GGT) with major adverse cardiovascular events (MACEs) in T2DM patients with ACS.

The clinical data of inpatients from January 2022 to December 2022 were analyzed retrospectively. According to different conditions, they were divided into the T2DM complicated with ACS group (T2DM + ACS, n = 96), simple T2DM group (T2DM, n = 85), and simple ACS group (ACS, n = 90). The clinical data and laboratory indices were compared among the three groups, and the correlations of serum total bilirubin (TBIL) levels and serum γ-GGT levels with other indices were discussed. T2DM + ACS patients received a 90-day follow-up after discharge and were divided into event (n = 15) and nonevent (n = 81) groups according to the occurrence of MACEs; Univariate and multivariate analyses were further used to screen the independent influencing factors of MACEs in patients.

The T2DM + ACS group showed higher γ-GGT, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and glycosylated hemoglobin (HbA1c) and lower TBIL and high-density lipoprotein cholesterol levels than the T2DM and ACS groups (P < 0.05). Based on univariate analysis, the event and nonevent groups were significantly different in age (t = 3.3612, P = 0.0011), TBIL level (t = 3.0742, P = 0.0028), γ-GGT level (t = 2.6887, P = 0.0085), LDL-C level (t = 2.0816, P = 0.0401), HbA1c level (t = 2.7862, P = 0.0065) and left ventricular ejection fraction (LEVF) levels (t=3.2047, P = 0.0018). Multivariate logistic regression analysis further identified that TBIL level and LEVF level were protective factor for MACEs, and age and γ-GGT level were risk factors (P < 0.05).

Serum TBIL levels are decreased and γ-GGT levels are increased in T2DM + ACS patients, and the two indices are significantly negatively correlated. TBIL and γ-GGT are independent influencing factors for MACEs in such patients.

Emerging data suggest that the interpretation of the association between obesity and lipids appears to be oversimplified. This study aimed to quantify the complex relationships between anthropometric indices and lipid profile.

This is a cross-sectional study including 9620 participants in Southern China. Anthropometric indices included the indices of general obesity (ie, body mass index (BMI)) and central obesity (ie, waist circumference (WC) and waist-to-hip ratio (WHR)). Lipids included low-density lipoprotein cholesterol (LDLc) and atherogenic lipids (ie, high-density lipoprotein cholesterol (HDLc), triglycerides (TG) and TG/HDLc ratio). LOESS regression and general linear model were the main statistical methods.

Almost all associations between anthropometric indices and lipids were lost in obese adults. The loss of association occurred quicker with LDLc than that with atherogenic lipids; the break point for the association loss was at BMI of 24 kg/m² with LDLc (Slope _{Below break-point} = 1.81, P<0.001; Slope _{Above break-point} = 0.29, P=0.121), while at 28 kg/m² with HDLC (Slope _{Below break-point} = -1.41, P<0.001; Slope _{Above break-point} = 0.07, P=0.666) or TG (Slope _{Below break-point} = 4.96, P<0.001; Slope _{Above break-point} = 2.93, P=0.01), and at 30 kg/m² with TG/HDLc ratio (Slope _{Below break-point} = 0.15, P<0.001; Slope _{Above break-point}= 0.01, P=0.936), respectively. Similar relationships were found for WC and WHR. Besides, the presence of other metabolic disorders contributed to the loss of anthropometry-lipids relationships, for example, the BMI-LDLc association attenuated to null in both obese adults and non-obese population but with more than one other metabolic disorders.

The relationships were lost between anthropometric indices and lipids in obese adults with different break points across different lipids, which appeared to be dependent on metabolic status.