Association between the atherogenic index of plasma trajectory and risk of heart failure among hypertensive patients: a prospective cohort study.

BACKGROUND: The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular events. However, it remains unclear whether hypertensive patients with long-term high AIP levels are at greater risk of developing heart failure (HF). Therefore, the aim of this study was to investigate the association between AIP trajectory and the incidence of HF in hypertensive patients. METHODS: This prospective study included 22,201 hypertensive patients from the Kailuan Study who underwent three waves of surveys between 2006 and 2010. Participants were free of HF or cancer before or during 2010. The AIP was calculated as the logarithmic conversion ratio of triglycerides to high-density lipoprotein cholesterol. Latent mixed modeling was employed to identify different trajectory patterns for AIP during the exposure period (2006-2010). Cox proportional hazard models were then used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for incident HF among different trajectory groups. RESULTS: Four distinct trajectory patterns were identified through latent mixture modeling analysis: low-stable group (n = 3,373; range, -0.82 to -0.70), moderate-low stable group (n = 12,700; range, -0.12 to -0.09), moderate-high stable group (n = 5,313; range, 0.53 to 0.58), and elevated-increasing group (n = 815; range, 1.22 to 1.56). During a median follow-up period of 9.98 years, a total of 822 hypertensive participants experienced HF. After adjusting for potential confounding factors, compared with those in the low-stable group, the HR and corresponding CI for incident HF in the elevated-increasing group, moderate-high stable group, and moderate-low stable group were estimated to be 1.79 (1.21,2.66), 1.49 (1.17,1.91), and 1.27 (1.02,1.58), respectively. These findings remained consistent across subgroup analyses and sensitivity analyses. CONCLUSION: Prolonged elevation of AIP in hypertensive patients is significantly associated with an increased risk of HF. This finding suggests that regular monitoring of AIP could aid in identifying individuals at a heightened risk of HF within the hypertensive population.

A longitudinal study on the impact of the TyG Index and TG/HDL-C ratio on the risk of type 2 diabetes in Chinese patients with prediabetes.

OBJECTIVE: To elucidate the impact and predictive value of the Triglyceride Glucose Index (TyG) and the ratio of Triglycerides to High-Density Lipoprotein Cholesterol (TG/HDL-C) in identifying the risk of diabetes progression in Chinese individuals with prediabetes. METHODS: This longitudinal study enrolled 15,012 prediabetic adults from the Rich Healthcare Group between 2010 and 2016. Diabetes was defined as self-reported diabetes or a fasting glucose level ≥ 7.0 mmol/L. The Cox proportional hazards models was utilized to assess the relationship between the two indices and the risk of developing diabetes. The predictive efficacy of the two markers was gauged by the area under the curve (AUC). RESULTS: Over a median follow-up period of 2.87 years, 1,730 (11.5%) prediabetic participants developed diabetes. The adjusted hazard ratios for the top quartile of the TyG index and the TG/HDL-C ratio were 2.03 (95% confidence interval [CI]: 1.71-2.40) and 2.59 (95% CI: 2.20-3.05), respectively, compared to the lowest quartile. A significant trend of increasing diabetes risk with higher quartiles of both indices was observed. The AUC for the adjusted prediction model for prediabetes-to-diabetes transition was 0.726 for the TyG index and 0.710 for the TG/HDL-C ratio. The difference in AUCs was statistically significant (P = 0.03). CONCLUSIONS: The baseline TyG index or TG/HDL-C ratio was significantly associated with an increased risk of diabetes in prediabetic individuals. The TyG index demonstrated superior predictive accuracy, underscoring its importance in preventing diabetes in prediabetic individuals.

Association of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and gallstones among US adults aged ≤ 50 years: a cross-sectional study from NHANES 2017-2020.

BACKGROUND: The chronic digestive condition gallstones is quite common around the world, the development of which is closely related to oxidative stress, inflammatory response and abnormalities of lipid metabolism. In the last few years, as a novel biomarker of lipid metabolism, the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has garnered significant interest. However, its relationship with gallstones has not been studied yet. METHODS: 3,772 people, all under 50, were included in this study, and their full data came from the National Health and Nutrition Examination Survey (NHANES) database for the years 2017-2020. Information on gallstones was obtained through self-reported questionnaires. Smoothed curve fitting multifactorial logistic regression was utilized to evaluate the connection of NHHR with gallstone formation incidence. Subsequently, subgroup analysis and interaction tests were applied. Finally, to create a prediction model, logistic regression and feature screening by last absolute shrinkage and selection operator (LASSO) were used. The resulting model was displayed using a nomogram. RESULTS: In multivariate logistic regression that accounted for all factors, there was a 77% increase in the likelihood of gallstones for every unit rise in lnNHHR (OR 1.77 [CI 1.11-2.83]). Following NHHR stratification, the Q4 NHHR level was substantially more linked to the risk of gallstones than the Q1 level (OR 1.86 [CI 1.04-3.32]). This correlation was stronger in women, people under 35, smokers, abstainers from alcohol, non-Hispanic White people, those with excessively high cholesterol, people with COPD, and people without diabetes. After feature screening, a predictive model and visualized nomogram for gallstones were constructed with an AUC of 0.785 (CI 0.745-0.819), which was assessed by DCA to be clinically important. CONCLUSION: In the group of people ≤ 50 years of age, elevated NHHR levels were substantially linked to a higher incidence of gallstones. This correlation was stronger in several specific groups such as females, under 35 years of age, smokers, and so on. Predictive models constructed using the NHHR have potential clinical value in assessing gallstone formation.

Higher genetically predicted triglyceride level increases the bladder cancer risk independent of LDL and HDL levels.

The causal relationship between lipid levels and bladder cancer is still inconclusive currently. We aimed to reveal the causal relationship between triglycerides, HDL, and LDL and the risk of bladder cancer by univariable and multivariable Mendelian randomization (MR) analysis. The single nucleotide polymorphisms (SNPs) of exposure (triglycerides: 441,016 samples; HDL: 403,943 samples; LDL: 440,546 samples) were obtained from UK Biobank. The Genetic variation related to bladder cancer included 1554 cases and 359,640 controls. Univariable and multivariable MR methods were conducted with subsequent analysis, and smoking was regarded as a confounder. The inverse-variance weighted (IVW), MR-Egger, weighted-median method, Cochran's Q test, and MR-PRESSO were considered the main MR analysis and sensitivity analysis methods. Univariable MR analysis results suggested the triglycerides level (P = 0.011, OR = 1.001, 95% CI = 1.000-1.002) was causally associated with increased risk of bladder cancer. Multivariable MR results indicated that higher triglyceride levels could still increase the risk of bladder cancer after adjusting the effects of HDL, LDL, and smoking (P = 0.042, OR = 1.001, 95% CI = 1.000-1.002). Our findings supported that triglyceride level is causally associated with an increased risk of bladder cancer independent of LDL and HDL at the genetic level. Timely attention to changes in blood lipid levels might reduce the risk of bladder cancer.

The association of platelet count, high-density lipoprotein cholesterol, and platelet/high-density lipoprotein cholesterol ratio with serum soluble Klotho.

BACKGROUND AND OBJECTIVE: Klotho is a protein that is closely related to human aging. Soluble Klotho (S-Klotho) is a circulating protein, and its level decreases in response to systemic inflammation. The relationship between the platelet/high-density lipoprotein cholesterol ratio (PHR), an emerging inflammatory index, and S-Klotho concentrations is still unclear. In addition, the mean platelet volume has been confirmed to have a significant negative association with S-Klotho concentrations, but the relationship between the platelet count (PC) and S-Klotho concentrations has not yet been reported. METHODS: Data from individuals who participated in the National Health and Nutrition Examination Survey (NHANES) during the five cycles from 2007 to 2016 were retrieved for analysis. Linear regression, two-piecewise linear regression, and restricted cubic spline (RCS) methods were used to analyze the associations of the PHR index and its components with S-Klotho concentrations. In addition, subgroup analysis and effect modification tests were conducted. RESULTS: A total of 11,123 participants (5463 men (48.17%)), with an average age of 56.2 years, were included. After full adjustment, the S-Klotho levels of participants in the highest quartile group of PHR (ß: -51.19, 95% CI: -75.41 to -26.97, P < 0.001) and the highest quartile group of PC (ß: -72.34, 95% CI: -93.32 to -51.37, P < 0.0001) were significantly lower than those in their respective lowest quartile groups, and a significant downward trend was presented among the four groups (P for trend < 0.05, respectively). However, high-density lipoprotein cholesterol (HDL-C) concentrations were not significantly associated with S-Klotho concentrations. RCS revealed that the PHR and PC were nonlinearly associated with S-Klotho concentrations; two-piecewise linear regression revealed that the inflection points were 175.269 and 152, respectively, and that these associations slightly weakened after the inflection point. According to the subgroup analysis, liver disease status enhanced the association between the PC and S-Klotho concentrations. CONCLUSIONS: Both the PHR and PC were significantly negatively associated with S-Klotho concentrations, and these associations were nonlinear. There was no significant association between HDL-C and S-Klotho concentrations. Liver disease status enhances the negative association between the PC and S-Klotho concentrations, and the specific mechanism deserves further exploration.

Coronary artery calcification burden, atherogenic index of plasma, and risk of adverse cardiovascular events in the general population: evidence from a mediation analysis.

BACKGROUND: Dyslipidemia and abnormal cholesterol metabolism are closely related to coronary artery calcification (CAC) and are also critical factors in cardiovascular disease death. In recent years, the atherogenic index of plasma (AIP) has been widely used to evaluate vascular sclerosis. This study aimed to investigate the potential association of AIP between CAC and major adverse cardiovascular events (MACEs). METHODS: This study included 1,121 participants whose CACs were measured by multislice spiral CT. Participants' CAC Agatston score, CAC mass, CAC volume, and number of vessels with CACs were assessed. AIP is defined as the base 10 logarithm of the ratio of triglyceride (TG) concentration to high-density lipoprotein-cholesterol (HDL-C) concentration. We investigated the multivariate-adjusted associations between AIP, CAC, and MACEs. The mediating role of the AIP in CAC and MACEs was subsequently discussed. RESULTS: During a median follow-up of 31 months, 74 MACEs were identified. For each additional unit of log-converted CAC, the MACE risk increased by 48% (HR 1.48 [95% CI 1.32-1.65]). For each additional unit of the AIP (multiplied by 10), the MACEs risk increased by 19%. Causal mediation analysis revealed that the AIP played a partial mediating role between CAC (CAC Agatston score, CAC mass) and MACEs, and the mediating proportions were 8.16% and 16.5%, respectively. However, the mediating effect of CAC volume tended to be nonsignificant (P = 0.137). CONCLUSIONS: An increased AIP can be a risk factor for CAC and MACEs. Biomarkers based on lipid ratios are a readily available and low-cost strategy for identifying MACEs and mediating the association between CAC and MACEs. These findings provide a new perspective on CAC treatment, early diagnosis, and prevention of MACEs.

Are maternal serum subfatin levels altered in women with one abnormal glucose tolerance test value?

BACKGROUND: Subfatin, a newly discovered adipokine, plays a pivotal role in the regulation of glucose metabolism. The relationship between gestational diabetes mellitus and maternal dyslipidemia is well-documented. AIMS: This study aims to assess serum subfatin levels and the triglyceride/high-density lipoprotein cholesterol ratio in women with one abnormal glucose tolerance test value and those with gestational diabetes mellitus. METHODS: In this case-control study, 105 pregnant women were categorized into three groups: women with normal 3-h oral glucose tolerance test results (n=35), women with one abnormal 3-h oral glucose tolerance test result (n=35), and women diagnosed with gestational diabetes mellitus (n=35). Serum subfatin levels were measured using human enzyme-linked immunosorbent assay kits. RESULTS: Serum subfatin levels were significantly lower in the gestational diabetes mellitus group (0.94±0.15 ng/mL) compared to the normal oral glucose tolerance test group (1.48±0.55 ng/mL) and the group with one abnormal oral glucose tolerance test result (1.50±0.59 ng/mL). The triglyceride/high-density lipoprotein cholesterol ratio was also lower in the healthy control group than in the gestational diabetes mellitus and one abnormal oral glucose tolerance test result groups. CONCLUSION: Serum subfatin levels in women with one abnormal abnormal glucose tolerance test value are compared to those in the control group, while the triglyceride/high-density lipoprotein cholesterol ratio is significantly altered in women with one abnormal abnormal glucose tolerance test value when compared to the control group.

Contributing role of metabolic genes APOE, FTO, and LPL in the development of atrial fibrillation: insights from a case-control study.

OBJECTIVE: The aim of the study was to examine the expression profile of genes (APOE, FTO, and LPL) associated with metabolic syndrome (MetS) in subjects with concomitant atrial fibrillation (AF). METHODS: A total of 690 subjects were categorized into control, AF without MetS, and AF with MetS. RESULTS: The expression profiles of the APOE, FTO, and LPL genes were decreased in AF subjects and AF subjects with MetS as compared to the controls. In AF without the MetS group, an inverse relationship was found between the expression of the LPL gene with body mass index (BMI) and a positive relationship with creatine kinase-MB, whereas expression of the FTO gene was inversely associated with fasting blood glucose and positively with cardiac troponin I in AF suffering from MetS. Expression of the LPL gene was directly linked with systolic blood pressure (SBP) and high-density lipoprotein-cholesterol (HDL-C), whereas an inverse correlation with heart rate and expression of the FTO gene in AF with MetS were shown. The expression of the LPL gene was inversely related to BMI in subjects with AF. The expression of the LPL gene was positively correlated with SBP and HDL-C and negatively correlated with heart rate, while the expression of the FTO gene was an important predictor of AF with MetS. CONCLUSION: The decreased expression of APOE, FTO, and LPL genes in AF with and without MetS indicates their potential contributing role in the pathogenesis of AF.

Genetically predicted lipid traits mediate the association between folic acid and atherosclerosis.

Atherosclerosis (AS) is one of the most common causes of death from cardiovascular disease, and low folic acid (FA) levels have been reported to be strongly associated with an increased risk of AS. We aimed to obtain causal estimates of the association between FA and AS and to quantify the mediating role of known modifiable risk factors. Based on the largest genome-wide association study (GWAS) from the IEU Open GWAS Project for all human studies, we conducted a two-sample Mendelian randomization (MR) study of genetically predicted FA and AS. A two-step MR design was then used to assess the causal mediating effect of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) on the relationship between FA and AS. This MR analysis showed that genetically determined FA levels [IVW: Odds Ratio (OR) = 0.623, 95% CI 0.421-0.924, P = 0.018] were associated with a reduced risk of AS. Inverse variance weighted (IVW) MR analysis also showed that genetically predicted FA was positively correlated with HDL-C levels (OR = 1.358, 95% CI 1.029-1.792, P = 0.031) and negatively correlated with LDL-C (OR = 0.956, 95% CI 0.920-0.994, P = 0.023) and TG levels (OR = 0.929, 95% CI 0.886-0.974, P = 0.003). LDL-C, HDL-C, and TG mediate 3.00%, 6.80%, and 4.40%, respectively, of the total impact of FA on AS. The combined effect of these three factors accounts for 13.04% of the total effect. Sensitivity analysis verifies the stability and reliability of the results. These results support a potential causal protective effect of FA on AS, with considerable mediation through many modifiable risk factors. Thus, interventions on levels of LDL-C, HDL-C, and TG have the potential to substantially reduce the burden of AS caused by low FA.

Lipids, Apolipoproteins, Lipid-Lowering Drugs, and the Risk of Cerebral Small Vessel Disease: A Mendelian Randomization Study.

BACKGROUND: Serum lipids are causally involved in the occurrence of atherosclerosis, but their roles in cerebral small vessel disease remain unclear. This study aimed to investigate the causal roles of lipid or apolipoprotein traits in cerebral small vessel disease and to determine the effects of lipid-lowering interventions on this disease. METHODS AND RESULTS: Data on genetic instruments of lipids/apolipoproteins, as well as characteristic cerebral small vessel disease manifestations, including small vessel stroke (SVS) and white matter hyperintensity (WMH), were obtained from publicly genome-wide association studies. Through 2-sample Mendelian randomization analyses, it was found that decreased levels of high-density lipoprotein cholesterol (odds ratio [OR], 0.85, P=0.007) and apolipoprotein A-I (OR, 0.83, P=0.005), as well as increased level of triglycerides (OR, 1.16, P=0.025) were associated with a higher risk of SVS. A low level of high-density lipoprotein cholesterol (OR, 0.93, P=0.032) was associated with larger WMH volume. Specifically, the genetically determined expressions of lipid fractions in various size-defined lipoprotein particles were more closely related to the risk of SVS than WMH. Moreover, it was found that the hypertension trait ranked at the top in mediating the causal effect of hyperlipidemia on SVS and WMH by using Mendelian randomization-based mediation analysis. For drug-target Mendelian randomization, the low-density lipoprotein cholesterol-reducing genetic variation alleles at HMGCR and NL1CL1 genes and the high-density lipoprotein cholesterol-raising genetic variation alleles at the CETP gene were predicted to decrease the risk of SVS. CONCLUSIONS: The present Mendelian randomization study indicates that genetically determined hyperlipidemia is closely associated with a higher risk of cerebral small vessel disease, especially SVS. Lipid-lowering drugs could be potentially considered for the therapies and preventions of SVS rather than WMH.

Periorbital melanosis and its possible association with insulin resistance and vitamin D deficiency: A pilot case-control study.

OBJECTIVE: To investigate the possible association of periorbital melanosis (POM) with insulin resistance (IR) and vitamin D serum levels. METHODS: In this pilot, case-control study, we included 100 adult patients with POM and 100 age- and sex-matched healthy control subjects. Vitamin D levels and IR indices (i.e., homeostatic model assessment-insulin resistance [HOMA-IR], triglycerides/high-density lipoprotein cholesterol (TG/HDL-c) ratio, adiponectin/leptin (A/L) ratio) were compared between cases and controls. RESULTS: Compared with controls, POM cases had significantly higher values of HOMA-IR and TG/HDL-c ratio, and significantly lower values of A/L and vitamin D. HOMA-IR and TG/HDL-c ratio were statistically significantly positively correlated with POM severity while Vitamin D and A/L ratio were statistically significantly negatively correlated. CONCLUSION: POM was associated with indices of IR and vitamin D deficiency. However, the exact causal link among POM, IR, and vitamin D needs to be established. However, the results of this pilot study suggest that POM may have potential as a cutaneous non-invasive marker of these metabolic disorders which would assist in detecting and treating them at an early stage.

Association of plant-based diet indexes with the metabolomic profile.

Plant-based diets have gained attention for their potential benefits on both human health and environmental sustainability. The objective of this study was to investigate the association of plant-based dietary patterns with the endogenous metabolites of healthy individuals and identify metabolites that may act as mediators of the associations between dietary intake and modifiable disease risk factors. Adherence to plant-based dietary patterns was assessed for 170 healthy adults using plant-based diet indexes (PDI). Individuals with higher healthful PDI had lower BMI and fasting glucose and higher HDL-C, while those with higher unhealthful PDI had higher BMI, triacylglycerol and fasting glucose and lower HDL-C. Unhealthful PDI was associated with higher levels of several amino acids and biogenic amines previously associated with cardiometabolic diseases and an opposite pattern was observed for healthful PDI. Furthermore, healthful PDI was associated with higher levels of glycerophosphocholines containing very long-chain fatty acids. Glutamate, isoleucine, proline, tyrosine, α-aminoadipate and kynurenine had a statistically significant mediation effect on the associations between PDI scores and LDL-C, HDL-C and fasting glucose. These findings contribute to the growing evidence supporting the role of plant-based diets in promoting metabolic health and shed light on the potential mechanisms explaining their beneficial health effects.

The relationship between cardiometabolic index and pulmonary function among U.S. adults: insights from the National Health and Nutrition Examination Survey (2007-2012).

BACKGROUND: Previous findings have revealed that disorders of lipid metabolism may be a risk factor for pulmonary function damage; however, the combined effect of dyslipidemia and central obesity on pulmonary function is unclear. The cardiometabolic index (CMI) is a composite of serum lipids (triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C)) and visceral fat parameters (waist-to-height ratio (WHtR)). This research aimed to investigate the link between CMI and pulmonary function, employing large-scale demographic data sourced from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: This cross-sectional study used data involving 4125 adults aged 20 and above collected by NHANES between 2007 and 2012. We defined CMI as the exposure variable and measured outcomes using forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC to evaluate pulmonary function. Weighted multiple linear regression models and subgroup analyses were employed to investigate separate relationships between CMI and pulmonary function. In addition, to investigate variations across different strata and evaluate the robustness of the findings, interaction tests and sensitivity analyses were conducted. RESULTS: Results from the weighted multiple linear regression analysis indicated a unit increase in log2-CMI was associated with a reduction of 82.63 mL in FEV1 and 112.92 mL in FVC. The negative association remained significant after transforming log2-CMI by quartile (Q). When the log2-CMI level reached Q4, ß coefficients (ß) were -128.49 (95% CI: -205.85, -51.13), -169.01 (95% CI: -266.72, -71.30), respectively. According to the interaction test findings, the negative association linking log2-CMI with FEV1 and FVC persists regardless of confounding factors including age, gender, BMI, physical activity (PA), and smoking status. A subsequent sensitivity analysis provided additional confirmation of the stability and reliability of the results. For females, the inflection points for the nonlinear relationships between log2-CMI and FEV1, as well as log2-CMI and FVC, were identified at 2.33 and 2.11, respectively. While in males, a consistent negative association was observed. CONCLUSIONS: Our findings suggest that higher CMI is associated with lower FEV1 and FVC. CMI may serve as a complementary consideration to the assessment and management of pulmonary function in clinical practice.

Apolipoprotein E knockout, but not cholesteryl ester transfer protein (CETP)-associated high-density lipoprotein cholesterol (HDL-C) lowering, exacerbates muscle wasting in dysferlin-null mice.

BACKGROUND: Dysferlin-deficient limb-girdle muscular dystrophy type 2B (Dysf) mice are notorious for their mild phenotype. Raising plasma total cholesterol (CHOL) via apolipoprotein E (ApoE) knockout (KO) drastically exacerbates muscle wasting in Dysf mice. However, dysferlinopathic patients have abnormally reduced plasma high-density lipoprotein cholesterol (HDL-C) levels. The current study aimed to determine whether HDL-C lowering can exacerbate the mild phenotype of dysferlin-null mice. METHODS: Human cholesteryl ester transfer protein (CETP), a plasma lipid transfer protein not found in mice that reduces HDL-C, and/or its optimal adapter protein human apolipoprotein B (ApoB), were overexpressed in Dysf mice. Mice received a 2% cholesterol diet from 2 months of age and characterized through ambulatory and hanging functional tests, plasma analyses, and muscle histology. RESULTS: CETP/ApoB expression in Dysf mice caused reduced HDL-C (54.5%) and elevated ratio of CHOL/HDL-C (181.3%) compared to control Dysf mice in plasma, but without raising CHOL. Compared to the severe muscle pathology found in high CHOL Dysf/ApoE double knockout mice, Dysf/CETP/ApoB mice did not show significant changes in ambulation, hanging capacity, increases in damaged area, collagen deposition, or decreases in cross-sectional area and healthy myofibre coverage. CONCLUSIONS: CETP/ApoB over-expression in Dysf mice decreases HDL-C without increasing CHOL or exacerbating muscle pathology. High CHOL or nonHDL-C caused by ApoE KO, rather than low HDL-C, likely lead to rodent muscular dystrophy phenotype humanization.

The value of the platelet/high-density lipoprotein cholesterol ratio in predicting depression and its cardiovascular disease mortality: a population-based observational study.

Background: Cardiovascular disease (CVD) and depression have a bidirectional association, with inflammation and metabolic factors being common important triggers for both conditions. However, as a novel inflammatory and metabolic marker, platelet-to-HDL-C ratio (PHR) has not been established in relation to depression and cardiovascular disease. Materials and methods: Participants aged 20 years and older were included in the 2005-2018 NHANES database. PHR was calculated as the ratio of platelet count (1000 cells/µL) to HDL-C (mmol/L). The Patient Health Questionnaire (PHQ-9) was used to diagnose depression, with a cutoff value of 10. Weighted logistic regression analysis and restricted cubic spline (RCS) analysis were employed to examine the association between PHR and depression-related features. Additionally, weighted COX regression and RCS were used to analyze the association of PHR with CVD mortality in patients with depression. Receiver operating characteristic curves were used to assess whether PHR had an advantage over HDL-C in predicting depression. Finally, the mediating role of PHR in the latest cardiovascular health indicator Life's Essential 8 and depression was explored. Results: A total of 26,970 eligible participants were included, including 2,308 individuals with depression, representing approximately 160 million U.S. adults when weighted. After full adjustment, we estimated that the odds ratio (OR) of depression associated with a per standard deviation (SD) increase in PHR was 1.06 (95% CI: 1.01-1.12, P=0.03). The restricted cubic spline (RCS) analysis indicated a linear association (Nonlinear P=0.113). When PHR was divided into four groups based on quartiles and included in the model after full adjustment for depression risk factors, participants in quartile 2, quartile 3, and quartile 4 of PHR showed a trend of increasing risk of depression compared to the lowest quartile group (P trend=0.01). In addition, weighted COX regression and RCS revealed that a per SD increase in PHR was associated with a higher risk of CVD mortality among patients with depression (HR: 1.38, 95% CI: 1.05-1.81, P=0.02, Nonlinear P=0.400). Subgroup analyses showed that current alcohol consumption enhanced the association between PHR and depression (P for interaction=0.017). Furthermore, the areas under the ROC curves (AUC) were 0.556 (95% CI, 0.544-0.568; P < 0.001) for PHR and 0.536 (95% CI, 0.524-0.549; P < 0.001) for HDL-C (PDeLong = 0.025). Finally, mediation analysis indicated that PHR was an intermediate mechanism between LE8 and depression (mediation proportion=5.02%, P=0.02). Conclusion: In U.S. adults, an increase in PHR linearly increases the risk of depression and CVD mortality among individuals with depression. Additionally, PHR has a better predictive advantage for depression compared to HDL-C. Furthermore, PHR significantly mediates the association between LE8 scores and depression.

The newly proposed plasma-glycosylated hemoglobin A1c/High-Density lipoprotein cholesterol ratio serves as a simple and practical indicator for screening metabolic associated fatty liver disease: an observational study based on a physical examination population.

BACKGROUND: Glycotoxicity and lipotoxicity are key pathophysiological mechanisms underlying the development of metabolic associated fatty liver disease (MAFLD). The primary objective of this study is to investigate the association between the newly proposed Plasma-Glycosylated Hemoglobin A1c/High-Density Lipoprotein Cholesterol Ratio (HbA1c/HDL-C ratio) and the risk of MAFLD. METHODS: A study population of 14,251 individuals undergoing health examinations was included. The association between the HbA1c/HDL-C ratio and MAFLD was analyzed using multivariable logistic regression and restricted cubic spline (RCS) analysis. Exploratory analyses were conducted to assess variations in this association across subgroups stratified by gender, age, body mass index (BMI), exercise habits, drinking status, and smoking status. The discriminatory value of the HbA1c/HDL-C ratio and its components for screening MAFLD was evaluated using receiver operating characteristic (ROC) curves. RESULTS: A total of 1,982 (13.91%) subjects were diagnosed with MAFLD. After adjusting for confounding factors, we found a significant positive association between the HbA1c/HDL-C ratio and MAFLD [odds ratio (OR) 1.34, 95% confidence interval (CI): 1.25, 1.44]. No significant differences in this association were observed across all subgroups (All P for interaction > 0.05). Furthermore, through RCS analysis, we observed a nonlinear positive correlation between the HbA1c/HDL-C ratio and MAFLD (P for non-linearity < 0.001), with a potential threshold effect point (approximately 3 for the HbA1c/HDL-C ratio). Beyond this threshold point, the slope of the MAFLD prevalence curve increased rapidly. Additionally, in further ROC analysis, we found that for the identification of MAFLD, the HbA1c/HDL-C ratio was significantly superior to HbA1c and HDL-C, with an area under the curve (AUC) and optimal threshold of 0.81 and 4.08, respectively. CONCLUSIONS: Our findings suggest that the newly proposed HbA1c/HDL-C ratio serves as a simple and practical indicator for assessing MAFLD, exhibiting well-discriminatory performance in screening for MAFLD.

Association of 28-day mortality with non-high-density lipoprotein cholesterol and the high-density lipoprotein cholesterol ratio (NHHR) in patients with sepsis: Results of MIMIC-IV database analysis.

BACKGROUND: The correlation between lipid profiles and sepsis has received increasing attention. The ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) is one of the key lipid profiles. However, in-depth exploration of the correlation between NHHR and the mortality risk of patients with sepsis is limited. METHODS: Data from the MIMIC-IV (v2.2) database, we review the NHHR relevance and the sepsis severity index using Spearman's correlation analysis. Additionally, we research NHHR associated with sepsis patients' survival rate of 28 days using Cox regression analyses of continuous and categorical models. To further validate our findings, we conducted subgroup and sensitivity analyses. RESULTS: The study involved 3,142 patients diagnosed with sepsis, according to 28 days after in-hospital survival condition, divided into two groups. In this study, 2932 patients were in the survival group and 210 patients died within 28 days (mortality group). Of note, the mean NHHR of patients in the mortality group exceeded that of the survival group (3.5 vs. 2.9). Additionally, NHHR was positively correlated with the severity index. After adjusting for demographic and laboratory data, an increased NHHR was positively correlated with higher sepsis mortality risk (OR = 1.06; 95% CI: 1.02-1.11; P = 0.013). Subgroup analysis shown the same results. Contributors were be categorized into two groups based on NHHR levels, with a threshold of 2.61. Contrast the mortality risk between low-NHHR group and high-NHHR group, high-NHHR show greater mortality risk on 28-day, 60-day, 90-day, in ICU, and in hospital. CONCLUSION: Elevated NHHR is to be correlated with an increased risk of mortality in patients with sepsis. Further research on NHHR may contribute to advancements in sepsis prevention and treatment.

[Association of serum irisin levels with glucose and lipid metabolism among adolescents in Yinchuan City from 2017 to 2020].

OBJECTIVE: To explore the relationship between serum irisin levels and glucose and lipid metabolism among adolescents in Yinchuan City. METHODS: From 2017 to 2020, a conbination of convenient sampling and stratified cluster random sampling method were used to select 1219 adolescents aged 12 to 18 years old in Yinchuan City as research subjects. The height and weight were measured using the height and sitting height meter and the bioelectrical impedance analyzer. Blood indicators such as fasting plasma glucose(FPG), totalcholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) were measured using fully automatic biochemical analyzer. Serum irisin levels were measured by enzyme-linked immunosorbent assay(ELISA). Binary logistic regression was used to analyze the correlation between irisin and abnormal glucose and lipid metabolism. RESULTS: The FPG, TC, HDL-C and LDL-C levels of subjects in the highest tertile of irisin levels were significantly lower than those of subjects in the lowest tertile of irisin levels(F values were 5.13, 3.15, 3.07 and 5.01, P<0.05), and the differences were statistically significant(all P<0.05). The serum irisin levels in the hyperglycemia group(t=2.87, P<0.01), hypercholesterolemia group(t=2.36, P=0.02) and hyperLDL-Cemia group(t=2.34, P=0.02) were significantly lower than those in the normoglycemia group, normal TC group and normal LDL-C group. Meanwhile, the irisin level in the low HDL-Cemia group(t=-2.57, P=0.01) was significantly higher than that in the normal HDL-C group, and the differences were statistically significant(P<0.05). Participants in the highest tertile of irisin had 0.51, 0.49 and 0.50 times the risk of hyperglycemia(OR=0.51, 95%CI 0.29-0.87), hypercholesterolemia(OR=0.49, 95%CI 0.27-0.89) and hyperLDL-cemia(OR=0.50, 95%CI 0.25-0.99) compared with those in the lowest tertile. CONCLUSION: Low levels of irisin are associated with the occurrence of hyperglycemia, hypercholesterolemia, and hyperLDL-Cemia in adolescents.

Spurious dyslipidemia due to paraprotein in a patient with Waldenström macroglobulinemia.

INTRODUCTION: Serum lipid profiles play a crucial role in diagnosing and evaluating cardiovascular diseases. However, the presence of paraprotein can lead to inaccurate dyslipidemia results on automated analyzers. CASE REPORT: A 65-year-old woman whose combined concentrations of HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) consistently surpassed her total serum cholesterol levels over a period of three months presented with unusual lipid component detection. Further analysis revealed the presence of a monoclonal paraprotein, identified as an IgMλ band, with a concentration of 28.0 g/L. The patient was subsequently diagnosed with Waldenström macroglobulinemia. The use of abnormal reaction kinetic curves and the ß quantification method, along with an alternative method that did not suffer from interference, revealed that the monoclonal paraprotein interfered with the measurements of HDL-C, LDL-C, apolipoprotein A-I (apoA-I), and apolipoprotein B (apoB) when using the Roche detection system. This interference led to spurious elevated HDL-C concentrations and falsely decreased apoA-I and apoB concentrations, while the LDL-C results were minimally affected. Although diluting the sample normalized the HDL-C and LDL-C measurements, the interference with the apoA-I and apoB assays persisted. No other common biochemical tests were interfered with this paraprotein. CONCLUSION: Caution is advised when using a homogenous method for direct measurement of HDL-C and LDL-C in patients with monoclonal paraprotein. Techniques to recognize and eliminate this interference are available. However, immunoturbidimetric detection of apoA-I and apoB levels is also susceptible to this interference, which is not readily removable.

The Causal Effect of Serum Lipid Levels Mediated by Neuregulin 4 on the Risk of Four Atherosclerosis Subtypes: Evidence from Mendelian Randomization Analysis.

Background: Neuregulin 4 (NRG4) was known to be associated with serum lipid levels and atherosclerosis. However, it is unknown whether the role of NRG4 in lipid homeostasis is causal to atherosclerosis and whether the effect is beneficial across different atherosclerosis subtypes. Methods: We investigated the causal role of the levels of serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides regulated by NRG4 in subtypes of atherosclerosis through two sample Mendelian randomization. Aggregated genome-wide association study (GWAS) summary data for serum lipid level of 1.32 million individuals with European ancestry were obtained from the Global Lipids Genetics Consortium. GWAS summary data for four atherosclerosis subtypes (peripheral, coronary, cerebral and the other atherosclerosis) were obtained from FinnGen Consortium. Generalized inverse-variance-weighted Mendelian randomization and several sensitivity analyses were used to obtain the causal estimates. Results: A 1-SD genetically elevated LDL-C level mediated by NRG4 was validated to be nominally associated with the risk of peripheral atherosclerosis (log (odds ratio)= 4.14, 95% confidence interval 0.11 to 8.17, P = 0.04), and the other associations were not significant or could not be validated by sensitivity analyses. Conclusion: LDL-C lowering mediated by NRG4 is likely to prevent peripheral atherosclerosis.