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The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a recently developed lipid parameter, but there is currently a lack of research exploring its relationship with periodontitis. This study aims to identify the potential association between NHHR and periodontitis. The association between NHHR and periodontitis were examined through univariate and multivariate weighted logistic regression utilizing the National Health and Nutrition Examination Survey data from 2009 to 2014. The participants were grouped based on the type of periodontitis. This study included a total of 9023 participants, with 1947 individuals having no periodontitis, and an additional 7076 individuals suffering from periodontitis. Patients in periodontitis group demonstrated a statistically significant elevation in NHHR values 2.82 (2.05–3.80) compared to those in no periodontitis group ( p  < 0.001). Logistic regression analysis of variables demonstrated a positive association between NHHR and periodontitis [1.07 (1.02, 1.12) p  = 0.0067]. The study revealed a positive association between NHHR and an elevated prevalence of periodontitis development. For each unit increase in NHHR, there is a 7% increase in the prevalence of periodontitis. Further investigations into NHHR may enhance our understanding of preventing and treating periodontitis. However, additional studies are required to validate these findings.

The ratio of non-high-density lipoprotein cholesterol (non-HDL-C) to HDL-C (NHHR) is a novel lipid parameter used to assess the risk of cardiovascular disease. Previous studies have demonstrated an association between the NHHR and risk of non-alcoholic fatty liver disease (NAFLD). Owing to the lack of research exploring this relationship in specific populations, this study aimed to determine the potential link between the NHHR and risk of NAFLD among American adults in the United States. Data were retrieved from the National Health and Nutrition Examination Survey (NHANES) spanning 2017–2020. After excluding individuals with other liver diseases, alcohol abuse, and missing lipid data, a total of 6809 eligible adults were included for analysis. The NHHR was calculated as the ratio of (non-HDL-C) to HDL-C, while NAFLD was identified by liver steatosis detected by transient elastography. Multivariable weighted logistic regression models and restricted cubic spline (RCS) models were employed to investigate the relationship between the NHHR and risk of NAFLD. Subgroup and sensitivity analyses were also conducted to test the robustness of the results. As the NHHR increased, the prevalence of NAFLD rose progressively (5.88% vs. 8.75% vs. 12.24% vs. 15.77%, p  < 0.001). In the overall population, after adjusting for confounding factors, each unit increase in the NHHR was associated with a 25% increase in NAFLD risk (OR = 1.25, 95% CI: 1.03–1.53, p  = 0.0372). When the NHHR was analyzed as a categorical variable (quartiles), participants in the highest quartile had a significantly higher risk of NAFLD than those in the lowest quartile (OR = 2.6, 95% CI: 1.75–3.85, p  = 0.009). RCS analysis further indicated a nonlinear dose–response relationship between the NHHR and risk of NAFLD ( p non-linearity < 0.0001). This association remained significant in both subgroup and sensitivity analyses. This study confirmed that the NHHR, particularly at higher levels, was an independent risk factor for NAFLD. As a comprehensive lipid indicator, the NHHR had the potential to predict NAFLD risk. These findings provided new insights for the prevention and clinical management of NAFLD.

To the best of our knowledge, no systematic review and meta-analysis has evaluated the cholesterol-lowering effects of intermittent fasting (IF) and energy-restricted diets (ERD) compared with control groups. The aim of this review and meta-analysis was to summarize the effects of controlled clinical trials examining the influence of IF and ERD on lipid profiles. A systematic review of four independent databases (PubMed/Medline, Scopus, Web of Science and Google Scholar) was performed to identify clinical trials reporting the effects of IF or ERD, relative to non-diet controls, on lipid profiles in humans. A random-effects model, employing the method of DerSimonian and Laird, was used to evaluate effect sizes, and results were expressed as weighted mean difference (WMD) and 95% confidence intervals (CIs). Heterogeneity between studies was calculated using Higgins I2, with values ≥50% considered to represent high heterogeneity. Subgroup analyses were performed to examine the influence of intervention type, baseline lipid concentrations, degree of energy deficit, sex, health status, and intervention duration. For the outcomes of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triacylglycerols (TG), there were 34, 33, 35, and 33 studies meeting all inclusion criteria, respectively. Overall, results from the random-effects model indicated that IF and ERD interventions resulted significant changes in TC (WMD, –6.93 mg/dL; 95% CI, –10.18 to –3.67; P < 0.001; I2 = 78.2%), LDL-C (WMD, –6.16 mg/dL; 95% CI, –8.42 to –3.90; P ˂ 0.001; I2 = 52%), and TG concentrations (WMD, –6.46 mg/dL; 95% CI, –10.64 to –2.27; P = 0.002; I2 = 61%). HDL-C concentrations did not change significantly after IF or ERD (WMD, 0.50 mg/dL; 95% CI, –0.69 to 1.70; P = 0.411; I2 = 80%). Subgroup analyses indicated potentially differential effects between subgroups for one or more lipid parameters in the majority of analyses. Relative to a non-diet control, IF and ERD are effective for the improvement of circulating TC, LDL-C, and TG concentrations, but have no meaningful effects on HDL-C concentration. These effects are influenced by several factors that may inform clinical practice and future research. The present results suggest that these dietary practices are a means of enhancing the lipid profile in humans. •Other than Ramadan intermittent fasting, specific intermittent fasting strategies may be adopted into clinical scenario.•Intermittent fasting and energy-restricted diets are effective in improving circulating total cholesterol, low-density lipoprotein cholesterol, and triacylglycerol levels.•However, intermittent fasting and energy-restricted diets have no meaningful effects on high-density lipoprotein cholesterol levels.

Introduction Previous studies have shown that the serum uric acid‐to‐high‐density lipoprotein cholesterol ratio (UHR) is related to metabolic syndrome. However, no existing study has examined the relationship between UHR and insulin resistance (IR). Therefore, this study aims to explore the association between the UHR and IR in patients with type 2 diabetes mellitus (T2DM). Methods Patients with type 2 diabetes mellitus (1,532 males and 1,013 females) were enrolled. Insulin resistance was measured by homeostatic model assessment of insulin resistance (HOMA‐IR) and was defined as HOMI‐IR ≥ 2.69. Pearson correlation, multiple logistic regression, ROC analysis, and subgroup analysis were used to evaluate the association between UHR and IR. Results UHR was associated with HOMA‐IR in patients with type 2 diabetes mellitus (pearson's correlation coefficient = 0.274 in males and 0.337 in females, P < 0.001). Multiple logistic regression analysis showed that UHR was significantly correlated with insulin resistance (OR = 1.06, 95%CI = 1.03–1.08 in males and OR = 1.11, 95%CI = 1.08–1.15 in females). The area under the ROC curve (AUC) of UHR (AUC = 0.665 for males and 0.717 for females, all P < 0.01) was the largest compared with that of UA and HDL‐C in insulin resistance. Subgroup analysis showed that there was a more significantly positive correlation among subjects with BMI ≥ 24 kg/m2, age < 60 years old, HbA1c < 7%, non‐hypertension, or in female subjects. Conclusion Elevated UHR is significantly correlated with insulin resistance, which can be used as an indicator of insulin resistance in patients with type 2 diabetes mellitus. UHR is positively correlated with an increase in HOMA‐IR and the risk of insulin resistance (IR) in a mass of patients with type 2 diabetes mellitus. UHR is more effective in detecting IR compared with uric acid or HDL‐C alone.

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid contained in High-density lipoproteins (HDL) and has drawn considerable attention in the lipoprotein field as numerous studies have demonstrated its contribution to several functions inherent to HDL. Some of them are partly and some entirely due to the S1P contained in HDL (HDL-S1P). Despite the presence of over 1000 different lipids in HDL, S1P stands out as it possesses its own cell surface receptors through which it exercises key physiological functions. Most of the S1P in human plasma is associated with HDL, and the amount of HDL-S1P influences the quality and quantity of HDL-dependent functions. The main binding partner of S1P in HDL is apolipoprotein M but others may also exist particularly under conditions of acute S1P elevations. HDL not only exercise functions through their S1P content but have also an impact on genuine S1P signaling by influencing S1P bioactivity and receptor presentation. HDL-S1P content is altered in human diseases such as atherosclerosis, coronary artery disease, myocardial infarction, renal insufficiency and diabetes mellitus. Low HDL-S1P has also been linked to impaired HDL functions associated with these disorders. Although the pathophysiological and molecular reasons for such disease-associated shifts in HDL-S1P are little understood, there have been successful approaches to circumvent their adverse implications by pharmacologically increasing HDL-S1P as means to improve HDL function. This mini-review will cover the current understanding of the contribution of HDL-S1P to physiological HDL function, its alteration in disease and ways for its restoration to correct HDL dysfunction.

Gallstone disease is a condition affecting the digestive system, strongly linked to inflammation and lipid metabolism. Inflammatory markers derived from high-density lipoprotein (HDL), incorporating both immune cells and HDL-C, play a crucial role in assessing inflammatory responses. This study aims to explore the relationship between these HDL-related inflammatory indices and gallstone disease. The study population was derived from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 and 2021-2023 datasets. To assess the association between HDL-related inflammatory indices and gallstone disease, weighted multivariable logistic regression and restricted cubic spline (RCS) analysis were utilized. Additionally, subgroup analysis was conducted to confirm the consistency of the results across different subpopulations. Among the 16,871 participants included in the study, 11.0% were diagnosed with gallstone disease. When compared to the lowest quartile, those in the highest quartile of lymphocyte-to-HDL cholesterol ratio (LHR), monocyte-to-HDL cholesterol ratio (MHR), neutrophil-to-HDL cholesterol ratio (NHR), and platelet-to-HDL cholesterol ratio (PHR) faced an elevated risk of gallstone disease by 58.6% (OR = 1.586, 95% CI: 1.143-2.2), 67.6% (OR = 1.676, 95% CI: 1.275-2.204), 68.7% (OR = 1.687, 95% CI: 1.244-2.287), and 42.7% (OR = 1.427, 95% CI: 1.101-1.849), respectively. The correlation between HDL-related inflammatory indices and gallstone disease was more pronounced in females, individuals without diabetes or hypertension, nonsmokers, and those who consumed alcohol. This research identified a positive correlation between HDL-related inflammatory indices and gallstone disease in a nationally representative sample. These indices can be derived from routine blood tests at no additional cost, making them practical and cost-effective tools for early risk stratification and potential large-scale screening.

Diabetes is one of the most prevalent chronic diseases in the world, and its prevalence is expected to rise further. To help understand the utility of the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) in diabetes prevention, this large-scale longitudinal cohort study aims to explore the association of NHHR with diabetes risk and compare it as a risk predictor with conventional lipid parameters. This observational study extracted data from the NAGALA longitudinal cohort study conducted in Japan between 2004 and 2015. Multivariate Cox regression analysis was used to evaluate the association between NHHR and the risk of diabetes. The dose-response relationship was analyzed by restricted cubic spline (RCS) regression and the potential risk threshold was estimated. The receiver operator characteristic curve (ROC) was used to analyze and calculate the predictive value and optimal threshold of NHHR and other conventional lipids for new-onset diabetes. Of the 15,464 people aged 18-79, 373 (2.41%) were diagnosed with new-onset diabetes during the study period, with a median age of 46 years. The sensitivity analysis based on multivariate adjustment showed that the independent positive correlation between diabetes and NHHR was stable in different populations. RCS and ROC analysis indicated that the association between NHHR and diabetes was non-linear, and the NHHR was a better marker for predicting diabetes risk than other conventional lipid parameters; Additionally, it is worth noting that an NHHR of approximately 2.74 may be the optimal threshold for intervention in diabetes risk. In the general population, NHHR is a better marker for predicting diabetes risk than conventional lipid parameters, and an NHHR of about 2.74 may be the optimal threshold for assessing diabetes risk.

Sepsis is a life-threatening condition that stems from a dysregulated host response to an infection, leading to multi-organ dysfunction and death. Sepsis has a remarkably high global burden and accounts for 20% of all deaths worldwide. Nonetheless, possibilities for treatment are limited mainly to early administration of broad-spectrum antibiotics and providing fluid resuscitation. Innovative strategies that target the excessive inflammatory response while supporting the immune system to clear the infection are highly warranted. It is well-established that sepsis significantly impacts lipoprotein metabolism, leading to a substantial decrease in high-density lipoprotein (HDL) as observed in both experimental and clinical studies. Meanwhile, a high HDL level is associated with better sepsis-related prognosis, indicating that strategies aimed at raising HDL could be beneficial in combating sepsis. In this review, we describe changes in lipoprotein metabolism that occur during sepsis, address the various protective functions of HDL based on its endotoxin-neutralizing, anti-bacterial, anti-inflammatory, and anti-oxidative properties, as well as demonstrate modulation of HDL as a potential therapeutic strategy in sepsis. Graphical abstract

Background Waist circumference, a metabolic syndrome (MetSy) criterion, is not routinely measured in clinical practice making early identification of individuals with MetSy challenging. It has been argued that ratios of commonly measured parameters such as lipids and lipoproteins may be an acceptable alternative for identifying individuals with MetSy. The objective of our study was to explore clinical utility of lipid ratios to identify men and women with MetSy; and to explore the association between lipid ratios and the number of MetSy components. Methods Men and women (N = 797) of Aboriginal, Chinese, European, and South Asian origin (35–60 years), recruited across ranges of body mass index (BMI), with no diagnosed cardiovascular disease (CVD) or on medications to treat CVD risk factors were assessed for anthropometrics, family history of CVD, MetSy components (waist circumference, blood pressure, glucose, triglycerides (TG), high-density-lipoprotein-cholesterol (HDL-C)), low-density-lipoprotein-cholesterol (LDL-C), nonHDL-C, and health-related behaviours. Results Mean levels of lipid ratios significantly increased with increasing number of MetSy components in men and women (p < 0.05). After adjustment for age, ethnicity, smoking, alcohol consumption, physical activity, family history of CVD and BMI, (and menopausal status in women), all lipid ratios were associated with the number of MetSy components in men and women (Poisson regression, p < 0.001). Compared to the rest of the lipid ratios (ROC curve analysis), TG/HDL-C was best able to discriminate between individuals with and without MetSy (AUC = 0.869 (95% CI: 0.830, 0.908) men; AUC = 0.872 (95% CI: 0.832, 0.912) women). The discriminatory power of TC/HDL-C and nonHDL-C/HDL-C to identify individuals with MetSY was the same (for both ratios, AUC = 0.793 (95% CI: 0.744, 0.842) men; 0.818 (95% CI: 0.772, 0.864) women). Additionally, LDL-C/HDL-C was a good marker for women (AUC = 0.759 (95% CI: 0.706, 0.812)), but not for men (AUC = 0.689 (95% CI: 0.631, 0.748)). Based on a multiethnic sample, we identified TG/HDL-C cut-off values of 1.62 in men and 1.18 in women that were best able to discriminate between men and women with and without MetSY. Conclusions Our results indicate that TG/HDL-C is a superior marker to identify men and women with MetSy compared to TC/HDL-C, LDL-C/HDL-C, and nonHDL-C/HDL-C.

Background Papillary thyroid carcinoma (PTC) is considered to be an inflammatory disease. This study aimed to investigate the association of monocyte to high‐density lipoprotein cholesterol ratio (MHR) with PTC. Methods Clinical parameters from 300 patients with PTC and 552 patients with benign thyroid nodule were compared. Serum renal function and liver enzymes, fasting plasma glucose, lipid profile, and blood cell count were measured. Results Patients with PTC had a higher MONO (p < 0.001) and MHR (p < 0.001). There was a step‐wise increase in the prevalence of PTC (p = 0.003) with the tertile of MHR. Logistic regression analysis revealed that MHR could be considered an independent risk factor (p < 0.001) in the case‐control study and the cohort study. Pearson correlation analysis and simple linear regression analysis indicated that MHR was positively associated with neutrophil (NEU) and lymphocyte (LYM) count as well as neutrophil‐to‐lymphocyte ratio (NLR). Area under the curve (AUC) was 0.711. The optimal cutoff of MHR was 0.33 × 109/mmol. Conclusion This study identifies novel evidence that patients with PTC have a higher MHR. MHR is an independent risk factor for PTC. These findings support the application of MHR to predict, diagnose, and evaluate the occurrence of PTC. Prevalence of PTC among three groups categorized by tertile of MHR. There was a step‐wise increase in the prevalence of PTC (30.4% vs 32.3% vs. 42.7%, p = 0.003) with MHR tertile.