Association Between Adequate Serum 25(OH)D Levels and Atherogenic Dyslipidemia in Young Adults.

AIM: This study aimed to investigate the association between vitamin D deficiency and novel biomarkers of atherogenic dyslipidemia among young adults. METHOD: A total of 976 young adults were recruited between 2011 and 2019. Their serum 25(OH)D levels were measured, and lipid profile markers, including low-density lipoprotein cholesterol (LDL-C), low-density lipoprotein triglyceride (LDL-TG), and small-dense low-density lipoprotein cholesterol (sdLDL-C), were assessed as novel biomarkers of atherogenic dyslipidemia. Multivariable linear regression was used to analyze the association between vitamin D levels and lipid profile markers. Odds ratios were calculated to assess the risk of atherogenic dyslipidemia in individuals with serum 25(OH)D levels below 30 ng/mL compared to those with levels above 30 ng/mL. Structural equation modeling (SEM) was employed to explore potential mediation pathways. RESULTS: The study found a significant association between vitamin D levels and lower levels of LDL-C, LDL-TG, sdLDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and total cholesterol. Individuals with serum 25(OH)D levels below 30 ng/mL exhibited significantly higher odds ratios for developing atherogenic dyslipidemia in a dose-response pattern compared to those with vitamin D levels above 30 ng/mL. Notably, structural equation modeling (SEM) analysis revealed that vitamin D did not affect atherogenic lipid markers through the mediation of insulin resistance markers or high-sensitivity C-reactive protein. CONCLUSION: This study provides evidence of an association between vitamin D deficiency and atherogenic dyslipidemia in young adults. It further highlights that individuals with serum 25(OH)D levels below 30 ng/mL are at a significantly higher risk of developing atherogenic dyslipidemia in a dose-response manner compared to those with higher vitamin D levels. These findings underscore the potential role of vitamin D in dyslipidemia management and emphasize the importance of maintaining sufficient vitamin D levels for cardiovascular health in young adults.

Association of Urinary Lead and Cadmium Levels, and Serum Lipids with Subclinical Arteriosclerosis: Evidence from Taiwan.

BACKGROUND: Exposure to lead and cadmium has been linked to changes in lipid metabolism and the development of arteriosclerosis, but the role of lipoprotein profiles in this relationship is not well understood, including the potential role of novel lipid biomarkers. METHODS: In this study, we enrolled 736 young Taiwanese subjects aged 12 to 30 years to assess the correlation between urine levels of lead and cadmium, lipoprotein profiles, and carotid intima-media thickness (CIMT). RESULTS: Higher levels of lead and cadmium were significantly associated with higher levels of low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), LDL-triglyceride (LDL-TG), and CIMT. Participants with higher levels of lead and cadmium had the highest mean values of CIMT, LDL-C, sdLDL-C, and LDL-TG. In a structural equation model, lead had a direct and indirect association with CIMT through LDL-C and sdLDL-C, whereas cadmium had a direct association with CIMT and an indirect association through LDL-C. CONCLUSION: Our results suggest higher levels of lead and cadmium are associated with abnormal lipid profiles and increased CIMT. These heavy metals could have additive effects on lipids and CIMT, and the relationship between them may be mediated by lipoprotein levels. Further research is needed to determine the causal relationship.

Glycative Stress, Glycated Hemoglobin, and Atherogenic Dyslipidemia in Patients with Hyperlipidemia.

(1) Background: Diabetes mellitus (DM) is a significant health problem and is associated with dyslipidemia; however, the association between glycative stress, in terms of glycated hemoglobin (HbA1c), and atherogenic dyslipidemia in hyperlipidemic patients with and without DM has rarely been reported. (2) Methods: We prospectively recruited 949 hyperlipidemic patients from the Lipid Clinic of the National Taiwan University Hospital. HbA1c and fasting serum lipids, including total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), small dense LDL-C (sdLDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglycerides, and advanced glycation end-products (AGEs), were measured. After fasting for 10-14 h, all subjects except those with DM underwent a standard oral glucose tolerance test (OGTT) with 75 g of glucose loading. All subjects were asked to discontinue the use of lipid-lowering agents for 8 weeks before recruitment. (3) Results: Patients with DM had a higher prevalence of hypertension and higher levels of triglyceride, TC/HDL-C ratio, AGEs, VLDL-C, and sdLDL-C. Among patients with higher HbA1c, the serum VLDL-C, AGEs, and TC/HDL-C ratio were significantly higher than those with lower HbA1c. After adjustment for covariates, multiple logistic regression analyses revealed different groups of dysglycemia with higher HbA1c had a higher odds ratio for TC/HDL-C ≥ 5, sdLDL-C ≥ 75th percentile, VLDL-C ≥ 75th percentile and AGEs ≥ 75th percentile. (4) Conclusions: A higher HbA1c was associated with a significant increase in the risk of atherogenic dyslipidemia and AGEs levels in patients with hyperlipidemia. The findings can be very promising in clinical application.

Association between Vitamin D Deficiency and High Serum Levels of Small Dense LDL in Middle-Aged Adults.

Recent studies suggested a potential link between vitamin D deficiency and cardiovascular risk factors, including dyslipidemia. This study aimed to investigate the association between serum 25(OH)D levels and atherogenic lipid profiles, specifically, that of small dense low-density lipoprotein-cholesterol (sdLDL-C). From 2009 to 2011, a total of 715 individuals aged 35-65 without evident cardiovascular disease (CVD) were enrolled. Their levels of serum 25(OH)D and lipid profiles were measured. Vitamin D deficiency was found to be more common in females, smokers, alcohol drinkers, individuals at a younger age, and those who do not exercise regularly. The analysis of lipid profiles revealed that high sdLDL-C levels were associated with low serum vitamin D levels and were more common among cigarette smokers; alcohol drinkers; individuals with hypertension; individuals with high BMI; and those with high levels of fasting blood glucose, triglycerides, LDL-C, and VLDL-C. The use of multivariate logistic regression verified a strong negative correlation between low vitamin D status (serum 25(OH)D < 15 ng/mL) and the three identified biomarkers of atherogenic dyslipidemia: high serum levels of sdLDL-C, triglycerides, and VLDL-C. This study provides strong evidence that vitamin D deficiency is associated with atherogenic dyslipidemia, and in particular, high sdLDL-C levels in middle-aged adults without CVD.

Positive Association Between Small Dense Low-Density Lipoprotein Cholesterol Concentration and Biomarkers of Inflammation, Thrombosis, and Prediabetes in Non-Diabetic Adults.

AIMS: Recent studies suggest elevated levels of small dense low-density lipoprotein cholesterol (sdLDL-C) can predict the risk of incident coronary heart disease (CHD), even in individuals considered to be at low risk for cardiovascular disease(CVD) based on their LDL-C levels. This study aims to prospectively investigate the association between sdLDL-C concentration and traditional and nontraditional CHD risk markers to explore the underlying roles of sdLDL-C in atherogenic processes. METHODS: Between 2009 and 2011, 594 healthy volunteers aged 35-65 years were recruited as control subjects in a study of work-related risk factors and acute CHD. All participants fasted for 12-14 h, and venous blood samples were collected in the morning to measure serum lipid profiles and other CHD-related markers. A standard oral glucose tolerance test was performed on all participants to assess their subclinical diabetes and prediabetes status. RESULTS: There were significantly positive associations between sdLDL-C concentration and traditional (age, smoking and alcohol drinking habit, blood pressure, body mass index (BMI), serum lipid profiles, and diabetes status) and nontraditional risk factors (complete blood counts, (CBC), fibrinogen, high-sensitivity C-reactive protein, and subclinical diabetes status) for CVD. After adjusting for confounding variables which include age, gender, BMI, hypertension, household income, and smoking and alcohol drinking habits, all atherosclerotic risk markers except D-dimer were significantly and positively associated with sdLDL-C. CONCLUSIONS: Our data indicated sdLDL-C is strongly associated with atherosclerotic risk markers, such as inflammation, thrombosis, hematological markers, and prediabetes. This study supports the hypothesis that sdLDL-C is a promising CVD risk biomarker.

Association of short-term exposure to fine particulate matter and nitrogen dioxide with acute cardiovascular effects.

This study evaluated whether exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) is associated with cardiovascular effects by examining a panel of 89 healthy subjects in Taipei, Taiwan. The subjects received two health examinations approximately 8months apart in 2013. Brachial-ankle pulse wave velocity (baPWV), a physiological indicator of arterial stiffness, and high-sensitivity C-reactive protein (hsCRP), a biomarker of vascular inflammations, were measured during each examination. Two exposure assessment methods were used for estimating the subjects' exposure to PM2.5 and NO2. The first method involved constructing daily land use regression (LUR) models according to measurements collected at ambient air quality monitoring stations. The second method required combining the LUR estimates with indoor monitoring data at the workplace of the subjects. Linear mixed models were used to examine the association between the exposure estimates and health outcomes. The results showed that a 10-µg/m(3) increase in PM2.5 concentration at a 1-day lag was associated with 2.1% (95% confidence interval: 0.7%-3.6%) and 2.4% (0.8%-4.0%) increases in baPWV based on the two exposure assessment methods, whereas no significant association was observed for NO2. The significant effects of PM2.5 remained in the two-pollutant models. By contrast, NO2, but not PM2.5, was significantly associated with increased hsCRP levels (16.0%-37.3% in single-pollutant models and 26.4%-44.6% in two-pollutant models, per 10-ppb increase in NO2). In conclusion, arterial stiffness might be more sensitive to short-term PM2.5 exposure than is inflammation.

Association of Psychosocial Work Hazards With Depression and Suboptimal Health in Executive Employees.

OBJECTIVES: This study aims to investigate whether psychosocial work-related hazards, measured by workplace justice and employment insecurity, are associated with depression and suboptimal health status in Taiwan's executive-level employees. METHODS: There were 365 executives who have received a series of cardiovascular health examinations, blood sampling, and self-reported questionnaires, which included the psychosocial work-related hazards and the CES-D scale. Suboptimal health status was defined as the presence of dyslipidemia or prediabetes. RESULTS: Executive-level employees perceived lower workplace justice and higher employment insecurity and had a significantly higher risk of depression (CES-D scores ≥16 or ≥23). However, workplace justice was identified as a significant determinant factor that was negative for dyslipidemia but protective for prediabetes. CONCLUSION: This study supports the fact that psychosocial work-related hazards can independently contribute to the risk of developing depression, prediabetes, and dyslipemia in executives.

Additive effects of postchallenge hyperglycemia and low-density lipoprotein particles on the risk of arterial stiffness in healthy adults.

BACKGROUND: To determine the effects of post-challenge hyperglycemia potentiate low-density lipoprotein cholesterol (LDL) particles on the risk of arterial stiffness in non-diabetic adults. METHODS: During 2009-2011, 592 adults without clinical diabetes (fasting glucose <7.0 mmol/L) or known coronary heart disease or stroke were recruited. All subjects underwent standard 75-g oral glucose tolerance test (OGTT) after overnight fasting. The glucose area under curve (GluAUC) after OGTT was defined as the postchallenge glucose load. Levels of LDL-C and small dense LDL-C (sdLDL-C) were measured. Arterial stiffness in terms of brachial-ankle pulse wave velocity (baPWV) was also measured. RESULTS: The baPWV in tertile distributions were significantly associated with all conventional cardiovascular risk factors, LDL-C, and sdLDL-C. Multivariate logistic regression analyses revealed that LDL-C (or sdLDL-C) combined with one of the seven glycemic indices (glucose levels at 0, 30, 60, 90, and 120 min; GluAUC; HbA1C) was associated with arterial stiffness after covariates being adjusted. Further interaction analyses showed only concurrent higher levels of both glycemic indices and atherogenic LDL-C or sdLDL-C have significant risk for arterial stiffness. CONCLUSIONS: Additive effects of both postchallenge hyperglycemia and LDL subclass particles potentiate the risk of arterial stiffness. The adverse joint effects of hyperlipidemia and postchallenge hyperglycemia on subclinical cardiovascular function provide important information in primary prevention of cardiovascular disease in subjects without clinical diabetes.

An overweight or obese status in childhood predicts subclinical atherosclerosis and prehypertension/hypertension in young adults.

AIM: The aim of this study, the YOung TAiwanese Cohort (YOTA) Study, was to investigate the relationship between a childhood overweight/obese status and young adult preclinical atherosclerosis, including assessments of the carotid intima-media thickness (CIMT) and prehypertension or hypertension. METHODS: From among children who participated in the 1992-2000 mass urine screening program in Taiwan, we recruited 303 subjects with an elevated blood pressure (EBP) and 486 subjects with a normal BP in childhood during the period of 2006-2008. These 789 young adults received health check-ups for cardiovascular health, including examinations of blood and urine parameters, anthropometrics, BP and the CIMT, a subclinical cardiovascular risk index. Data analyses were used to evaluate the associated risks in both childhood and young adulthood. RESULTS: The school students with a childhood overweight/obese status had a higher risk of prehypertension or hypertension, with a relative risk of 3.20 (1.40-7.33) for being overweight and 6.51 (3.36-12.63) for being obese in young adulthood at an average age of 21. A childhood overweight/obese status also predicted a higher risk of having a thicker CIMT, with a relative risk of 2.82 (1.26-6.28) and 4.17 (2.21-7.85) for being overweight and obese in adulthood, respectively, after a mean follow-up of 8.5 years. The body mass index exhibited a consistent trend from childhood to adulthood, with an adjusted R square of 0.551. The participants who were not overweight/obese in childhood also demonstrated a higher risk of prehypertension or hypertension if they became overweight or obese in adulthood. CONCLUSIONS: This study highlights the importance of preventing and treating an overweight or obese status in childhood for the primary prevention of cardiovascular disease in adulthood.

Human interleukin-10 genotypes are associated with different precore/core gene mutation patterns in children with chronic hepatitis B virus infection.

OBJECTIVE: To elucidate the association between human interleukin-10 (IL-10) genotypes and hepatitis B virus (HBV) precore/core gene mutation in children with chronic HBV infection. STUDY DESIGN: The study group comprised of 21 children with chronic HBV infection with spontaneous hepatitis B e antigen (HBeAg) seroconversion who were followed for more than 10 years. Another nine children without HBeAg seroconversion served as the control subjects. Sera at the immune tolerance and inflammatory phase (alanine aminotransferase, >80 IU/L) were subjected to HBV precore/core sequence analysis. IL-10 -1082 polymorphism was also determined. RESULTS: HBV precore/core gene mutation increased significantly more in the inflammatory phase than in the tolerance phase (G1896A, 76.2% versus 4.8%; C1913A, 33.3% versus 0%; C2189A, 28.6% versus 4.8%; G2304A, 52.4% versus 14.3%) in study group (n = 21) but not the control group (n = 9). Subjects with the G/G genotype at the IL-10-1082 polymorphism site had higher C2189A mutation rate than the A allele carriers (P = .02). C2189A mutation carriers are associated with more viral load decrement from tolerance to inflammatory phase (P = .01) and earlier spontaneous HBeAg seroconversion (P = .01). CONCLUSIONS: The G/G genotype at the IL-10 -1082 polymorphism is associated with higher C2189A mutations, lower HBV viral load at immune inflammatory phase, and earlier spontaneous HBeAg seroconversion than A allele carriers.

Tumour necrosis factor-α promoter region polymorphisms affect the course of spontaneous HBsAg clearance.

BACKGROUND: This study aimed to investigate the roles of tumour necrosis factor-α (TNF-α) gene polymorphisms in the spontaneous clearance of HBsAg after a hepatitis B virus (HBV) infection. METHODS: Polymorphisms in the TNF-α (-1031 T to C, -863 C to A, -857 C to T, -308 G to A and -238 G to A transition) gene were evaluated in 274 chronic HBV-infected patients and 194 patients with resolved HBV infection. The peripheral blood mononuclear cells (PBMC) isolated from 77 (28%) of the 274 chronic HBV-infected patients with negative HBeAg and positive antibody to HBeAg were stimulated with HBcAg. Data on TNF-α genotypes and phenotypes in subjects with/without the A allele at the TNF-α-863 promoter single nucleotide polymorphism (rs1800630) were compared. RESULTS: The A allele in the -863 promoter region of the TNF-α gene was present in 154 (56.2%) chronic HBV-infected patients and 87 (44.8%) patients who recovered from HBV infection (odds ratio 1.58; P<0.01). The TNF-α-863 A allele genotype predicted lower TNF-α production by PBMC after in vitro HBcAg stimulation (P<0.02). CONCLUSIONS: The A allele at the -863 locus of the promoter region of the TNF-α gene predicts lower HBcAg-inducible TNF-α secretion. It is also associated with chronicity of HBV infection.

Hyperuricemia associated with rapid renal function decline in elderly Taiwanese subjects.

BACKGROUND/PURPOSE: Hyperuricemia is encountered frequently in patients with chronic kidney disease (CKD). We tested the hypothesis that uric acid influences glomerular filtration rate (GFR) and is associated with renal function decline in elderly Taiwanese subjects. METHODS: We enrolled 800 elderly Taiwanese subjects for a health checkup. Estimated GFR (eGFR) was measured using the Modification of Diet in Renal Disease Study equation. eGFR < 60 mL/min/1.73 m2 was used to analyze the prevalence and incidence of CKD. Significant renal function decline was defined as a decrease in eGFR of > or = 3 mL/min/1.73 m2 per year. RESULTS: The prevalence of CKD was 18.0% in the elderly subjects. Mean serum uric acid level was 6.6 mg/dL in male and 5.6 mg/dL in female subjects, and eGFR was 71.7 mL/min/1.73 m2. Uric acid levels were associated independently and negatively with eGFR after adjusting for conventional factors of renal function decline. One hundred and sixty-two individuals (31.2%) had a significant decline in renal function. As uric acid level increased by 1 mg/dL, the odds of a significant eGFR decline increased by 1.208. CONCLUSION: Serum uric acid level was associated with eGFR and decline in renal function in elderly Taiwanese subjects. Whether hypouricemic therapy could retard the progression of CKD deserves further in-depth study.

Association of circulating matrix metalloproteinase-1, but not adiponectin, with advanced coronary artery disease.

OBJECTIVE: Recent evidence suggests that high tissue matrix metalloproteinase-1 (MMP-1) and low adiponectin may serve as biomarkers of atherosclerosis. Results on the associations of circulating MMP-1 and adiponectin concentrations are scarce. We hypothesized that patients with multivessel coronary artery disease (CAD) have elevated high-sensitivity C-reactive protein (hs-CRP), MMP-1 but low adiponectin levels, and concomitant measurements of these biomarkers could improve predictive strength for advanced CAD. RESEARCH DESIGN AND METHODS: We analyzed concentrations of MMP-1, hs-CRP and adiponectin in 217 subjects with angiographically documented multivessel CAD (two-, or three-vessel disease by luminal stenosis >or=50%) and 81 controls. MMP-1 and hs-CRP were notably higher in patients with CAD; while adiponectin was not significantly different between two groups. Levels of hs-CRP positively correlated with body mass index and left ventricular dysfunction (R(2)=0.16, P<0.0001); while adiponectin was significantly associated with age, gender, and levels of cholesterol and triglyceride (R(2)=0.09, P<0.0001). On the contrary, MMP-1 was not associated with any clinical cardiovascular risk factors, and still an independent predictor (OR=1.49, P<0.0001) of multivessel CAD after the adjustment of clinical risk factors and hs-CRP. CONCLUSION: Elevated MMP-1 and hs-CRP, but not low adiponectin concentrations, could predict the presence of advanced coronary atherosclerosis. In addition, MMP-1 may serve as a more specific marker for significant CAD independent of hs-CRP.