BACKGROUND: Recent studies have demonstrated that very high high-density lipoprotein cholesterol (HDL-C) level was paradoxically linked with higher risk of cardiovascular mortality, all-cause mortality, and several age-related diseases. However, whether very high HDL-C level is associated with a higher risk of sarcopenia in older adults remains unclear. We aimed to investigate the association between HDL-C level and the risk of developing sarcopenia and low grip strength over time in older adults.
METHODS: Participants were from the ongoing China Health and Retirement Longitudinal Study (CHARLS), which includes a nationally representative sample of adults aged ≥45 years and was performed from 2011 to 2020 with follow-ups every two to three years. The current study included 4031 participants aged ≥60 years. Muscle health-related data were collected in waves 2011, 2013, and 2015. Based on HDL-C level at baseline, participants were categorized into five groups: <35 mg/dl, 35-40 mg/dl, 40-60 mg/dl, 60-70 mg/dl and >70 mg/dl. The main outcomes were incident sarcopenia and incident low grip strength over follow-up. Low grip strength and sarcopenia were defined according to the 2019 Consensus by the Asian Working Group for Sarcopenia. Cox proportional-hazard regression was performed to investigate the association between HDL-C level and the risk of developing sarcopenia and low grip strength in older adults.
RESULTS: The mean age of study sample was 67.3 (SD 6.1) years, and 49.6% were male. During an average 3.7-year follow-up, 409 (10.1%) participants developed sarcopenia and 771 (21.1%) developed low grip strength. Non-linear association was observed between HDL-C level and the hazard of developing sarcopenia and low grip strength. The multivariable model showed that compared to the reference group (40-60 mg/dl), older adults with very high HDL-C level (>70 mg/dl) had a significantly higher risk of developing sarcopenia (HR 1.69, 95% CI 1.28-2.23) and low grip strength (HR 1.23 95% CI 1.00-1.51). Stratified analyses by sex revealed similar association.
CONCLUSIONS: We present the first longitudinal evidence that very high HDL-C level was associated with a significantly higher risk of muscle strength decline and developing sarcopenia in older adults. It is essential to monitor the muscle health of older adults with very high HDL-C level in clinical practice.

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.

Observational studies have shown that non-alcoholic fatty liver disease (NAFLD) is strongly associated with metabolic dysfunction. However, there is a paucity of research on whether changes in indicators of serum metabolism contribute to the development of NAFLD. This study was conducted with 4084 participants who underwent healthy physical examinations at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China, in 2022 and 2023. Baseline and follow-up measurements, including anthropometric data, abdominal ultrasound and blood samples were collected. The diagnosis of NAFLD was based on the 2010 Chinese Guidelines on Diagnosis and Treatment of NAFLD. Multiple logistic regression was utilized to analyze the odds ratios (ORs) for the 1-year risk of NAFLD in connection with both baseline metabolic indicators and changes in metabolic indicators observed over the course of 1 year. A total of 3425 study participants who were free of NAFLD at baseline, including 1146 men and 2279 women, were included in the final analysis. The mean age was 34.43 ± 7.20 years. Participants who developed NAFLD were older, male and had higher levels of body mass index (BMI), blood pressure, fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), free triiodothyronine (fT3), uric acid (UA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and lower levels of high-density lipoprotein cholesterol (HDL-C) and free thyroxine (fT4) (all P values < 0.05). The multivariable model showed that baseline BMI, diastolic blood pressure (DBP), TG, TC, HDL-C, LDL-C, UA, fT4, fT3, ALT and changes in TG, HDL-C, and UA were associated with the 1-year risk of developing NAFLD. The risk of NAFLD increased by 56% [OR 1.56, 95% Confidence Interval (CI) 1.32-1.87] and 40% (OR 1.40, 95% CI 1.19-1.64) for each standard deviation (SD) increase in altered TG values (1.01 mmol/L) and altered UA values (55 µmol/L) respectively. Conversely, for each SD (0.27 mmol/L) increase in HDL-C change, the 1-year risk of incident NAFLD was reduced by 50% (OR 0.50, 95% CI 0.40-0.62). The present study suggested that increases in TG and UA, and decreases in HDL-C, significantly increase the risk of developing NAFLD. Therefore, more attention should be paid to these factors in the management and prevention of NAFLD.

UNASSIGNED: High-density lipoprotein cholesterol (HDL-C) is one of 5 components [high blood pressure, glucose, triglycerides, waist circumference, low HDL-C], 3 of which, needed to diagnose metabolic syndrome (MetS). Evolving research shows that higher HDL-C is not necessarily cardioprotective in midlife women, supporting a need to re-evaluate HDL-C\'s contribution to risks related to MetS. We tested whether risk of future diabetes and higher carotid intima-media thickness (cIMT) differ by HDL-C status in midlife women diagnosed with MetS based on the other 4 components.
UNASSIGNED: 1) no MetS, 2) MetS with HDL-C ≥ 50 mg/dL (MetS hiHDL), and 3) MetS with HDL-C < 50 mg/dL (MetS loHDL). cIMT was measured 13.8 ± 0.6 years post baseline. Incident diabetes was assessed yearly.
UNASSIGNED: Among 2773 women (1350 (48 %) of them had cIMT), 2383 (86 %) had no MetS, 117 (4 %) had MetS hiHDL, 273 (10 %) had MetS loHDL. Compared with no MetS, both MetS- hiHDL and loHDL groups had higher cIMT and diabetes risk. Risk of having high cIMT did not differ between MetS loHDL vs. hiHDL groups. Adjusting for levels of MetS criteria other than HDL-C at baseline explained the associations of each of the two MetS groups with cIMT. Conversely, after adjustment, associations of MetS hiHDL and MetS loHDL with incident diabetes persisted.
UNASSIGNED: In midlife women, HDL-C status matters for predicting risk of incident diabetes but not higher cIMT beyond other MetS components.

BACKGROUND: Cancer and sarcopenia are both closely related to lipid metabolism, but the relationship between lipid metabolism and patients with cancer and sarcopenia has not been thoroughly studied. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a reliable measure of lipid metabolism. The purpose of this study was to determine the possible relationship between the NHHR and sarcopenia in individuals with cancer.
METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) database for individuals with cancer, with and without sarcopenia was analyzed using weighted multiple regression equations, weighted regression cubic spline (RCS) analysis, and weighted subgroup analysis.
RESULTS: In total, 1,602 individuals with cancer were included, of whom 17.1% had sarcopenia. In Adjusted Model 2, the occurrence of sarcopenia was found to be significantly associated with a higher NHHR in cancer (95% confidence interval [CI]:1.01-1.39, P = 0.036). Individuals with high a NHHR had a 2.09-fold higher risk of developing sarcopenia in comparison to those with a low NHHR (95% CI:1.12-3.92, P = 0.022). RCS analysis further identified a U-shaped non-linear relationship between females with cancer and the muscle index. Subgroup analysis indicated that sex was a significant stratifying factor, whereas age, race, marital status, smoking and drinking habits, and history of cardiovascular disease, arthritis, hypertension, and diabetes had no significant impact.
CONCLUSIONS: From the perspective of lipid metabolism, the NHHR may serve as an indicator for monitoring and preventing the occurrence of sarcopenia in individuals with cancer, particularly for females with cancer who appear to have greater sensitivity.

OBJECTIVE: This cross-sectional study aimed to characterize the differences of metabolic profiles and atherogenicity between various levels of fatigue severity in patients with major depressive disorder (MDD), and examine the extent to which metabolic abnormality correlates with fatigue severity.
METHODS: We recruited 119 patients with MDD and assessed fatigue severity using Krupp\'s Fatigue Severity Scale. Blood samples were collected to determine plasma levels of fasting glucose, high-density lipoprotein cholesterol (HDL-C), triglycerides, total cholesterol and low-density lipoprotein cholesterol. The atherogenic index of plasma (AIP) was calculated as log10 (triglycerides/HDL-C).
RESULTS: MDD with severe fatigue were more likely to be younger (43.3 ± 10.3 years vs. 49.4 ± 8.5 years, p = 0.001), had a younger age of onset (34.7 ± 9.7 years vs. 40.7 ± 9.5 years, p = 0.001), demonstrated higher HAMD scores (18.0 ± 7.6 vs. 10.9 ± 7.5, p < 0.001), as well as lower HDL-C levels (48.5 ± 10.8 vs. 55.3 ± 13.9, p = 0.003), a greater prevalence of low HDL-C (43.9% vs. 22.6%, p = 0.015) and higher AIP levels (0.4 ± 0.3 vs. 0.3 ± 0.3, p = 0.046). Both a decreased plasma HDL-C level (OR = 0.95, 95% CI = 0.91-0.99, p = 0.009) and a diagnosis of low HDL-C (OR = 3.29, 95% CI = 1.27-8.57, p = 0.015) were significantly correlated with an increased risk of fatigue severity.
CONCLUSIONS: HDL-C could potentially protect patients with MDD from severe fatigue and the associated risk of cardiovascular disease.

UNASSIGNED: The current study investigated and compared serum levels of vitamin D (VD) and vaspin in AMI patients and healthy subjects and correlated these biomarkers with other biochemical risk factors for AMI.
UNASSIGNED: The research was carried out at King Abdulaziz University Hospital (KAUH) in Jeddah. Blood samples and additional information were gathered from 110 admitted AMI patients in the Intensive Coronary Care Unit (ICCU) (ages 40-65 years) and 50 adult, healthy volunteers whose BMI and age were similar to those of the patients.
UNASSIGNED: AMI patients had significantly lower vaspin (p < 0.001) and VD levels (p < 0.001) than the control group. Fasting plasma glucose (FPG), hemoglobin A1C (HbA1c), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were shown to be significantly different between AMI patients and controls. Among the AMI patients, 15 (13.6%) had deficient serum VD levels (≤20 ng/mL), 60 (54.5%) had insufficient levels (>20 - <30 ng/mL), and 35 (31.8%) had sufficient levels (≥30 ng/mL). In healthy subjects, VD levels were deficient in 4(8%), insufficient in 13 (26%), and sufficient in 33 (66%). VD insufficiency was more prevalent in AMI patients compared to the healthy group (54.5% vs 26%; p < 0.001). In AMI patients, serum vaspin was found to be related to age and HbA1c in the control group. VD did not show a significant correlation with any variable in AMI patients and healthy subjects. Serum vaspin (p = 0.89) and VD levels (p = 0.29) did not differ significantly between female and male control groups.
UNASSIGNED: Compared to the healthy group, AMI patients showed significantly lower vaspin and VD levels. Additionally, AMI patients had a higher prevalence of VD deficiency and insufficiency, suggesting its possible role in the occurrence of AMI.

UNASSIGNED: To analyze the influencing factors for progression from newly diagnosed prediabetes (PreDM) to diabetes within 3 years and establish a prediction model to assess the 3-year risk of developing diabetes in patients with PreDM.
UNASSIGNED: Subjects who were diagnosed with new-onset PreDM at the Physical Examination Center of the First Affiliated Hospital of Soochow University from October 1, 2015 to May 31, 2023 and completed the 3-year follow-up were selected as the study population. Data on gender, age, body mass index (BMI), waist circumference, etc. were collected. After 3 years of follow-up, subjects were divided into a diabetes group and a non-diabetes group. Baseline data between the two groups were compared. A prediction model based on logistic regression was established with nomogram drawn. The calibration was also depicted.
UNASSIGNED: Comparison between diabetes group and non-diabetes group: Differences in 24 indicators including gender, age, history of hypertension, fatty liver, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, HbA1c, etc. were statistically significant between the two groups (P<0.05). Differences in smoking, creatinine and platelet count were not statistically significant between the two groups (P>0.05). Logistic regression analysis showed that ageing, elevated BMI, male gender, high fasting blood glucose, increased LDL-C, fatty liver, liver dysfunction were risk factors for progression from PreDM to diabetes within 3 years (P<0.05), while HDL-C was a protective factor (P<0.05). The derived formula was: In(p/1-p)=0.181×age (40-54 years old)/0.973×age (55-74 years old)/1.868×age (≥75 years old)-0.192×gender (male)+0.151×blood glucose-0.538×BMI (24-28)-0.538×BMI (≥28)-0.109×HDL-C+0.021×LDL-C+0.365×fatty liver (yes)+0.444×liver dysfunction (yes)-10.038. The AUC of the model for predicting progression from PreDM to diabetes within 3 years was 0.787, indicating good predictive ability of the model.
UNASSIGNED: The risk prediction model for developing diabetes within 3 years in patients with PreDM constructed based on 8 influencing factors including age, BMI, gender, fasting blood glucose, LDL-C, HDL-C, fatty liver and liver dysfunction showed good discrimination and calibration.

UNASSIGNED: Pre-eclampsia is associated with significant maternal and perinatal mortality and morbidity. Increased oxidative stress due to endothelial dysfunction in pre-eclampsia has been linked with lipid abnormality. This study compared the fasting serum lipid levels in pre-eclamptic and normotensive pregnant women.
UNASSIGNED: A case-control study in which venous blood samples (5mls) were collected from 50 consenting pregnant healthy normotensive women and 50 women with pre-eclampsia accessing care at the hospital. Study participants were matched for maternal age, parity, and gestational age after 8-12 hours of fasting. The fasting serum levels of total cholesterol (TC), low-density lipoprotein (LDL-C), very low-density lipoprotein (VLDL-C), high-density lipoprotein (HDL-C) and triglycerides (TGs) of the participants were evaluated using standard enzymatic methods.
UNASSIGNED: Of the 50 pre-eclamptic and 50 pregnant normotensive women who participated in the study, the mean maternal age was 24.92±4.38 and 24.90±4.27 years respectively (p=0.98).There were statistically significant higher mean levels of TC, triglycerides, and VLDL-C among women with pre-eclampsia compared to normotensive pregnant women (p<0.001, p<0.001, p=0.007 respectively). The mean HDL-C level was significantly reduced among women with pre-eclampsia compared to controls (p<0.001). However, there was no statistically significant difference in the mean serum level of LDL-C in both groups (p=0.068). The serum lipid profile did not significantly change with the severity of pre-eclampsia.
UNASSIGNED: Women with pre-eclampsia have increased serum levels of TC, triglycerides, and VLDL-C and decreased levels of HDL-C compared to normotensive pregnant women. However, the lipid profile of women with severe pre-eclampsia did not differ significantly from those with mild pre-eclampsia.

BACKGROUND: Previous studies into relationship between high-density lipoprotein cholesterol (HDL-C) and cognitive decline were constrained to a single measurement, leaving the association between HDL-C variability and risk of cognitive decline unclear.
METHODS: We identified 5930 participants from the China Health and Retirement Longitudinal Study (CHARLS) who were devoid for stroke, dementia, and memory-related diseases at baseline and underwent a minimum of 2 sequential health examinations during 2011-2015. Variability in HDL-C was defined as (1) variability independent of the mean (VIM), (2) average real variability (ARV), and (3) standard deviation (SD) of HDL-C change from baseline and follow-up visits. Cognitive function was evaluated in 2018 by Mini-mental state examination (MMSE) in the Chinese version. Logistic regression was employed to explore the association between HDL-C variability and cognitive decline. Odd ratios (OR) and 95 % confidence intervals (CI) were reported.
RESULTS: The study included participants from CHARLS, mean age of 57.84±8.44 years and 44 % male. After adjustment for covariates, the highest quartile of VIM was associated with an increased risk of cognitive decline [OR:1.049, 95 %CI: 1.014-1.086] compared to the lowest quartile. For each SD increment of VIM, the OR was 1.015 (95 %CI:1.003-1.027). Strong dose-response relationships were identified (P for trend: 0.005). Consistent results were obtained for other measures of HDL-C variability (ARV and SD). Similar patterns were identified in different dimensions of cognition.
CONCLUSIONS: Elevated HDL-C variability was associated with increased cognitive decline risk. Strategies to reducing HDL-C variability may lower the risks of cognitive decline among the general population.