Serum 25-hydroxyvitamin D3 is associated with homocysteine more than with apolipoprotein B.

BACKGROUND/OBJECTIVES: The incidence of cardiovascular diseases (CVDs) has increased worldwide. Although a low serum vitamin D level is known to be associated with the risk of CVD, the mechanism is not well understood yet. The aim of this study was to determine the relationship of serum 25-hydroxyvitamin D3 (25[OH]D) with homocysteine and apolipoprotein B (ApoB). SUBJECTS/METHODS: Of 777 subjects recruited from one health promotion center for routine heath exam from January 2010 to December 2016, 518 subjects were included in this study. Serum 25(OH)D, serum homocysteine, and other metabolic parameters including ApoB were analyzed. Simple and partial correlations were carried out after adjustments. Simple linear regression analysis was used for precise correlation of parameters. Multivariate regression analysis was done to know which factor (serum homocysteine or ApoB) was more related to serum 25(OH)D after adjustments. Finally, logarithms of homocysteine concentrations according to tertiles of serum 25(OH)D were compared. RESULTS: After sex and age adjustments, serum 25(OH)D showed negative correlations with serum homocysteine (r' = -0.114) and ApoB (r' = -0.098). In simple linear regression analysis, serum 25(OH)D showed a significant negative correlation with ApoB (P = 0.035). However, in multivariate regression analysis, serum 25(OH)D was significantly associated with serum homocysteine after adjustments (P = 0.022). In addition, serum homocysteine concentration was significantly high in the lowest 25(OH)D group (P = 0.046). CONCLUSION: Serum 25(OH)D concentration showed a stronger negative association with serum homocysteine than with ApoB.

Serum Homocysteine and Vascular Calcification: Advances in Mechanisms, Related Diseases, and Nutrition.

Identifying and preventing modifiable risk factors for cardiovascular disease is very important. Vascular calcification has been studied clinically as an asymptomatic preclinical marker of atherosclerosis and a risk factor for cardio-cerebrovascular disease. It is known that higher homocysteine levels are associated with calcified plaques and the higher the homocysteine level, the higher the prevalence and progression of vascular calcification. Homocysteine is a byproduct of methionine metabolism and is generally maintained at a physiological level. Moreover, it may increase if the patient has a genetic deficiency of metabolic enzymes, nutritional deficiencies of related cofactors (vitamins), chronic diseases, or a poor lifestyle. Homocysteine is an oxidative stress factor that can lead to calcified plaques and trigger vascular inflammation. Hyperhomocysteinemia causes endothelial dysfunction, transdifferentiation of vascular smooth muscle cells, and the induction of apoptosis. As a result of transdifferentiation and cell apoptosis, hydroxyapatite accumulates in the walls of blood vessels. Several studies have reported on the mechanisms of multiple cellular signaling pathways that cause inflammation and calcification in blood vessels. Therefore, in this review, we take a closer look at understanding the clinical consequences of hyperhomocysteinemia and apply clinical approaches to reduce its prevalence.

Cut-off value of serum homocysteine in relation to increase of coronary artery calcification.

A recent study reported that coronary artery calcification (CAC) and serum homocysteine were well associated; however, no report is available for the cut-off value of serum homocysteine according to increase of coronary-artery calcification volume score (CVS). The data of 469 out of 777 subjects in 1 health promotion center located in Seoul were selected after exclusion of the missing data of serum homocysteine and CVS. CVS was categorized into 2 groups: CVS=0 and CVS>0. Serum homocysteine according to the CVS groups was compared, and the cut-off value of serum homocysteine according to the increase of CVS (>0) was calculated using the receiver operating characteristic curve. Mean age was 54.5 years and the proportion of females was 22.2%. Mean serum homocysteine concentration and CVS were 11.2 µmol/L and 50.4, respectively. After adjustments for age and sex, serum homocysteine was associated with CVS (r=0.167, p=0.001), and Log(Homocysteine) also showed a significant difference according to the CVS groups. The cut-off value of serum homocysteine according to the increase of CVS (>0) was 9.45 µmol/L (area under the curve=0.569 (95% CI 0.512 to 0.625), p=0.015). The cut-off value of serum homocysteine was 9.45 µmol/L according to the increase of coronary-artery CVS.

Association of serum 25-hydroxyvitamin D and serum total cholesterol with depressive symptoms in Korean adults: the Fifth Korean National Health and Nutrition Examination Survey (KNHANES V, 2010-2012).

OBJECTIVE: To examine the hypothesis that the association between vitamin D deficiency and depressive symptoms is dependent upon total cholesterol level in a representative national sample of the South Korean population. DESIGN: This was a population-based cross-sectional study. SETTING: The Fifth Korean National Health and Nutrition Examination Survey (KNHANES V, 2010-2012). SUBJECTS: We included 7198 adults aged 20-88 years. RESULTS: The incidence of depressive symptoms in individuals with vitamin D deficiency (serum 25-hydroxyvitamin D<20 ng/ml) was 1·54-fold (95 % CI 1·20, 1·98) greater than in individuals without vitamin D deficiency (serum 25-hydroxyvitamin D ≥20 ng/ml). The relationship was stronger in individuals with normal-to-borderline serum total cholesterol (serum total cholesterol<240 mg/dl; OR=1·60; 95 % CI 1·23, 2·08) and non-significant in individuals with high serum total cholesterol (OR=0·97; 95 % CI 0·52, 1·81) after adjustment for confounding variables (age, sex, BMI, alcohol consumption, smoking status, regular exercise, income level, education level, marital status, changes in body weight, perceived body shape, season of examination date and cholesterol profiles). CONCLUSIONS: The association between vitamin D deficiency and depressive symptoms was weakened by high serum total cholesterol status. These findings suggest that both vitamin D and total cholesterol are important targets for the prevention and treatment of depression.

The Cut-off Value of Blood Mercury Concentration in Relation to Insulin Resistance.

BACKGROUND: Increased blood mercury concentration is associated with inflammation, and chronic inflammation can cause insulin resistance. We examined the cut-off value of blood mercury in relation to an increased score on the homeostasis model assessment for insulin resistance (HOMA-IR). METHODS: We used data from the Korean National Health and Nutrition Examination Survey (2008-2010). Relevant data from 5,184 subjects (2,523 men and 2,661 women) were analyzed cross-sectionally. General linear analysis was performed to evaluate the relationship between HOMA-IR score and blood mercury concentration. In addition, we determined the cut-off value of blood mercury concentration in relation to increased HOMA-IR score (> 2.34) using an ROC curve. RESULTS: The mean value of blood mercury concentration in men and women was 5.88 µg/L and 4.11 µg/L, respectively. In men, comparing to the first quartile, HOMA-IR score increased significantly in the third and fourth blood mercury quartiles. In women, however, the increase in HOMA-IR score was not significant. The cut-off value that best represented the association between increased HOMA-IR score and blood mercury concentration in men was found to be 4.71 µg/L. CONCLUSION: Blood mercury concentration was associated with increased HOMA-IR score in men, and the cut-off value of blood mercury concentration that was correlated with increased HOMA-IR score was around 4.71 µg/L.

Dietary Calcium Intake May Contribute to the HOMA-IR Score in Korean Females with Vitamin D Deficiency (2008-2012 Korea National Health and Nutrition Examination Survey).

BACKGROUND: Vitamin D and calcium are important factors involved in the regulation of blood glucose and insulin secretion. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score is a useful variable for evaluating insulin resistance, and therefore we cross-sectionally compared HOMA-IR scores according to serum vitamin D levels and dietary calcium intake. METHODS: We selected data from healthy males (n=5,163) and females (n=7,506) analyzed over 5 years (2008-2012) via the Korea National Health and Nutrition Examination Survey (KNHANES). We calculated HOMA-IR scores and compared them according to serum 25-hydroxyvitamin D (25(OH)D) concentration classification (<20, 20-30, >30 ng/mL) and dietary calcium quintile after adjustment for relevant variables using complex sample analysis. Comparisons were done after data weighting. RESULTS: The mean dietary calcium intake in males and females was 558.1 mg/day and 445.9 mg/day, respectively. The mean serum 25(OH)D concentration in males and females was 19.4 ng/mL and 16.8 ng/mL, respectively. After adjustment for relevant variables, HOMA-IR score was significantly correlated with serum 25(OH)D concentration and dietary calcium intake in females, whereas it was only correlated with serum 25(OH)D concentration in males. HOMA-IR was significantly lower in the top quintile of dietary calcium intake (mean, 866 mg/day) within females with vitamin D deficiency (P=0.047). CONCLUSION: Adequate dietary calcium intake may be important for normal HOMA-IR in females with vitamin D deficiency.

Cut-off values of blood mercury concentration in relation to increased body mass index and waist circumference in Koreans.

Blood mercury (methyl-mercury) from environmental exposure may be related to inflammation in our body. We investigated the cut-off values of blood mercury concentration in relation to increased body mass index (BMI) and waist circumference. On the basis of data obtained from the Korea National Health and Nutrition Examination Survey (KNHANES, 2008-2012), 11,159 subjects (5543 males and 5616 females) were analyzed cross-sectionally. Partial correlation, linear regression, and analysis of covariance (according to the mercury quartile) tests were performed to evaluate the relationship between blood mercury and BMI or waist circumference. In addition, we determined the cut-off values of blood mercury concentration in relation to increased BMI and waist circumference in both genders. Mean values of blood mercury concentration were 5.07 ± 0.07 µg/L in males and 3.59 ± 0.04 µg/L in females. After log transformation of blood mercury, significant (p < 0.001) correlation was found between blood mercury concentration and BMI or waist circumference. BMI and waist circumference showed a significant and gradual increase as mercury quartile increased in both genders. Blood mercury concentration was weakly but significantly (p < 0.001) associated with BMI and waist circumference. Cut-off values of blood mercury concentration correlated with increased BMI and waist circumference were around 3.95 µg/L in males and 3.40 µg/L in females.

Low Level of Osteocalcin Is Related With Arterial Stiffness in Korean Adults: An Inverse J-Shaped Relationship.

CONTEXT: The relationship between bone turnover markers and atherosclerosis is controversial. OBJECTIVE: The purpose of this study was to determine the association of arterial stiffness with the levels of osteocalcin and C-terminal telopeptide of type I collagen (CTx). DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included 1691 men and 1913 women who participated in the medical examination programs of a hospital from March 2008 to December 2011. MAIN OUTCOME MEASURES: Arterial stiffness was estimated by brachial-ankle pulse wave velocity (baPWV). Osteocalcin and CTx were assayed by chemiluminescence immunoassay. Bone mineral density was measured by dual-energy X-ray absorptiometry. RESULTS: The mean baPWV was elevated at both ends of the osteocalcin quintiles in both men and women. However, the adjusted mean was higher in the lowest quintile of osteocalcin than in the other quintiles in men and women. Before adjustment, negative and positive relationships of baPWV with the levels of osteocalcin and CTx were observed in men (ß = -0.123 and -0.078 for osteocalcin and CTx, respectively) and women (ß = 0.151 and 0.193), respectively. After adjustment for age and metabolic parameters, osteocalcin was negatively related with baPWV at lower osteocalcin levels (Q1-Q2) in both sexes (in the fully adjusted model, ß = -0.090 for men and -0.053 for women). No significant relationship was observed at higher values. The osteocalcin level was fit for a quadratic model for baPWV showing an inverse J-shape. CONCLUSIONS: The level of serum osteocalcin showed an inverse J-shaped relationship with arterial stiffness in both men and women. However, the association between the CTx level and arterial stiffness was not significant.

Blood Mercury and Insulin Resistance in Nondiabetic Koreans (KNHANES 2008-2010).

PURPOSE: Blood mercury levels are associated with inflammation, and chronic low-grade inflammation is a cause of insulin resistance. This study aimed to investigate the association between serum mercury and insulin resistance. MATERIALS AND METHODS: Subjects from the 2008-2010 Korean National Health and Nutrition Examination Survey were selected (n=29235) and the relevant data of 5388 subjects (2643 males and 2745 females) were analyzed cross-sectionally. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was compared according to blood mercury quartiles, and the odds ratio (OR) of having the highest quartile of HOMA-IR according to blood mercury quartiles was calculated. RESULTS: Blood mercury levels in men and women were 29.4 nmol/L and 20.5 nmol/L, respectively, and fasting blood sugar (FBS), insulin, and HOMA-IR were significantly correlated with blood mercury levels. The correlation was stronger in men than in women. In men, FBS and HOMA-IR showed step-wise increases as the quartiles of blood mercury increased; only HOMA-IR differed significantly in the third and fourth blood mercury quartiles, compared to the first quartile. In women, however, both FBS and HOMA-IR differed significantly in the third and fourth blood mercury quartiles, compared to the first quartile. Among men, the OR of being in the highest HOMA-IR quartile was greatest for the highest blood mercury quartile (OR=1.720, 95% CI; 1.172-2.526), compared with the lowest quartile. CONCLUSION: In this large population-based study, blood mercury levels were weakly correlated with HOMA-IR and may be a risk factor for insulin resistance in nondiabetic Koreans.

Coronary artery calcification is associated with high serum concentration of undercarboxylated osteocalcin in asymptomatic Korean men.

CONTEXT: Osteocalcin is associated with energy metabolism and atherosclerosis, besides bone metabolism. However, the association between osteocalcin or its undercarboxylated form (ucOC) and coronary artery calcification is controversial. OBJECTIVE: To evaluate the relationship between coronary artery calcium score (CACS) and the concentration of serum osteocalcin and ucOC. DESIGN: Cross-sectional. PATIENTS: A total of 162 subjects (114 men and 48 women) with no angina symptom. MEASUREMENTS: Serum analyses included glucose, insulin and lipid profiles as well as osteocalcin and ucOC. Bone mineral density (BMD) was measured by dual X-ray absorptiometry. CACS was measured using multidetector computed tomography and categorized into CACS = 0 and CACS > 0. RESULTS: The mean osteocalcin concentration in men was 15·6 ± 4·2 for CACS = 0 group and 14·1 ± 4·0 for CACS > 0 group, respectively (P = 0·050). In women, the osteocalcin concentration, ucOC concentration and ucOC to osteocalcin ratio (OCR) were not different between the CACS groups. However, the concentrations of osteocalcin and ucOC were significantly lower in women with hypertension or diabetes than those without, respectively. In the multivariate logistic regression models adjusted for medical history, body mass index, lipid profiles, insulin resistance and BMD in men, the higher concentration of ucOC and higher OCR showed significant association with coronary calcification (CACS > 0). CONCLUSION: Higher ucOC concentration was associated with coronary artery calcification independent of conventional cardiovascular risk factors and BMD in men.

Dietary calcium and Framingham Risk Score in vitamin D deficient male (KNHANES 2009-2011).

PURPOSE: The association between excess calcium intake and cardiovascular mortality has already been reported. In the present study, we investigated the relation between dietary calcium intake and Framingham Risk Score (FRS) according to serum 25-hydroxyvitamin D [25(OH)D] status. MATERIALS AND METHODS: A total of 7809 subjects (3452 males and 4357 female) aged over 40 years were selected for this cross-sectional study from data obtained from the Korea National Health and Nutrition Examination Survey (2008-2011). Daily dietary calcium intake was categorized into <300, 300-600, 600-900, 900-1200, and >1200 mg/day and serum 25(OH)D concentration classified into <50, 50-75, >75 mmol/L. The FRS was compared by the daily dietary calcium intake categories according to 25(OH)D concentration after adjustment with relevant variables in both genders. RESULTS: Higher FRS was observed in males with both <300 mg and >1200 mg of dietary calcium intake and females with <300 mg of dietary calcium intake without adjustment. The significantly higher FRS remained in the <300 mg and >1200 mg of dietary calcium intake groups in both genders after adjustments for relevant variables. FRS was significantly higher in the group with >1200 mg of dietary calcium intake and serum 25(OH)D <50 nmol/L, which was the male only vitamin D deficient group. CONCLUSION: Very low (<300 mg/day) and excess (>1200 mg/day) dietary calcium intake were related with higher FRS in both genders. In particular, higher FRS was observed in the excess (>1200 mg/day) dietary calcium intake male group under vitamin D deficiency (<50 nmol/L).

Blood mercury can be a factor of elevated serum ferritin: analysis of Korea National Health and Nutrition Examination Survey (KNHANES 2008-2012).

Serum ferritin as well as blood mercury are reported to be associated with chronic inflammation. However, the relation between serum ferritin and blood mercury has not yet been established. We utilized the Korea National Health and Nutrition Examination Survey (KNHANES, 2008-2012) 10,977 subjects (5433 males and 5544 females). To evaluate the association of serum ferritin and blood mercury cross-sectionally, complex sample analysis was conducted after adjustment for the relevant variables. Serum concentrations of ferritin and blood mercury were higher in males than in females (115.7 ± 1.7 vs. 40.9 ± 0.7 ng/mL and 5.0 ± 0.1 vs. 3.6 ± 0.1 µg/L, respectively). Serum ferritin and blood mercury concentrations had significant correlations in both genders after adjustment (r = 0.062, P < 0.001 in males; r = 0.055, P < 0.001 in females). The analysis of covariance (ANCOVA) test showed significantly higher serum ferritin according to the tertile of blood mercury (P = 0.007) in males. The adjusted odds ratio of having the highest tertile of serum ferritin in the top tertile of blood mercury in males was 1.52 (95 % confidence interval (CI), 1.05-2.21). Thus, the current study indicates that blood mercury concentration can be a factor for the elevated serum ferritin concentration.

Elevated serum ferritin and mercury concentrations are associated with hypertension; analysis of the fourth and fifth Korea national health and nutrition examination survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010).

The impact of simultaneously elevated serum ferritin and mercury concentrations on hypertension in the general population is not known. To determine the association of serum ferritin and mercury concentrations with hypertension, 6213 subjects (3060 men and 3153 women) over 20 years of age from 2008 to 2010 Korea National Health and Nutrition Examination Survey were divided into tertiles according to serum ferritin and mercury concentrations in each gender. Serum ferritin (258.2 vs. 94.8 pmol/L) and mercury concentrations (28.4 vs. 19.9 nmol/L) were higher in men than in women. Serum ferritin (men; P = 0.029, women; P < 0.001) and mercury (men; P < 0.001, women; P = 0.003) concentrations were significantly associated with the prevalence of hypertension. In addition, significant correlation between serum ferritin and mercury concentrations in both men (r = 0.193, P < 0.001) and women (r = 0.145, P < 0.001) were found. Also, the increase of serum ferritin concentrations were more prominent in men (P < 0.001) than in women (P = 0.017) as the serum mercury tertiles increased after proper adjustments. Furthermore, significantly higher odds ratios of hypertension were found in the second (OR = 1.86, 95% CI; 1.05-3.30), and third (OR = 1.84, 95% CI; 1.01-3.36) tertiles of serum ferritin with the top tertile of serum mercury in men. The current study indicate that serum ferritin and mercury concentrations are associated with the prevalence of hypertension and that simultaneously elevated serum ferritin and mercury concentrations are related to the risk for hypertension in men.

Vitamin K supplement along with vitamin D and calcium reduced serum concentration of undercarboxylated osteocalcin while increasing bone mineral density in Korean postmenopausal women over sixty-years-old.

There are inconsistent findings on the effects of vitamin K on bone mineral density (BMD) and undercarboxylated osteocalcin (UcOC). The present intervention study evaluated the effect in subjects over 60-yr-old. The vitamin K group (vitamin K + vitamin D + calcium supplement; 15 mg of vitamin K2 [menatetrenone] three times daily, 400 IU of vitamin D once a day, and 315 mg of calcium twice daily) and the control group (vitamin D + calcium supplement) were randomly assigned. During the six months of treatment, seventy eight women participated (38 in the vitamin K group and 40 in the control group) and 45 women completed the study. The baseline characteristics of study participants did not differ between the vitamin K and the control groups. In a per protocol analysis after 6 months, L3 bone mineral density has increased statistically significantly in the vitamin K group compared to the control group (0.01 ± 0.03 g/cm(2) vs -0.008 ± 0.04 g/cm(2), P = 0.049). UcOC concentration was also significantly decreased in the vitamin K group (-1.6 ± 1.6 ng/dL vs -0.4 ± 1.1 ng/dL, P = 0.008). In conclusion, addition of vitamin K to vitamin D and calcium supplements in the postmenopausal Korean women increase the L3 BMD and reduce the UcOC concentration.